{"ID":103423,"post_author":"9412100","post_date":"2022-06-28 14:10:19","post_date_gmt":"0000-00-00 00:00:00","post_content":"","post_title":"LIMSjournal - Summer 2022","post_excerpt":"","post_status":"draft","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"","to_ping":"","pinged":"","post_modified":"2022-06-28 14:10:19","post_modified_gmt":"2022-06-28 18:10:19","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.limsforum.com\/?post_type=ebook&p=103423","menu_order":0,"post_type":"ebook","post_mime_type":"","comment_count":"0","filter":"","_ebook_metadata":{"enabled":"on","private":"0","guid":"A7DC1A13-DFF7-463D-A9A7-C884EB76ECD9","title":"LIMSjournal - Summer 2022","subtitle":"Volume 8, Issue 2","cover_theme":"nico_21","cover_image":"https:\/\/www.limsforum.com\/wp-content\/plugins\/rdp-ebook-builder\/pl\/cover.php?cover_style=nico_21&subtitle=Volume+8%2C+Issue+2&editor=Shawn+Douglas&title=LIMSjournal+-+Summer+2022&title_image=https%3A%2F%2Fs3.limsforum.com%2Fwww.limsforum.com%2Fwp-content%2Fuploads%2FFig4_Temprana-Salvado_Diagnostics22_12-4.png&publisher=LabLynx+Press","editor":"Shawn Douglas","publisher":"LabLynx Press","author_id":"26","image_url":"","items":{"033f483b8781387c15eeaf676086cc6e_type":"article","033f483b8781387c15eeaf676086cc6e_title":"Development of a smart laboratory information management system: A case study of NM-AIST Arusha of Tanzania (Mwambe et al. 2022)","033f483b8781387c15eeaf676086cc6e_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania","033f483b8781387c15eeaf676086cc6e_plaintext":"\n\nJournal:Development of a smart laboratory information management system: A case study of NM-AIST Arusha of TanzaniaFrom LIMSWikiJump to navigationJump to searchFull article title\n \nDevelopment of a smart laboratory information management system: A case study of NM-AIST Arusha of TanzaniaJournal\n \nInternational Journal of Advances in Scientific Research and EngineeringAuthor(s)\n \nMwambe, Edson; Wangere, Joseph N.; Flavian, Daudi; Sinde, RamadhaniAuthor affiliation(s)\n \nNelson Mandela African Institution of Science and TechnologyPrimary contact\n \nEmail: mwambee at nm-aist dot ac dot tzYear published\n \n2022Volume and issue\n \n8(4)Page(s)\n \n1\u201314DOI\n \n10.31695\/IJASRE.2022.8.4.1ISSN\n \n2454-8006Distribution license\n \nCreative Commons Attribution-NonCommercial 4.0 InternationalWebsite\n \nhttps:\/\/ijasre.net\/index.php\/ijasre\/article\/view\/1500Download\n \nhttps:\/\/ijasre.net\/index.php\/ijasre\/article\/view\/1500\/1921 (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n\n2.1 Background \n2.2 Problem statement \n2.3 Objectives and research questions \n2.4 Conceptual framework \n2.5 Significance of the study \n\n\n3 Literature survey \n4 Materials and methods \n\n4.1 Study area and scope \n4.2 Data collection method \n4.3 System requirements \n4.4 System development approach \n4.5 System design \n\n4.5.1 Simulation \n\n\n\n\n5 Results and discussion \n\n5.1 Web application \n5.2 Hardware subsystem \n5.3 Discussion \n\n\n6 Conclusion and recommendations \n7 Acknowledgements \n\n7.1 Conflict of interest \n\n\n8 References \n9 Notes \n\n\n\nAbstract \nTesting laboratories in higher learning institutions of science, technology, and engineering are used by institutional staff, researchers, and external stakeholders in conducting research experiments, sample analysis, and result dissemination. However, there exists a challenge in the management of laboratory operations and processing of laboratory-based data. Operations carried out in the laboratory at Nelson Mandela African Institution of Science and Technology (NM-AIST), in Arusha, Tanzania\u2014where this case study was carried out\u2014are paper-based. There is no automated way of sample registration and identification, and researchers are prone to making errors when handling sensitive reagents. Users have to physically visit the laboratory to enquire about available equipment or reagents before borrowing or reserving those resources. Additionally, paper-based forms have to be filled out and handed to the laboratory manager for approval. These manual operations make it difficult to keep track of expiry dates of reagents, stock remaining, storage conditions, software licenses, tools, and data regarding borrowed equipment, as these facets lack automated notification mechanisms. \nThis study, therefore, was carried out to investigate the development of a smart laboratory information management system (LIMS) integrated with internet of things (IoT) devices, a wireless sensor network (WSN), and radio frequency identification (RFID) technology for real-time monitoring of sample and reagents storage conditions, as well as digital sample identification and tracking. A web application was developed to allow remote access to laboratory information by users. Based on the performance test, it is concluded that WSNs can be integrated with IoT devices to automate recurring tasks in laboratories, aid in monitoring, and eliminate paper-based record keeping.\nKeywords: radio frequency identification, wireless sensor network, internet of things, MQTT, ZigBee protocol, ThingSpeak, laboratory information management system\n\nIntroduction \nBackground \nHigher learning institutions of science, technology, and engineering conduct experiments in testing laboratories. According to the Oxford Learner\u2019s Dictionary, a laboratory is a building or a part of a building or any other place set aside and equipped for conducting scientific experiments or investigations, in order to develop new products. These testing laboratories are accessible to institutional staff, researchers, and external stakeholders. The Nelson Mandela African Institution of Science and Technology (NM-AIST), based in East Africa (Arusha, Tanzania), has one such testing laboratory that is subdivided into three subsections. Each subsection deals with a different thematic research focus area and is led by a section head. The flow of information in testing laboratories is complex, from sample registration to assigning the sample to an analyst, recording the sample results for each parameter tested, and relaying the results back to the client or researcher. Conventional paper-based approaches for recording all this information are not efficient. A lot of time is bound to be wasted following up on paperwork, and crucial details might be missed or lost in the process. There is therefore a need to aggregate laboratory information on a single platform that can be accessed remotely in order to guarantee real-time access of laboratory data, as well as automate manual processes to increase efficiency, speed, and accuracy. This study therefore proposes a web-based smart laboratory information management system (LIMS) integrated with wireless sensor network (WSN) technology, internet of things (IoT) devices, and radio frequency identification (RFID) to streamline laboratory operations and consolidate all data on a single platform for easy accessibility and tracking.\n\nProblem statement \nThere exists a challenge in the management of most testing laboratories, in that operations are carried out manually. There is no established mechanism of sample identification, and researchers are prone to making errors when handling sensitive reagents. If users need to borrow laboratory equipment, they have to physically visit the laboratory office, enquire about the availability of equipment, and manually fill out a paper-based form before handing it to the laboratory manager for approval. Due to such manual operations, it is difficult to keep track of expiry dates of reagents, remaining stock, software licenses, tools, data regarding borrowed items, and more. It is therefore in light of the aforementioned setbacks that this study was carried out to investigate the development of a smart LIMS to automate processes in testing laboratories, enabling researchers to plan activities.\n\nObjectives and research questions \nThe main objective of this research was to investigate the development of a smart LIMS. The specific objectives were:\n\nDetermine and gather requirements for the design and development of a smart LIMS.\nDesign and develop a smart LIMS based on those requirements.\nValidate the developed system.\nA series of research questions tie into those objectives:\n\nWhat are the requirements for developing a smart LIMS?\nHow should the smart LIMS be designed and developed?\nHow will the study ensure the developed system meets the specified user requirements?\nConceptual framework \nFigure 1 below represents a conceptual framework model that guided the development of the smart LIMS. A web application links an IoT module and inventory module to different user categories, e.g., researchers and laboratory staff.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. Conceptual framework for a smart laboratory information management system\n\n\n\nSignificance of the study \nThe implementation of the system is significant in the following outlined aspects:\n\nReduction of overhead in the reporting and management processes within laboratories\nEnabling of a central database of all laboratory data in order to digitize operations\nMinimizing operational costs of the laboratory\nFacilitating enforcement of laboratory policies, rules, and standard operating procedures\nFacilitating appropriate and timely calibration of laboratory instruments\nEasy monitoring of inventory, including equipment, samples, supplies, and reagents\nLiterature survey \nA LIMS is a database software application used to acquire, store, analyze, manage, and monitor data in a testing laboratory. The LIMS improves laboratory workflow and productivity by managing the data of samples, reagents, laboratory equipment, analyses, and other activities and stakeholders. A LIMS can act as a single repository of all laboratory information and reduce the communication gaps among the laboratory manager, quality assurance manager, and other stakeholders.[1]\nDifferent researchers have previously attempted to address the automation and digitization of laboratories. We critically analyzed different research to identify gaps and inconsistencies. For example, an RFID-based functioning model for managing laboratory inventory was developed by Hazura et al.[2] RFID is a wireless, contactless identification technology that does not require line of sight. The technology operates in both the low-frequency and ultra-high-frequency RFID standards. However, in their proposed model, a control unit was used to relay data between a 13.56-megahertz (MHz) micro RFID reader and a programmable integrated circuit (PIC), before then sending the data to a computer. The drawback of their proposed solution was a lack of a mechanism for remote or wireless accessibility to the system.\nIn another study, Hsieh et al.[3] developed an IoT-based smart laboratory administrator system for intrusion and sound detection, as well as monitoring temperature and controlling laboratory access. The system employed OpenCV technology to detect invasion of objects and an Arduino microcontroller with IoT sensors to collect environmental sounds and temperature. The system detected movement, temperature, and voice in real-time and sent immediate messages through an application or email. The limitation of the study, however, was the use of a quick response (QR) code to manage the inventory through a mobile application. The QR code requires line of sight, needs objects to be scanned one by one, and are read-only with a short scanning range.\nA system to manage laboratory information and track large amounts of DNA sequencing data was developed by Vu et al.[4] The system employed barcode technology to label the sequenced samples and track experimental procedures. However, sample parameters were still manually fed into the system, which could be prone to error and result in lack of validated data.\nAnother laboratory equipment management system based on RFID technology was developed for colleges and universities by Zhang and Reha.[5] The system was customized to monitor and track laboratory equipment in real time. It was based on RFID technology, which is superior over other identification technologies because it is automatic, contactless, has a strong ability to be adaptable in demanding environments, and possesses a high data capacity, up to 116 bytes of data. However, RFID implementations cost more compared to barcode implementations.\nRFID is among the more popular technologies used for identification of assets in a laboratory. Wahab et al.[6] developed a study similar to Zhang and Reha, examining a web-based laboratory equipment monitoring system that used RFID technology. The system architecture consisted of an RFID reader, RFID tag, RS232 cable, personal computer, and a local area network (LAN) hub. RFID was tested to be 100% accurate in terms of real-time data capture of outbound and inbound equipment in the database. However, a passive RFID tag with an operating frequency of 125 kilohertz (kHz) was used. Its limitation is short response distance, and the metal shield in the RFID tag can block and interfere with the electromagnetic field produced by the RFID reader, thus preventing the tag from being read properly.\nIn a different study, a system to manage the maintenance of equipment was developed based on mobile two-dimensional (2D) barcode and RFID technology. In the study, it was demonstrated that both RFID and barcode systems can be used on the same equipment. Both 2D barcode and RFID technologies store and provide information. However, RFID tags are easier and faster to read compared to 2D barcodes. In terms of cost, 2D barcodes are cheaper than RFID.[7]\nAnother RFID system was developed by Ma and Wang to manage and track students\u2019 experiments. RFID was selected over other technologies such as magnetic cards due to being contactless, robust, having high data reading speed, being user friendly, and demonstrating an ability to read multiple tags simultaneously.[8]\nRFID technology has also been employed in the development of a library system for automating activities related to the borrowing, renewal, and return of books. The system employs GSM technology to alert the users on the return due date. The system is efficient in terms of speeding up the processes of searching, borrowing and returning books. However, users cannot access the system remotely.[9]\nMore recent studies have focused on RFID technology due to its superior features over other identification technologies in terms of long response distance range, longer lifespan, reusability, and robustness. In the reviewed studies, the systems were implemented to be accessed locally when a client is in the same LAN. Based on functionality, the studies focused primarily on laboratory equipment and not the management of samples, reagents, and analytical data. This study therefore was carried out to bridge the gaps identified in the previous works.\n\nMaterials and methods \nStudy area and scope \nThis study was carried out in the United Republic of Tanzania, whereby the NM-AIST was used as a case study. The scope entailed the development of a web-based smart LIMS that integrated with RFID technology for scanning and tracking samples, as well as an IoT module for real-time monitoring of sample storage conditions (i.e., humidity and temperature).\n\nData collection method \nPrimary data was collected from laboratory staff, management, and researchers using group discussions, observation, and face-to-face interviews. Secondary data was collected from policy documents, journal articles, research reports, articles, websites, and white papers.\n\nSystem requirements \nThe system requirements were categorized into both software requirements and hardware requirements. The software requirements were tabulated as represented in Table 1.\n\n\n\n\n\n\n\nTable 1. Software requirements for the smart LIMS\n\n\nSoftware\n\nPurpose\n\n\nSTM32 Cube Programmer (STM32CUBEPROG)\n\nFlashing bootloader application on STM32F103C8T6 microcontroller\n\n\nDigi XCTU software\n\nFor configuring the XBee S2C radio modules\n\n\nDraw.IO\n\nModelling the Unified Modeling Language (UML) diagram for the system\n\n\nVisual Paradigm 16.3\n\nModelling the entity relationship\n\n\nKiCad 5\n\nPrinted circuit design and implementation\n\n\nVisual Studio Code source code editor\n\nWriting PHP, HTML, CSS, and JavaScript code\n\n\nArduino IDE\n\nWriting sketches for the ESP32 microcontroller\n\n\nMySQL\n\nDatabase design and queries\n\n\nApache\n\nHTTP server\n\n\nThingSpeak\n\nCloud for aggregating and visualizing source data from internet of things hardware devices\n\n\nTwilio\n\nCommunication API platform for sending SMS notifications\n\n\n\nHardware requirements on the other hand were captured as represented in Table 2. XBee S2C modules were selected due to their range of more than 60 meters when indoors and up to 1200 meters when outdoors, with a data rate of up to 250,000 bits per second. They operate using the IEEE 802.15.4 technical standard for low-rate wireless personal area networks, within the 2.4GHz unlicensed industrial, scientific, and medical (ISM) band. Communication peripherals include a Serial Peripheral Interface (SPI) and universal asynchronous receiver-transmitter (UART) interfaces.[10]\n\n\n\n\n\n\n\nTable 2. Hardware requirements for the smart LIMS\n\n\nHardware\n\nModel\n\n\nProgrammer\n\nST-LINK\/V2 Mini Programmer\n\n\nZigBee wireless module\n\nXBee 3mW Wire Antenna Series 2C (ZigBee Mesh)\n\n\nXBee adapter\n\nFunduino XBee USB Adapter\n\n\nMicrocontroller boards\n\nESP32, STM32F103C8T6\n\n\nRFID reader and tags\n\nRC522 13.56Mhz Mifare S50 Card\n\n\nLiquid crystal display (LCD)\n\nLCD1602\n\n\nI2C LCD display interface Adapter\n\nPCF8574\n\n\nTemperature sensor\n\nAM2302 (Wired DHT22) Temperature-Humidity Sensor\n\n\nBuzzer\n\nPiezo buzzer\n\n\nLED\n\nStandard 5mm LEDs\n\n\nPrototyping boards\n\nPCB Copper Veroboards\n\n\nPower supply\n\n3.7V Li-ion rechargeable batteries\n\n\nStep down converters\n\nLM2596 DC-DC Buck Converter Step Down\n\n\nToggle switch (two-pin)\n\nMini Rocker Switch 117S 2-Pin 125V\/6A\n\n\n\nThe study\u2019s proposed ZigBee topology is as illustrated in Figure 2, consisting of router nodes and a coordinator node.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. ZigBee network topology\n\n\n\nSystem development approach \nThe Agile software development methodology was adopted in the development phase of this study due to the short development cycles in terms of iterations, as well as integrated testing throughout the entire lifecycle of the project. Extreme programming (XP) was particularly used due to its ability to speed up development within the limited timeframe of three months, as well as its emphasis on producing high-quality software, ensuring the small team has high-quality outcomes.\n\nSystem design \nThe design framework consisted of a web-based application integrated with an IoT module, made up of a WSN, ThingSpeak Cloud, and an RFID module. The WSN was responsible for collection of data regarding sample and reagents storage conditions, i.e., temperature and humidity. The overall system architectural design is represented in Figure 3. \nXBee S2C modules were integrated with STM32F103C8T6 microcontroller boards and an AM2303 temperature-humidity sensor to form sensor nodes. Each sensor was configured to transmit both temperature and humidity values as bytes to a coordinator XBee module connected to an ESP32 microcontroller. The ESP32 microcontroller was configured to convert the temperature and humidity from bytes to float values and then transmit that information to ThingSpeak Cloud using Wi-Fi. The smart LIMS web application was configured to fetch the temperature and humidity graphs for each node from the cloud using an application programming interface (API) provided by ThingSpeak Cloud.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. The hardware and software architecture\n\n\n\nRequirements were modeled using Unified Modeling Language (UML). Initially, the gathered requirements were modeled into a use-case diagram, with the main actors being the laboratory manager, quality assurance officer, laboratory staff categorized as section heads, laboratory engineers, and laboratory scientists. \nActivity diagrams were modeled to represent the different activities within the system. Figure 4 provides an example of these activity diagrams, depicting the sequence of activities involved in user log-in.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 4. User log-in activity diagram\n\n\n\nAfter successful log-in, there are different activities a user can perform depending on the level of access. Figure 5 provides an example of these logged-in activities, depicting the activity diagram for requesting reagents.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 5. Reagent request activity diagram\n\n\n\nSimulation \nThe hardware prototype design was first simulated using software, mainly Fritzing and KiCad. The simulation results enabled the actual hardware implementation to minimize risk of errors and hardware fault, which bears cost implications. Figure 6 represents the design of the sensor node, as captured using Fritzing software.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 6. Sensor node design using Fritzing\n\n\n\nThe sensor node design as represented in Figure 6 was replicated to produce two sensor nodes. Additionally, the coordinator node using the ESP32 microcontroller was designed, as captured in Figure 7.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 7. Coordinator node design using Fritzing\n\n\n\nAfter experimental set-up was tested using breadboards, as presented by Fritzing diagrams in Figures 6 and 7, the circuit schematic design and printed circuit board (PCB) were designed using KiCad software version 5. KiCad was selected because it is open-source and has all the full features of a professional computer-aided design tool\u2014ranging from schematic capture and PCB layout to three-dimensional modeling and visualization of the mechanical version of the circuit board\u2014while being free to use and supporting multiple operating systems platforms, whether Windows or Linux. Figure 8 illustrates a three-dimensional model of the final printed circuit board for the sensor nodes.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 8. Three-dimensional model of the sensor node circuit using KiCad\n\n\n\nResults and discussion \nA web application integrated with hardware for storage conditions monitoring, as well as sample registration and tracking, was developed.\n\nWeb application \nThe web application consisted of a log-in page where users first log in. However, the admin is required to add users and give them specific privileges and access levels within the system. The log-in page, as illustrated in Figure 9, requires a registered user email address and a password in order to grant access.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 9. User log-in page\n\n\n\nIn addition to the log-in page, a dashboard was added, as illustrated in Figure 10, where an authorized user can see an overview of the total number of samples analyzed and even revenue collected.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 10. Analytics dashboard view\n\n\n\nA sample registration page was also added, as shown on Figure 11, where sample parameters are recorded and attached with an RFID tag with a unique identifier after scanning. Details of the sample can later be retrieved by simply placing the sample close to the RFID reader. Each sample is tagged to a particular storage unit that has an identifier in the system.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 11. Sample registration page\n\n\n\nThe storage units are constantly monitored by a wireless sensor node for each storage unit. The parameters monitored are temperature and humidity. This information was made available to a user using real-time graphs generated from the data sent by the wireless sensor nodes, as illustrated in Figure 12.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 12. Storage conditions monitoring page\n\n\n\nTwilio software was integrated with the system to provide message alerts when temperature or humidity thresholds of the storage conditions are exceeded. Figure 13 shows a sample message alert, as received on a staff member\u2019s mobile phone.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 13. Twilio message alert on a mobile phone\n\n\n\nHardware subsystem \nThe hardware part of the system consisted of two main elements. The first element was a coordinator node, as illustrated in Figure 14 and 15, consisting of an ESP32 Wi-Fi-based microcontroller, an XBee coordinator module, and an RFID reader. This module was responsible for receiving temperature and humidity data of the storage units and transmitting it to the cloud. The RFID reader was responsible for tagging samples with a unique RFID identifier to simplify sample registration and tracking.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 14. Coordinator node external view\n\n\n\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 15. Coordinator node internal view, with RFID reader (right)\n\n\n\nThe second hardware element consisted of the sensor nodes, as illustrated by Figure 16, developed by integrating an STM32F103C8T6 microcontroller (\u201cBlue-pill\u201d) with XBee router modules, an LCD module, an AM2303 temperature-humidity sensor, lithium polymer rechargeable batteries, and a DC-DC buck converter module for stepping down the 7.4 volts from the batteries to the 5 volts required by the microcontroller board and sensors.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 16. Wireless sensor nodes\n\n\n\nDiscussion \nThe system was validated by issuing a user acceptance survey, of which six participants from the laboratory department answered. The six participants found the system useful in the streamlining of laboratory information and aggregation of laboratory data on a single platform. On average, when asked to rate the system on a scale of five, all participants rated the system with at least four out of a possible five, as presented in Figure 17. With anticipated growth in research capacity in East Africa and the world at large, there is a need for testing laboratories to digitize their operations and automate tasks as much as possible to increase efficiency and save on operational cost and time. In this advent of IoT devices, there is room for automating nearly all activities by employing the sophisticated technologies that are advancing every day.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 17. Summary of results from the user acceptance survey\n\n\n\nConclusion and recommendations \nThe main objective of this study was to investigate the development of a smart LIMS, by integrating RFID technology with IoT and WSN. A web-based application was developed and integrated with hardware elements consisting of the WSN and an RFID modules. The system was configured to provide real-time notifications regarding sample storage conditions. Customization was done to enable remote accessibility to the system. The developed system was tested with laboratory staff at the NM-AIST. The option for generating reports was included to enable the laboratory manager to view, generate, print, and sign result reports after first level approval by junior staff. Based on the performance test, it is concluded that WSNs can effectively be integrated with IoT devices to automate recurring tasks in laboratories, aid in monitoring, and eliminate paper-based record keeping. Using such a smart LIMS, researchers can better plan research activities.\nIn the future, this work can be improved by increasing the number of sensors to detect more parameters such as fire, light intensity, and toxic gases. Also, a theft-detection module can be integrated to monitor intrusion and outbound equipment from the laboratories. Machine learning algorithms can be used to analyze the number of experiments and sample analysis carried out periodically and even predict revenue or forecast expected number of samples for analysis. A payment module can be added to facilitate real-time processing of payments by external clients for analysis without the need for them to physically visit the offices. This work can also be extended to other testing laboratories in other sectors such as healthcare, agriculture, and manufacturing and R&D. If the laboratory sections are located far apart from each other, alternative low-power wireless communication technologies should be considered, such as the Long-Range Wide Area Network (LoRAWAN) specification, SIGFOX, etc.\n\nAcknowledgements \nThis work is financed by the CENIT@EA Project (Centre of Excellence for ICT in East Africa), funded by the German Federal Ministry for Economic Cooperation and Development (BMZ)and implemented by the Deutsche Gesellschaft f\u00fcr Internationale Zusammenarbeit (GIZ) and the German Academic Exchange Service (DAAD). Many thanks to the laboratory scientists, laboratory engineers, and laboratory manager at NM-AIST for their participation in this research and offering technical advice. We would also like to acknowledge the NM-AIST for availing research facilities throughout the course of this study.\n\nConflict of interest \nNone stated.\n\nReferences \n\n\n\u2191 Schmieder, Florian; Polk, Christoph; Gottl\u00f6ber, Felix; Sch\u00f6ps, Patrick; Sonntag, Frank; Deuse, Ronny; Jede, Aline; Petzold, Thomas (1 September 2019). \"Universal LIMS based platform for the automated processing of cell-based assays\" (in en). Current Directions in Biomedical Engineering 5 (1): 437\u2013439. doi:10.1515\/cdbme-2019-0110. ISSN 2364-5504. https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cdbme-2019-0110\/html .   \n \n\n\u2191 Hazura, H.; Mardiana, B.; Fauziyah, S.; Zahariah, M.; Hanim, A.R.; Siti Normi, Z. (1 November 2009). \"RFID Based Laboratory Management System\". 2009 International Conference on Computer Technology and Development (Kota Kinabalu, Malaysia: IEEE): 289\u2013291. doi:10.1109\/ICCTD.2009.176. ISBN 978-0-7695-3892-1. https:\/\/ieeexplore.ieee.org\/document\/5360154\/ .   \n \n\n\u2191 Hsieh, Nan Kai; Kang, Tsan Ching; Chen, Tzer Long; Chang, Jhih Chung; Wang, Min Chien; Chen, Tzer Shyong; Chung, Yu Fang (12 December 2020). \"The Implementation of IoT-based Smart Laboratory Management System\" (in en). Proceedings of the 2020 ACM International Conference on Intelligent Computing and its Emerging Applications (GangWon Republic of Korea: ACM): 1\u20133. doi:10.1145\/3440943.3442721. ISBN 978-1-4503-8304-2. https:\/\/dl.acm.org\/doi\/10.1145\/3440943.3442721 .   \n \n\n\u2191 Vu, Thuy Duong; Eberhardt, Ursula; Sz\u00f6ke, Sz\u00e1niszl\u00f3; Groenewald, Marizeth; Robert, Vincent (25 June 2012). \"A laboratory information management system for DNA barcoding workflows\" (in en). Integrative Biology 4 (7): 744\u2013755. doi:10.1039\/c2ib00146b. ISSN 1757-9708. https:\/\/academic.oup.com\/ib\/article\/4\/7\/744\/5204443 .   \n \n\n\u2191 Zhang, Renshang; Reha, Ahmed Oulad (31 December 2014). \"RFID-Based Logistics Technology of Laboratory Equipments in University\" (in en). The Open Electrical & Electronic Engineering Journal 8 (1): 615\u2013619. doi:10.2174\/1874129001408010615. ISSN 1874-1290. https:\/\/openelectricalandelectronicengineeringjournal.com\/VOLUME\/8\/PAGE\/615\/ .   \n \n\n\u2191 Wahab, Mohd Helmy A; Kadir, Herdawatie A; Tukiran, Zarina; Tomari, Md Razali; Mutalib, Ariffin A; Mohsin, M Farhan M; Idrus, Mohd Nazrul Effendy Mohd (1 June 2010). \"Web-based laboratory equipment monitoring system using RFID\". 2010 International Conference on Intelligent and Advanced Systems (Kuala Lumpur, Malaysia: IEEE): 1\u20135. doi:10.1109\/ICIAS.2010.5716177. ISBN 978-1-4244-6623-8. http:\/\/ieeexplore.ieee.org\/document\/5716177\/ .   \n \n\n\u2191 Lin, Yu-Cheng; Cheung, Weng-Fong; Siao, Fu-Cih (1 January 2014). \"Developing mobile 2D barcode\/RFID-based maintenance management system\" (in en). Automation in Construction 37: 110\u2013121. doi:10.1016\/j.autcon.2013.10.004. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0926580513001611 .   \n \n\n\u2191 Ma, Shu Qing; Wang, Chuan Jun (1 June 2014). \"Design of Laboratory Management System Based on RFID\". Advanced Materials Research 945-949: 2689\u20132692. doi:10.4028\/www.scientific.net\/AMR.945-949.2689. ISSN 1662-8985. https:\/\/www.scientific.net\/AMR.945-949.2689 .   \n \n\n\u2191 Malipatil, N.; Roopashree, V.; Gowda, R.H.S. et al. (2020). \"RFID Based Library Management System\". International Journal of Research in Engineering, Science and Management 3 (7): 112\u2013115. https:\/\/www.journals.resaim.com\/ijresm\/article\/view\/31 .   \n \n\n\u2191 \"XBee\/XBee-PRO S2C Zigbee RF Module\" (PDF). Digi International, Inc. October 2020. https:\/\/www.digi.com\/resources\/documentation\/digidocs\/pdfs\/90002002.pdf .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added. Tables 1 and 2 were practically unreadable images, but with great effort they were translated into textual tables. Figure 4, claiming to depict a modeled use-case diagram, was entirely unreadable and was not included for this version; this bumped all subsequent figure numbers up one from their original. The original Figures 11\u201313 are hardly readable but are included nonetheless as they still show placement of UI elements.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\">https:\/\/www.limswiki.org\/index.php\/Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on laboratory informaticsLIMSwiki journal articles on softwareNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 24 May 2022, at 19:53.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 163 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","033f483b8781387c15eeaf676086cc6e_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Development_of_a_smart_laboratory_information_management_system_A_case_study_of_NM-AIST_Arusha_of_Tanzania rootpage-Journal_Development_of_a_smart_laboratory_information_management_system_A_case_study_of_NM-AIST_Arusha_of_Tanzania skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Development of a smart laboratory information management system: A case study of NM-AIST Arusha of Tanzania<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Testing laboratories in higher learning institutions of science, technology, and engineering are used by institutional staff, researchers, and external stakeholders in conducting research experiments, <a href=\"https:\/\/www.limswiki.org\/index.php\/Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"7f8cd41a077a88d02370c02a3ba3d9d6\">sample<\/a> analysis, and result dissemination. However, there exists a challenge in the management of <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> operations and processing of laboratory-based data. Operations carried out in the laboratory at Nelson Mandela African Institution of Science and Technology (NM-AIST), in Arusha, Tanzania\u2014where this case study was carried out\u2014are paper-based. There is no automated way of sample registration and identification, and researchers are prone to making errors when handling sensitive reagents. Users have to physically visit the laboratory to enquire about available equipment or reagents before borrowing or reserving those resources. Additionally, paper-based forms have to be filled out and handed to the laboratory manager for approval. These manual operations make it difficult to keep track of expiry dates of reagents, stock remaining, storage conditions, software licenses, tools, and data regarding borrowed equipment, as these facets lack automated notification mechanisms. \n<\/p><p>This study, therefore, was carried out to investigate the development of a smart <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management system<\/a> (LIMS) integrated with <a href=\"https:\/\/www.limswiki.org\/index.php\/Internet_of_things\" title=\"Internet of things\" class=\"wiki-link\" data-key=\"13e0b826fa1770fe4bea72e3cb942f0f\">internet of things<\/a> (IoT) devices, a wireless sensor network (WSN), and radio frequency identification (RFID) technology for real-time monitoring of sample and reagents storage conditions, as well as digital sample identification and tracking. A web application was developed to allow remote access to laboratory <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> by users. Based on the performance test, it is concluded that WSNs can be integrated with IoT devices to automate recurring tasks in laboratories, aid in monitoring, and eliminate paper-based record keeping.\n<\/p><p><b>Keywords<\/b>: radio frequency identification, wireless sensor network, internet of things, MQTT, ZigBee protocol, ThingSpeak, laboratory information management system\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h3>\n<p>Higher learning institutions of science, technology, and engineering conduct experiments in testing <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a>. According to the Oxford Learner\u2019s Dictionary, a laboratory is a building or a part of a building or any other place set aside and equipped for conducting scientific experiments or investigations, in order to develop new products. These testing laboratories are accessible to institutional staff, researchers, and external stakeholders. The Nelson Mandela African Institution of Science and Technology (NM-AIST), based in East Africa (Arusha, Tanzania), has one such testing laboratory that is subdivided into three subsections. Each subsection deals with a different thematic research focus area and is led by a section head. The flow of <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> in testing laboratories is complex, from <a href=\"https:\/\/www.limswiki.org\/index.php\/Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"7f8cd41a077a88d02370c02a3ba3d9d6\">sample<\/a> registration to assigning the sample to an analyst, recording the sample results for each parameter tested, and relaying the results back to the client or researcher. Conventional paper-based approaches for recording all this information are not efficient. A lot of time is bound to be wasted following up on paperwork, and crucial details might be missed or lost in the process. There is therefore a need to aggregate laboratory information on a single platform that can be accessed remotely in order to guarantee real-time access of laboratory data, as well as automate manual processes to increase efficiency, speed, and accuracy. This study therefore proposes a web-based smart <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management system<\/a> (LIMS) integrated with wireless sensor network (WSN) technology, <a href=\"https:\/\/www.limswiki.org\/index.php\/Internet_of_things\" title=\"Internet of things\" class=\"wiki-link\" data-key=\"13e0b826fa1770fe4bea72e3cb942f0f\">internet of things<\/a> (IoT) devices, and radio frequency identification (RFID) to streamline laboratory operations and consolidate all data on a single platform for easy accessibility and tracking.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Problem_statement\">Problem statement<\/span><\/h3>\n<p>There exists a challenge in the management of most testing laboratories, in that operations are carried out manually. There is no established mechanism of sample identification, and researchers are prone to making errors when handling sensitive reagents. If users need to borrow laboratory equipment, they have to physically visit the laboratory office, enquire about the availability of equipment, and manually fill out a paper-based form before handing it to the laboratory manager for approval. Due to such manual operations, it is difficult to keep track of expiry dates of reagents, remaining stock, software licenses, tools, data regarding borrowed items, and more. It is therefore in light of the aforementioned setbacks that this study was carried out to investigate the development of a smart LIMS to automate processes in testing laboratories, enabling researchers to plan activities.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Objectives_and_research_questions\">Objectives and research questions<\/span><\/h3>\n<p>The main objective of this research was to investigate the development of a smart LIMS. The specific objectives were:\n<\/p>\n<ol><li>Determine and gather requirements for the design and development of a smart LIMS.<\/li>\n<li>Design and develop a smart LIMS based on those requirements.<\/li>\n<li>Validate the developed system.<\/li><\/ol>\n<p>A series of research questions tie into those objectives:\n<\/p>\n<ol><li>What are the requirements for developing a smart LIMS?<\/li>\n<li>How should the smart LIMS be designed and developed?<\/li>\n<li>How will the study ensure the developed system meets the specified user requirements?<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"Conceptual_framework\">Conceptual framework<\/span><\/h3>\n<p>Figure 1 below represents a conceptual framework model that guided the development of the smart LIMS. A web application links an IoT module and inventory module to different user categories, e.g., researchers and laboratory staff.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"16576bd3ac5f4a623d2203f808eb3e1c\"><img alt=\"Fig1 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/22\/Fig1_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> Conceptual framework for a smart laboratory information management system<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Significance_of_the_study\">Significance of the study<\/span><\/h3>\n<p>The implementation of the system is significant in the following outlined aspects:\n<\/p>\n<ul><li>Reduction of overhead in the reporting and management processes within laboratories<\/li>\n<li>Enabling of a central database of all laboratory data in order to digitize operations<\/li>\n<li>Minimizing operational costs of the laboratory<\/li>\n<li>Facilitating enforcement of laboratory policies, rules, and standard operating procedures<\/li>\n<li>Facilitating appropriate and timely calibration of laboratory instruments<\/li>\n<li>Easy monitoring of inventory, including equipment, samples, supplies, and reagents<\/li><\/ul>\n<h2><span class=\"mw-headline\" id=\"Literature_survey\">Literature survey<\/span><\/h2>\n<p>A LIMS is a database software application used to acquire, store, analyze, manage, and monitor data in a testing laboratory. The LIMS improves laboratory <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> and productivity by managing the data of samples, reagents, laboratory equipment, analyses, and other activities and stakeholders. A LIMS can act as a single repository of all laboratory information and reduce the communication gaps among the laboratory manager, <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_assurance\" title=\"Quality assurance\" class=\"wiki-link\" data-key=\"2ede4490f0ea707b14456f44439c0984\">quality assurance<\/a> manager, and other stakeholders.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup>\n<\/p><p>Different researchers have previously attempted to address the <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_automation\" title=\"Laboratory automation\" class=\"wiki-link\" data-key=\"0061880849aeaca05f8aa27ae171f331\">automation<\/a> and digitization of laboratories. We critically analyzed different research to identify gaps and inconsistencies. For example, an RFID-based functioning model for managing laboratory inventory was developed by Hazura <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup> RFID is a wireless, contactless identification technology that does not require line of sight. The technology operates in both the low-frequency and ultra-high-frequency RFID standards. However, in their proposed model, a control unit was used to relay data between a 13.56-megahertz (MHz) micro RFID reader and a programmable integrated circuit (PIC), before then sending the data to a computer. The drawback of their proposed solution was a lack of a mechanism for remote or wireless accessibility to the system.\n<\/p><p>In another study, Hsieh <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup> developed an IoT-based smart laboratory administrator system for intrusion and sound detection, as well as monitoring temperature and controlling laboratory access. The system employed OpenCV technology to detect invasion of objects and an Arduino microcontroller with IoT sensors to collect environmental sounds and temperature. The system detected movement, temperature, and voice in real-time and sent immediate messages through an application or email. The limitation of the study, however, was the use of a quick response (QR) code to manage the inventory through a mobile application. The QR code requires line of sight, needs objects to be scanned one by one, and are read-only with a short scanning range.\n<\/p><p>A system to <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">manage laboratory information<\/a> and track large amounts of DNA <a href=\"https:\/\/www.limswiki.org\/index.php\/Sequencing\" class=\"mw-disambig wiki-link\" title=\"Sequencing\" data-key=\"e36167a9eb152ca16a0c4c4e6d13f323\">sequencing<\/a> data was developed by Vu <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> The system employed <a href=\"https:\/\/www.limswiki.org\/index.php\/Barcode\" title=\"Barcode\" class=\"wiki-link\" data-key=\"e0952b5b262392be0995237aec36d355\">barcode<\/a> technology to label the sequenced samples and track experimental procedures. However, sample parameters were still manually fed into the system, which could be prone to error and result in lack of validated data.\n<\/p><p>Another laboratory equipment management system based on RFID technology was developed for colleges and universities by Zhang and Reha.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> The system was customized to monitor and track laboratory equipment in real time. It was based on RFID technology, which is superior over other identification technologies because it is automatic, contactless, has a strong ability to be adaptable in demanding environments, and possesses a high data capacity, up to 116 bytes of data. However, RFID implementations cost more compared to barcode implementations.\n<\/p><p>RFID is among the more popular technologies used for identification of assets in a laboratory. Wahab <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup> developed a study similar to Zhang and Reha, examining a web-based laboratory equipment monitoring system that used RFID technology. The system architecture consisted of an RFID reader, RFID tag, RS232 cable, personal computer, and a local area network (LAN) hub. RFID was tested to be 100% accurate in terms of real-time data capture of outbound and inbound equipment in the database. However, a passive RFID tag with an operating frequency of 125 kilohertz (kHz) was used. Its limitation is short response distance, and the metal shield in the RFID tag can block and interfere with the electromagnetic field produced by the RFID reader, thus preventing the tag from being read properly.\n<\/p><p>In a different study, a system to manage the maintenance of equipment was developed based on mobile two-dimensional (2D) barcode and RFID technology. In the study, it was demonstrated that both RFID and barcode systems can be used on the same equipment. Both 2D barcode and RFID technologies store and provide information. However, RFID tags are easier and faster to read compared to 2D barcodes. In terms of cost, 2D barcodes are cheaper than RFID.<sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup>\n<\/p><p>Another RFID system was developed by Ma and Wang to manage and track students\u2019 experiments. RFID was selected over other technologies such as magnetic cards due to being contactless, robust, having high data reading speed, being user friendly, and demonstrating an ability to read multiple tags simultaneously.<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup>\n<\/p><p>RFID technology has also been employed in the development of a library system for automating activities related to the borrowing, renewal, and return of books. The system employs GSM technology to alert the users on the return due date. The system is efficient in terms of speeding up the processes of searching, borrowing and returning books. However, users cannot access the system remotely.<sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup>\n<\/p><p>More recent studies have focused on RFID technology due to its superior features over other identification technologies in terms of long response distance range, longer lifespan, reusability, and robustness. In the reviewed studies, the systems were implemented to be accessed locally when a client is in the same LAN. Based on functionality, the studies focused primarily on laboratory equipment and not the management of samples, reagents, and analytical data. This study therefore was carried out to bridge the gaps identified in the previous works.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Study_area_and_scope\">Study area and scope<\/span><\/h3>\n<p>This study was carried out in the United Republic of Tanzania, whereby the NM-AIST was used as a case study. The scope entailed the development of a web-based smart LIMS that integrated with RFID technology for scanning and tracking samples, as well as an IoT module for real-time monitoring of sample storage conditions (i.e., humidity and temperature).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_collection_method\">Data collection method<\/span><\/h3>\n<p>Primary data was collected from laboratory staff, management, and researchers using group discussions, observation, and face-to-face interviews. Secondary data was collected from policy documents, journal articles, research reports, articles, websites, and white papers.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"System_requirements\">System requirements<\/span><\/h3>\n<p>The system requirements were categorized into both software requirements and hardware requirements. The software requirements were tabulated as represented in Table 1.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Software requirements for the smart LIMS\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Software\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Purpose\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">STM32 Cube Programmer (STM32CUBEPROG)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Flashing bootloader application on STM32F103C8T6 microcontroller\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Digi XCTU software\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">For configuring the XBee S2C radio modules\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Draw.IO\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Modelling the Unified Modeling Language (UML) diagram for the system\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Visual Paradigm 16.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Modelling the entity relationship\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">KiCad 5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Printed circuit design and implementation\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Visual Studio Code source code editor\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Writing PHP, HTML, CSS, and JavaScript code\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Arduino IDE\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Writing sketches for the ESP32 microcontroller\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MySQL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Database design and queries\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Apache\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">HTTP server\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ThingSpeak\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Cloud for aggregating and visualizing source data from internet of things hardware devices\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Twilio\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Communication API platform for sending SMS notifications\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Hardware requirements on the other hand were captured as represented in Table 2. XBee S2C modules were selected due to their range of more than 60 meters when indoors and up to 1200 meters when outdoors, with a data rate of up to 250,000 bits per second. They operate using the IEEE 802.15.4 technical standard for low-rate wireless personal area networks, within the 2.4GHz unlicensed industrial, scientific, and medical (ISM) band. Communication peripherals include a Serial Peripheral Interface (SPI) and universal asynchronous receiver-transmitter (UART) interfaces.<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup>\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Hardware requirements for the smart LIMS\n<\/td><\/tr>\n<tr>\n<th style=\"padding-left:10px; padding-right:10px;\">Hardware\n<\/th>\n<th style=\"padding-left:10px; padding-right:10px;\">Model\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Programmer\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ST-LINK\/V2 Mini Programmer\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ZigBee wireless module\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XBee 3mW Wire Antenna Series 2C (ZigBee Mesh)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XBee adapter\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Funduino XBee USB Adapter\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Microcontroller boards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ESP32, STM32F103C8T6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">RFID reader and tags\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">RC522 13.56Mhz Mifare S50 Card\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Liquid crystal display (LCD)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LCD1602\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">I2C LCD display interface Adapter\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PCF8574\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Temperature sensor\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">AM2302 (Wired DHT22) Temperature-Humidity Sensor\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Buzzer\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Piezo buzzer\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LED\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Standard 5mm LEDs\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Prototyping boards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PCB Copper Veroboards\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Power supply\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.7V Li-ion rechargeable batteries\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Step down converters\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LM2596 DC-DC Buck Converter Step Down\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Toggle switch (two-pin)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Mini Rocker Switch 117S 2-Pin 125V\/6A\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The study\u2019s proposed ZigBee topology is as illustrated in Figure 2, consisting of router nodes and a coordinator node.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"1eb53aaabd236efce1f553bdf994d332\"><img alt=\"Fig2 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/80\/Fig2_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> ZigBee network topology<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"System_development_approach\">System development approach<\/span><\/h3>\n<p>The Agile software development methodology was adopted in the development phase of this study due to the short development cycles in terms of iterations, as well as integrated testing throughout the entire lifecycle of the project. Extreme programming (XP) was particularly used due to its ability to speed up development within the limited timeframe of three months, as well as its emphasis on producing high-quality software, ensuring the small team has high-quality outcomes.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"System_design\">System design<\/span><\/h3>\n<p>The design framework consisted of a web-based application integrated with an IoT module, made up of a WSN, ThingSpeak Cloud, and an RFID module. The WSN was responsible for collection of data regarding sample and reagents storage conditions, i.e., temperature and humidity. The overall system architectural design is represented in Figure 3. \n<\/p><p>XBee S2C modules were integrated with STM32F103C8T6 microcontroller boards and an AM2303 temperature-humidity sensor to form sensor nodes. Each sensor was configured to transmit both temperature and humidity values as bytes to a coordinator XBee module connected to an ESP32 microcontroller. The ESP32 microcontroller was configured to convert the temperature and humidity from bytes to float values and then transmit that information to ThingSpeak Cloud using Wi-Fi. The smart LIMS web application was configured to fetch the temperature and humidity graphs for each node from the <a href=\"https:\/\/www.limswiki.org\/index.php\/Cloud_computing\" title=\"Cloud computing\" class=\"wiki-link\" data-key=\"fcfe5882eaa018d920cedb88398b604f\">cloud<\/a> using an <a href=\"https:\/\/www.limswiki.org\/index.php\/Application_programming_interface\" title=\"Application programming interface\" class=\"wiki-link\" data-key=\"36fc319869eba4613cb0854b421b0934\">application programming interface<\/a> (API) provided by ThingSpeak Cloud.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"3deabdc44b284986507f1d89f41112bd\"><img alt=\"Fig3 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/98\/Fig3_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> The hardware and software architecture<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Requirements were modeled using Unified Modeling Language (UML). Initially, the gathered requirements were modeled into a use-case diagram, with the main actors being the laboratory manager, quality assurance officer, laboratory staff categorized as section heads, laboratory engineers, and laboratory scientists. \n<\/p><p>Activity diagrams were modeled to represent the different activities within the system. Figure 4 provides an example of these activity diagrams, depicting the sequence of activities involved in user log-in.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"1123e1a1b2df2d907f669a459b7ee481\"><img alt=\"Fig4 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/ea\/Fig4_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 4.<\/b> User log-in activity diagram<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>After successful log-in, there are different activities a user can perform depending on the level of access. Figure 5 provides an example of these logged-in activities, depicting the activity diagram for requesting reagents.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"644bbe46f03833d9ef72963d49c2a4e0\"><img alt=\"Fig5 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/eb\/Fig5_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 5.<\/b> Reagent request activity diagram<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h4><span class=\"mw-headline\" id=\"Simulation\">Simulation<\/span><\/h4>\n<p>The hardware prototype design was first simulated using software, mainly Fritzing and KiCad. The simulation results enabled the actual hardware implementation to minimize risk of errors and hardware fault, which bears cost implications. Figure 6 represents the design of the sensor node, as captured using Fritzing software.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"69970d1823b2527485f1ce17fbbe2725\"><img alt=\"Fig6 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/4a\/Fig6_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 6.<\/b> Sensor node design using Fritzing<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The sensor node design as represented in Figure 6 was replicated to produce two sensor nodes. Additionally, the coordinator node using the ESP32 microcontroller was designed, as captured in Figure 7.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig7_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"a6015199d5ce1eea1e02982c06637dc3\"><img alt=\"Fig7 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/4b\/Fig7_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 7.<\/b> Coordinator node design using Fritzing<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>After experimental set-up was tested using breadboards, as presented by Fritzing diagrams in Figures 6 and 7, the circuit schematic design and printed circuit board (PCB) were designed using KiCad software version 5. KiCad was selected because it is open-source and has all the full features of a professional computer-aided design tool\u2014ranging from schematic capture and PCB layout to three-dimensional modeling and visualization of the mechanical version of the circuit board\u2014while being free to use and supporting multiple operating systems platforms, whether Windows or Linux. Figure 8 illustrates a three-dimensional model of the final printed circuit board for the sensor nodes.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig8_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"e9aed73ed87a514c0e27adfbb6804553\"><img alt=\"Fig8 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c0\/Fig8_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 8.<\/b> Three-dimensional model of the sensor node circuit using KiCad<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussion\">Results and discussion<\/span><\/h2>\n<p>A web application integrated with hardware for storage conditions monitoring, as well as sample registration and tracking, was developed.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Web_application\">Web application<\/span><\/h3>\n<p>The web application consisted of a log-in page where users first log in. However, the admin is required to add users and give them specific privileges and access levels within the system. The log-in page, as illustrated in Figure 9, requires a registered user email address and a password in order to grant access.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig9_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"bfcc372b5e4455697523abbbbb64b1f7\"><img alt=\"Fig9 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/0\/0a\/Fig9_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 9.<\/b> User log-in page<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>In addition to the log-in page, a dashboard was added, as illustrated in Figure 10, where an authorized user can see an overview of the total number of samples analyzed and even revenue collected.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig10_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"afa1113bfbceed8d0044feefb70a139d\"><img alt=\"Fig10 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d4\/Fig10_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 10.<\/b> Analytics dashboard view<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>A sample registration page was also added, as shown on Figure 11, where sample parameters are recorded and attached with an RFID tag with a unique identifier after scanning. Details of the sample can later be retrieved by simply placing the sample close to the RFID reader. Each sample is tagged to a particular storage unit that has an identifier in the system.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig11_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"419299befe3cf7343e73fea8b7039e32\"><img alt=\"Fig11 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c6\/Fig11_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 11.<\/b> Sample registration page<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The storage units are constantly monitored by a wireless sensor node for each storage unit. The parameters monitored are temperature and humidity. This information was made available to a user using real-time graphs generated from the data sent by the wireless sensor nodes, as illustrated in Figure 12.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig12_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"4dba35427f6dd8891abe81f8b4a730c2\"><img alt=\"Fig12 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d1\/Fig12_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 12.<\/b> Storage conditions monitoring page<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Twilio software was integrated with the system to provide message alerts when temperature or humidity thresholds of the storage conditions are exceeded. Figure 13 shows a sample message alert, as received on a staff member\u2019s mobile phone.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig13_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"75fabeb972abce2f893917ef3ee230cb\"><img alt=\"Fig13 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a9\/Fig13_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 13.<\/b> Twilio message alert on a mobile phone<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Hardware_subsystem\">Hardware subsystem<\/span><\/h3>\n<p>The hardware part of the system consisted of two main elements. The first element was a coordinator node, as illustrated in Figure 14 and 15, consisting of an ESP32 Wi-Fi-based microcontroller, an XBee coordinator module, and an RFID reader. This module was responsible for receiving temperature and humidity data of the storage units and transmitting it to the cloud. The RFID reader was responsible for tagging samples with a unique RFID identifier to simplify sample registration and tracking.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig14_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" class=\"image wiki-link\" data-key=\"8b038ec4ef7f4b46860f5d0b16a0b639\"><img alt=\"Fig14 Mwambe IntJofAdvSciResEng22 8-4.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/9a\/Fig14_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 14.<\/b> Coordinator node external view<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig15_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" class=\"image wiki-link\" data-key=\"b6364afaae2bdb034fcdb26cb3ffc00b\"><img alt=\"Fig15 Mwambe IntJofAdvSciResEng22 8-4.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1f\/Fig15_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 15.<\/b> Coordinator node internal view, with RFID reader (right)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The second hardware element consisted of the sensor nodes, as illustrated by Figure 16, developed by integrating an STM32F103C8T6 microcontroller (\u201cBlue-pill\u201d) with XBee router modules, an LCD module, an AM2303 temperature-humidity sensor, lithium polymer rechargeable batteries, and a DC-DC buck converter module for stepping down the 7.4 volts from the batteries to the 5 volts required by the microcontroller board and sensors.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig16_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" class=\"image wiki-link\" data-key=\"4eac9ccd3728e1102dbe7c29b9c19239\"><img alt=\"Fig16 Mwambe IntJofAdvSciResEng22 8-4.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f9\/Fig16_Mwambe_IntJofAdvSciResEng22_8-4.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 16.<\/b> Wireless sensor nodes<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h3>\n<p>The system was validated by issuing a user acceptance survey, of which six participants from the laboratory department answered. The six participants found the system useful in the streamlining of laboratory information and aggregation of laboratory data on a single platform. On average, when asked to rate the system on a scale of five, all participants rated the system with at least four out of a possible five, as presented in Figure 17. With anticipated growth in research capacity in East Africa and the world at large, there is a need for testing laboratories to digitize their operations and automate tasks as much as possible to increase efficiency and save on operational cost and time. In this advent of IoT devices, there is room for automating nearly all activities by employing the sophisticated technologies that are advancing every day.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig17_Mwambe_IntJofAdvSciResEng22_8-4.png\" class=\"image wiki-link\" data-key=\"1be685b0ead5099d7efabe1960b60034\"><img alt=\"Fig17 Mwambe IntJofAdvSciResEng22 8-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7a\/Fig17_Mwambe_IntJofAdvSciResEng22_8-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 17.<\/b> Summary of results from the user acceptance survey<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Conclusion_and_recommendations\">Conclusion and recommendations<\/span><\/h2>\n<p>The main objective of this study was to investigate the development of a smart LIMS, by integrating RFID technology with IoT and WSN. A web-based application was developed and integrated with hardware elements consisting of the WSN and an RFID modules. The system was configured to provide real-time notifications regarding sample storage conditions. Customization was done to enable remote accessibility to the system. The developed system was tested with laboratory staff at the NM-AIST. The option for generating reports was included to enable the laboratory manager to view, generate, print, and sign result reports after first level approval by junior staff. Based on the performance test, it is concluded that WSNs can effectively be integrated with IoT devices to automate recurring tasks in laboratories, aid in monitoring, and eliminate paper-based record keeping. Using such a smart LIMS, researchers can better plan research activities.\n<\/p><p>In the future, this work can be improved by increasing the number of sensors to detect more parameters such as fire, light intensity, and toxic gases. Also, a theft-detection module can be integrated to monitor intrusion and outbound equipment from the laboratories. <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">Machine learning<\/a> algorithms can be used to analyze the number of experiments and sample analysis carried out periodically and even predict revenue or forecast expected number of samples for analysis. A payment module can be added to facilitate real-time processing of payments by external clients for analysis without the need for them to physically visit the offices. This work can also be extended to other testing laboratories in other sectors such as healthcare, agriculture, and manufacturing and R&D. If the laboratory sections are located far apart from each other, alternative low-power wireless communication technologies should be considered, such as the Long-Range Wide Area Network (LoRAWAN) specification, SIGFOX, etc.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>This work is financed by the CENIT@EA Project (Centre of Excellence for ICT in East Africa), funded by the German Federal Ministry for Economic Cooperation and Development (BMZ)and implemented by the Deutsche Gesellschaft f\u00fcr Internationale Zusammenarbeit (GIZ) and the German Academic Exchange Service (DAAD). Many thanks to the laboratory scientists, laboratory engineers, and laboratory manager at NM-AIST for their participation in this research and offering technical advice. We would also like to acknowledge the NM-AIST for availing research facilities throughout the course of this study.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>None stated.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schmieder, Florian; Polk, Christoph; Gottl\u00f6ber, Felix; Sch\u00f6ps, Patrick; Sonntag, Frank; Deuse, Ronny; Jede, Aline; Petzold, Thomas (1 September 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cdbme-2019-0110\/html\" target=\"_blank\">\"Universal LIMS based platform for the automated processing of cell-based assays\"<\/a> (in en). <i>Current Directions in Biomedical Engineering<\/i> <b>5<\/b> (1): 437\u2013439. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1515%2Fcdbme-2019-0110\" target=\"_blank\">10.1515\/cdbme-2019-0110<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2364-5504\" target=\"_blank\">2364-5504<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cdbme-2019-0110\/html\" target=\"_blank\">https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cdbme-2019-0110\/html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Universal+LIMS+based+platform+for+the+automated+processing+of+cell-based+assays&rft.jtitle=Current+Directions+in+Biomedical+Engineering&rft.aulast=Schmieder&rft.aufirst=Florian&rft.au=Schmieder%2C%26%2332%3BFlorian&rft.au=Polk%2C%26%2332%3BChristoph&rft.au=Gottl%C3%B6ber%2C%26%2332%3BFelix&rft.au=Sch%C3%B6ps%2C%26%2332%3BPatrick&rft.au=Sonntag%2C%26%2332%3BFrank&rft.au=Deuse%2C%26%2332%3BRonny&rft.au=Jede%2C%26%2332%3BAline&rft.au=Petzold%2C%26%2332%3BThomas&rft.date=1+September+2019&rft.volume=5&rft.issue=1&rft.pages=437%E2%80%93439&rft_id=info:doi\/10.1515%2Fcdbme-2019-0110&rft.issn=2364-5504&rft_id=https%3A%2F%2Fwww.degruyter.com%2Fdocument%2Fdoi%2F10.1515%2Fcdbme-2019-0110%2Fhtml&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-2\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-2\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hazura, H.; Mardiana, B.; Fauziyah, S.; Zahariah, M.; Hanim, A.R.; Siti Normi, Z. 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Kang, Tsan Ching; Chen, Tzer Long; Chang, Jhih Chung; Wang, Min Chien; Chen, Tzer Shyong; Chung, Yu Fang (12 December 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3440943.3442721\" target=\"_blank\">\"The Implementation of IoT-based Smart Laboratory Management System\"<\/a> (in en). <i>Proceedings of the 2020 ACM International Conference on Intelligent Computing and its Emerging Applications<\/i> (GangWon Republic of Korea: ACM): 1\u20133. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3440943.3442721\" target=\"_blank\">10.1145\/3440943.3442721<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-8304-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3440943.3442721\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3440943.3442721<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Implementation+of+IoT-based+Smart+Laboratory+Management+System&rft.jtitle=Proceedings+of+the+2020+ACM+International+Conference+on+Intelligent+Computing+and+its+Emerging+Applications&rft.aulast=Hsieh&rft.aufirst=Nan+Kai&rft.au=Hsieh%2C%26%2332%3BNan+Kai&rft.au=Kang%2C%26%2332%3BTsan+Ching&rft.au=Chen%2C%26%2332%3BTzer+Long&rft.au=Chang%2C%26%2332%3BJhih+Chung&rft.au=Wang%2C%26%2332%3BMin+Chien&rft.au=Chen%2C%26%2332%3BTzer+Shyong&rft.au=Chung%2C%26%2332%3BYu+Fang&rft.date=12+December+2020&rft.pages=1%E2%80%933&rft.place=GangWon+Republic+of+Korea&rft.pub=ACM&rft_id=info:doi\/10.1145%2F3440943.3442721&rft.isbn=978-1-4503-8304-2&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3440943.3442721&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-4\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vu, Thuy Duong; 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Reha, Ahmed Oulad (31 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/openelectricalandelectronicengineeringjournal.com\/VOLUME\/8\/PAGE\/615\/\" target=\"_blank\">\"RFID-Based Logistics Technology of Laboratory Equipments in University\"<\/a> (in en). <i>The Open Electrical & Electronic Engineering Journal<\/i> <b>8<\/b> (1): 615\u2013619. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2174%2F1874129001408010615\" target=\"_blank\">10.2174\/1874129001408010615<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1874-1290\" target=\"_blank\">1874-1290<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/openelectricalandelectronicengineeringjournal.com\/VOLUME\/8\/PAGE\/615\/\" target=\"_blank\">https:\/\/openelectricalandelectronicengineeringjournal.com\/VOLUME\/8\/PAGE\/615\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=RFID-Based+Logistics+Technology+of+Laboratory+Equipments+in+University&rft.jtitle=The+Open+Electrical+%26+Electronic+Engineering+Journal&rft.aulast=Zhang&rft.aufirst=Renshang&rft.au=Zhang%2C%26%2332%3BRenshang&rft.au=Reha%2C%26%2332%3BAhmed+Oulad&rft.date=31+December+2014&rft.volume=8&rft.issue=1&rft.pages=615%E2%80%93619&rft_id=info:doi\/10.2174%2F1874129001408010615&rft.issn=1874-1290&rft_id=https%3A%2F%2Fopenelectricalandelectronicengineeringjournal.com%2FVOLUME%2F8%2FPAGE%2F615%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-6\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wahab, Mohd Helmy A; Kadir, Herdawatie A; Tukiran, Zarina; Tomari, Md Razali; Mutalib, Ariffin A; Mohsin, M Farhan M; Idrus, Mohd Nazrul Effendy Mohd (1 June 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5716177\/\" target=\"_blank\">\"Web-based laboratory equipment monitoring system using RFID\"<\/a>. <i>2010 International Conference on Intelligent and Advanced Systems<\/i> (Kuala Lumpur, Malaysia: IEEE): 1\u20135. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FICIAS.2010.5716177\" target=\"_blank\">10.1109\/ICIAS.2010.5716177<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4244-6623-8<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5716177\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/5716177\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Web-based+laboratory+equipment+monitoring+system+using+RFID&rft.jtitle=2010+International+Conference+on+Intelligent+and+Advanced+Systems&rft.aulast=Wahab&rft.aufirst=Mohd+Helmy+A&rft.au=Wahab%2C%26%2332%3BMohd+Helmy+A&rft.au=Kadir%2C%26%2332%3BHerdawatie+A&rft.au=Tukiran%2C%26%2332%3BZarina&rft.au=Tomari%2C%26%2332%3BMd+Razali&rft.au=Mutalib%2C%26%2332%3BAriffin+A&rft.au=Mohsin%2C%26%2332%3BM+Farhan+M&rft.au=Idrus%2C%26%2332%3BMohd+Nazrul+Effendy+Mohd&rft.date=1+June+2010&rft.pages=1%E2%80%935&rft.place=Kuala+Lumpur%2C+Malaysia&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FICIAS.2010.5716177&rft.isbn=978-1-4244-6623-8&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F5716177%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-7\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-7\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lin, Yu-Cheng; Cheung, Weng-Fong; Siao, Fu-Cih (1 January 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0926580513001611\" target=\"_blank\">\"Developing mobile 2D barcode\/RFID-based maintenance management system\"<\/a> (in en). <i>Automation in Construction<\/i> <b>37<\/b>: 110\u2013121. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.autcon.2013.10.004\" target=\"_blank\">10.1016\/j.autcon.2013.10.004<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0926580513001611\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0926580513001611<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Developing+mobile+2D+barcode%2FRFID-based+maintenance+management+system&rft.jtitle=Automation+in+Construction&rft.aulast=Lin&rft.aufirst=Yu-Cheng&rft.au=Lin%2C%26%2332%3BYu-Cheng&rft.au=Cheung%2C%26%2332%3BWeng-Fong&rft.au=Siao%2C%26%2332%3BFu-Cih&rft.date=1+January+2014&rft.volume=37&rft.pages=110%E2%80%93121&rft_id=info:doi\/10.1016%2Fj.autcon.2013.10.004&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0926580513001611&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ma, Shu Qing; Wang, Chuan Jun (1 June 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.scientific.net\/AMR.945-949.2689\" target=\"_blank\">\"Design of Laboratory Management System Based on RFID\"<\/a>. <i>Advanced Materials Research<\/i> <b>945-949<\/b>: 2689\u20132692. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4028%2Fwww.scientific.net%2FAMR.945-949.2689\" target=\"_blank\">10.4028\/www.scientific.net\/AMR.945-949.2689<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1662-8985\" target=\"_blank\">1662-8985<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.scientific.net\/AMR.945-949.2689\" target=\"_blank\">https:\/\/www.scientific.net\/AMR.945-949.2689<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Design+of+Laboratory+Management+System+Based+on+RFID&rft.jtitle=Advanced+Materials+Research&rft.aulast=Ma&rft.aufirst=Shu+Qing&rft.au=Ma%2C%26%2332%3BShu+Qing&rft.au=Wang%2C%26%2332%3BChuan+Jun&rft.date=1+June+2014&rft.volume=945-949&rft.pages=2689%E2%80%932692&rft_id=info:doi\/10.4028%2Fwww.scientific.net%2FAMR.945-949.2689&rft.issn=1662-8985&rft_id=https%3A%2F%2Fwww.scientific.net%2FAMR.945-949.2689&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-9\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Malipatil, N.; Roopashree, V.; Gowda, R.H.S. et al. (2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.journals.resaim.com\/ijresm\/article\/view\/31\" target=\"_blank\">\"RFID Based Library Management System\"<\/a>. <i>International Journal of Research in Engineering, Science and Management<\/i> <b>3<\/b> (7): 112\u2013115<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.journals.resaim.com\/ijresm\/article\/view\/31\" target=\"_blank\">https:\/\/www.journals.resaim.com\/ijresm\/article\/view\/31<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=RFID+Based+Library+Management+System&rft.jtitle=International+Journal+of+Research+in+Engineering%2C+Science+and+Management&rft.aulast=Malipatil%2C+N.%3B+Roopashree%2C+V.%3B+Gowda%2C+R.H.S.+et+al.&rft.au=Malipatil%2C+N.%3B+Roopashree%2C+V.%3B+Gowda%2C+R.H.S.+et+al.&rft.date=2020&rft.volume=3&rft.issue=7&rft.pages=112%E2%80%93115&rft_id=https%3A%2F%2Fwww.journals.resaim.com%2Fijresm%2Farticle%2Fview%2F31&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.digi.com\/resources\/documentation\/digidocs\/pdfs\/90002002.pdf\" target=\"_blank\">\"XBee\/XBee-PRO S2C Zigbee RF Module\"<\/a> (PDF). Digi International, Inc. October 2020<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.digi.com\/resources\/documentation\/digidocs\/pdfs\/90002002.pdf\" target=\"_blank\">https:\/\/www.digi.com\/resources\/documentation\/digidocs\/pdfs\/90002002.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=XBee%2FXBee-PRO+S2C+Zigbee+RF+Module&rft.atitle=&rft.date=October+2020&rft.pub=Digi+International%2C+Inc&rft_id=https%3A%2F%2Fwww.digi.com%2Fresources%2Fdocumentation%2Fdigidocs%2Fpdfs%2F90002002.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added. Tables 1 and 2 were practically unreadable images, but with great effort they were translated into textual tables. Figure 4, claiming to depict a modeled use-case diagram, was entirely unreadable and was not included for this version; this bumped all subsequent figure numbers up one from their original. The original Figures 11\u201313 are hardly readable but are included nonetheless as they still show placement of UI elements.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628181033\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.235 seconds\nReal time usage: 1.097 seconds\nPreprocessor visited node count: 11873\/1000000\nPost\u2010expand include size: 95549\/2097152 bytes\nTemplate argument size: 30627\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 23286\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 142.500 1 -total\n 76.04% 108.363 1 Template:Reflist\n 57.24% 81.565 9 Template:Cite_journal\n 57.05% 81.290 10 Template:Citation\/core\n 17.17% 24.474 1 Template:Infobox_journal_article\n 14.09% 20.085 1 Template:Infobox\n 10.63% 15.151 9 Template:Date\n 8.34% 11.885 15 Template:Citation\/identifier\n 7.89% 11.246 80 Template:Infobox\/row\n 6.79% 9.675 1 Template:Cite_web\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13246-0!canonical and timestamp 20220628181032 and revision id 47966. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania\">https:\/\/www.limswiki.org\/index.php\/Journal:Development_of_a_smart_laboratory_information_management_system:_A_case_study_of_NM-AIST_Arusha_of_Tanzania<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","033f483b8781387c15eeaf676086cc6e_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/22\/Fig1_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/80\/Fig2_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/98\/Fig3_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/ea\/Fig4_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/eb\/Fig5_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/4a\/Fig6_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/4b\/Fig7_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c0\/Fig8_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/0\/0a\/Fig9_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d4\/Fig10_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c6\/Fig11_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d1\/Fig12_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a9\/Fig13_Mwambe_IntJofAdvSciResEng22_8-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/9a\/Fig14_Mwambe_IntJofAdvSciResEng22_8-4.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1f\/Fig15_Mwambe_IntJofAdvSciResEng22_8-4.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f9\/Fig16_Mwambe_IntJofAdvSciResEng22_8-4.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7a\/Fig17_Mwambe_IntJofAdvSciResEng22_8-4.png"],"033f483b8781387c15eeaf676086cc6e_timestamp":1656439832,"7d0d518d42d836f46cc21938cfd66d37_type":"article","7d0d518d42d836f46cc21938cfd66d37_title":"Food informatics: Review of the current state-of-the-art, revised definition, and classification into the research landscape (Krupitzer and Stein 2021)","7d0d518d42d836f46cc21938cfd66d37_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape","7d0d518d42d836f46cc21938cfd66d37_plaintext":"\n\nJournal:Food informatics: Review of the current state-of-the-art, revised definition, and classification into the research landscapeFrom LIMSWikiJump to navigationJump to searchFull article title\n \nFood informatics: Review of the current state-of-the-art, revised definition, and classification into the research landscapeJournal\n \nFoodsAuthor(s)\n \nKrupitzer, Christian; Stein, AnthonyAuthor affiliation(s)\n \nUniversity of HohenheimPrimary contact\n \nchristian dot krupitzer at uni-hohenheim dot deEditors\n \nJaiswal, Amit K.Year published\n \n2021Volume and issue\n \n10(11)Article #\n \n2889DOI\n \n10.3390\/foods10112889ISSN\n \n2304-8158Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2304-8158\/10\/11\/2889\/htmDownload\n \nhttps:\/\/www.mdpi.com\/2304-8158\/10\/11\/2889\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Delineation of concepts \n\n3.1 Precision agriculture \n3.2 Smart agriculture \n3.3 Industry 4.0 or industrial IoT \n3.4 Internet of food \n3.5 Food computing \n3.6 Smart health or pervasive health \n3.7 Food supply and logistics \n3.8 Food safety and authentication \n3.9 Summary \n\n\n4 A revised definition of food informatics \n5 Food informatics in practice: Today and tomorrow \n\n5.1 Autonomous robotics in precision agriculture \n5.2 AI- and ML-supported smart agriculture \n5.3 Internet of things and blockchain-supported food supply \n5.4 Items-focused data collection in food production \n5.5 An adaptive, flexible food production process \n5.6 Predictive maintenance in food production \n5.7 Demand-driven food production \n\n\n6 Threats to validity \n7 Related work \n8 Conclusions \n9 Acknowledgements \n\n9.1 Author contributions \n9.2 Funding \n9.3 Conflicts of interest \n\n\n10 References \n11 Notes \n\n\n\nAbstract \nBackground: The increasing population of humans and their changing food consumption behavior, as well as the recent developments in the awareness for food sustainability, lead to new challenges for the production of food. Advances in the internet of things (IoT) and artificial intelligence (AI) technology, including machine learning and data analytics, might help to account for these challenges. \nScope and approach: Several research perspectives\u2014among them precision agriculture, industrial IoT, internet of food, and smart health\u2014already provide new opportunities through digitalization. In this paper, we review the current state-of-the-art of the mentioned concepts. An additional concept to address is food informatics, which so far is mostly recognized as a mainly data-driven approach to support the production of food. In this review paper, we propose and discuss a new perspective for the concept of food informatics as a supportive discipline that subsumes the incorporation of information technology, mainly IoT and AI, in order to support the variety of aspects tangential to the food production process and delineate it from other existing research streams in the domain. \nKey Findings and conclusions: Many different concepts related to digitalization in food science overlap. Further, food informatics is vaguely defined. In this paper, we provide a clear definition of food informatics and delineate it from related concepts. We corroborate our new perspective on food informatics by presenting several case studies about how it can support food production (as well as the intermediate steps until its consumption), and further describe its integration with related concepts.\nKeywords: food informatics, internet of things, precision agriculture, smart agriculture, internet of food, food computing, food supply chain management\n\nIntroduction \nScientists have been alerting the world about climate change for a very long time; examples include the World Scientists\u2019 Warning to Humanity from 1992[1] and the more recent World Scientists\u2019 Warning to Humanity: A Second Notice in 2017.[2] However, it required Greta Thunberg and Fridays for Future to raise the awareness about climate change and the necessity to protect the environment and society.\nOne aspect that, on the one hand, impacts climate change but on the other hand is also highly influenced by it, is the production of food. Roughly 11% of the Earth\u2019s population was unable to meet their dietary energy requirements between 2014 and 2016, representing approximately 795 million people.[3] On the contrary, food production for the population of industrial nations in particular highly contributes to climate change due to a meat-focused diet, with the expectation of seasonal fruits throughout the entire year, as well as a high waste of food.[4] Both situations will become more complex in the next decades as the global population is predicted to grow to 10 billion by 2050 according to the United Nations.[3] This might increase the number of people with insufficiently satisfied dietary energy requirements. The increasing welfare in emerging countries will likely lead to more people adopting the resource-demanding nutrition of the industrial nations.\nTraditional food production approaches will not be able to deal with those issues sufficiently; hence, novel approaches are required. The integration of current research advances in the internet of things (IoT) seems especially promising in supporting various aspects of food production, including farming, supply chain management, monitoring, processing, or demand estimation. Whereas a commonly accepted definition of IoT is not present in the literature, it is agreed that IoT refers to connected computational resources and sensors which often supplement everyday objects. The sensors support the collection of data which can be analyzed for identifying changes in the environment, and the IoT system can react to accommodating those changes. Procedures from artificial intelligence (AI)\u2014the idea that machines should be able to carry out tasks in a smart way\u2014and machine learning (ML)\u2014techniques for machines to learn from data\u2014can complement the analysis and system controlling process in IoT systems. The actions of analyzing and controlling IoT systems are also named as a reason for adaptation.[5] The purposeful application of those methods can complement and optimize many existing processes. The research in this field is distributed across several domains, such as precision agriculture, smart farming, internet of food, food supply chain management, food authentication, industrial IoT (IIoT, or Industry 4.0) for food production, food safety and authentication, \"food computing,\" or smart\/pervasive health. Often, those concepts overlap and are not completely distinguished.\nAnother research stream can be recognized under the notion of food informatics, which is often understood as data-centric research for supporting food production and consumption.[6][7][8][9] However, research alone does not provide a clear concept of food informatics. In this review paper, we want to distinguish the various research streams related to the topics of food production and consumption. Further, we motivate our perspective on food informatics as a supportive research stream that can contribute to the wide field of applying IoT and AI\/ML to optimize food production and, hence, can be seen as an underlying technological foundation for the other information and communication technology (ICT)-related research streams that target aspects of the food supply chain. Additionally, we present several case studies related to the production of food, discuss how food informatics contributes to those applications, and highlight the relation to the other presented research streams. However, we do not aim at providing a full-fledged survey as this would be not possible for a broad coverage of topics. Accordingly, we target providing a systematic mapping[10] approach to offer a cross section of the research landscape. \nIn summary, our contributions are threefold:\n\nDelineation of concepts: We provide a delineation of various concepts related to the digitalization of food science production.\nDefinition of \"food informatics\": We review the state-of-the-art in food informatics and motivate a new understanding of food informatics as a supportive discipline for food production and an underlying technical foundation for digitalization.\nApplication: We discuss the potential of IoT and AI\/ML to support the process of food production and supply\u2014in our understanding, the central role of food informatics\u2014with regard to the socio-technical perspective of the various stakeholders.\nThe remainder of this paper is structured as follows: The next section compares research streams related to the production and consumption of food, and the subsequent section presents a new definition of food informatics. We then present several research perspectives, as well as research challenges, when applying ICT in the food production domain. The penultimate section discusses possible threats to the validity of our claims. Finally, we close with related work and our conclusions.\n\nDelineation of concepts \nThe production of food is a highly complex process. On the one hand, there is a high diversity in the combination of ingredients and intermediaries with many dependencies, for example, in the order of processing. Further, byproducts, side-products, or co-products might arise, such as butter milk when producing butter. On the other hand, food has hygienic, olfactory, sensory, or preservation requirements. In general, the food production process can be divided into several phases:\n\nAgriculture: Production of ingredients\/food\nLogistics': Transportation of food while obeying hygienic constraints\nProcessing: Processing of ingredients into food products in an industrial process, while obeying hygienic constraints\nRetail: Selling of food\nConsumer use: Consumption by humans or animals\nFood waste handling: Handling and disposal of food waste in an intelligent and sustainable way (not in the scope of this paper)\nIn this paper, we see this process as a sequential process. However, in practice, a circular economy might be favorable from a sustainability viewpoint. Further, the mentioned byproducts, side-products, or co-products create a value-added network rather than a traditional value chain. However, in this paper we focus on how to support the different steps through informatics or ICT. Consequently, a sequential view on food production will not limit the validity of our arguments.\nTake for example the different processing phases for the production of Sp\u00e4tzle, a German pasta (see Figure 1). Production starts with the planting and harvesting of wheat (crop cultivation) as well as the production of eggs (livestock production). Both ingredients are transported to the production facility, where Sp\u00e4tzle is produced by adding water and salt. Subsequently, the product is delivered to wholesale trades, food retail markets, or directly to the consumer\/restaurants, where the product is eventually consumed. In all phases, IoT devices can be integrated to either support data collection or actively control the processes through adaptation. (Adaptation is essentially an adjustment of the production process to handle machine faults, use traffic forecasts to re-calculate routes, or adjust production plans to most any delay. Additionally, technology known from smart health research, such as wearables, can help observe the consumption behavior of consumers. Data collection and analysis is supported by cloud and edge technology. With cloud resources, we refer to flexible server resources that can be used to complement the often limited computational resources of production machines. Those can be in-house resources, shared by multiple factories, or external resources like Google Cloud, Amazon Web Services, or Microsoft Azure. Edge devices act as additional computational resources within a factory that extend the computational resources of production machines.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. Overview on the different activities in the food supply chain using the example of Sp\u00e4tzle production.\n\n\n\nSeveral concepts apply methods and technology from computer science, mainly from IoT and AI\/ML, in order to support the food production process. Those concepts often address only one phase of the production process. In the following subsections, we discuss and compare the different concepts. The purpose is to delineate the different research streams rather than provide a detailed review of each of them.\n\nPrecision agriculture \nClearly, the first step in the food supply chain is comprised by the cultivation of crops, husbandry of livestock, and the overall management of farmland. Besides the actual operations and business aspects, which are usually summarized by the term \"farming,\" the more general notion of \"agriculture\" refers to all the tangent scientific and technological aspirations around it. We therefore use the notion of agriculture as an umbrella term in this article.\nThe presence of variability and uncertainty inherent in many facets of agriculture has been recognized for many decades.[11] With this increasing awareness and a focus on the \u201cfield\u201d (in the sense of farmland)\u2014that is, recognizing that, for instance, soil and crops might exhibit varying conditions\u2014combined with technological innovations such as global positioning systems (GPS), computational and information management systems, as well as the advent of autonomous systems and robotics into agricultural machinery, a subarea of agricultural sciences\u2014namely precision agriculture\u2014can be defined. With the focus on the cultivation land in mind, Gebbers and Adamchuk provide a concise definition of the term precision agriculture as \"a way to apply the right treatment in the right place at the right time.\"[12] \nThey further specify and summarize the goals of precision agriculture as three-fold: (1) The optimization of required resources (e.g., the utilized amount of seeds and fertilizers) for obtaining at least the same amount and quality of crops in a more sustainable manner; (2) the alleviation of negative environmental impacts; and (3) improvements regarding the work environments and social aspects of farming in general. An alternative, intuitive definition is provided by Sundmaeker et al., who describe the field of precision agriculture as \"the very precise monitoring, control and treatment of animals, crops or m2 of land in order to manage spatial and temporal variability of soil, crop and animal factors.\"[13]\n\nSmart agriculture \nAdvances over the last several decades in ICT\u2014such as smart devices, cloud and edge computing, and near field communication (NFC)\u2014as well as the resulting technological possibilities in nearly any branch of society and industry (summarized by the term \"IoT\"; see next subsection) naturally also opens up a wide variety of adoption scenarios for agriculture. Smart agriculture appears as the most common notion in that respect.\nWolfert et al. review the application of big data in the context of smart farming. Their survey further provides another concise definition of the term, as \"a development that emphasizes the use of information and communication technology in the cyber-physical farm management cycle.\"[14]\nWe note that a new term is introduced in the above definition: \"cyber-physical farm.\" As is often the case when new technologies are emerging, a variety of terms referring to essentially the same thing appear in the literature. Another terms that also shows up occasionally is \"digital farming.\" For the sake of completeness, we want to highlight that the notion of digital farming or agriculture is sometimes also conveyed to mean the integrated and combined utilization of both precision and smart agriculture concepts. The interested reader is referred to a recent position paper of the Deutsche Landwirtschafts Gesellschaft (DLG) (the German Agricultural Society).[15] Since this article focuses on the notion of food informatics and not solely smart agriculture, we proceed without a further differentiation; throughout this work, we only differentiate between precision agriculture and smart agriculture, for the sake of simplicity. (However, note our differentiation of \u201cE-Farming\u201d or \"Farming 4.0,\" with the German term being \u201cLandwirtschaft 4.0,\u201d the latter intended to relate to the German-coined notion of Industry 4.0.)\n\nIndustry 4.0 or industrial IoT \nThe vision of Industry 4.0 is to integrate cyberspace and the physical world through the digitization of production facilities and industrial products.[16] This synchronizes the physical world and a digital model of it, the so called \"digital twin.\" The \"industrial internet,\" also known as industrial IoT (IIoT), enables a flexible process control of an entire plant.[17] The current interpretation of the term appeared with the rise of cloud technologies. The central elements of both concepts\u2014digital twin aside\u2014are the smart factory, cyber-physical production systems, and an intelligent and fast communication infrastructure.\nFood production may benefit from Industry 4.0 approaches. Predictive maintenance can lead to improved production efficiencies, especially as machine defects in the context of food production have a more serious impact due to the perishability of ingredients, in contrast to tangible product elements in the production area. Further, the flexibility of Industry 4.0 approaches can help to facilitate the production of individual, customized food articles. Luque et al. review the state-of-the-art of applying Industry 4.0 technology for the food sector and propose a framework for implementing Industry 4.0 for food production centered around the activities of the supply chain.[18]\n\nInternet of food \nThe term \"internet of food\" was first used by Kouma and Liu in 2011.[19] They proposed to equip food items with IP address-like identifiers for continuous monitoring using technology known from the IoT. Hence, it is a combination of identifiers, hardware, and software to monitor food and allow an observation of the consumers for optimizing nutrition. Somewhat contrarily, other authors describe the use of IoT for food-related purposes rather than the identification aspect as the internet of food, an example being smart refrigerators.[20] Holden et al.[21] review current developments in the area of the internet of food with a focus on the support of sustainability.\n\nFood computing \nMin et al.[22] present a definition of the term \"food computing\" in combination with a review of the current state-of-the-art. According to them, food computing is concerned with the acquisition and analysis of food-related data from various sources, focusing on the perception, recognition, retrieval, recommendation, and monitoring of food. Hence, food computing is a consumer-focused research stream, with the objective being to support the consumer with respect to optimal nutrition. Data sources can include pictures taken with smartphones, and data from web sites or social media data. Accordingly, the research integrates approaches from information retrieval, picture recognition, recommendation systems, and prediction tools. For further information on the relevant approaches, the interested reader is referred to overviews on the current state-of-the-art.[22][23][24][25]\n\nSmart health or pervasive health \nAccording to Varshney[26]], pervasive healthcare can be defined as \"healthcare to anyone, anytime, and anywhere by removing locational, time, and other restraints while increasing both the coverage and the quality of healthcare.\"\nIn a similar fashion, authors define the research for smart health or mobile health.[27] Applications in those areas include health monitoring, intelligent emergency management systems, smart data access and analysis, and ubiquitous mobile telemedicine. Often, those applications rely on wearables\u2014that is, small devices with sensors attached to the body of users\u2014for data collection and signaling of critical health conditions. This requires efficient communication technology, smart IoT devices, and intelligent data analytics. Nutrition monitoring might be a relevant aspect in such health monitoring, as well as telemedicine. Vice versa, smart health apps might influence the consumption of food.[28] Additionally, somewhat related to this area, are newer works that target the field of (personalized) nutrition (e.g., smart food choices that support the choice for food of a consumer[29]), as well as nutrition informatics, which \u201cdescribes approaches to understand the interactions between an organism and its nutritional environment via bioinformatics-based integration of nutrition study data sets.\u201d[30]\n\nFood supply and logistics \nSupply chain management describes the optimization of the intra- and extralogistics. In the case of food production, this includes the transportation of ingredients to the production facility, the moving of ingredients and products in the facility, and final transportation to retailers or customers. In contrast to other tangible goods, food has specific requirements concerning temperature, hygiene, and storage, for example, avoiding pressure on the products. In the following, we focus on the extralogistics of food, its transportation outside of a production facility. Current approaches try to integrate IoT technology for monitoring of logistics, especially the monitoring of temperature and air quality. The application of RFID improves the tracking of food and furthers information management.[31] Currently, approaches propose to integrate blockchain technology into the food supply chain to guarantee traceability[32][33], i.e., food provenance. Introini et al.[34] provide an overview on traceability in the food supply chain.\n\nFood safety and authentication \nAccording to a recent overview by Danezis et al., \"food authentication is the process that verifies that a food is in compliance with its label description.\"[35] Food authentication is one element of food safety, which comprises the monitoring and control of food to guarantee its quality throughout the value chain. Some authors present works that integrate IoT technology, mainly based on sensors for monitoring to achieve food safety.[36][37] Recent approaches propose integrating blockchain technologies to achieve a high reliability and availability of information.[32][33] This might help to increase the security of the stored information. However, one common issue for data-related analysis is the \u201cgarbage in, garbage out\u201d (GIGO) principle, which says that the quality of the output of an analysis is determined by the quality of the input. GIGO is not solved by blockchain technology as it just acts as secure data storage.\n\nSummary \nThe presented concepts share some similarities. First, they can be grouped along the mentioned phases of the food production process: agriculture, logistics, production, and consumption. For retail, we focus on the logistics part. Hence, we did not explicitly discuss the specifics of retail activities. Precision and smart agriculture is mainly concerned with the operational (and scientific) aspects of crop and livestock production as well as farmland husbandry and management. IIoT and internet of food approaches concentrate on supporting the production of food. The consumer-centered research domains of smart health and food computing target the optimization of food consumption behavior. The logistics aspects of food supply links the different phases of the process. Food authentication spans the whole process chain, as it provides a continual monitoring of food; however, it is limited to the activity of monitoring the process to guarantee the authenticity of the ingredients and products. Accordingly, those concepts provide customized mechanisms for specific tasks, though they are not generically applicable or reusable in several phases of the food production process.\nSecond, the presented research streams rely on advances in IoT (mainly on sensors for data collection) and AI (mostly autonomous robotics and ML). However, researchers mostly try to integrate or customize existing technology instead of developing new methodologies optimized for the requirements specific to food production. Furthermore, often the suggested technology is customized to specific purposes instead of providing more generic and flexible frameworks that can, with only minor adjustments, be used in several phases of the entire food production process.\nThird, some research streams are related. Smart agriculture and precision agriculture both address agricultural processing and can be integrated to maximize their benefits. The internet of food research stream overlaps with food supply, as it addresses the monitoring of food. Further, as monitoring of food is an inevitable element for food authentication, internet of food is also related to food authentication and food safety. Lastly, food computing and smart health overlap in their purpose as well as some other methods, for example, data extraction from pictures captured with smartphones.\nConsequently, we propose the development of generic approaches relying on IoT and AI that can support various process steps. This seems especially beneficial for data analytics procedures that analyze sensor data or forecast future system states, as those implement generic ML mechanisms. In the next section, we present how food informatics could step into the breach by means of proposing a new definition, which comprises our notion of the term.\n\nA revised definition of food informatics \nA particular research direction from the food-related literature that incorporates concepts from computer science as an enabling technology in food production is that of food informatics. As shown in Figure 2, food informatics can be vaguely defined by integrating the different perspectives and research streams as delineated above.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. This work's presented scientific concepts mapped to the food supply chain.\n\n\n\nKoenderink et al.[6] understand and motivate food informatics from a mainly data-driven perspective. This includes the development of tools and technologies to enable the application of ontologies for sharing knowledge specific to the food production process.[7][8][9] Similarly, according to some authors[38][39], food informatics deals with collecting information and documenting health- and medicine-related information. On the contrary, TU Delft includes the related reaction on the analysis of the collected information while limiting the application to the end users in their definition, which says \"food informatics is a specific eHealth area for the prevention and management of overweight and obesity.\"[40] \nLastly, Martinez-Mayorga and Medina-Franco[41] relate chemoinformatics\u2014the use of computers to collect and manage chemical information\u2014to food informatics. They define food informatics as the application of chemical information to food chemistry. For the interested, Martinez-Mayorga et al.[42] present an overview of databases and software for chemoinformatics.\nThe significant diversity of definitions demonstrates that the meaning of the term \u201cfood informatics\u201d has not yet converged to a consensus. Still, all definitions at least focus on data collection and use of the data related to food. However, while some works focus on food production[6][7][41], others highlight the importance of integrating consumers.[38][40] This shows a large diversification and spans almost the whole process of food production. Additionally, the application of the collected information differs from providing ontologies[6][7], integrating technology for data collection[7], using informatics to analyze the collected data and reacting accordingly[38][40], or even integrating other natural and life science disciplines for information retrieval.[41] Summarizing, no currently available definition for food informatics covers all relevant aspects.\nThe existing definitions largely target the phases of food production and data management, as well as aspects of smart health. As the production of food is an interplay of many different processes in agriculture, production systems, supply chain management, and smart health with obvious interdependencies, we propose to also include the data and information acquisition from the very beginning (i.e., during crop and livestock production; in other words, smart agriculture), and to also take information collection for logistics and transportation into consideration. We deem a span over the entire process important, as issues in one process step might impact other process steps. For instance, insufficient handling of food during transportation can negatively impact food quality for customers. Accordingly, a holistic information perspective is important. \nVarious technologies can support the collection of such information, especially IoT technology. Furthermore, the analysis of collected data can highly benefit from deep or machine learning and data analytics techniques. Approaches from the research domains concerned with adaptive systems (e.g., self-adaptive systems[5], self-aware computing systems[43], or organic computing[44]) can support the implementation of mechanisms that allow for adequate reactions according to the analyzed information. A robust self-reconfiguration to react to unexpected events, such as machine defects in food production facilities, constitutes an example of that. However, due to the hygienic, taste-related, or legal constraints, the area of food production has many domain-specific requirements that must be satisfied. Hence, we propose the customization of computational approaches optimized for the specifics of the food domain. This is exactly what, from our point of view, should be the central task of food informatics. \nReflecting on all above considerations, we therefore suggest a new definition:\n\nFood informatics is the intelligent collection, preparation, analysis and use of data from agriculture, the food supply chain, food processing, retail, and smart (consumer) health for the purposes of extracting knowledge to conduct an intelligent analysis of and reveal optimizations to be applied to food production, food consumption, food security, and the end-of-life of food products.\nThis new definition stresses the relevance for integrating computer systems and ICT into the food production process. It is related to the other concepts we previously delineated, as those concepts can be seen as specialized subfields of food informatics. The definition covers all aspects of the food production process and can also include relevant aspects from a circular economy perspective. It very much benefits from recent advances in the field of AI, as those contributions support intelligent reasoning, i.e., the analysis of current and forecasted system states and situations to optimize the food production processes through adaptations and adjustments. The intelligent and purposeful application of informatics opens a variety of use cases concerning food production, testing, and consumption. This can also support the transformation from linear supply chains to a circular economy as the digitization of information supports the analysis of data and the optimization of side streams and the end of life of products, and hence, support the creation of a feedback or circular loop. The next section presents such use cases.\n\nFood informatics in practice: Today and tomorrow \nAs discussed in the prior section, we define food informatics as the purposeful application of methods from different areas of computer science to the food production process. This is a rather technology-oriented, holistic view. However, this is what was intended by us: we claim that food informatics provides the underlying technological foundation, that is, representing the digitalization of the food industry, and its specific facets can be seen in many different manifestations of scientific concepts that address specific concerns in the food supply chain. As ICT always includes a socio-technological perspective, this section presents several case studies that show how food informatics can support all the consecutive phases of the food supply and how stakeholders interact, as well as how food informatics is delineated from but also complements the other prior-presented research streams. The case studies are ordered \u201cfrom the field to the customer,\u201d that is, in the chronological order of the production steps. Figure 3 provides an overview of these use cases and integrates them along the food production chain. In the following subsections, we explain each case study in detail and describe how food informatics can contribute to the use cases and discuss how it is related to the presented research streams.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. Landscape of use cases mapped to the food supply chain.\n\n\n\nAutonomous robotics in precision agriculture \nAs previously defined, precision agriculture is concerned with handling the spatial and temporal variability inherent in many facets of agricultural processes. For instance, autonomous land machines or robots are utilized to monitor soil quality via the attached soil sampling equipment (sensors) and precisely apply a site-specific amount of fertilizers to compensate for nutrient deficiency. This methodology is called variable rate nutrient application (VRNA). Here, AI methodology can be applied to infer so-called prescription maps with the most effective and cost-efficient soil sampling schemes, as presented by Israeli et al.[45]\nNeedless to say, cost-efficiency plays a central role when creating such field mappings to predict crop yield or make use of VRNA. According to Boubin et al.[46], computation costs for frequent yield mappings might consume a large fraction of the profits obtained by the farmers for crop cultivation. Therefore, fully autonomous aerial systems (FAAS; i.e., drones) not operated by human pilots are deemed more cost-efficient. FAAS, however, demand a non-negligible amount of computing resources in order to leverage powerful vision capabilities and AI technology. This is where swarms of drones enter the field, together with cloud- and edge-based computing infrastructures.[46]\nAs a collective of FAAS, tasks such as achieving complete field coverage can be distributed among the swarm. For instance, within the current research project, called SAGA, fully autonomous drones operate on different levels of altitude to partition the monitored field into sectors and instruct lower flying drones to inspect the crop sectors for weed or plant diseases.[47][48] The utilization of ensembles of self-integrating heterogeneous autonomous\/robotic systems\u2014where FAAS collaborate with mobile ground robots equipped with sensors and actuators, for example, for precise weed treatment or fertilizer application\u2014bears great potential for modern precision agriculture, but it also presents technological challenges that need to be overcome.[49]\nIn the context of our definition of food informatics, it becomes apparent that access to food IoT services hosted in the cloud constitutes a key aspect. As a result, business intelligence (BI) or other data analytics applications can be leveraged. This leads to potential food informatics use cases such as:\n\ndemand-based supply from the input industry (e.g., fertilizers, herbicides, pesticides) in line with current field conditions (e.g., soil nutrients, plant health) and environmental factors (e.g., droughts, long winters);\ncondition-aware and treatment-specific adaptive pricing models for wholesale and, in turn, final retail of crops; and\nexact, site-specific crop\/livestock treatment information (using GPS or NFC technology) to allow for food traceability \"from field to fork.\"\nFurthermore, the deployed swarm robots or autonomous land machines can be equipped or retrofitted with special-purpose sensors to continually monitor their functional status. Using the acquired data, predictive services can adequately plan maintenance works and consequently reduce down times and, therefore, possible yield losses or food waste.\n\nAI- and ML-supported smart agriculture \nThe rise of AI technology and especially deep learning solutions, which address the increasing amount of available big data and continually progressing advances in high-performance computation capabilities for their processing[13], offer various potentials for the application of ML to agriculture. Recent surveys on the use of ML applications for smart agriculture highlight this.[50][51]\nWahby et al.[52] present an intriguing example of ML applied in a smart gardening scenario, which appears seamlessly adoptable to crop plant growth in the agricultural context. They train an ML model based on recurrent LSTM networks which predicts the underlying plant growth dynamics, that is, the stiffening and motion behavior of a bean plant as a response to controllable light stimuli. This model is subsequently used to evolve a controller for an entire bio-hybrid setup, which allows the modification of the plant\u2019s growing behavior by exploiting the phototropism property. Such sensor-actor (robotic) systems will attract more attention in the future and will prove crucial for robust indoor-cultivation of crops in urban areas (urban\/indoor farming). Further, applications of organic computing[44] target livestock management[53] and autonomous off-highway machines.[54]\nSince AI and ML both constitute two of the most investigated subfields of computer science these days, they clearly also play a central role in smart agriculture and, thus, in food informatics. Scenarios are imaginable where urban greenhouses, equipped with self-adaptive bio-hybrid systems (as delineated above), support a sustainable and robust crop cultivation regardless of the season and current weather conditions in order to ensure food security. Connected to cloud and IoT services, demand analysis and weather forecasts can be incorporated to approach intelligent food production systems that are more cost-effective and at the same time minimize food waste while still satisfying current needs. This would allow for, e.g., site-specific production of crops on-demand, which bears the potential of reducing logistic costs and pollution.\n\nInternet of things and blockchain-supported food supply \nThe food supply chain integrates all process steps and supports a continuous tracking of food throughout the production process. Hence, many parties work together. Such a cooperation requires reliable data exchange. However, a central shared data repository constitutes a single point of failure as well as a potential performance bottleneck. Further, the diversity of actors triggers the question about where to establish such a central data repository. Accordingly, distributed data management solutions might be beneficial, as those reduce data duplication and increase the robustness of the data access. Carrefour is among the first industry companies relying on blockchain technology for the purpose of food supply chain data management. However, so far the roll-out of this technology is limited and mainly serves as an experimental marketing use case for a specific product. Several authors[32][33]) have proposes integrating the blockchain for traceability purposes, as the complete documentation of the origin of ingredients and food is highly important and often a legal obligation. Kamilaris et al.[55] provide an overview of the use of blockchain in the agri-food supply chain.\nA key task in the food supply chain is managing logistics. Contrary to the logistics of common products, food entails several requirements due to its perishability. This includes cooling, hygienic constraints, or avoiding pressure on the surface of food. RFID and NFC technology might support the traceability of food items.[37] IoT technology, mainly intelligent sensors, can improve the monitoring of conditions during the transportation of goods.[31] Further, ML-supported analysis of data can help to optimize the process, for example, by forecasting the arrival of items in the production facility and, thus, reducing delays regarding subsequent processing steps.\nFood informatics can contribute in several ways, for example, as with the definition of common data description and knowledge representation formats in the form of ontologies.[7][8][9] Further, food informatics can support data exchange with generic services to store and access data in the cloud or on the blockchain. Additional services can offer generic interfaces to store data sensed by IoT devices into the shared data storage or generic tools for ML-supported data analytics. Such services will further contribute to various activities in the food supply chain.\n\nItems-focused data collection in food production \nIndustry 4.0 and IIoT approaches promise flexible production by means of collecting and analyzing data. The reconsideration that a product itself should determine its production steps rather than the processing machines constitutes one key aspect, for instance. Therefore, Industry 4.0 and IIoT approaches integrate intelligent data analytics. So far, the collection of the required data mainly focuses on the state of machines or the quality of the intermediate or final products, based upon pre-defined quality ranges. However, for a detailed analysis of products\u2019 quality issues, the collection of machine data alone might not be sufficient to identify production issues; this also requires the collection of product-related data.\nMaa\u00df et al.[56] describe the design of a smart potato. Using IoT technology and sensors, a dummy potato can deliver information from the harvesting process, for example, the pressure of the harvesting machine on the potatoes. In several studies, the authors captured the effects of different acceleration patterns on the skin of a potato. Using these data, they trained deep learning algorithms to automatically analyze whether the pressure of a harvesting machine can damage a potato.\nSuch an approach might be plausibly transferred to the realm of food production. Using IoT dummy food items throughout the production process in order to collect data from the products\u2019 viewpoints can complement the purely machine-centered data. With this food-item-related data perspective, quality issues, such as too much exerted pressure on the ingredients, can be straightforwardly identified. Again, food informatics can contribute with generic data collection based on sensors from the IoT and ML-driven data analytics services.\n\n An adaptive, flexible food production process \nOne of the main objectives for Industry 4.0 and IIoT is to drive flexible production that supports the individualization of products.[17][57][58] Examples of this type of manufacture include cars, furniture, or personalized books. Consequently, a targeted lot size of one requires a flexible product design as well as an adaptive production process.\nA recent study in the German food industry[59] identified that two thirds of surveyed companies pursue a lot size of one by 2030. Hence, it seems beneficial to integrate mechanisms known from the areas of self-adaptive systems[5], self-aware computing systems[43], or organic computing[44] to support flexible, robust, and adaptive food production. Further, such a robust adaptive production process is able to tolerate fluctuations in the quality\/size of the ingredients.\nFood informatics can provide a powerful framework for supporting the adaption of intelligent production systems, which are customized to the specifics of the food industry. Furthermore, it can support the integration of emerging technologies that can foster the individualization of food items, such as additive manufacturing via 3D printers.[60]\n\nPredictive maintenance in food production \nPredictive maintenance is based on the idea that certain characteristics of machinery can be monitored, and the gathered data can be used to derive an estimation about the remaining useful lifetime of the equipment.[61] This can help to predict potential machine defects in advance and reduce or even eliminate delays in the production process as a result of machine defects and downtimes. The underlying problem hereby is the detection of anomalies in the machine data.[62]\nAlthough it is clearly understood that such production delays imply monetary losses in the production of normal goods, the consequences of such unexpected production downtimes are even worse for the production of food due to its perishability. Accordingly, the utilized prediction and forecasting methodologies demand for customized algorithms and, thus, advanced development and domain knowledge.\nRecommendation systems such as those proposed by Z\u00fcfle et al.[63] can aid the process of automatic identification of the most adequate forecasting algorithm fitting the underlying data patterns. The selection of the most appropriate algorithm might then be combined with automatic algorithm configuration or hyperparameter tuning[64] for optimizing the parameter setting of the algorithm to be utilized. Food informatics should contribute here by means of conducting research in both areas. For example, food informatics implementations could provide predictive maintenance automatically optimized to the specific requirements of food production by focusing on forecasts of machine defects with time horizons that consider the foods\u2019 perishability and cooling requirements. Further, those recommendation systems can be re-used for other forecasts, for example, forecasting the transportation time or the demand for specific food.\n\nDemand-driven food production \nFor particular industries, it is common to start production just after an incoming order, for example, for cars. This reduces the likelihood of overproduction but on the other hand results in waiting time for customers. In the case of food, such a policy bears additional benefits due to the perishability of the produced food items. Additionally, such forecasts help to identify trends early: given the time required from planting ingredients to the final products, the forecasts help to change the supply chain early in advance to accommodate the trends.\nA sensible trade-off between a production in stock, as well as a purely demand-driven production, could be the integration of demand forecasting by identifying food consumption trends. Research streams like food computing[22] and smart health[28] can contribute to the analysis of consumption behaviors and forecasting of food demands due to their methods of information extraction. Embedding such demand forecasts into a feedback loop can optimize the various aspects, from food production to consumption behavior, and eventually reduce food waste. Coupled with adaptive food production systems, as outlined above, this constitutes a promising way for achieving sustainable food chains.\nFood Informatics can contribute by offering services of knowledge extraction regarding food trends, for example, from social media and smart health technology. This can be combined with powerful data analytics and forecasting techniques, such as the already proposed forecasting recommendation systems for choosing the prediction algorithms.\n\nThreats to validity \nIn this paper, we target providing a systematic mapping[10] approach to offer a cross section of the research landscape. Consequently, we do not follow a systematic approach to identify all relevant works for an area. On the one hand, this is hardly feasible. Our aim is to provide an overview paper on the application of ICT on the agri-food industry. This is a broad field, such that it is impossible to cover each facet in detail. On the other hand, this is not our intention; we want to focus on the application of the term \u201cfood informatics\u201d and position this concept in the research landscape.\nWe omit in this paper a detailed analysis of the identified approaches. Again, this is not our purpose; rather, we want to span the scope of the research landscape. Accordingly, we do not analyze approaches in detail. Several other surveys with a more narrow scope provide that sort of information (see the next section).\nFinally, instead of providing a full-fledged survey, we aim to present an overview including a broad coverage of topics. Still, it is feasible that we miss some topics. Further, at some point we had to limit the granularity of topics. For example, when talking about food safety it would also be possible to cover the related topics\u2019 shelf-life prediction of HACCP, or when discussing food logistics, it might include topics as cold chain and live animal transportation. Again, as we do not want to go into detail, we had to cut at some point and narrow our analysis for the covered topics.\n\nRelated work \nSeveral surveys and overview articles focus on at least one of the presented research areas. Min et al.[22] review approaches from information retrieval and picture recognition and recommendation systems, as well as prediction tools and their applicability in food computing. Zhong et al.[65] discuss and compare systems and implementations for managing the food supply chain. Verdouw et al.[66] and Tzounis et al.[67] review systems and challenges for supporting agriculture with IoT. Wolfert et al.[14] emphasize the chances for integrating big data concepts for analyzing agricultural processes. Holden et al.[21] review approaches for the internet of food and discuss how those contribute to sustainability. However, none of the aforementioned reviews target several aspects of the food production to consumption chain as is deemed essential in our perspective on food informatics.\nOther review articles focusing on IoT\/IIoT present the application of those topics in the food industry. Al-Fuqaha et al.[68] present an overview on technologies and protocols for IoT and discuss their applicability in an eating order use case. Similarly, Javed et al.[69] and Triantafyllou et al.[70] review recent IoT technology and describe its application in the context of smart agriculture. Xu et al.[17], Sisinni et al.[57], and Liao et al.[58] review approaches for IIoT and explicitly describe how to adopt them for food production. Ben-Daya et al.[71] review supply chain management approaches and identified that many approaches target the delivery supply chain process and food supply chains. Food production constitutes one among many aspects in all of those overviews, but it is not treated as the central issue there. Further, those works focus on only one aspect of the food production process.\n\nConclusions \nThe production and consumption of food highly benefits from the application of IoT and AI technology. This can especially reduce the wastage of food by optimizing production according to customer demand. So far, various research streams focus on different aspects of the production process. However, they miss the methods and approaches that can be applied across several steps along the food production process. Further, they often use generic IoT technology and data analytics methods rather than devising methods that are customized for the food production sector. Consequently, we propose to extend the often data-driven perspective on food informatics to a generic ICT-fueled perspective, which comprises the application of ICT\u2014mainly IoT and AI\/ML\u2014in order to optimize the various aspects and processes concerning food production, consumption, and security.\nThis paper provides a motivation and revised definition for food informatics and corroborates our perspective with potential use cases. As next steps, we will provide a comprehensive framework based on the revised definition and the envisaged applications. Furthermore, we will present how to adopt existing IoT and AI-based procedures and tools, and subsequently demonstrate their applicability in use cases of digital farming (i.e., precision and smart agriculture) and the processing of food in the context of Industry 4.0. Additionally, in this paper we focus on the traditional economy model. For future work, we plan to further elaborate the application of food informatics to support the transition towards a circular economy, and also extend the perspective towards bio-based industries beyond food products.\n\nAcknowledgements \nThe authors would like to thank their students Florian Erhard and Maximilian Mei\u00dfner for their support in the search of relevant literature.\n\nAuthor contributions \nConceptualization, C.K. and A.S.; methodology, C.K.; validation, C.K. and A.S.; investigation, C.K. and A.S.; data curation, C.K. and A.S.; writing\u2014original draft preparation, C.K. and A.S.; writing\u2014review and editing, C.K. and A.S. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis research received no external funding.\n\nConflicts of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 Union of Concerned Scientists (16 July 1992). \"1992 World Scientists' Warning to Humanity\". 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(1 August 2014). \"Smart health: A context-aware health paradigm within smart cities\". IEEE Communications Magazine 52 (8): 74\u201381. doi:10.1109\/MCOM.2014.6871673. ISSN 1558-1896. https:\/\/ieeexplore.ieee.org\/document\/6871673\/ .   \n \n\n\u2191 28.0 28.1 Subramaniyaswamy, V.; Manogaran, Gunasekaran; Logesh, R.; Vijayakumar, V.; Chilamkurti, Naveen; Malathi, D.; Senthilselvan, N. (1 June 2019). \"An ontology-driven personalized food recommendation in IoT-based healthcare system\" (in en). The Journal of Supercomputing 75 (6): 3184\u20133216. doi:10.1007\/s11227-018-2331-8. ISSN 1573-0484. https:\/\/doi.org\/10.1007\/s11227-018-2331-8 .   \n \n\n\u2191 Hartwell, H.; Appleton, K. M.; Bray, J.; Price, S.; Mavridis, I.; Giboreau, A.; Perez\u2010Cueto, F. J. A.; Ronge, M. (25 April 2019). \"Shaping smarter consumer food choices: The Food SMART project\". Nutrition Bulletin 44 (2): 138\u2013144. doi:10.1111\/nbu.12376. 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(2017). \"A Supply Chain Traceability System for Food Safety Based on HACCP, Blockchain & Internet of Things\" (in English). The 14th International Conference on Services Systems and Services Management (ICSSSM2017) June 16-18, 2017, Dalian, China: proceedings. Institute of Electrical and Electronics Engineers (IEEE). pp. 21\u201326. ISBN 978-1-5090-6370-3. OCLC 1003129448. http:\/\/ieeexplore.ieee.org\/servlet\/opac?punumber=7988695 .   \n \n\n\u2191 33.0 33.1 33.2 Mondal, Saikat; Wijewardena, Kanishka P.; Karuppuswami, Saranraj; Kriti, Nitya; Kumar, Deepak; Chahal, Premjeet (1 June 2019). \"Blockchain Inspired RFID-Based Information Architecture for Food Supply Chain\". IEEE Internet of Things Journal 6 (3): 5803\u20135813. doi:10.1109\/JIOT.2019.2907658. ISSN 2327-4662. https:\/\/ieeexplore.ieee.org\/document\/8674550\/ .   \n \n\n\u2191 Cruz Introini, S.; Boza, A.; Alemany D\u00edaz, M.D.M. (2018). \"Traceability in the Food Supply Chain: Review of the literature from a technological perspective\". Direccion y Organizacion 64: 50\u201355. ISSN 1132-175X. http:\/\/hdl.handle.net\/10251\/121089 .   \n \n\n\u2191 Danezis, Georgios P.; Tsagkaris, Aristidis S.; Camin, Federica; Brusic, Vladimir; Georgiou, Constantinos A. (1 December 2016). \"Food authentication: Techniques, trends & emerging approaches\" (in en). TrAC Trends in Analytical Chemistry 85: 123\u2013132. doi:10.1016\/j.trac.2016.02.026. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993615301291 .   \n \n\n\u2191 DOINEA, Mihai; BOJA, Catalin; BATAGAN, Lorena; TOMA, Cristian; POPA, Marius (30 March 2015). \"Internet of Things Based Systems for Food Safety Management\". Informatica Economica 19 (1\/2015): 87\u201397. doi:10.12948\/issn14531305\/19.1.2015.08. 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ISBN 978-1-5386-5175-9. https:\/\/ieeexplore.ieee.org\/document\/8599549\/ .   \n \n\n\u2191 Kamilaris, A.; Prenafeta-Bold\u00fa, F.X. (1 April 2018). \"Deep learning in agriculture: A survey\" (in en). Computers and Electronics in Agriculture 147: 70\u201390. doi:10.1016\/j.compag.2018.02.016. ISSN 0168-1699. https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0168169917308803 .   \n \n\n\u2191 Liakos, Konstantinos G.; Busato, Patrizia; Moshou, Dimitrios; Pearson, Simon; Bochtis, Dionysis (2018\/8). \"Machine Learning in Agriculture: A Review\" (in en). Sensors 18 (8): 2674. doi:10.3390\/s18082674. ISSN 1424-8220. PMC PMC6111295. 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Proceedings of the 20th international conference on Architecture of computing systems: 209\u201323. doi:10.5555\/1763274.1763290. https:\/\/dl.acm.org\/doi\/10.5555\/1763274.1763290 .   \n \n\n\u2191 Wuensche, Micaela; Mostaghim, Sanaz; Schmeck, Hartmut; Kautzmann, Timo; Geimer, Marcus (2010). \"Organic computing in off-highway machines\" (in en). Proceeding of the second international workshop on Self-organizing architectures - SOAR '10 (Washington, DC, USA: ACM Press): 51. doi:10.1145\/1809036.1809048. ISBN 978-1-4503-0087-2. http:\/\/portal.acm.org\/citation.cfm?doid=1809036.1809048 .   \n \n\n\u2191 Kamilaris, A.; Fonts, A.; Prenafeta-Boldu, F.X. (1 September 2019). \"The rise of blockchain technology in agriculture and food supply chains\" (in en). Trends in Food Science & Technology 91: 640\u2013652. doi:10.1016\/j.tifs.2019.07.034. ISSN 0924-2244. https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0924224418303686 .   \n \n\n\u2191 Maa\u00df, Wolfgang; Pier, Marcus; Moser, Benedikt (2018), Meyer, Kyrill; Klingner, Stephan; Zinke, Christian, eds., \"Smart Services in der Landwirtschaft\" (in de), Service Engineering (Wiesbaden: Springer Fachmedien Wiesbaden): 167\u2013181, doi:10.1007\/978-3-658-20905-6_11, ISBN 978-3-658-20904-9, http:\/\/link.springer.com\/10.1007\/978-3-658-20905-6_11 . Retrieved 2022-03-22   \n \n\n\u2191 57.0 57.1 Sisinni, Emiliano; Saifullah, Abusayeed; Han, Song; Jennehag, Ulf; Gidlund, Mikael (1 November 2018). \"Industrial Internet of Things: Challenges, Opportunities, and Directions\". IEEE Transactions on Industrial Informatics 14 (11): 4724\u20134734. doi:10.1109\/TII.2018.2852491. 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ISSN 1553-877X. https:\/\/ieeexplore.ieee.org\/document\/8320780\/ .   \n \n\n\u2191 Triantafyllou, Anna; Sarigiannidis, Panagiotis; Lagkas, Thomas D. (13 September 2018). \"Network Protocols, Schemes, and Mechanisms for Internet of Things (IoT): Features, Open Challenges, and Trends\" (in en). Wireless Communications and Mobile Computing 2018: 1\u201324. doi:10.1155\/2018\/5349894. ISSN 1530-8669. https:\/\/www.hindawi.com\/journals\/wcmc\/2018\/5349894\/ .   \n \n\n\u2191 Ben-Daya, Mohamed; Hassini, Elkafi; Bahroun, Zied (29 August 2019). \"Internet of things and supply chain management: a literature review\" (in en). International Journal of Production Research 57 (15-16): 4719\u20134742. doi:10.1080\/00207543.2017.1402140. ISSN 0020-7543. https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/00207543.2017.1402140 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation and updates to spelling and grammar. In some cases important information was missing from the references, and that information was added. The authors did not provide citations for the \"World Scientists'\" papers; citations were added for this version.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\">https:\/\/www.limswiki.org\/index.php\/Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on food informaticsLIMSwiki journal articles on internet of thingsNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 23 March 2022, at 16:47.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 385 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","7d0d518d42d836f46cc21938cfd66d37_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Food_informatics_Review_of_the_current_state-of-the-art_revised_definition_and_classification_into_the_research_landscape rootpage-Journal_Food_informatics_Review_of_the_current_state-of-the-art_revised_definition_and_classification_into_the_research_landscape skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Food informatics: Review of the current state-of-the-art, revised definition, and classification into the research landscape<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background<\/b>: The increasing population of humans and their changing food consumption behavior, as well as the recent developments in the awareness for food sustainability, lead to new challenges for the production of food. Advances in the <a href=\"https:\/\/www.limswiki.org\/index.php\/Internet_of_things\" title=\"Internet of things\" class=\"wiki-link\" data-key=\"13e0b826fa1770fe4bea72e3cb942f0f\">internet of things<\/a> (IoT) and <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI) technology, including <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> and <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_analysis\" title=\"Data analysis\" class=\"wiki-link\" data-key=\"545c95e40ca67c9e63cd0a16042a5bd1\">data analytics<\/a>, might help to account for these challenges. \n<\/p><p><b>Scope and approach<\/b>: Several research perspectives\u2014among them precision agriculture, industrial IoT, internet of food, and smart health\u2014already provide new opportunities through digitalization. In this paper, we review the current state-of-the-art of the mentioned concepts. An additional concept to address is food informatics, which so far is mostly recognized as a mainly data-driven approach to support the production of food. In this review paper, we propose and discuss a new perspective for the concept of food informatics as a supportive discipline that subsumes the incorporation of information technology, mainly IoT and AI, in order to support the variety of aspects tangential to the food production process and delineate it from other existing research streams in the domain. \n<\/p><p><b>Key Findings and conclusions<\/b>: Many different concepts related to digitalization in <a href=\"https:\/\/www.limswiki.org\/index.php\/Agriculture_industry\" title=\"Agriculture industry\" class=\"wiki-link\" data-key=\"4882fd1b1f6fb6017adf6f0c0741eafc\">food science<\/a> overlap. Further, food informatics is vaguely defined. In this paper, we provide a clear definition of food informatics and delineate it from related concepts. We corroborate our new perspective on food informatics by presenting several case studies about how it can support food production (as well as the intermediate steps until its consumption), and further describe its integration with related concepts.\n<\/p><p><b>Keywords<\/b>: food informatics, internet of things, precision agriculture, smart agriculture, internet of food, food computing, food supply chain management\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Scientists have been alerting the world about climate change for a very long time; examples include the <i>World Scientists\u2019 Warning to Humanity<\/i> from 1992<sup id=\"rdp-ebb-cite_ref-UCSWorld92_1-0\" class=\"reference\"><a href=\"#cite_note-UCSWorld92-1\">[1]<\/a><\/sup> and the more recent <i>World Scientists\u2019 Warning to Humanity: A Second Notice<\/i> in 2017.<sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup> However, it required Greta Thunberg and Fridays for Future to raise the awareness about climate change and the necessity to protect the environment and society.\n<\/p><p>One aspect that, on the one hand, impacts climate change but on the other hand is also highly influenced by it, is the production of food. Roughly 11% of the Earth\u2019s population was unable to meet their dietary energy requirements between 2014 and 2016, representing approximately 795 million people.<sup id=\"rdp-ebb-cite_ref-:0_3-0\" class=\"reference\"><a href=\"#cite_note-:0-3\">[3]<\/a><\/sup> On the contrary, food production for the population of industrial nations in particular highly contributes to climate change due to a meat-focused diet, with the expectation of seasonal fruits throughout the entire year, as well as a high waste of food.<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> Both situations will become more complex in the next decades as the global population is predicted to grow to 10 billion by 2050 according to the United Nations.<sup id=\"rdp-ebb-cite_ref-:0_3-1\" class=\"reference\"><a href=\"#cite_note-:0-3\">[3]<\/a><\/sup> This might increase the number of people with insufficiently satisfied dietary energy requirements. The increasing welfare in emerging countries will likely lead to more people adopting the resource-demanding nutrition of the industrial nations.\n<\/p><p>Traditional food production approaches will not be able to deal with those issues sufficiently; hence, novel approaches are required. The integration of current research advances in the <a href=\"https:\/\/www.limswiki.org\/index.php\/Internet_of_things\" title=\"Internet of things\" class=\"wiki-link\" data-key=\"13e0b826fa1770fe4bea72e3cb942f0f\">internet of things<\/a> (IoT) seems especially promising in supporting various aspects of food production, including farming, supply chain management, monitoring, processing, or demand estimation. Whereas a commonly accepted definition of IoT is not present in the literature, it is agreed that IoT refers to connected computational resources and sensors which often supplement everyday objects. The sensors support the collection of data which can be <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_analysis\" title=\"Data analysis\" class=\"wiki-link\" data-key=\"545c95e40ca67c9e63cd0a16042a5bd1\">analyzed<\/a> for identifying changes in the environment, and the IoT system can react to accommodating those changes. Procedures from <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI)\u2014the idea that machines should be able to carry out tasks in a smart way\u2014and <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> (ML)\u2014techniques for machines to learn from data\u2014can complement the analysis and system controlling process in IoT systems. The actions of analyzing and controlling IoT systems are also named as a reason for adaptation.<sup id=\"rdp-ebb-cite_ref-:1_5-0\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup> The purposeful application of those methods can complement and optimize many existing processes. The research in this field is distributed across several domains, such as precision agriculture, smart farming, internet of food, food supply chain management, food authentication, industrial IoT (IIoT, or Industry 4.0) for food production, food safety and authentication, \"food computing,\" or smart\/pervasive health. Often, those concepts overlap and are not completely distinguished.\n<\/p><p>Another research stream can be recognized under the notion of food informatics, which is often understood as data-centric research for supporting food production and consumption.<sup id=\"rdp-ebb-cite_ref-:2_6-0\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-0\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_8-0\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_9-0\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup> However, research alone does not provide a clear concept of food informatics. In this review paper, we want to distinguish the various research streams related to the topics of food production and consumption. Further, we motivate our perspective on food informatics as a supportive research stream that can contribute to the wide field of applying IoT and AI\/ML to optimize food production and, hence, can be seen as an underlying technological foundation for the other information and communication technology (ICT)-related research streams that target aspects of the food supply chain. Additionally, we present several case studies related to the production of food, discuss how food informatics contributes to those applications, and highlight the relation to the other presented research streams. However, we do not aim at providing a full-fledged survey as this would be not possible for a broad coverage of topics. Accordingly, we target providing a systematic mapping<sup id=\"rdp-ebb-cite_ref-:18_10-0\" class=\"reference\"><a href=\"#cite_note-:18-10\">[10]<\/a><\/sup> approach to offer a cross section of the research landscape. \n<\/p><p>In summary, our contributions are threefold:\n<\/p>\n<ul><li>Delineation of concepts: We provide a delineation of various concepts related to the digitalization of food science production.<\/li>\n<li>Definition of \"food informatics\": We review the state-of-the-art in food informatics and motivate a new understanding of food informatics as a supportive discipline for food production and an underlying technical foundation for digitalization.<\/li>\n<li>Application: We discuss the potential of IoT and AI\/ML to support the process of food production and supply\u2014in our understanding, the central role of food informatics\u2014with regard to the socio-technical perspective of the various stakeholders.<\/li><\/ul>\n<p>The remainder of this paper is structured as follows: The next section compares research streams related to the production and consumption of food, and the subsequent section presents a new definition of food informatics. We then present several research perspectives, as well as research challenges, when applying ICT in the food production domain. The penultimate section discusses possible threats to the validity of our claims. Finally, we close with related work and our conclusions.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Delineation_of_concepts\">Delineation of concepts<\/span><\/h2>\n<p>The production of food is a highly complex process. On the one hand, there is a high diversity in the combination of ingredients and intermediaries with many dependencies, for example, in the order of processing. Further, byproducts, side-products, or co-products might arise, such as butter milk when producing butter. On the other hand, food has hygienic, olfactory, sensory, or preservation requirements. In general, the food production process can be divided into several phases:\n<\/p>\n<ul><li><b>Agriculture<\/b>: Production of ingredients\/food<\/li>\n<li><b>Logistics'<\/b>: Transportation of food while obeying hygienic constraints<\/li>\n<li><b>Processing<\/b>: Processing of ingredients into food products in an industrial process, while obeying hygienic constraints<\/li>\n<li><b>Retail<\/b>: Selling of food<\/li>\n<li><b>Consumer use<\/b>: Consumption by humans or animals<\/li>\n<li><b>Food waste handling<\/b>: Handling and disposal of food waste in an intelligent and sustainable way (not in the scope of this paper)<\/li><\/ul>\n<p>In this paper, we see this process as a sequential process. However, in practice, a circular economy might be favorable from a sustainability viewpoint. Further, the mentioned byproducts, side-products, or co-products create a value-added network rather than a traditional value chain. However, in this paper we focus on how to support the different steps through <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics_(academic_field)\" title=\"Informatics (academic field)\" class=\"wiki-link\" data-key=\"0391318826a5d9f9a1a1bcc88394739f\">informatics<\/a> or ICT. Consequently, a sequential view on food production will not limit the validity of our arguments.\n<\/p><p>Take for example the different processing phases for the production of Sp\u00e4tzle, a German pasta (see Figure 1). Production starts with the planting and harvesting of wheat (crop cultivation) as well as the production of eggs (livestock production). Both ingredients are transported to the production facility, where Sp\u00e4tzle is produced by adding water and salt. Subsequently, the product is delivered to wholesale trades, food retail markets, or directly to the consumer\/restaurants, where the product is eventually consumed. In all phases, IoT devices can be integrated to either support data collection or actively control the processes through adaptation. (Adaptation is essentially an adjustment of the production process to handle machine faults, use traffic forecasts to re-calculate routes, or adjust production plans to most any delay. Additionally, technology known from smart health research, such as wearables, can help observe the consumption behavior of consumers. Data collection and analysis is supported by <a href=\"https:\/\/www.limswiki.org\/index.php\/Cloud_computing\" title=\"Cloud computing\" class=\"wiki-link\" data-key=\"fcfe5882eaa018d920cedb88398b604f\">cloud<\/a> and edge technology. With cloud resources, we refer to flexible server resources that can be used to complement the often limited computational resources of production machines. Those can be in-house resources, shared by multiple factories, or external resources like <a href=\"https:\/\/www.limswiki.org\/index.php\/Google_Cloud\" title=\"Google Cloud\" class=\"wiki-link\" data-key=\"cba743b045cae23df5415fc78c061dab\">Google Cloud<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Amazon_Web_Services\" title=\"Amazon Web Services\" class=\"wiki-link\" data-key=\"aa59005d6d3f6c0608f84c7ec811f8d6\">Amazon Web Services<\/a>, or <a href=\"https:\/\/www.limswiki.org\/index.php\/Microsoft_Azure\" title=\"Microsoft Azure\" class=\"wiki-link\" data-key=\"7681c52cec6f9c9f1cdd85f4aa70a424\">Microsoft Azure<\/a>. Edge devices act as additional computational resources within a factory that extend the computational resources of production machines.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Krupitzer_Foods21_10-11.png\" class=\"image wiki-link\" data-key=\"658a172d4bd9b789d781e3d70261b82b\"><img alt=\"Fig1 Krupitzer Foods21 10-11.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/93\/Fig1_Krupitzer_Foods21_10-11.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> Overview on the different activities in the food supply chain using the example of Sp\u00e4tzle production.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Several concepts apply methods and technology from computer science, mainly from IoT and AI\/ML, in order to support the food production process. Those concepts often address only one phase of the production process. In the following subsections, we discuss and compare the different concepts. The purpose is to delineate the different research streams rather than provide a detailed review of each of them.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Precision_agriculture\">Precision agriculture<\/span><\/h3>\n<p>Clearly, the first step in the food supply chain is comprised by the cultivation of crops, husbandry of livestock, and the overall management of farmland. Besides the actual operations and business aspects, which are usually summarized by the term \"farming,\" the more general notion of \"agriculture\" refers to all the tangent scientific and technological aspirations around it. We therefore use the notion of agriculture as an umbrella term in this article.\n<\/p><p>The presence of variability and uncertainty inherent in many facets of agriculture has been recognized for many decades.<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup> With this increasing awareness and a focus on the \u201cfield\u201d (in the sense of farmland)\u2014that is, recognizing that, for instance, soil and crops might exhibit varying conditions\u2014combined with technological innovations such as global positioning systems (GPS), computational and <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">information management<\/a> systems, as well as the advent of autonomous systems and robotics into agricultural machinery, a subarea of agricultural sciences\u2014namely precision agriculture\u2014can be defined. With the focus on the cultivation land in mind, Gebbers and Adamchuk provide a concise definition of the term precision agriculture as \"a way to apply the right treatment in the right place at the right time.\"<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup> \n<\/p><p>They further specify and summarize the goals of precision agriculture as three-fold: (1) The optimization of required resources (e.g., the utilized amount of seeds and fertilizers) for obtaining at least the same amount and <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_(business)\" title=\"Quality (business)\" class=\"wiki-link\" data-key=\"c4ac43430d1c3a3a15d1255257aaea37\">quality<\/a> of crops in a more sustainable manner; (2) the alleviation of negative environmental impacts; and (3) improvements regarding the work environments and social aspects of farming in general. An alternative, intuitive definition is provided by Sundmaeker <i>et al.<\/i>, who describe the field of precision agriculture as \"the very precise monitoring, control and treatment of animals, crops or <i>m<\/i><sup>2<\/sup> of land in order to manage spatial and temporal variability of soil, crop and animal factors.\"<sup id=\"rdp-ebb-cite_ref-:6_13-0\" class=\"reference\"><a href=\"#cite_note-:6-13\">[13]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Smart_agriculture\">Smart agriculture<\/span><\/h3>\n<p>Advances over the last several decades in ICT\u2014such as smart devices, cloud and edge computing, and near field communication (NFC)\u2014as well as the resulting technological possibilities in nearly any branch of society and industry (summarized by the term \"IoT\"; see next subsection) naturally also opens up a wide variety of adoption scenarios for agriculture. Smart agriculture appears as the most common notion in that respect.\n<\/p><p>Wolfert <i>et al.<\/i> review the application of big data in the context of smart farming. Their survey further provides another concise definition of the term, as \"a development that emphasizes the use of information and communication technology in the cyber-physical farm management cycle.\"<sup id=\"rdp-ebb-cite_ref-:19_14-0\" class=\"reference\"><a href=\"#cite_note-:19-14\">[14]<\/a><\/sup>\n<\/p><p>We note that a new term is introduced in the above definition: \"cyber-physical farm.\" As is often the case when new technologies are emerging, a variety of terms referring to essentially the same thing appear in the literature. Another terms that also shows up occasionally is \"digital farming.\" For the sake of completeness, we want to highlight that the notion of digital farming or agriculture is sometimes also conveyed to mean the integrated and combined utilization of both precision and smart agriculture concepts. The interested reader is referred to a recent position paper of the Deutsche Landwirtschafts Gesellschaft (DLG) (the German Agricultural Society).<sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup> Since this article focuses on the notion of food informatics and not solely smart agriculture, we proceed without a further differentiation; throughout this work, we only differentiate between precision agriculture and smart agriculture, for the sake of simplicity. (However, note our differentiation of \u201cE-Farming\u201d or \"Farming 4.0,\" with the German term being \u201cLandwirtschaft 4.0,\u201d the latter intended to relate to the German-coined notion of Industry 4.0.)\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Industry_4.0_or_industrial_IoT\">Industry 4.0 or industrial IoT<\/span><\/h3>\n<p>The vision of Industry 4.0 is to integrate cyberspace and the physical world through the digitization of production facilities and industrial products.<sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[16]<\/a><\/sup> This synchronizes the physical world and a digital model of it, the so called \"digital twin.\" The \"industrial internet,\" also known as industrial IoT (IIoT), enables a flexible process control of an entire plant.<sup id=\"rdp-ebb-cite_ref-:7_17-0\" class=\"reference\"><a href=\"#cite_note-:7-17\">[17]<\/a><\/sup> The current interpretation of the term appeared with the rise of cloud technologies. The central elements of both concepts\u2014digital twin aside\u2014are the smart factory, cyber-physical production systems, and an intelligent and fast communication infrastructure.\n<\/p><p>Food production may benefit from Industry 4.0 approaches. <a href=\"https:\/\/www.limswiki.org\/index.php\/Predictive_maintenance\" title=\"Predictive maintenance\" class=\"wiki-link\" data-key=\"fad029fc2cfce528b947912a1100541b\">Predictive maintenance<\/a> can lead to improved production efficiencies, especially as machine defects in the context of food production have a more serious impact due to the perishability of ingredients, in contrast to tangible product elements in the production area. Further, the flexibility of Industry 4.0 approaches can help to facilitate the production of individual, customized food articles. Luque <i>et al.<\/i> review the state-of-the-art of applying Industry 4.0 technology for the food sector and propose a framework for implementing Industry 4.0 for food production centered around the activities of the supply chain.<sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Internet_of_food\">Internet of food<\/span><\/h3>\n<p>The term \"internet of food\" was first used by Kouma and Liu in 2011.<sup id=\"rdp-ebb-cite_ref-19\" class=\"reference\"><a href=\"#cite_note-19\">[19]<\/a><\/sup> They proposed to equip food items with IP address-like identifiers for continuous monitoring using technology known from the IoT. Hence, it is a combination of identifiers, hardware, and software to monitor food and allow an observation of the consumers for optimizing nutrition. Somewhat contrarily, other authors describe the use of IoT for food-related purposes rather than the identification aspect as the internet of food, an example being smart refrigerators.<sup id=\"rdp-ebb-cite_ref-20\" class=\"reference\"><a href=\"#cite_note-20\">[20]<\/a><\/sup> Holden <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:20_21-0\" class=\"reference\"><a href=\"#cite_note-:20-21\">[21]<\/a><\/sup> review current developments in the area of the internet of food with a focus on the support of sustainability.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Food_computing\">Food computing<\/span><\/h3>\n<p>Min <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:8_22-0\" class=\"reference\"><a href=\"#cite_note-:8-22\">[22]<\/a><\/sup> present a definition of the term \"food computing\" in combination with a review of the current state-of-the-art. According to them, food computing is concerned with the acquisition and analysis of food-related data from various sources, focusing on the perception, recognition, retrieval, recommendation, and monitoring of food. Hence, food computing is a consumer-focused research stream, with the objective being to support the consumer with respect to optimal nutrition. Data sources can include pictures taken with smartphones, and data from web sites or social media data. Accordingly, the research integrates approaches from information retrieval, picture recognition, recommendation systems, and prediction tools. For further information on the relevant approaches, the interested reader is referred to overviews on the current state-of-the-art.<sup id=\"rdp-ebb-cite_ref-:8_22-1\" class=\"reference\"><a href=\"#cite_note-:8-22\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[25]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Smart_health_or_pervasive_health\">Smart health or pervasive health<\/span><\/h3>\n<p>According to Varshney<sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup>], pervasive healthcare can be defined as \"healthcare to anyone, anytime, and anywhere by removing locational, time, and other restraints while increasing both the coverage and the quality of healthcare.\"\n<\/p><p>In a similar fashion, authors define the research for smart health or mobile health.<sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup> Applications in those areas include <a href=\"https:\/\/www.limswiki.org\/index.php\/Monitoring_(medicine)\" title=\"Monitoring (medicine)\" class=\"wiki-link\" data-key=\"53fbc571860de409fc48331d7d9362cb\">health monitoring<\/a>, intelligent emergency management systems, smart data access and analysis, and ubiquitous mobile <a href=\"https:\/\/www.limswiki.org\/index.php\/Telemedicine\" title=\"Telemedicine\" class=\"wiki-link\" data-key=\"d2cc9ab69dbfb679bcee20472b08fe93\">telemedicine<\/a>. Often, those applications rely on wearables\u2014that is, small devices with sensors attached to the body of users\u2014for data collection and signaling of critical health conditions. This requires efficient communication technology, smart IoT devices, and intelligent data analytics. Nutrition monitoring might be a relevant aspect in such health monitoring, as well as telemedicine. Vice versa, smart health apps might influence the consumption of food.<sup id=\"rdp-ebb-cite_ref-:21_28-0\" class=\"reference\"><a href=\"#cite_note-:21-28\">[28]<\/a><\/sup> Additionally, somewhat related to this area, are newer works that target the field of (personalized) nutrition (e.g., smart food choices that support the choice for food of a consumer<sup id=\"rdp-ebb-cite_ref-29\" class=\"reference\"><a href=\"#cite_note-29\">[29]<\/a><\/sup>), as well as nutrition informatics, which \u201cdescribes approaches to understand the interactions between an organism and its nutritional environment via <a href=\"https:\/\/www.limswiki.org\/index.php\/Bioinformatics\" title=\"Bioinformatics\" class=\"wiki-link\" data-key=\"8f506695fdbb26e3f314da308f8c053b\">bioinformatics<\/a>-based integration of nutrition study data sets.\u201d<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Food_supply_and_logistics\">Food supply and logistics<\/span><\/h3>\n<p>Supply chain management describes the optimization of the intra- and extralogistics. In the case of food production, this includes the transportation of ingredients to the production facility, the moving of ingredients and products in the facility, and final transportation to retailers or customers. In contrast to other tangible goods, food has specific requirements concerning temperature, hygiene, and storage, for example, avoiding pressure on the products. In the following, we focus on the extralogistics of food, its transportation outside of a production facility. Current approaches try to integrate IoT technology for monitoring of logistics, especially the monitoring of temperature and air quality. The application of RFID improves the tracking of food and furthers information management.<sup id=\"rdp-ebb-cite_ref-:9_31-0\" class=\"reference\"><a href=\"#cite_note-:9-31\">[31]<\/a><\/sup> Currently, approaches propose to integrate <a href=\"https:\/\/www.limswiki.org\/index.php\/Blockchain\" title=\"Blockchain\" class=\"wiki-link\" data-key=\"ae8b186c311716aca561aaee91944f8e\">blockchain<\/a> technology into the food supply chain to guarantee traceability<sup id=\"rdp-ebb-cite_ref-:10_32-0\" class=\"reference\"><a href=\"#cite_note-:10-32\">[32]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:11_33-0\" class=\"reference\"><a href=\"#cite_note-:11-33\">[33]<\/a><\/sup>, i.e., food provenance. Introini <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[34]<\/a><\/sup> provide an overview on traceability in the food supply chain.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Food_safety_and_authentication\">Food safety and authentication<\/span><\/h3>\n<p>According to a recent overview by Danezis <i>et al.<\/i>, \"food authentication is the process that verifies that a food is in compliance with its label description.\"<sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup> Food authentication is one element of food safety, which comprises the monitoring and control of food to guarantee its quality throughout the value chain. Some authors present works that integrate IoT technology, mainly based on sensors for monitoring to achieve food safety.<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:12_37-0\" class=\"reference\"><a href=\"#cite_note-:12-37\">[37]<\/a><\/sup> Recent approaches propose integrating blockchain technologies to achieve a high reliability and availability of <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>.<sup id=\"rdp-ebb-cite_ref-:10_32-1\" class=\"reference\"><a href=\"#cite_note-:10-32\">[32]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:11_33-1\" class=\"reference\"><a href=\"#cite_note-:11-33\">[33]<\/a><\/sup> This might help to increase the security of the stored information. However, one common issue for data-related analysis is the \u201cgarbage in, garbage out\u201d (GIGO) principle, which says that the quality of the output of an analysis is determined by the quality of the input. GIGO is not solved by blockchain technology as it just acts as secure data storage.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Summary\">Summary<\/span><\/h3>\n<p>The presented concepts share some similarities. First, they can be grouped along the mentioned phases of the food production process: agriculture, logistics, production, and consumption. For retail, we focus on the logistics part. Hence, we did not explicitly discuss the specifics of retail activities. Precision and smart agriculture is mainly concerned with the operational (and scientific) aspects of crop and livestock production as well as farmland husbandry and management. IIoT and internet of food approaches concentrate on supporting the production of food. The consumer-centered research domains of smart health and food computing target the optimization of food consumption behavior. The logistics aspects of food supply links the different phases of the process. Food authentication spans the whole process chain, as it provides a continual monitoring of food; however, it is limited to the activity of monitoring the process to guarantee the authenticity of the ingredients and products. Accordingly, those concepts provide customized mechanisms for specific tasks, though they are not generically applicable or reusable in several phases of the food production process.\n<\/p><p>Second, the presented research streams rely on advances in IoT (mainly on sensors for data collection) and AI (mostly autonomous robotics and ML). However, researchers mostly try to integrate or customize existing technology instead of developing new methodologies optimized for the requirements specific to food production. Furthermore, often the suggested technology is customized to specific purposes instead of providing more generic and flexible frameworks that can, with only minor adjustments, be used in several phases of the entire food production process.\n<\/p><p>Third, some research streams are related. Smart agriculture and precision agriculture both address agricultural processing and can be integrated to maximize their benefits. The internet of food research stream overlaps with food supply, as it addresses the monitoring of food. Further, as monitoring of food is an inevitable element for food authentication, internet of food is also related to food authentication and food safety. Lastly, food computing and smart health overlap in their purpose as well as some other methods, for example, data extraction from pictures captured with smartphones.\n<\/p><p>Consequently, we propose the development of generic approaches relying on IoT and AI that can support various process steps. This seems especially beneficial for data analytics procedures that analyze sensor data or forecast future system states, as those implement generic ML mechanisms. In the next section, we present how food informatics could step into the breach by means of proposing a new definition, which comprises our notion of the term.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"A_revised_definition_of_food_informatics\">A revised definition of food informatics<\/span><\/h2>\n<p>A particular research direction from the food-related literature that incorporates concepts from computer science as an enabling technology in food production is that of food informatics. As shown in Figure 2, food informatics can be vaguely defined by integrating the different perspectives and research streams as delineated above.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Krupitzer_Foods21_10-11.png\" class=\"image wiki-link\" data-key=\"418f10bd080032313a4076e7723441b2\"><img alt=\"Fig2 Krupitzer Foods21 10-11.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/df\/Fig2_Krupitzer_Foods21_10-11.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> This work's presented scientific concepts mapped to the food supply chain.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Koenderink <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:2_6-1\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> understand and motivate food informatics from a mainly data-driven perspective. This includes the development of tools and technologies to enable the application of <a href=\"https:\/\/www.limswiki.org\/index.php\/Ontology_(information_science)\" title=\"Ontology (information science)\" class=\"wiki-link\" data-key=\"52d0664bde4b458e81fbc128b911a4a6\">ontologies<\/a> for sharing knowledge specific to the food production process.<sup id=\"rdp-ebb-cite_ref-:3_7-1\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_8-1\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_9-1\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup> Similarly, according to some authors<sup id=\"rdp-ebb-cite_ref-:13_38-0\" class=\"reference\"><a href=\"#cite_note-:13-38\">[38]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup>, food informatics deals with collecting information and documenting health- and medicine-related information. On the contrary, TU Delft includes the related reaction on the analysis of the collected information while limiting the application to the end users in their definition, which says \"food informatics is a specific eHealth area for the prevention and management of overweight and obesity.\"<sup id=\"rdp-ebb-cite_ref-:14_40-0\" class=\"reference\"><a href=\"#cite_note-:14-40\">[40]<\/a><\/sup> \n<\/p><p>Lastly, Martinez-Mayorga and Medina-Franco<sup id=\"rdp-ebb-cite_ref-:15_41-0\" class=\"reference\"><a href=\"#cite_note-:15-41\">[41]<\/a><\/sup> relate <a href=\"https:\/\/www.limswiki.org\/index.php\/Chemical_informatics\" title=\"Chemical informatics\" class=\"wiki-link\" data-key=\"f351334854570f46a1227e6e952840c1\">chemoinformatics<\/a>\u2014the use of computers to collect and manage chemical information\u2014to food informatics. They define food informatics as the application of chemical information to food chemistry. For the interested, Martinez-Mayorga <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup> present an overview of databases and software for chemoinformatics.\n<\/p><p>The significant diversity of definitions demonstrates that the meaning of the term \u201cfood informatics\u201d has not yet converged to a consensus. Still, all definitions at least focus on data collection and use of the data related to food. However, while some works focus on food production<sup id=\"rdp-ebb-cite_ref-:2_6-2\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-2\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:15_41-1\" class=\"reference\"><a href=\"#cite_note-:15-41\">[41]<\/a><\/sup>, others highlight the importance of integrating consumers.<sup id=\"rdp-ebb-cite_ref-:13_38-1\" class=\"reference\"><a href=\"#cite_note-:13-38\">[38]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:14_40-1\" class=\"reference\"><a href=\"#cite_note-:14-40\">[40]<\/a><\/sup> This shows a large diversification and spans almost the whole process of food production. Additionally, the application of the collected information differs from providing ontologies<sup id=\"rdp-ebb-cite_ref-:2_6-3\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-3\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup>, integrating technology for data collection<sup id=\"rdp-ebb-cite_ref-:3_7-4\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup>, using informatics to analyze the collected data and reacting accordingly<sup id=\"rdp-ebb-cite_ref-:13_38-2\" class=\"reference\"><a href=\"#cite_note-:13-38\">[38]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:14_40-2\" class=\"reference\"><a href=\"#cite_note-:14-40\">[40]<\/a><\/sup>, or even integrating other natural and life science disciplines for information retrieval.<sup id=\"rdp-ebb-cite_ref-:15_41-2\" class=\"reference\"><a href=\"#cite_note-:15-41\">[41]<\/a><\/sup> Summarizing, no currently available definition for food informatics covers all relevant aspects.\n<\/p><p>The existing definitions largely target the phases of food production and data management, as well as aspects of smart health. As the production of food is an interplay of many different processes in agriculture, production systems, supply chain management, and smart health with obvious interdependencies, we propose to also include the data and information acquisition from the very beginning (i.e., during crop and livestock production; in other words, smart agriculture), and to also take information collection for logistics and transportation into consideration. We deem a span over the entire process important, as issues in one process step might impact other process steps. For instance, insufficient handling of food during transportation can negatively impact food quality for customers. Accordingly, a holistic information perspective is important. \n<\/p><p>Various technologies can support the collection of such information, especially IoT technology. Furthermore, the analysis of collected data can highly benefit from deep or machine learning and data analytics techniques. Approaches from the research domains concerned with adaptive systems (e.g., self-adaptive systems<sup id=\"rdp-ebb-cite_ref-:1_5-1\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup>, self-aware computing systems<sup id=\"rdp-ebb-cite_ref-:22_43-0\" class=\"reference\"><a href=\"#cite_note-:22-43\">[43]<\/a><\/sup>, or organic computing<sup id=\"rdp-ebb-cite_ref-:16_44-0\" class=\"reference\"><a href=\"#cite_note-:16-44\">[44]<\/a><\/sup>) can support the implementation of mechanisms that allow for adequate reactions according to the analyzed information. A robust self-reconfiguration to react to unexpected events, such as machine defects in food production facilities, constitutes an example of that. However, due to the hygienic, taste-related, or legal constraints, the area of food production has many domain-specific requirements that must be satisfied. Hence, we propose the customization of computational approaches optimized for the specifics of the food domain. This is exactly what, from our point of view, should be the central task of food informatics. \n<\/p><p>Reflecting on all above considerations, we therefore suggest a new definition:\n<\/p>\n<blockquote><p>Food informatics is the intelligent collection, preparation, analysis and use of data from agriculture, the food supply chain, food processing, retail, and smart (consumer) health for the purposes of extracting knowledge to conduct an intelligent analysis of and reveal optimizations to be applied to food production, food consumption, food security, and the end-of-life of food products.<\/p><\/blockquote>\n<p>This new definition stresses the relevance for integrating computer systems and ICT into the food production process. It is related to the other concepts we previously delineated, as those concepts can be seen as specialized subfields of food informatics. The definition covers all aspects of the food production process and can also include relevant aspects from a circular economy perspective. It very much benefits from recent advances in the field of AI, as those contributions support intelligent reasoning, i.e., the analysis of current and forecasted system states and situations to optimize the food production processes through adaptations and adjustments. The intelligent and purposeful application of informatics opens a variety of use cases concerning food production, testing, and consumption. This can also support the transformation from linear supply chains to a circular economy as the digitization of information supports the analysis of data and the optimization of side streams and the end of life of products, and hence, support the creation of a feedback or circular loop. The next section presents such use cases.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Food_informatics_in_practice:_Today_and_tomorrow\">Food informatics in practice: Today and tomorrow<\/span><\/h2>\n<p>As discussed in the prior section, we define food informatics as the purposeful application of methods from different areas of computer science to the food production process. This is a rather technology-oriented, holistic view. However, this is what was intended by us: we claim that food informatics provides the underlying technological foundation, that is, representing the digitalization of the food industry, and its specific facets can be seen in many different manifestations of scientific concepts that address specific concerns in the food supply chain. As ICT always includes a socio-technological perspective, this section presents several case studies that show how food informatics can support all the consecutive phases of the food supply and how stakeholders interact, as well as how food informatics is delineated from but also complements the other prior-presented research streams. The case studies are ordered \u201cfrom the field to the customer,\u201d that is, in the chronological order of the production steps. Figure 3 provides an overview of these use cases and integrates them along the food production chain. In the following subsections, we explain each case study in detail and describe how food informatics can contribute to the use cases and discuss how it is related to the presented research streams.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Krupitzer_Foods21_10-11.png\" class=\"image wiki-link\" data-key=\"1070ed4a067954b0f85565e1b07c36e8\"><img alt=\"Fig3 Krupitzer Foods21 10-11.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/9d\/Fig3_Krupitzer_Foods21_10-11.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> Landscape of use cases mapped to the food supply chain.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Autonomous_robotics_in_precision_agriculture\">Autonomous robotics in precision agriculture<\/span><\/h3>\n<p>As previously defined, precision agriculture is concerned with handling the spatial and temporal variability inherent in many facets of agricultural processes. For instance, autonomous land machines or robots are utilized to monitor soil quality via the attached soil sampling equipment (sensors) and precisely apply a site-specific amount of fertilizers to compensate for nutrient deficiency. This methodology is called variable rate nutrient application (VRNA). Here, AI methodology can be applied to infer so-called prescription maps with the most effective and cost-efficient soil sampling schemes, as presented by Israeli <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[45]<\/a><\/sup>\n<\/p><p>Needless to say, cost-efficiency plays a central role when creating such field mappings to predict crop yield or make use of VRNA. According to Boubin <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:17_46-0\" class=\"reference\"><a href=\"#cite_note-:17-46\">[46]<\/a><\/sup>, computation costs for frequent yield mappings might consume a large fraction of the profits obtained by the farmers for crop cultivation. Therefore, fully autonomous aerial systems (FAAS; i.e., drones) not operated by human pilots are deemed more cost-efficient. FAAS, however, demand a non-negligible amount of computing resources in order to leverage powerful vision capabilities and AI technology. This is where swarms of drones enter the field, together with cloud- and edge-based computing infrastructures.<sup id=\"rdp-ebb-cite_ref-:17_46-1\" class=\"reference\"><a href=\"#cite_note-:17-46\">[46]<\/a><\/sup>\n<\/p><p>As a collective of FAAS, tasks such as achieving complete field coverage can be distributed among the swarm. For instance, within the current research project, called SAGA, fully autonomous drones operate on different levels of altitude to partition the monitored field into sectors and instruct lower flying drones to inspect the crop sectors for weed or plant diseases.<sup id=\"rdp-ebb-cite_ref-47\" class=\"reference\"><a href=\"#cite_note-47\">[47]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[48]<\/a><\/sup> The utilization of ensembles of self-integrating heterogeneous autonomous\/robotic systems\u2014where FAAS collaborate with mobile ground robots equipped with sensors and actuators, for example, for precise weed treatment or fertilizer application\u2014bears great potential for modern precision agriculture, but it also presents technological challenges that need to be overcome.<sup id=\"rdp-ebb-cite_ref-49\" class=\"reference\"><a href=\"#cite_note-49\">[49]<\/a><\/sup>\n<\/p><p>In the context of our definition of food informatics, it becomes apparent that access to food IoT services hosted in the cloud constitutes a key aspect. As a result, business intelligence (BI) or other data analytics applications can be leveraged. This leads to potential food informatics use cases such as:\n<\/p>\n<ul><li>demand-based supply from the input industry (e.g., fertilizers, herbicides, pesticides) in line with current field conditions (e.g., soil nutrients, plant health) and environmental factors (e.g., droughts, long winters);<\/li>\n<li>condition-aware and treatment-specific adaptive pricing models for wholesale and, in turn, final retail of crops; and<\/li>\n<li>exact, site-specific crop\/livestock treatment information (using GPS or NFC technology) to allow for food traceability \"from field to fork.\"<\/li><\/ul>\n<p>Furthermore, the deployed swarm robots or autonomous land machines can be equipped or retrofitted with special-purpose sensors to continually monitor their functional status. Using the acquired data, predictive services can adequately plan maintenance works and consequently reduce down times and, therefore, possible yield losses or food waste.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"AI-_and_ML-supported_smart_agriculture\">AI- and ML-supported smart agriculture<\/span><\/h3>\n<p>The rise of AI technology and especially deep learning solutions, which address the increasing amount of available big data and continually progressing advances in high-performance computation capabilities for their processing<sup id=\"rdp-ebb-cite_ref-:6_13-1\" class=\"reference\"><a href=\"#cite_note-:6-13\">[13]<\/a><\/sup>, offer various potentials for the application of ML to agriculture. Recent surveys on the use of ML applications for smart agriculture highlight this.<sup id=\"rdp-ebb-cite_ref-50\" class=\"reference\"><a href=\"#cite_note-50\">[50]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-51\" class=\"reference\"><a href=\"#cite_note-51\">[51]<\/a><\/sup>\n<\/p><p>Wahby <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-52\" class=\"reference\"><a href=\"#cite_note-52\">[52]<\/a><\/sup> present an intriguing example of ML applied in a smart gardening scenario, which appears seamlessly adoptable to crop plant growth in the agricultural context. They train an ML model based on recurrent LSTM networks which predicts the underlying plant growth dynamics, that is, the stiffening and motion behavior of a bean plant as a response to controllable light stimuli. This model is subsequently used to evolve a controller for an entire bio-hybrid setup, which allows the modification of the plant\u2019s growing behavior by exploiting the phototropism property. Such sensor-actor (robotic) systems will attract more attention in the future and will prove crucial for robust indoor-cultivation of crops in urban areas (urban\/indoor farming). Further, applications of organic computing<sup id=\"rdp-ebb-cite_ref-:16_44-1\" class=\"reference\"><a href=\"#cite_note-:16-44\">[44]<\/a><\/sup> target livestock management<sup id=\"rdp-ebb-cite_ref-53\" class=\"reference\"><a href=\"#cite_note-53\">[53]<\/a><\/sup> and autonomous off-highway machines.<sup id=\"rdp-ebb-cite_ref-54\" class=\"reference\"><a href=\"#cite_note-54\">[54]<\/a><\/sup>\n<\/p><p>Since AI and ML both constitute two of the most investigated subfields of computer science these days, they clearly also play a central role in smart agriculture and, thus, in food informatics. Scenarios are imaginable where urban greenhouses, equipped with self-adaptive bio-hybrid systems (as delineated above), support a sustainable and robust crop cultivation regardless of the season and current weather conditions in order to ensure food security. Connected to cloud and IoT services, demand analysis and weather forecasts can be incorporated to approach intelligent food production systems that are more cost-effective and at the same time minimize food waste while still satisfying current needs. This would allow for, e.g., site-specific production of crops on-demand, which bears the potential of reducing logistic costs and pollution.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Internet_of_things_and_blockchain-supported_food_supply\">Internet of things and blockchain-supported food supply<\/span><\/h3>\n<p>The food supply chain integrates all process steps and supports a continuous tracking of food throughout the production process. Hence, many parties work together. Such a cooperation requires reliable data exchange. However, a central shared data repository constitutes a single point of failure as well as a potential performance bottleneck. Further, the diversity of actors triggers the question about where to establish such a central data repository. Accordingly, distributed data management solutions might be beneficial, as those reduce data duplication and increase the robustness of the data access. Carrefour is among the first industry companies relying on blockchain technology for the purpose of food supply chain data management. However, so far the roll-out of this technology is limited and mainly serves as an experimental marketing use case for a specific product. Several authors<sup id=\"rdp-ebb-cite_ref-:10_32-2\" class=\"reference\"><a href=\"#cite_note-:10-32\">[32]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:11_33-2\" class=\"reference\"><a href=\"#cite_note-:11-33\">[33]<\/a><\/sup>) have proposes integrating the blockchain for traceability purposes, as the complete documentation of the origin of ingredients and food is highly important and often a legal obligation. Kamilaris <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-55\" class=\"reference\"><a href=\"#cite_note-55\">[55]<\/a><\/sup> provide an overview of the use of blockchain in the agri-food supply chain.\n<\/p><p>A key task in the food supply chain is managing logistics. Contrary to the logistics of common products, food entails several requirements due to its perishability. This includes cooling, hygienic constraints, or avoiding pressure on the surface of food. RFID and NFC technology might support the traceability of food items.<sup id=\"rdp-ebb-cite_ref-:12_37-1\" class=\"reference\"><a href=\"#cite_note-:12-37\">[37]<\/a><\/sup> IoT technology, mainly intelligent sensors, can improve the monitoring of conditions during the transportation of goods.<sup id=\"rdp-ebb-cite_ref-:9_31-1\" class=\"reference\"><a href=\"#cite_note-:9-31\">[31]<\/a><\/sup> Further, ML-supported analysis of data can help to optimize the process, for example, by forecasting the arrival of items in the production facility and, thus, reducing delays regarding subsequent processing steps.\n<\/p><p>Food informatics can contribute in several ways, for example, as with the definition of common data description and knowledge representation formats in the form of ontologies.<sup id=\"rdp-ebb-cite_ref-:3_7-5\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_8-2\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_9-2\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup> Further, food informatics can support data exchange with generic services to store and access data in the cloud or on the blockchain. Additional services can offer generic interfaces to store data sensed by IoT devices into the shared data storage or generic tools for ML-supported data analytics. Such services will further contribute to various activities in the food supply chain.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Items-focused_data_collection_in_food_production\">Items-focused data collection in food production<\/span><\/h3>\n<p>Industry 4.0 and IIoT approaches promise flexible production by means of collecting and analyzing data. The reconsideration that a product itself should determine its production steps rather than the processing machines constitutes one key aspect, for instance. Therefore, Industry 4.0 and IIoT approaches integrate intelligent data analytics. So far, the collection of the required data mainly focuses on the state of machines or the quality of the intermediate or final products, based upon pre-defined quality ranges. However, for a detailed analysis of products\u2019 quality issues, the collection of machine data alone might not be sufficient to identify production issues; this also requires the collection of product-related data.\n<\/p><p>Maa\u00df <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-56\" class=\"reference\"><a href=\"#cite_note-56\">[56]<\/a><\/sup> describe the design of a smart potato. Using IoT technology and sensors, a dummy potato can deliver information from the harvesting process, for example, the pressure of the harvesting machine on the potatoes. In several studies, the authors captured the effects of different acceleration patterns on the skin of a potato. Using these data, they trained deep learning algorithms to automatically analyze whether the pressure of a harvesting machine can damage a potato.\n<\/p><p>Such an approach might be plausibly transferred to the realm of food production. Using IoT dummy food items throughout the production process in order to collect data from the products\u2019 viewpoints can complement the purely machine-centered data. With this food-item-related data perspective, quality issues, such as too much exerted pressure on the ingredients, can be straightforwardly identified. Again, food informatics can contribute with generic data collection based on sensors from the IoT and ML-driven data analytics services.\n<\/p>\n<h3><span id=\"rdp-ebb-An_adaptive,_flexible_food_production_process\"><\/span><span class=\"mw-headline\" id=\"An_adaptive.2C_flexible_food_production_process\">An adaptive, flexible food production process<\/span><\/h3>\n<p>One of the main objectives for Industry 4.0 and IIoT is to drive flexible production that supports the individualization of products.<sup id=\"rdp-ebb-cite_ref-:7_17-1\" class=\"reference\"><a href=\"#cite_note-:7-17\">[17]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:23_57-0\" class=\"reference\"><a href=\"#cite_note-:23-57\">[57]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:24_58-0\" class=\"reference\"><a href=\"#cite_note-:24-58\">[58]<\/a><\/sup> Examples of this type of manufacture include cars, furniture, or personalized books. Consequently, a targeted lot size of one requires a flexible product design as well as an adaptive production process.\n<\/p><p>A recent study in the German food industry<sup id=\"rdp-ebb-cite_ref-59\" class=\"reference\"><a href=\"#cite_note-59\">[59]<\/a><\/sup> identified that two thirds of surveyed companies pursue a lot size of one by 2030. Hence, it seems beneficial to integrate mechanisms known from the areas of self-adaptive systems<sup id=\"rdp-ebb-cite_ref-:1_5-2\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup>, self-aware computing systems<sup id=\"rdp-ebb-cite_ref-:22_43-1\" class=\"reference\"><a href=\"#cite_note-:22-43\">[43]<\/a><\/sup>, or organic computing<sup id=\"rdp-ebb-cite_ref-:16_44-2\" class=\"reference\"><a href=\"#cite_note-:16-44\">[44]<\/a><\/sup> to support flexible, robust, and adaptive food production. Further, such a robust adaptive production process is able to tolerate fluctuations in the quality\/size of the ingredients.\n<\/p><p>Food informatics can provide a powerful framework for supporting the adaption of intelligent production systems, which are customized to the specifics of the food industry. Furthermore, it can support the integration of emerging technologies that can foster the individualization of food items, such as additive manufacturing via 3D printers.<sup id=\"rdp-ebb-cite_ref-60\" class=\"reference\"><a href=\"#cite_note-60\">[60]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Predictive_maintenance_in_food_production\">Predictive maintenance in food production<\/span><\/h3>\n<p>Predictive maintenance is based on the idea that certain characteristics of machinery can be monitored, and the gathered data can be used to derive an estimation about the remaining useful lifetime of the equipment.<sup id=\"rdp-ebb-cite_ref-61\" class=\"reference\"><a href=\"#cite_note-61\">[61]<\/a><\/sup> This can help to predict potential machine defects in advance and reduce or even eliminate delays in the production process as a result of machine defects and downtimes. The underlying problem hereby is the detection of anomalies in the machine data.<sup id=\"rdp-ebb-cite_ref-62\" class=\"reference\"><a href=\"#cite_note-62\">[62]<\/a><\/sup>\n<\/p><p>Although it is clearly understood that such production delays imply monetary losses in the production of normal goods, the consequences of such unexpected production downtimes are even worse for the production of food due to its perishability. Accordingly, the utilized prediction and forecasting methodologies demand for customized algorithms and, thus, advanced development and domain knowledge.\n<\/p><p>Recommendation systems such as those proposed by Z\u00fcfle <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[63]<\/a><\/sup> can aid the process of automatic identification of the most adequate forecasting algorithm fitting the underlying data patterns. The selection of the most appropriate algorithm might then be combined with automatic algorithm configuration or hyperparameter tuning<sup id=\"rdp-ebb-cite_ref-64\" class=\"reference\"><a href=\"#cite_note-64\">[64]<\/a><\/sup> for optimizing the parameter setting of the algorithm to be utilized. Food informatics should contribute here by means of conducting research in both areas. For example, food informatics implementations could provide predictive maintenance automatically optimized to the specific requirements of food production by focusing on forecasts of machine defects with time horizons that consider the foods\u2019 perishability and cooling requirements. Further, those recommendation systems can be re-used for other forecasts, for example, forecasting the transportation time or the demand for specific food.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Demand-driven_food_production\">Demand-driven food production<\/span><\/h3>\n<p>For particular industries, it is common to start production just after an incoming order, for example, for cars. This reduces the likelihood of overproduction but on the other hand results in waiting time for customers. In the case of food, such a policy bears additional benefits due to the perishability of the produced food items. Additionally, such forecasts help to identify trends early: given the time required from planting ingredients to the final products, the forecasts help to change the supply chain early in advance to accommodate the trends.\n<\/p><p>A sensible trade-off between a production in stock, as well as a purely demand-driven production, could be the integration of demand forecasting by identifying food consumption trends. Research streams like food computing<sup id=\"rdp-ebb-cite_ref-:8_22-2\" class=\"reference\"><a href=\"#cite_note-:8-22\">[22]<\/a><\/sup> and smart health<sup id=\"rdp-ebb-cite_ref-:21_28-1\" class=\"reference\"><a href=\"#cite_note-:21-28\">[28]<\/a><\/sup> can contribute to the analysis of consumption behaviors and forecasting of food demands due to their methods of information extraction. Embedding such demand forecasts into a feedback loop can optimize the various aspects, from food production to consumption behavior, and eventually reduce food waste. Coupled with adaptive food production systems, as outlined above, this constitutes a promising way for achieving sustainable food chains.\n<\/p><p>Food Informatics can contribute by offering services of knowledge extraction regarding food trends, for example, from social media and smart health technology. This can be combined with powerful data analytics and forecasting techniques, such as the already proposed forecasting recommendation systems for choosing the prediction algorithms.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Threats_to_validity\">Threats to validity<\/span><\/h2>\n<p>In this paper, we target providing a systematic mapping<sup id=\"rdp-ebb-cite_ref-:18_10-1\" class=\"reference\"><a href=\"#cite_note-:18-10\">[10]<\/a><\/sup> approach to offer a cross section of the research landscape. Consequently, we do not follow a systematic approach to identify all relevant works for an area. On the one hand, this is hardly feasible. Our aim is to provide an overview paper on the application of ICT on the agri-food industry. This is a broad field, such that it is impossible to cover each facet in detail. On the other hand, this is not our intention; we want to focus on the application of the term \u201cfood informatics\u201d and position this concept in the research landscape.\n<\/p><p>We omit in this paper a detailed analysis of the identified approaches. Again, this is not our purpose; rather, we want to span the scope of the research landscape. Accordingly, we do not analyze approaches in detail. Several other surveys with a more narrow scope provide that sort of information (see the next section).\n<\/p><p>Finally, instead of providing a full-fledged survey, we aim to present an overview including a broad coverage of topics. Still, it is feasible that we miss some topics. Further, at some point we had to limit the granularity of topics. For example, when talking about food safety it would also be possible to cover the related topics\u2019 shelf-life prediction of HACCP, or when discussing food logistics, it might include topics as cold chain and live animal transportation. Again, as we do not want to go into detail, we had to cut at some point and narrow our analysis for the covered topics.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Related_work\">Related work<\/span><\/h2>\n<p>Several surveys and overview articles focus on at least one of the presented research areas. Min <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:8_22-3\" class=\"reference\"><a href=\"#cite_note-:8-22\">[22]<\/a><\/sup> review approaches from information retrieval and picture recognition and recommendation systems, as well as prediction tools and their applicability in food computing. Zhong <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-65\" class=\"reference\"><a href=\"#cite_note-65\">[65]<\/a><\/sup> discuss and compare systems and implementations for managing the food supply chain. Verdouw <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[66]<\/a><\/sup> and Tzounis <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-67\" class=\"reference\"><a href=\"#cite_note-67\">[67]<\/a><\/sup> review systems and challenges for supporting agriculture with IoT. Wolfert <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:19_14-1\" class=\"reference\"><a href=\"#cite_note-:19-14\">[14]<\/a><\/sup> emphasize the chances for integrating big data concepts for analyzing agricultural processes. Holden <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:20_21-1\" class=\"reference\"><a href=\"#cite_note-:20-21\">[21]<\/a><\/sup> review approaches for the internet of food and discuss how those contribute to sustainability. However, none of the aforementioned reviews target several aspects of the food production to consumption chain as is deemed essential in our perspective on food informatics.\n<\/p><p>Other review articles focusing on IoT\/IIoT present the application of those topics in the food industry. Al-Fuqaha <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-68\" class=\"reference\"><a href=\"#cite_note-68\">[68]<\/a><\/sup> present an overview on technologies and protocols for IoT and discuss their applicability in an eating order use case. Similarly, Javed <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-69\" class=\"reference\"><a href=\"#cite_note-69\">[69]<\/a><\/sup> and Triantafyllou <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-70\" class=\"reference\"><a href=\"#cite_note-70\">[70]<\/a><\/sup> review recent IoT technology and describe its application in the context of smart agriculture. Xu <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:7_17-2\" class=\"reference\"><a href=\"#cite_note-:7-17\">[17]<\/a><\/sup>, Sisinni <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:23_57-1\" class=\"reference\"><a href=\"#cite_note-:23-57\">[57]<\/a><\/sup>, and Liao <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:24_58-1\" class=\"reference\"><a href=\"#cite_note-:24-58\">[58]<\/a><\/sup> review approaches for IIoT and explicitly describe how to adopt them for food production. Ben-Daya <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-71\" class=\"reference\"><a href=\"#cite_note-71\">[71]<\/a><\/sup> review supply chain management approaches and identified that many approaches target the delivery supply chain process and food supply chains. Food production constitutes one among many aspects in all of those overviews, but it is not treated as the central issue there. Further, those works focus on only one aspect of the food production process.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>The production and consumption of food highly benefits from the application of IoT and AI technology. This can especially reduce the wastage of food by optimizing production according to customer demand. So far, various research streams focus on different aspects of the production process. However, they miss the methods and approaches that can be applied across several steps along the food production process. Further, they often use generic IoT technology and data analytics methods rather than devising methods that are customized for the food production sector. Consequently, we propose to extend the often data-driven perspective on food informatics to a generic ICT-fueled perspective, which comprises the application of ICT\u2014mainly IoT and AI\/ML\u2014in order to optimize the various aspects and processes concerning food production, consumption, and security.\n<\/p><p>This paper provides a motivation and revised definition for food informatics and corroborates our perspective with potential use cases. As next steps, we will provide a comprehensive framework based on the revised definition and the envisaged applications. Furthermore, we will present how to adopt existing IoT and AI-based procedures and tools, and subsequently demonstrate their applicability in use cases of digital farming (i.e., precision and smart agriculture) and the processing of food in the context of Industry 4.0. Additionally, in this paper we focus on the traditional economy model. For future work, we plan to further elaborate the application of food informatics to support the transition towards a circular economy, and also extend the perspective towards bio-based industries beyond food products.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The authors would like to thank their students Florian Erhard and Maximilian Mei\u00dfner for their support in the search of relevant literature.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Conceptualization, C.K. and A.S.; methodology, C.K.; validation, C.K. and A.S.; investigation, C.K. and A.S.; data curation, C.K. and A.S.; writing\u2014original draft preparation, C.K. and A.S.; writing\u2014review and editing, C.K. and A.S. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This research received no external funding.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-UCSWorld92-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-UCSWorld92_1-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Union of Concerned Scientists (16 July 1992). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ucsusa.org\/resources\/1992-world-scientists-warning-humanity\" target=\"_blank\">\"1992 World Scientists' Warning to Humanity\"<\/a>. 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(1 February 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1007\/s12571-019-00893-3\" target=\"_blank\">\"Global food and nutrition security: from challenges to solutions\"<\/a> (in en). <i>Food Security<\/i> <b>11<\/b> (1): 249\u2013252. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs12571-019-00893-3\" target=\"_blank\">10.1007\/s12571-019-00893-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1876-4525\" target=\"_blank\">1876-4525<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1007\/s12571-019-00893-3\" target=\"_blank\">https:\/\/doi.org\/10.1007\/s12571-019-00893-3<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Global+food+and+nutrition+security%3A+from+challenges+to+solutions&rft.jtitle=Food+Security&rft.aulast=Dillard&rft.aufirst=Helene+R.&rft.au=Dillard%2C%26%2332%3BHelene+R.&rft.date=1+February+2019&rft.volume=11&rft.issue=1&rft.pages=249%E2%80%93252&rft_id=info:doi\/10.1007%2Fs12571-019-00893-3&rft.issn=1876-4525&rft_id=https%3A%2F%2Fdoi.org%2F10.1007%2Fs12571-019-00893-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-4\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Farr-Wharton, Geremy; Foth, Marcus; Choi, Jaz Hee-Jeong (7 July 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1002\/cb.1488\" target=\"_blank\">\"Identifying factors that promote consumer behaviours causing expired domestic food waste\"<\/a>. <i>Journal of Consumer Behaviour<\/i> <b>13<\/b> (6): 393\u2013402. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fcb.1488\" target=\"_blank\">10.1002\/cb.1488<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1472-0817\" target=\"_blank\">1472-0817<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1002\/cb.1488\" target=\"_blank\">https:\/\/doi.org\/10.1002\/cb.1488<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identifying+factors+that+promote+consumer+behaviours+causing+expired+domestic+food+waste&rft.jtitle=Journal+of+Consumer+Behaviour&rft.aulast=Farr-Wharton&rft.aufirst=Geremy&rft.au=Farr-Wharton%2C%26%2332%3BGeremy&rft.au=Foth%2C%26%2332%3BMarcus&rft.au=Choi%2C%26%2332%3BJaz+Hee-Jeong&rft.date=7+July+2014&rft.volume=13&rft.issue=6&rft.pages=393%E2%80%93402&rft_id=info:doi\/10.1002%2Fcb.1488&rft.issn=1472-0817&rft_id=https%3A%2F%2Fdoi.org%2F10.1002%2Fcb.1488&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-5\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_5-0\">5.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_5-1\">5.1<\/a><\/sup> <sup><a href=\"#cite_ref-:1_5-2\">5.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Krupitzer, C.; Roth, F.M.; VanSyckel, S. et al. (1 February 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S157411921400162X\" target=\"_blank\">\"A survey on engineering approaches for self-adaptive systems\"<\/a> (in en). <i>Pervasive and Mobile Computing<\/i> <b>17<\/b>: 184\u2013206. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.pmcj.2014.09.009\" target=\"_blank\">10.1016\/j.pmcj.2014.09.009<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1574-1192\" target=\"_blank\">1574-1192<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S157411921400162X\" target=\"_blank\">https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S157411921400162X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+survey+on+engineering+approaches+for+self-adaptive+systems&rft.jtitle=Pervasive+and+Mobile+Computing&rft.aulast=Krupitzer%2C+C.%3B+Roth%2C+F.M.%3B+VanSyckel%2C+S.+et+al.&rft.au=Krupitzer%2C+C.%3B+Roth%2C+F.M.%3B+VanSyckel%2C+S.+et+al.&rft.date=1+February+2015&rft.volume=17&rft.pages=184%E2%80%93206&rft_id=info:doi\/10.1016%2Fj.pmcj.2014.09.009&rft.issn=1574-1192&rft_id=https%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fabs%2Fpii%2FS157411921400162X&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_6-0\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-1\">6.1<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-2\">6.2<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-3\">6.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Koenderink, N.J.J.P.; Hulzebos,, J.L.; Rijgersberg, H. et al. (2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/edepot.wur.nl\/52275\" target=\"_blank\">\"Food informatics : Sharing food knowledge for research and development\"<\/a>. <i>Proceedings of the EFITA\/WCCA 2005 Joint conference<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/edepot.wur.nl\/52275\" target=\"_blank\">https:\/\/edepot.wur.nl\/52275<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Food+informatics+%3A+Sharing+food+knowledge+for+research+and+development&rft.jtitle=Proceedings+of+the+EFITA%2FWCCA+2005+Joint+conference&rft.aulast=Koenderink%2C+N.J.J.P.%3B+Hulzebos%2C%2C+J.L.%3B+Rijgersberg%2C+H.+et+al.&rft.au=Koenderink%2C+N.J.J.P.%3B+Hulzebos%2C%2C+J.L.%3B+Rijgersberg%2C+H.+et+al.&rft.date=2005&rft_id=https%3A%2F%2Fedepot.wur.nl%2F52275&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_7-0\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-1\">7.1<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-2\">7.2<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-3\">7.3<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-4\">7.4<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-5\">7.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Koenderink, N.J.J.P.; Hulzebos,, J.L.; Rijgersberg, H. et al. (4 March 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.slideshare.net\/CIARD_AIMS\/food-informatics-sharing-food\" target=\"_blank\">\"Food Informatics: Sharing Food Knowledge for Research & Development\"<\/a>. <i>Slideshare<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.slideshare.net\/CIARD_AIMS\/food-informatics-sharing-food\" target=\"_blank\">https:\/\/www.slideshare.net\/CIARD_AIMS\/food-informatics-sharing-food<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Food+Informatics%3A+Sharing+Food+Knowledge+for+Research+%26+Development&rft.atitle=Slideshare&rft.aulast=Koenderink%2C+N.J.J.P.%3B+Hulzebos%2C%2C+J.L.%3B+Rijgersberg%2C+H.+et+al.&rft.au=Koenderink%2C+N.J.J.P.%3B+Hulzebos%2C%2C+J.L.%3B+Rijgersberg%2C+H.+et+al.&rft.date=4+March+2011&rft_id=https%3A%2F%2Fwww.slideshare.net%2FCIARD_AIMS%2Ffood-informatics-sharing-food&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_8-0\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_8-1\">8.1<\/a><\/sup> <sup><a href=\"#cite_ref-:4_8-2\">8.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Dooley, Damion M.; Griffiths, Emma J.; Gosal, Gurinder S.; Buttigieg, Pier L.; Hoehndorf, Robert; Lange, Matthew C.; Schriml, Lynn M.; Brinkman, Fiona S. L. <i>et al.<\/i> (18 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nature.com\/articles\/s41538-018-0032-6\" target=\"_blank\">\"FoodOn: a harmonized food ontology to increase global food traceability, quality control and data integration\"<\/a> (in en). <i>npj Science of Food<\/i> <b>2<\/b> (1): 23. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41538-018-0032-6\" target=\"_blank\">10.1038\/s41538-018-0032-6<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2396-8370\" target=\"_blank\">2396-8370<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6550238\/\" target=\"_blank\">PMC6550238<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31304272\" target=\"_blank\">31304272<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nature.com\/articles\/s41538-018-0032-6\" target=\"_blank\">https:\/\/www.nature.com\/articles\/s41538-018-0032-6<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=FoodOn%3A+a+harmonized+food+ontology+to+increase+global+food+traceability%2C+quality+control+and+data+integration&rft.jtitle=npj+Science+of+Food&rft.aulast=Dooley&rft.aufirst=Damion+M.&rft.au=Dooley%2C%26%2332%3BDamion+M.&rft.au=Griffiths%2C%26%2332%3BEmma+J.&rft.au=Gosal%2C%26%2332%3BGurinder+S.&rft.au=Buttigieg%2C%26%2332%3BPier+L.&rft.au=Hoehndorf%2C%26%2332%3BRobert&rft.au=Lange%2C%26%2332%3BMatthew+C.&rft.au=Schriml%2C%26%2332%3BLynn+M.&rft.au=Brinkman%2C%26%2332%3BFiona+S.+L.&rft.au=Hsiao%2C%26%2332%3BWilliam+W.+L.&rft.date=18+December+2018&rft.volume=2&rft.issue=1&rft.pages=23&rft_id=info:doi\/10.1038%2Fs41538-018-0032-6&rft.issn=2396-8370&rft_id=info:pmc\/PMC6550238&rft_id=info:pmid\/31304272&rft_id=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41538-018-0032-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_9-0\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_9-1\">9.1<\/a><\/sup> <sup><a href=\"#cite_ref-:5_9-2\">9.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Griffiths, E.J.; Dooley, D.M.; Buttigieg, P.L. et al. (2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ceur-ws.org\/Vol-1747\/IP21_ICBO2016.pdf\" target=\"_blank\">\"FoodON: A Global Farm-to-Fork Food Ontology\"<\/a> (PDF). <i>Proceedings of ICBO\/BioCreative 2016<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ceur-ws.org\/Vol-1747\/IP21_ICBO2016.pdf\" target=\"_blank\">http:\/\/ceur-ws.org\/Vol-1747\/IP21_ICBO2016.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=FoodON%3A+A+Global+Farm-to-Fork+Food+Ontology&rft.jtitle=Proceedings+of+ICBO%2FBioCreative+2016&rft.aulast=Griffiths%2C+E.J.%3B+Dooley%2C+D.M.%3B+Buttigieg%2C+P.L.+et+al.&rft.au=Griffiths%2C+E.J.%3B+Dooley%2C+D.M.%3B+Buttigieg%2C+P.L.+et+al.&rft.date=2016&rft_id=http%3A%2F%2Fceur-ws.org%2FVol-1747%2FIP21_ICBO2016.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:18-10\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:18_10-0\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-:18_10-1\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Petersen, K.; Vakkalanka, S.; Kuzniarz, L. (1 August 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0950584915000646\" target=\"_blank\">\"Guidelines for conducting systematic mapping studies in software engineering: An update\"<\/a> (in en). <i>Information and Software Technology<\/i> <b>64<\/b>: 1\u201318. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.infsof.2015.03.007\" target=\"_blank\">10.1016\/j.infsof.2015.03.007<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0950-5849\" target=\"_blank\">0950-5849<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0950584915000646\" target=\"_blank\">https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0950584915000646<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Guidelines+for+conducting+systematic+mapping+studies+in+software+engineering%3A+An+update&rft.jtitle=Information+and+Software+Technology&rft.aulast=Petersen%2C+K.%3B+Vakkalanka%2C+S.%3B+Kuzniarz%2C+L.&rft.au=Petersen%2C+K.%3B+Vakkalanka%2C+S.%3B+Kuzniarz%2C+L.&rft.date=1+August+2015&rft.volume=64&rft.pages=1%E2%80%9318&rft_id=info:doi\/10.1016%2Fj.infsof.2015.03.007&rft.issn=0950-5849&rft_id=https%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fabs%2Fpii%2FS0950584915000646&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Auernhammer, Hermann (1 February 2001). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169900001538\" target=\"_blank\">\"Precision farming \u2014 the environmental challenge\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>30<\/b> (1-3): 31\u201343. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0168-1699%2800%2900153-8\" target=\"_blank\">10.1016\/S0168-1699(00)00153-8<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169900001538\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169900001538<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Precision+farming+%E2%80%94+the+environmental+challenge&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Auernhammer&rft.aufirst=Hermann&rft.au=Auernhammer%2C%26%2332%3BHermann&rft.date=1+February+2001&rft.volume=30&rft.issue=1-3&rft.pages=31%E2%80%9343&rft_id=info:doi\/10.1016%2FS0168-1699%2800%2900153-8&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169900001538&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gebbers, Robin; Adamchuk, Viacheslav I. (12 February 2010). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1126\/science.1183899\" target=\"_blank\">\"Precision Agriculture and Food Security\"<\/a>. <i>Science<\/i> <b>327<\/b> (5967): 828\u2013831. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1126%2Fscience.1183899\" target=\"_blank\">10.1126\/science.1183899<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0036-8075\" target=\"_blank\">0036-8075<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1126\/science.1183899\" target=\"_blank\">https:\/\/doi.org\/10.1126\/science.1183899<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Precision+Agriculture+and+Food+Security&rft.jtitle=Science&rft.aulast=Gebbers&rft.aufirst=Robin&rft.au=Gebbers%2C%26%2332%3BRobin&rft.au=Adamchuk%2C%26%2332%3BViacheslav+I.&rft.date=12+February+2010&rft.volume=327&rft.issue=5967&rft.pages=828%E2%80%93831&rft_id=info:doi\/10.1126%2Fscience.1183899&rft.issn=0036-8075&rft_id=https%3A%2F%2Fdoi.org%2F10.1126%2Fscience.1183899&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_13-0\">13.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_13-1\">13.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Sundmaeker, H.; Verdouw, C.; Wolfert, S. et al. (2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/983214747\" target=\"_blank\">\"Internet of Food and Farm 2020\"<\/a>. In Vermesan, Ovidiu; Friess, Peter. <i>Digitising the industry: Internet of Things connecting the physical, digital and virtual worlds<\/i>. River Publishers series in communications. Gistrup, Denmark: River Publishers. pp. 129\u2013151. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-87-93379-81-7. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/983214747\" target=\"_blank\">983214747<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/983214747\" target=\"_blank\">https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/983214747<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Internet+of+Food+and+Farm+2020&rft.atitle=Digitising+the+industry%3A+Internet+of+Things+connecting+the+physical%2C+digital+and+virtual+worlds&rft.aulast=Sundmaeker%2C+H.%3B+Verdouw%2C+C.%3B+Wolfert%2C+S.+et+al.&rft.au=Sundmaeker%2C+H.%3B+Verdouw%2C+C.%3B+Wolfert%2C+S.+et+al.&rft.date=2016&rft.series=River+Publishers+series+in+communications&rft.pages=pp.%26nbsp%3B129%E2%80%93151&rft.place=Gistrup%2C+Denmark&rft.pub=River+Publishers&rft.isbn=978-87-93379-81-7&rft_id=info:oclcnum\/983214747&rft_id=https%3A%2F%2Fwww.worldcat.org%2Ftitle%2Fmediawiki%2Foclc%2F983214747&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:19-14\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:19_14-0\">14.0<\/a><\/sup> <sup><a href=\"#cite_ref-:19_14-1\">14.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wolfert, S.; Ge, L.; Verdouw, C. et al. 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(2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.dlg.org\/en\/agriculture\/topics\/a-dlg-position-paper\" target=\"_blank\">\"Digital Agriculture - Opportunities. Risks. Acceptance.\"<\/a>. DLG<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.dlg.org\/en\/agriculture\/topics\/a-dlg-position-paper\" target=\"_blank\">https:\/\/www.dlg.org\/en\/agriculture\/topics\/a-dlg-position-paper<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Digital+Agriculture+-+Opportunities.+Risks.+Acceptance.&rft.atitle=&rft.aulast=Griepentrog%2C+H.W.%3B+Uppenkamp%2C+N.%3B+H%C3%B6rner%2C+R.+et+al.&rft.au=Griepentrog%2C+H.W.%3B+Uppenkamp%2C+N.%3B+H%C3%B6rner%2C+R.+et+al.&rft.date=2018&rft.pub=DLG&rft_id=https%3A%2F%2Fwww.dlg.org%2Fen%2Fagriculture%2Ftopics%2Fa-dlg-position-paper&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-16\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Liao, Yongxin; Deschamps, Fernando; Loures, Eduardo de Freitas Rocha; Ramos, Luiz Felipe Pierin (18 June 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1080\/00207543.2017.1308576\" target=\"_blank\">\"Past, present and future of Industry 4.0 - a systematic literature review and research agenda proposal\"<\/a>. <i>International Journal of Production Research<\/i> <b>55<\/b> (12): 3609\u20133629. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F00207543.2017.1308576\" target=\"_blank\">10.1080\/00207543.2017.1308576<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0020-7543\" target=\"_blank\">0020-7543<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1080\/00207543.2017.1308576\" target=\"_blank\">https:\/\/doi.org\/10.1080\/00207543.2017.1308576<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Past%2C+present+and+future+of+Industry+4.0+-+a+systematic+literature+review+and+research+agenda+proposal&rft.jtitle=International+Journal+of+Production+Research&rft.aulast=Liao&rft.aufirst=Yongxin&rft.au=Liao%2C%26%2332%3BYongxin&rft.au=Deschamps%2C%26%2332%3BFernando&rft.au=Loures%2C%26%2332%3BEduardo+de+Freitas+Rocha&rft.au=Ramos%2C%26%2332%3BLuiz+Felipe+Pierin&rft.date=18+June+2017&rft.volume=55&rft.issue=12&rft.pages=3609%E2%80%933629&rft_id=info:doi\/10.1080%2F00207543.2017.1308576&rft.issn=0020-7543&rft_id=https%3A%2F%2Fdoi.org%2F10.1080%2F00207543.2017.1308576&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-17\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_17-0\">17.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_17-1\">17.1<\/a><\/sup> <sup><a href=\"#cite_ref-:7_17-2\">17.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Xu, Li Da; He, Wu; Li, Shancang (1 November 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/6714496\/\" target=\"_blank\">\"Internet of Things in Industries: A Survey\"<\/a>. <i>IEEE Transactions on Industrial Informatics<\/i> <b>10<\/b> (4): 2233\u20132243. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTII.2014.2300753\" target=\"_blank\">10.1109\/TII.2014.2300753<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1941-0050\" target=\"_blank\">1941-0050<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/6714496\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/6714496\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+Things+in+Industries%3A+A+Survey&rft.jtitle=IEEE+Transactions+on+Industrial+Informatics&rft.aulast=Xu&rft.aufirst=Li+Da&rft.au=Xu%2C%26%2332%3BLi+Da&rft.au=He%2C%26%2332%3BWu&rft.au=Li%2C%26%2332%3BShancang&rft.date=1+November+2014&rft.volume=10&rft.issue=4&rft.pages=2233%E2%80%932243&rft_id=info:doi\/10.1109%2FTII.2014.2300753&rft.issn=1941-0050&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6714496%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Luque, A.; Peralta, M.E.; de las Heras, A. et al. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S235197891730834X\" target=\"_blank\">\"State of the Industry 4.0 in the Andalusian food sector\"<\/a> (in en). <i>Procedia Manufacturing<\/i> <b>13<\/b>: 1199\u20131205. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.promfg.2017.09.195\" target=\"_blank\">10.1016\/j.promfg.2017.09.195<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2351-9789\" target=\"_blank\">2351-9789<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S235197891730834X\" target=\"_blank\">https:\/\/www.sciencedirect.com\/science\/article\/pii\/S235197891730834X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=State+of+the+Industry+4.0+in+the+Andalusian+food+sector&rft.jtitle=Procedia+Manufacturing&rft.aulast=Luque%2C+A.%3B+Peralta%2C+M.E.%3B+de+las+Heras%2C+A.+et+al.&rft.au=Luque%2C+A.%3B+Peralta%2C+M.E.%3B+de+las+Heras%2C+A.+et+al.&rft.date=2017&rft.volume=13&rft.pages=1199%E2%80%931205&rft_id=info:doi\/10.1016%2Fj.promfg.2017.09.195&rft.issn=2351-9789&rft_id=https%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS235197891730834X&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-19\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kouma, Jean-Paul; Liu, Li (1 October 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6142168\/\" target=\"_blank\">\"Internet of Food\"<\/a>. <i>2011 International Conference on Internet of Things and 4th International Conference on Cyber, Physical and Social Computing<\/i> (Dalian, China: IEEE): 713\u2013716. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FiThings%2FCPSCom.2011.120\" target=\"_blank\">10.1109\/iThings\/CPSCom.2011.120<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4577-1976-9<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6142168\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/6142168\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+Food&rft.jtitle=2011+International+Conference+on+Internet+of+Things+and+4th+International+Conference+on+Cyber%2C+Physical+and+Social+Computing&rft.aulast=Kouma&rft.aufirst=Jean-Paul&rft.au=Kouma%2C%26%2332%3BJean-Paul&rft.au=Liu%2C%26%2332%3BLi&rft.date=1+October+2011&rft.pages=713%E2%80%93716&rft.place=Dalian%2C+China&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FiThings%2FCPSCom.2011.120&rft.isbn=978-1-4577-1976-9&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6142168%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-20\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Osisanwo, F.Y.; Kuyoro, S.O.; Awodele, O. (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/iieng.org\/images\/proceedings_pdf\/2602E0315051.pdf\" target=\"_blank\">\"Internet Refrigerator \u2013A typical Internet of Things (IoT)\"<\/a>. <i>Proceedings of the ICAESAM 2015<\/i>: 59\u201363. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.15242%2FIIE.E0315051\" target=\"_blank\">10.15242\/IIE.E0315051<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-93-84422-12-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/iieng.org\/images\/proceedings_pdf\/2602E0315051.pdf\" target=\"_blank\">http:\/\/iieng.org\/images\/proceedings_pdf\/2602E0315051.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+Refrigerator+%E2%80%93A+typical+Internet+of+Things+%28IoT%29&rft.jtitle=Proceedings+of+the+ICAESAM+2015&rft.aulast=Osisanwo%2C+F.Y.%3B+Kuyoro%2C+S.O.%3B+Awodele%2C+O.&rft.au=Osisanwo%2C+F.Y.%3B+Kuyoro%2C+S.O.%3B+Awodele%2C+O.&rft.date=2015&rft.pages=59%E2%80%9363&rft_id=info:doi\/10.15242%2FIIE.E0315051&rft.isbn=978-93-84422-12-7&rft_id=http%3A%2F%2Fiieng.org%2Fimages%2Fproceedings_pdf%2F2602E0315051.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:20-21\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:20_21-0\">21.0<\/a><\/sup> <sup><a href=\"#cite_ref-:20_21-1\">21.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Holden, Nicholas M.; White, Eoin P.; Lange, Matthew C.; Oldfield, Thomas L. (9 October 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nature.com\/articles\/s41538-018-0027-3\" target=\"_blank\">\"Review of the sustainability of food systems and transition using the Internet of Food\"<\/a> (in en). <i>npj Science of Food<\/i> <b>2<\/b> (1): 18. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41538-018-0027-3\" target=\"_blank\">10.1038\/s41538-018-0027-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2396-8370\" target=\"_blank\">2396-8370<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6550226\/\" target=\"_blank\">PMC6550226<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31304268\" target=\"_blank\">31304268<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nature.com\/articles\/s41538-018-0027-3\" target=\"_blank\">https:\/\/www.nature.com\/articles\/s41538-018-0027-3<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Review+of+the+sustainability+of+food+systems+and+transition+using+the+Internet+of+Food&rft.jtitle=npj+Science+of+Food&rft.aulast=Holden&rft.aufirst=Nicholas+M.&rft.au=Holden%2C%26%2332%3BNicholas+M.&rft.au=White%2C%26%2332%3BEoin+P.&rft.au=Lange%2C%26%2332%3BMatthew+C.&rft.au=Oldfield%2C%26%2332%3BThomas+L.&rft.date=9+October+2018&rft.volume=2&rft.issue=1&rft.pages=18&rft_id=info:doi\/10.1038%2Fs41538-018-0027-3&rft.issn=2396-8370&rft_id=info:pmc\/PMC6550226&rft_id=info:pmid\/31304268&rft_id=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41538-018-0027-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-22\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_22-0\">22.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_22-1\">22.1<\/a><\/sup> <sup><a href=\"#cite_ref-:8_22-2\">22.2<\/a><\/sup> <sup><a href=\"#cite_ref-:8_22-3\">22.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Min, Weiqing; Jiang, Shuqiang; Liu, Linhu; Rui, Yong; Jain, Ramesh (13 September 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1145\/3329168\" target=\"_blank\">\"A Survey on Food Computing\"<\/a>. <i>ACM Computing Surveys<\/i> <b>52<\/b> (5): 92:1\u201392:36. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3329168\" target=\"_blank\">10.1145\/3329168<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1145\/3329168\" target=\"_blank\">https:\/\/doi.org\/10.1145\/3329168<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Survey+on+Food+Computing&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Min&rft.aufirst=Weiqing&rft.au=Min%2C%26%2332%3BWeiqing&rft.au=Jiang%2C%26%2332%3BShuqiang&rft.au=Liu%2C%26%2332%3BLinhu&rft.au=Rui%2C%26%2332%3BYong&rft.au=Jain%2C%26%2332%3BRamesh&rft.date=13+September+2019&rft.volume=52&rft.issue=5&rft.pages=92%3A1%E2%80%9392%3A36&rft_id=info:doi\/10.1145%2F3329168&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdoi.org%2F10.1145%2F3329168&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Khot, Rohit Ashok; Mueller, Florian (28 August 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nowpublishers.com\/article\/Details\/HCI-074\" target=\"_blank\">\"Human-Food Interaction\"<\/a> (in English). <i>Foundations and Trends\u00ae in Human\u2013Computer Interaction<\/i> <b>12<\/b> (4): 238\u2013415. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1561%2F1100000074\" target=\"_blank\">10.1561\/1100000074<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1551-3955\" target=\"_blank\">1551-3955<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nowpublishers.com\/article\/Details\/HCI-074\" target=\"_blank\">https:\/\/www.nowpublishers.com\/article\/Details\/HCI-074<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Human-Food+Interaction&rft.jtitle=Foundations+and+Trends%C2%AE+in+Human%E2%80%93Computer+Interaction&rft.aulast=Khot&rft.aufirst=Rohit+Ashok&rft.au=Khot%2C%26%2332%3BRohit+Ashok&rft.au=Mueller%2C%26%2332%3BFlorian&rft.date=28+August+2019&rft.volume=12&rft.issue=4&rft.pages=238%E2%80%93415&rft_id=info:doi\/10.1561%2F1100000074&rft.issn=1551-3955&rft_id=https%3A%2F%2Fwww.nowpublishers.com%2Farticle%2FDetails%2FHCI-074&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Grimes, Andrea; Harper, Richard (2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1357054.1357130\" target=\"_blank\">\"Celebratory technology: new directions for food research in HCI\"<\/a> (in en). <i>Proceeding of the twenty-sixth annual CHI conference on Human factors in computing systems - CHI '08<\/i> (Florence, Italy: ACM Press): 467. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1357054.1357130\" target=\"_blank\">10.1145\/1357054.1357130<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-60558-011-1<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1357054.1357130\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=1357054.1357130<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Celebratory+technology%3A+new+directions+for+food+research+in+HCI&rft.jtitle=Proceeding+of+the+twenty-sixth+annual+CHI+conference+on+Human+factors+in+computing+systems++-+CHI+%2708&rft.aulast=Grimes&rft.aufirst=Andrea&rft.au=Grimes%2C%26%2332%3BAndrea&rft.au=Harper%2C%26%2332%3BRichard&rft.date=2008&rft.pages=467&rft.place=Florence%2C+Italy&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F1357054.1357130&rft.isbn=978-1-60558-011-1&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D1357054.1357130&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Choi, Jaz Hee-jeong; Foth, Marcus; Hearn, Greg, eds. (2014). <i>Eat, cook, grow: mixing human-computer interactions with human-food interactions<\/i>. Cambridge, Massachusetts: The MIT Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-262-02685-7.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Eat%2C+cook%2C+grow%3A+mixing+human-computer+interactions+with+human-food+interactions&rft.date=2014&rft.place=Cambridge%2C+Massachusetts&rft.pub=The+MIT+Press&rft.isbn=978-0-262-02685-7&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-26\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Varshney, Upkar (1 June 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1007\/s11036-007-0017-1\" target=\"_blank\">\"Pervasive Healthcare and Wireless Health Monitoring\"<\/a> (in en). <i>Mobile Networks and Applications<\/i> <b>12<\/b> (2): 113\u2013127. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11036-007-0017-1\" target=\"_blank\">10.1007\/s11036-007-0017-1<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1572-8153\" target=\"_blank\">1572-8153<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1007\/s11036-007-0017-1\" target=\"_blank\">https:\/\/doi.org\/10.1007\/s11036-007-0017-1<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pervasive+Healthcare+and+Wireless+Health+Monitoring&rft.jtitle=Mobile+Networks+and+Applications&rft.aulast=Varshney&rft.aufirst=Upkar&rft.au=Varshney%2C%26%2332%3BUpkar&rft.date=1+June+2007&rft.volume=12&rft.issue=2&rft.pages=113%E2%80%93127&rft_id=info:doi\/10.1007%2Fs11036-007-0017-1&rft.issn=1572-8153&rft_id=https%3A%2F%2Fdoi.org%2F10.1007%2Fs11036-007-0017-1&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Solanas, Agusti; Patsakis, Constantinos; Conti, Mauro; Vlachos, Ioannis S.; Ramos, Victoria; Falcone, Francisco; Postolache, Octavian; Perez-martinez, Pablo A. <i>et al.<\/i> (1 August 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/6871673\/\" target=\"_blank\">\"Smart health: A context-aware health paradigm within smart cities\"<\/a>. <i>IEEE Communications Magazine<\/i> <b>52<\/b> (8): 74\u201381. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FMCOM.2014.6871673\" target=\"_blank\">10.1109\/MCOM.2014.6871673<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1558-1896\" target=\"_blank\">1558-1896<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/6871673\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/6871673\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Smart+health%3A+A+context-aware+health+paradigm+within+smart+cities&rft.jtitle=IEEE+Communications+Magazine&rft.aulast=Solanas&rft.aufirst=Agusti&rft.au=Solanas%2C%26%2332%3BAgusti&rft.au=Patsakis%2C%26%2332%3BConstantinos&rft.au=Conti%2C%26%2332%3BMauro&rft.au=Vlachos%2C%26%2332%3BIoannis+S.&rft.au=Ramos%2C%26%2332%3BVictoria&rft.au=Falcone%2C%26%2332%3BFrancisco&rft.au=Postolache%2C%26%2332%3BOctavian&rft.au=Perez-martinez%2C%26%2332%3BPablo+A.&rft.au=Pietro%2C%26%2332%3BRoberto+Di&rft.date=1+August+2014&rft.volume=52&rft.issue=8&rft.pages=74%E2%80%9381&rft_id=info:doi\/10.1109%2FMCOM.2014.6871673&rft.issn=1558-1896&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6871673%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:21-28\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:21_28-0\">28.0<\/a><\/sup> <sup><a href=\"#cite_ref-:21_28-1\">28.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Subramaniyaswamy, V.; Manogaran, Gunasekaran; Logesh, R.; Vijayakumar, V.; Chilamkurti, Naveen; Malathi, D.; Senthilselvan, N. (1 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1007\/s11227-018-2331-8\" target=\"_blank\">\"An ontology-driven personalized food recommendation in IoT-based healthcare system\"<\/a> (in en). <i>The Journal of Supercomputing<\/i> <b>75<\/b> (6): 3184\u20133216. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11227-018-2331-8\" target=\"_blank\">10.1007\/s11227-018-2331-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1573-0484\" target=\"_blank\">1573-0484<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1007\/s11227-018-2331-8\" target=\"_blank\">https:\/\/doi.org\/10.1007\/s11227-018-2331-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=An+ontology-driven+personalized+food+recommendation+in+IoT-based+healthcare+system&rft.jtitle=The+Journal+of+Supercomputing&rft.aulast=Subramaniyaswamy&rft.aufirst=V.&rft.au=Subramaniyaswamy%2C%26%2332%3BV.&rft.au=Manogaran%2C%26%2332%3BGunasekaran&rft.au=Logesh%2C%26%2332%3BR.&rft.au=Vijayakumar%2C%26%2332%3BV.&rft.au=Chilamkurti%2C%26%2332%3BNaveen&rft.au=Malathi%2C%26%2332%3BD.&rft.au=Senthilselvan%2C%26%2332%3BN.&rft.date=1+June+2019&rft.volume=75&rft.issue=6&rft.pages=3184%E2%80%933216&rft_id=info:doi\/10.1007%2Fs11227-018-2331-8&rft.issn=1573-0484&rft_id=https%3A%2F%2Fdoi.org%2F10.1007%2Fs11227-018-2331-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-29\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hartwell, H.; Appleton, K. M.; Bray, J.; Price, S.; Mavridis, I.; Giboreau, A.; Perez\u2010Cueto, F. J. A.; Ronge, M. (25 April 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1111\/nbu.12376\" target=\"_blank\">\"Shaping smarter consumer food choices: The Food SMART project\"<\/a>. <i>Nutrition Bulletin<\/i> <b>44<\/b> (2): 138\u2013144. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fnbu.12376\" target=\"_blank\">10.1111\/nbu.12376<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-9827\" target=\"_blank\">1471-9827<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1111\/nbu.12376\" target=\"_blank\">https:\/\/doi.org\/10.1111\/nbu.12376<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Shaping+smarter+consumer+food+choices%3A+The+Food+SMART+project&rft.jtitle=Nutrition+Bulletin&rft.aulast=Hartwell&rft.aufirst=H.&rft.au=Hartwell%2C%26%2332%3BH.&rft.au=Appleton%2C%26%2332%3BK.+M.&rft.au=Bray%2C%26%2332%3BJ.&rft.au=Price%2C%26%2332%3BS.&rft.au=Mavridis%2C%26%2332%3BI.&rft.au=Giboreau%2C%26%2332%3BA.&rft.au=Perez%E2%80%90Cueto%2C%26%2332%3BF.+J.+A.&rft.au=Ronge%2C%26%2332%3BM.&rft.date=25+April+2019&rft.volume=44&rft.issue=2&rft.pages=138%E2%80%93144&rft_id=info:doi\/10.1111%2Fnbu.12376&rft.issn=1471-9827&rft_id=https%3A%2F%2Fdoi.org%2F10.1111%2Fnbu.12376&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chan, Lauren; Vasilevsky, Nicole; Thessen, Anne; McMurry, Julie; Haendel, Melissa (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1093\/database\/baab003\" target=\"_blank\">\"The landscape of nutri-informatics: a review of current resources and challenges for integrative nutrition research\"<\/a>. <i>Database<\/i> <b>2021<\/b>: baab003. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fdatabase%2Fbaab003\" target=\"_blank\">10.1093\/database\/baab003<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1758-0463\" target=\"_blank\">1758-0463<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7833928\/\" target=\"_blank\">PMC7833928<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33494105\" target=\"_blank\">33494105<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1093\/database\/baab003\" target=\"_blank\">https:\/\/doi.org\/10.1093\/database\/baab003<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+landscape+of+nutri-informatics%3A+a+review+of+current+resources+and+challenges+for+integrative+nutrition+research&rft.jtitle=Database&rft.aulast=Chan&rft.aufirst=Lauren&rft.au=Chan%2C%26%2332%3BLauren&rft.au=Vasilevsky%2C%26%2332%3BNicole&rft.au=Thessen%2C%26%2332%3BAnne&rft.au=McMurry%2C%26%2332%3BJulie&rft.au=Haendel%2C%26%2332%3BMelissa&rft.date=1+January+2021&rft.volume=2021&rft.pages=baab003&rft_id=info:doi\/10.1093%2Fdatabase%2Fbaab003&rft.issn=1758-0463&rft_id=info:pmc\/PMC7833928&rft_id=info:pmid\/33494105&rft_id=https%3A%2F%2Fdoi.org%2F10.1093%2Fdatabase%2Fbaab003&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-31\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_31-0\">31.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_31-1\">31.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Abad, E.; Palacio, F.; Nuin, M.; Z\u00e1rate, A. Gonz\u00e1lez de; Juarros, A.; G\u00f3mez, J.M.; Marco, S. (1 August 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0260877409000661\" target=\"_blank\">\"RFID smart tag for traceability and cold chain monitoring of foods: Demonstration in an intercontinental fresh fish logistic chain\"<\/a> (in en). <i>Journal of Food Engineering<\/i> <b>93<\/b> (4): 394\u2013399. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jfoodeng.2009.02.004\" target=\"_blank\">10.1016\/j.jfoodeng.2009.02.004<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0260877409000661\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0260877409000661<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=RFID+smart+tag+for+traceability+and+cold+chain+monitoring+of+foods%3A+Demonstration+in+an+intercontinental+fresh+fish+logistic+chain&rft.jtitle=Journal+of+Food+Engineering&rft.aulast=Abad&rft.aufirst=E.&rft.au=Abad%2C%26%2332%3BE.&rft.au=Palacio%2C%26%2332%3BF.&rft.au=Nuin%2C%26%2332%3BM.&rft.au=Z%C3%A1rate%2C%26%2332%3BA.+Gonz%C3%A1lez+de&rft.au=Juarros%2C%26%2332%3BA.&rft.au=G%C3%B3mez%2C%26%2332%3BJ.M.&rft.au=Marco%2C%26%2332%3BS.&rft.date=1+August+2009&rft.volume=93&rft.issue=4&rft.pages=394%E2%80%93399&rft_id=info:doi\/10.1016%2Fj.jfoodeng.2009.02.004&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0260877409000661&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-32\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_32-0\">32.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_32-1\">32.1<\/a><\/sup> <sup><a href=\"#cite_ref-:10_32-2\">32.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Tian, F. (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/servlet\/opac?punumber=7988695\" target=\"_blank\">\"A Supply Chain Traceability System for Food Safety Based on HACCP, Blockchain & Internet of Things\"<\/a> (in English). <i>The 14th International Conference on Services Systems and Services Management (ICSSSM2017) June 16-18, 2017, Dalian, China: proceedings<\/i>. Institute of Electrical and Electronics Engineers (IEEE). pp. 21\u201326. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5090-6370-3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/1003129448\" target=\"_blank\">1003129448<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/servlet\/opac?punumber=7988695\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/servlet\/opac?punumber=7988695<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=A+Supply+Chain+Traceability+System+for+Food+Safety+Based+on+HACCP%2C+Blockchain+%26+Internet+of+Things&rft.atitle=The+14th+International+Conference+on+Services+Systems+and+Services+Management+%28ICSSSM2017%29+June+16-18%2C+2017%2C+Dalian%2C+China%3A+proceedings&rft.aulast=Tian%2C+F.&rft.au=Tian%2C+F.&rft.date=2017&rft.pages=pp.%26nbsp%3B21%E2%80%9326&rft.pub=Institute+of+Electrical+and+Electronics+Engineers+%28IEEE%29&rft.isbn=978-1-5090-6370-3&rft_id=info:oclcnum\/1003129448&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fservlet%2Fopac%3Fpunumber%3D7988695&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-33\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_33-0\">33.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_33-1\">33.1<\/a><\/sup> <sup><a href=\"#cite_ref-:11_33-2\">33.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mondal, Saikat; Wijewardena, Kanishka P.; Karuppuswami, Saranraj; Kriti, Nitya; Kumar, Deepak; Chahal, Premjeet (1 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8674550\/\" target=\"_blank\">\"Blockchain Inspired RFID-Based Information Architecture for Food Supply Chain\"<\/a>. <i>IEEE Internet of Things Journal<\/i> <b>6<\/b> (3): 5803\u20135813. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJIOT.2019.2907658\" target=\"_blank\">10.1109\/JIOT.2019.2907658<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2327-4662\" target=\"_blank\">2327-4662<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8674550\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8674550\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Blockchain+Inspired+RFID-Based+Information+Architecture+for+Food+Supply+Chain&rft.jtitle=IEEE+Internet+of+Things+Journal&rft.aulast=Mondal&rft.aufirst=Saikat&rft.au=Mondal%2C%26%2332%3BSaikat&rft.au=Wijewardena%2C%26%2332%3BKanishka+P.&rft.au=Karuppuswami%2C%26%2332%3BSaranraj&rft.au=Kriti%2C%26%2332%3BNitya&rft.au=Kumar%2C%26%2332%3BDeepak&rft.au=Chahal%2C%26%2332%3BPremjeet&rft.date=1+June+2019&rft.volume=6&rft.issue=3&rft.pages=5803%E2%80%935813&rft_id=info:doi\/10.1109%2FJIOT.2019.2907658&rft.issn=2327-4662&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8674550%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-34\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cruz Introini, S.; Boza, A.; Alemany D\u00edaz, M.D.M. (2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/hdl.handle.net\/10251\/121089\" target=\"_blank\">\"Traceability in the Food Supply Chain: Review of the literature from a technological perspective\"<\/a>. <i>Direccion y Organizacion<\/i> <b>64<\/b>: 50\u201355. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1132-175X\" target=\"_blank\">1132-175X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/hdl.handle.net\/10251\/121089\" target=\"_blank\">http:\/\/hdl.handle.net\/10251\/121089<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Traceability+in+the+Food+Supply+Chain%3A+Review+of+the+literature+from+a+technological+perspective&rft.jtitle=Direccion+y+Organizacion&rft.aulast=Cruz+Introini%2C+S.%3B+Boza%2C+A.%3B+Alemany+D%C3%ADaz%2C+M.D.M.&rft.au=Cruz+Introini%2C+S.%3B+Boza%2C+A.%3B+Alemany+D%C3%ADaz%2C+M.D.M.&rft.date=2018&rft.volume=64&rft.pages=50%E2%80%9355&rft.issn=1132-175X&rft_id=http%3A%2F%2Fhdl.handle.net%2F10251%2F121089&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Danezis, Georgios P.; Tsagkaris, Aristidis S.; Camin, Federica; Brusic, Vladimir; Georgiou, Constantinos A. (1 December 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993615301291\" target=\"_blank\">\"Food authentication: Techniques, trends & emerging approaches\"<\/a> (in en). <i>TrAC Trends in Analytical Chemistry<\/i> <b>85<\/b>: 123\u2013132. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.trac.2016.02.026\" target=\"_blank\">10.1016\/j.trac.2016.02.026<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993615301291\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993615301291<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Food+authentication%3A+Techniques%2C+trends+%26+emerging+approaches&rft.jtitle=TrAC+Trends+in+Analytical+Chemistry&rft.aulast=Danezis&rft.aufirst=Georgios+P.&rft.au=Danezis%2C%26%2332%3BGeorgios+P.&rft.au=Tsagkaris%2C%26%2332%3BAristidis+S.&rft.au=Camin%2C%26%2332%3BFederica&rft.au=Brusic%2C%26%2332%3BVladimir&rft.au=Georgiou%2C%26%2332%3BConstantinos+A.&rft.date=1+December+2016&rft.volume=85&rft.pages=123%E2%80%93132&rft_id=info:doi\/10.1016%2Fj.trac.2016.02.026&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165993615301291&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">DOINEA, Mihai; BOJA, Catalin; BATAGAN, Lorena; TOMA, Cristian; POPA, Marius (30 March 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.12948\/issn14531305\/19.1.2015.08\" target=\"_blank\">\"Internet of Things Based Systems for Food Safety Management\"<\/a>. <i>Informatica Economica<\/i> <b>19<\/b> (1\/2015): 87\u201397. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.12948%2Fissn14531305%2F19.1.2015.08\" target=\"_blank\">10.12948\/issn14531305\/19.1.2015.08<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1453-1305\" target=\"_blank\">1453-1305<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.12948\/issn14531305\/19.1.2015.08\" target=\"_blank\">https:\/\/doi.org\/10.12948\/issn14531305\/19.1.2015.08<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+Things+Based+Systems+for+Food+Safety+Management&rft.jtitle=Informatica+Economica&rft.aulast=DOINEA&rft.aufirst=Mihai&rft.au=DOINEA%2C%26%2332%3BMihai&rft.au=BOJA%2C%26%2332%3BCatalin&rft.au=BATAGAN%2C%26%2332%3BLorena&rft.au=TOMA%2C%26%2332%3BCristian&rft.au=POPA%2C%26%2332%3BMarius&rft.date=30+March+2015&rft.volume=19&rft.issue=1%2F2015&rft.pages=87%E2%80%9397&rft_id=info:doi\/10.12948%2Fissn14531305%2F19.1.2015.08&rft.issn=1453-1305&rft_id=https%3A%2F%2Fdoi.org%2F10.12948%2Fissn14531305%2F19.1.2015.08&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-37\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_37-0\">37.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_37-1\">37.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ying, Fu; Fengquan, Li (1 June 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6597990\/\" target=\"_blank\">\"Application of Internet of Things to the Monitoring System for Food Quality Safety\"<\/a>. <i>2013 Fourth International Conference on Digital Manufacturing & Automation<\/i> (Shinan District of Qingdao \u00bfShangdong Province, China: IEEE): 296\u2013298. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FICDMA.2013.71\" target=\"_blank\">10.1109\/ICDMA.2013.71<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-7695-5016-9<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6597990\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/6597990\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Application+of+Internet+of+Things+to+the+Monitoring+System+for+Food+Quality+Safety&rft.jtitle=2013+Fourth+International+Conference+on+Digital+Manufacturing+%26+Automation&rft.aulast=Ying&rft.aufirst=Fu&rft.au=Ying%2C%26%2332%3BFu&rft.au=Fengquan%2C%26%2332%3BLi&rft.date=1+June+2013&rft.pages=296%E2%80%93298&rft.place=Shinan+District+of+Qingdao+%C2%BFShangdong+Province%2C+China&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FICDMA.2013.71&rft.isbn=978-0-7695-5016-9&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6597990%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:13-38\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:13_38-0\">38.0<\/a><\/sup> <sup><a href=\"#cite_ref-:13_38-1\">38.1<\/a><\/sup> <sup><a href=\"#cite_ref-:13_38-2\">38.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Paul, P.; Aithal, P.S.; Bhuimali, A. (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jrrset.com\/volume5_issue9.html\" target=\"_blank\">\"Food Informatics and Its Challenges and Opportunities - A Review\"<\/a>. <i>International Journal on Recent Researches in Science, Engineering & Technology<\/i> <b>5<\/b> (9): 46\u201353. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2347-6729\" target=\"_blank\">2347-6729<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jrrset.com\/volume5_issue9.html\" target=\"_blank\">http:\/\/www.jrrset.com\/volume5_issue9.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Food+Informatics+and+Its+Challenges+and+Opportunities+-+A+Review&rft.jtitle=International+Journal+on+Recent+Researches+in+Science%2C+Engineering+%26+Technology&rft.aulast=Paul%2C+P.%3B+Aithal%2C+P.S.%3B+Bhuimali%2C+A.&rft.au=Paul%2C+P.%3B+Aithal%2C+P.S.%3B+Bhuimali%2C+A.&rft.date=2017&rft.volume=5&rft.issue=9&rft.pages=46%E2%80%9353&rft.issn=2347-6729&rft_id=http%3A%2F%2Fwww.jrrset.com%2Fvolume5_issue9.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Epstein, Daniel A. (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2800835.2801643\" target=\"_blank\">\"Personal informatics in everyday life\"<\/a> (in en). <i>Proceedings of the 2015 ACM International Joint Conference on Pervasive and Ubiquitous Computing and Proceedings of the 2015 ACM International Symposium on Wearable Computers - UbiComp '15<\/i> (Osaka, Japan: ACM Press): 429\u2013434. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2800835.2801643\" target=\"_blank\">10.1145\/2800835.2801643<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-3575-1<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2800835.2801643\" target=\"_blank\">http:\/\/dl.acm.org\/citation.cfm?doid=2800835.2801643<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Personal+informatics+in+everyday+life&rft.jtitle=Proceedings+of+the+2015+ACM+International+Joint+Conference+on+Pervasive+and+Ubiquitous+Computing+and+Proceedings+of+the+2015+ACM+International+Symposium+on+Wearable+Computers+-+UbiComp+%2715&rft.aulast=Epstein&rft.aufirst=Daniel+A.&rft.au=Epstein%2C%26%2332%3BDaniel+A.&rft.date=2015&rft.pages=429%E2%80%93434&rft.place=Osaka%2C+Japan&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F2800835.2801643&rft.isbn=978-1-4503-3575-1&rft_id=http%3A%2F%2Fdl.acm.org%2Fcitation.cfm%3Fdoid%3D2800835.2801643&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:14-40\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:14_40-0\">40.0<\/a><\/sup> <sup><a href=\"#cite_ref-:14_40-1\">40.1<\/a><\/sup> <sup><a href=\"#cite_ref-:14_40-2\">40.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">TU Delft (July 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/studiolab.ide.tudelft.nl\/studiolab\/romero\/files\/2018\/07\/20180520-DfIIPD-MasterProject-FoodSampler.pdf\" target=\"_blank\">\"Design food informatics for vulnerable groups\"<\/a>. TU Delft<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/studiolab.ide.tudelft.nl\/studiolab\/romero\/files\/2018\/07\/20180520-DfIIPD-MasterProject-FoodSampler.pdf\" target=\"_blank\">https:\/\/studiolab.ide.tudelft.nl\/studiolab\/romero\/files\/2018\/07\/20180520-DfIIPD-MasterProject-FoodSampler.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 19 November 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Design+food+informatics+for+vulnerable+groups&rft.atitle=&rft.aulast=TU+Delft&rft.au=TU+Delft&rft.date=July+2018&rft.pub=TU+Delft&rft_id=https%3A%2F%2Fstudiolab.ide.tudelft.nl%2Fstudiolab%2Fromero%2Ffiles%2F2018%2F07%2F20180520-DfIIPD-MasterProject-FoodSampler.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:15-41\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:15_41-0\">41.0<\/a><\/sup> <sup><a href=\"#cite_ref-:15_41-1\">41.1<\/a><\/sup> <sup><a href=\"#cite_ref-:15_41-2\">41.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Martinez-Mayorga, Karina; Medina-Franco, Jos\u00e9 Luis, eds. (2014). \"Preface\". <i>Foodinformatics: Applications of Chemical Information to Food Chemistry<\/i> (1st ed. 2014 ed.). Cham: Springer International Publishing : Imprint: Springer. pp. vii. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-10226-9\" target=\"_blank\">10.1007\/978-3-319-10226-9<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-10226-9.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Preface&rft.atitle=Foodinformatics%3A+Applications+of+Chemical+Information+to+Food+Chemistry&rft.date=2014&rft.pages=pp.%26nbsp%3Bvii&rft.edition=1st+ed.+2014&rft.place=Cham&rft.pub=Springer+International+Publishing+%3A+Imprint%3A+Springer&rft_id=info:doi\/10.1007%2F978-3-319-10226-9&rft.isbn=978-3-319-10226-9&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFMartinez-MayorgaPeppardMedina-Franco2014\">Martinez-Mayorga, Karina; Peppard, Terry L.; Medina-Franco, Jos\u00e9 L. (2014), Martinez-Mayorga, Karina; Medina-Franco, Jos\u00e9 Luis, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-10226-9_9\" target=\"_blank\">\"Software and Online Resources: Perspectives and Potential Applications\"<\/a> (in en), <i>Foodinformatics<\/i> (Cham: Springer International Publishing): 233\u2013248, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-10226-9_9\" target=\"_blank\">10.1007\/978-3-319-10226-9_9<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-10225-2<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-10226-9_9\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-10226-9_9<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-03-22<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Software+and+Online+Resources%3A+Perspectives+and+Potential+Applications&rft.jtitle=Foodinformatics&rft.aulast=Martinez-Mayorga&rft.aufirst=Karina&rft.au=Martinez-Mayorga%2C%26%2332%3BKarina&rft.au=Peppard%2C%26%2332%3BTerry+L.&rft.au=Medina-Franco%2C%26%2332%3BJos%C3%A9+L.&rft.date=2014&rft.pages=233%E2%80%93248&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-10226-9_9&rft.isbn=978-3-319-10225-2&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-10226-9_9&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:22-43\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:22_43-0\">43.0<\/a><\/sup> <sup><a href=\"#cite_ref-:22_43-1\">43.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFKounevLewisBellmanBencomo2017\">Kounev, Samuel; Lewis, Peter; Bellman, Kirstie L.; Bencomo, Nelly; Camara, Javier; Diaconescu, Ada; Esterle, Lukas; Geihs, Kurt <i>et al.<\/i>. (2017), Kounev, Samuel; Kephart, Jeffrey O.; Milenkoski, Aleksandar <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-47474-8_1\" target=\"_blank\">\"The Notion of Self-aware Computing\"<\/a> (in en), <i>Self-Aware Computing Systems<\/i> (Cham: Springer International Publishing): 3\u201316, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-47474-8_1\" target=\"_blank\">10.1007\/978-3-319-47474-8_1<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-47472-4<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-47474-8_1\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-47474-8_1<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-03-22<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Notion+of+Self-aware+Computing&rft.jtitle=Self-Aware+Computing+Systems&rft.aulast=Kounev&rft.aufirst=Samuel&rft.au=Kounev%2C%26%2332%3BSamuel&rft.au=Lewis%2C%26%2332%3BPeter&rft.au=Bellman%2C%26%2332%3BKirstie+L.&rft.au=Bencomo%2C%26%2332%3BNelly&rft.au=Camara%2C%26%2332%3BJavier&rft.au=Diaconescu%2C%26%2332%3BAda&rft.au=Esterle%2C%26%2332%3BLukas&rft.au=Geihs%2C%26%2332%3BKurt&rft.au=Giese%2C%26%2332%3BHolger&rft.date=2017&rft.pages=3%E2%80%9316&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-47474-8_1&rft.isbn=978-3-319-47472-4&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-47474-8_1&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:16-44\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:16_44-0\">44.0<\/a><\/sup> <sup><a href=\"#cite_ref-:16_44-1\">44.1<\/a><\/sup> <sup><a href=\"#cite_ref-:16_44-2\">44.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">M\u00fcller-Schloer, Christian; Tomforde, Sven (2017) (in en). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-68477-2\" target=\"_blank\"><i>Organic Computing \u2013 Technical Systems for Survival in the Real World<\/i><\/a>. Autonomic Systems. Cham: Springer International Publishing. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-68477-2\" target=\"_blank\">10.1007\/978-3-319-68477-2<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-68476-5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-68477-2\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-68477-2<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Organic+Computing+%E2%80%93+Technical+Systems+for+Survival+in+the+Real+World&rft.aulast=M%C3%BCller-Schloer&rft.aufirst=Christian&rft.au=M%C3%BCller-Schloer%2C%26%2332%3BChristian&rft.au=Tomforde%2C%26%2332%3BSven&rft.date=2017&rft.series=Autonomic+Systems&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-68477-2&rft.isbn=978-3-319-68476-5&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-68477-2&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Israeli, Assaf; Emmerich, Michael; Litaor, Michael (Iggy); Shir, Ofer M. (13 July 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3321707.3321809\" target=\"_blank\">\"Statistical learning in soil sampling design aided by pareto optimization\"<\/a> (in en). <i>Proceedings of the Genetic and Evolutionary Computation Conference<\/i> (Prague Czech Republic: ACM): 1198\u20131205. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3321707.3321809\" target=\"_blank\">10.1145\/3321707.3321809<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-6111-8<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3321707.3321809\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3321707.3321809<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Statistical+learning+in+soil+sampling+design+aided+by+pareto+optimization&rft.jtitle=Proceedings+of+the+Genetic+and+Evolutionary+Computation+Conference&rft.aulast=Israeli&rft.aufirst=Assaf&rft.au=Israeli%2C%26%2332%3BAssaf&rft.au=Emmerich%2C%26%2332%3BMichael&rft.au=Litaor%2C%26%2332%3BMichael+%28Iggy%29&rft.au=Shir%2C%26%2332%3BOfer+M.&rft.date=13+July+2019&rft.pages=1198%E2%80%931205&rft.place=Prague+Czech+Republic&rft.pub=ACM&rft_id=info:doi\/10.1145%2F3321707.3321809&rft.isbn=978-1-4503-6111-8&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3321707.3321809&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:17-46\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:17_46-0\">46.0<\/a><\/sup> <sup><a href=\"#cite_ref-:17_46-1\">46.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Boubin, Jayson; Chumley, John; Stewart, Christopher; Khanal, Sami (1 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8831204\/\" target=\"_blank\">\"Autonomic Computing Challenges in Fully Autonomous Precision Agriculture\"<\/a>. <i>2019 IEEE International Conference on Autonomic Computing (ICAC)<\/i> (Umea, Sweden: IEEE): 11\u201317. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FICAC.2019.00012\" target=\"_blank\">10.1109\/ICAC.2019.00012<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-7281-2411-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8831204\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8831204\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Autonomic+Computing+Challenges+in+Fully+Autonomous+Precision+Agriculture&rft.jtitle=2019+IEEE+International+Conference+on+Autonomic+Computing+%28ICAC%29&rft.aulast=Boubin&rft.aufirst=Jayson&rft.au=Boubin%2C%26%2332%3BJayson&rft.au=Chumley%2C%26%2332%3BJohn&rft.au=Stewart%2C%26%2332%3BChristopher&rft.au=Khanal%2C%26%2332%3BSami&rft.date=1+June+2019&rft.pages=11%E2%80%9317&rft.place=Umea%2C+Sweden&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FICAC.2019.00012&rft.isbn=978-1-7281-2411-7&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8831204%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-47\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-47\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Albani, Dario; Nardi, Daniele; Trianni, Vito (1 September 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/8206296\/\" target=\"_blank\">\"Field coverage and weed mapping by UAV swarms\"<\/a>. <i>2017 IEEE\/RSJ International Conference on Intelligent Robots and Systems (IROS)<\/i> (Vancouver, BC: IEEE): 4319\u20134325. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FIROS.2017.8206296\" target=\"_blank\">10.1109\/IROS.2017.8206296<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5386-2682-5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/8206296\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/8206296\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Field+coverage+and+weed+mapping+by+UAV+swarms&rft.jtitle=2017+IEEE%2FRSJ+International+Conference+on+Intelligent+Robots+and+Systems+%28IROS%29&rft.aulast=Albani&rft.aufirst=Dario&rft.au=Albani%2C%26%2332%3BDario&rft.au=Nardi%2C%26%2332%3BDaniele&rft.au=Trianni%2C%26%2332%3BVito&rft.date=1+September+2017&rft.pages=4319%E2%80%934325&rft.place=Vancouver%2C+BC&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FIROS.2017.8206296&rft.isbn=978-1-5386-2682-5&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8206296%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFAlbaniManoniArikNardi2019\">Albani, Dario; Manoni, Tiziano; Arik, Arikhan; Nardi, Daniele; Trianni, Vito (2019), Compagnoni, Adriana; Casey, William; Cai, Yang <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-030-24202-2_10\" target=\"_blank\">\"Field Coverage for Weed Mapping: Toward Experiments with a UAV Swarm\"<\/a> (in en), <i>Bio-inspired Information and Communication Technologies<\/i> (Cham: Springer International Publishing) <b>289<\/b>: 132\u2013146, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-030-24202-2_10\" target=\"_blank\">10.1007\/978-3-030-24202-2_10<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-030-24201-5<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-030-24202-2_10\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-030-24202-2_10<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-03-22<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Field+Coverage+for+Weed+Mapping%3A+Toward+Experiments+with+a+UAV+Swarm&rft.jtitle=Bio-inspired+Information+and+Communication+Technologies&rft.aulast=Albani&rft.aufirst=Dario&rft.au=Albani%2C%26%2332%3BDario&rft.au=Manoni%2C%26%2332%3BTiziano&rft.au=Arik%2C%26%2332%3BArikhan&rft.au=Nardi%2C%26%2332%3BDaniele&rft.au=Trianni%2C%26%2332%3BVito&rft.date=2019&rft.volume=289&rft.pages=132%E2%80%93146&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-030-24202-2_10&rft.isbn=978-3-030-24201-5&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-030-24202-2_10&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-49\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-49\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bellman, Kirstie; Botev, Jean; Diaconescu, Ada; Esterle, Lukas; Gruhl, Christian; Landauer, Chris; Lewis, Peter R.; Stein, Anthony <i>et al.<\/i> (1 September 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8599549\/\" target=\"_blank\">\"Self-Improving System Integration - Status and Challenges after Five Years of SISSY\"<\/a>. <i>2018 IEEE 3rd International Workshops on Foundations and Applications of Self* Systems (FAS*W)<\/i> (Trento: IEEE): 160\u2013167. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FFAS-W.2018.00042\" target=\"_blank\">10.1109\/FAS-W.2018.00042<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5386-5175-9<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8599549\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8599549\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Self-Improving+System+Integration+-+Status+and+Challenges+after+Five+Years+of+SISSY&rft.jtitle=2018+IEEE+3rd+International+Workshops+on+Foundations+and+Applications+of+Self%2A+Systems+%28FAS%2AW%29&rft.aulast=Bellman&rft.aufirst=Kirstie&rft.au=Bellman%2C%26%2332%3BKirstie&rft.au=Botev%2C%26%2332%3BJean&rft.au=Diaconescu%2C%26%2332%3BAda&rft.au=Esterle%2C%26%2332%3BLukas&rft.au=Gruhl%2C%26%2332%3BChristian&rft.au=Landauer%2C%26%2332%3BChris&rft.au=Lewis%2C%26%2332%3BPeter+R.&rft.au=Stein%2C%26%2332%3BAnthony&rft.au=Tomforde%2C%26%2332%3BSven&rft.date=1+September+2018&rft.pages=160%E2%80%93167&rft.place=Trento&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FFAS-W.2018.00042&rft.isbn=978-1-5386-5175-9&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8599549%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-50\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-50\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kamilaris, A.; Prenafeta-Bold\u00fa, F.X. (1 April 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0168169917308803\" target=\"_blank\">\"Deep learning in agriculture: A survey\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>147<\/b>: 70\u201390. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2018.02.016\" target=\"_blank\">10.1016\/j.compag.2018.02.016<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0168-1699\" target=\"_blank\">0168-1699<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0168169917308803\" target=\"_blank\">https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0168169917308803<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Deep+learning+in+agriculture%3A+A+survey&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Kamilaris%2C+A.%3B+Prenafeta-Bold%C3%BA%2C+F.X.&rft.au=Kamilaris%2C+A.%3B+Prenafeta-Bold%C3%BA%2C+F.X.&rft.date=1+April+2018&rft.volume=147&rft.pages=70%E2%80%9390&rft_id=info:doi\/10.1016%2Fj.compag.2018.02.016&rft.issn=0168-1699&rft_id=https%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fabs%2Fpii%2FS0168169917308803&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-51\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-51\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Liakos, Konstantinos G.; Busato, Patrizia; Moshou, Dimitrios; Pearson, Simon; Bochtis, Dionysis (2018\/8). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1424-8220\/18\/8\/2674\" target=\"_blank\">\"Machine Learning in Agriculture: A Review\"<\/a> (in en). <i>Sensors<\/i> <b>18<\/b> (8): 2674. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fs18082674\" target=\"_blank\">10.3390\/s18082674<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1424-8220\" target=\"_blank\">1424-8220<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6111295\/\" target=\"_blank\">PMC6111295<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30110960\" target=\"_blank\">30110960<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1424-8220\/18\/8\/2674\" target=\"_blank\">https:\/\/www.mdpi.com\/1424-8220\/18\/8\/2674<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Machine+Learning+in+Agriculture%3A+A+Review&rft.jtitle=Sensors&rft.aulast=Liakos&rft.aufirst=Konstantinos+G.&rft.au=Liakos%2C%26%2332%3BKonstantinos+G.&rft.au=Busato%2C%26%2332%3BPatrizia&rft.au=Moshou%2C%26%2332%3BDimitrios&rft.au=Pearson%2C%26%2332%3BSimon&rft.au=Bochtis%2C%26%2332%3BDionysis&rft.date=2018%2F8&rft.volume=18&rft.issue=8&rft.pages=2674&rft_id=info:doi\/10.3390%2Fs18082674&rft.issn=1424-8220&rft_id=info:pmc\/PMC6111295&rft_id=info:pmid\/30110960&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1424-8220%2F18%2F8%2F2674&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-52\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-52\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wahby, Mostafa; Heinrich, Mary Katherine; Hofstadler, Daniel Nicolas; Zahadat, Payam; Risi, Sebastian; Ayres, Phil; Schmickl, Thomas; Hamann, Heiko (2 July 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3205455.3205516\" target=\"_blank\">\"A robot to shape your natural plant: the machine learning approach to model and control bio-hybrid systems\"<\/a> (in en). <i>Proceedings of the Genetic and Evolutionary Computation Conference<\/i> (Kyoto Japan: ACM): 165\u2013172. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3205455.3205516\" target=\"_blank\">10.1145\/3205455.3205516<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-5618-3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3205455.3205516\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3205455.3205516<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+robot+to+shape+your+natural+plant%3A+the+machine+learning+approach+to+model+and+control+bio-hybrid+systems&rft.jtitle=Proceedings+of+the+Genetic+and+Evolutionary+Computation+Conference&rft.aulast=Wahby&rft.aufirst=Mostafa&rft.au=Wahby%2C%26%2332%3BMostafa&rft.au=Heinrich%2C%26%2332%3BMary+Katherine&rft.au=Hofstadler%2C%26%2332%3BDaniel+Nicolas&rft.au=Zahadat%2C%26%2332%3BPayam&rft.au=Risi%2C%26%2332%3BSebastian&rft.au=Ayres%2C%26%2332%3BPhil&rft.au=Schmickl%2C%26%2332%3BThomas&rft.au=Hamann%2C%26%2332%3BHeiko&rft.date=2+July+2018&rft.pages=165%E2%80%93172&rft.place=Kyoto+Japan&rft.pub=ACM&rft_id=info:doi\/10.1145%2F3205455.3205516&rft.isbn=978-1-4503-5618-3&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3205455.3205516&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-53\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-53\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mnif, M.; Richter, U.; Branke, J. et al. (2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.5555\/1763274.1763290\" target=\"_blank\">\"Measurement and control of self-organised behaviour in robot swarms\"<\/a>. <i>Proceedings of the 20th international conference on Architecture of computing systems<\/i>: 209\u201323. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5555%2F1763274.1763290\" target=\"_blank\">10.5555\/1763274.1763290<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.5555\/1763274.1763290\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.5555\/1763274.1763290<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Measurement+and+control+of+self-organised+behaviour+in+robot+swarms&rft.jtitle=Proceedings+of+the+20th+international+conference+on+Architecture+of+computing+systems&rft.aulast=Mnif%2C+M.%3B+Richter%2C+U.%3B+Branke%2C+J.+et+al.&rft.au=Mnif%2C+M.%3B+Richter%2C+U.%3B+Branke%2C+J.+et+al.&rft.date=2007&rft.pages=209%E2%80%9323&rft_id=info:doi\/10.5555%2F1763274.1763290&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.5555%2F1763274.1763290&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-54\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-54\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wuensche, Micaela; Mostaghim, Sanaz; Schmeck, Hartmut; Kautzmann, Timo; Geimer, Marcus (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1809036.1809048\" target=\"_blank\">\"Organic computing in off-highway machines\"<\/a> (in en). <i>Proceeding of the second international workshop on Self-organizing architectures - SOAR '10<\/i> (Washington, DC, USA: ACM Press): 51. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1809036.1809048\" target=\"_blank\">10.1145\/1809036.1809048<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-0087-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1809036.1809048\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=1809036.1809048<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Organic+computing+in+off-highway+machines&rft.jtitle=Proceeding+of+the+second+international+workshop+on+Self-organizing+architectures+-+SOAR+%2710&rft.aulast=Wuensche&rft.aufirst=Micaela&rft.au=Wuensche%2C%26%2332%3BMicaela&rft.au=Mostaghim%2C%26%2332%3BSanaz&rft.au=Schmeck%2C%26%2332%3BHartmut&rft.au=Kautzmann%2C%26%2332%3BTimo&rft.au=Geimer%2C%26%2332%3BMarcus&rft.date=2010&rft.pages=51&rft.place=Washington%2C+DC%2C+USA&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F1809036.1809048&rft.isbn=978-1-4503-0087-2&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D1809036.1809048&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-55\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-55\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kamilaris, A.; Fonts, A.; Prenafeta-Boldu, F.X. 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Retrieved 2022-03-22<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Smart+Services+in+der+Landwirtschaft&rft.jtitle=Service+Engineering&rft.aulast=Maa%C3%9F&rft.aufirst=Wolfgang&rft.au=Maa%C3%9F%2C%26%2332%3BWolfgang&rft.au=Pier%2C%26%2332%3BMarcus&rft.au=Moser%2C%26%2332%3BBenedikt&rft.date=2018&rft.pages=167%E2%80%93181&rft.place=Wiesbaden&rft.pub=Springer+Fachmedien+Wiesbaden&rft_id=info:doi\/10.1007%2F978-3-658-20905-6_11&rft.isbn=978-3-658-20904-9&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-658-20905-6_11&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:23-57\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:23_57-0\">57.0<\/a><\/sup> <sup><a href=\"#cite_ref-:23_57-1\">57.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sisinni, Emiliano; Saifullah, Abusayeed; Han, Song; Jennehag, Ulf; Gidlund, Mikael (1 November 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8401919\/\" target=\"_blank\">\"Industrial Internet of Things: Challenges, Opportunities, and Directions\"<\/a>. <i>IEEE Transactions on Industrial Informatics<\/i> <b>14<\/b> (11): 4724\u20134734. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTII.2018.2852491\" target=\"_blank\">10.1109\/TII.2018.2852491<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1941-0050\" target=\"_blank\">1941-0050<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8401919\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8401919\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Industrial+Internet+of+Things%3A+Challenges%2C+Opportunities%2C+and+Directions&rft.jtitle=IEEE+Transactions+on+Industrial+Informatics&rft.aulast=Sisinni&rft.aufirst=Emiliano&rft.au=Sisinni%2C%26%2332%3BEmiliano&rft.au=Saifullah%2C%26%2332%3BAbusayeed&rft.au=Han%2C%26%2332%3BSong&rft.au=Jennehag%2C%26%2332%3BUlf&rft.au=Gidlund%2C%26%2332%3BMikael&rft.date=1+November+2018&rft.volume=14&rft.issue=11&rft.pages=4724%E2%80%934734&rft_id=info:doi\/10.1109%2FTII.2018.2852491&rft.issn=1941-0050&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8401919%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:24-58\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:24_58-0\">58.0<\/a><\/sup> <sup><a href=\"#cite_ref-:24_58-1\">58.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Liao, Yongxin; de Freitas Rocha Loures, Eduardo; Deschamps, Fernando (1 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8355897\/\" target=\"_blank\">\"Industrial Internet of Things: A Systematic Literature Review and Insights\"<\/a>. <i>IEEE Internet of Things Journal<\/i> <b>5<\/b> (6): 4515\u20134525. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJIOT.2018.2834151\" target=\"_blank\">10.1109\/JIOT.2018.2834151<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2327-4662\" target=\"_blank\">2327-4662<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8355897\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8355897\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Industrial+Internet+of+Things%3A+A+Systematic+Literature+Review+and+Insights&rft.jtitle=IEEE+Internet+of+Things+Journal&rft.aulast=Liao&rft.aufirst=Yongxin&rft.au=Liao%2C%26%2332%3BYongxin&rft.au=de+Freitas+Rocha+Loures%2C%26%2332%3BEduardo&rft.au=Deschamps%2C%26%2332%3BFernando&rft.date=1+December+2018&rft.volume=5&rft.issue=6&rft.pages=4515%E2%80%934525&rft_id=info:doi\/10.1109%2FJIOT.2018.2834151&rft.issn=2327-4662&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8355897%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-59\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-59\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Rohleder, B.; 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Ghosh, Rumi; Srinivasan, Soundar (1 May 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7933925\/\" target=\"_blank\">\"Manufacturing Analytics and Industrial Internet of Things\"<\/a>. <i>IEEE Intelligent Systems<\/i> <b>32<\/b> (3): 74\u201379. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FMIS.2017.49\" target=\"_blank\">10.1109\/MIS.2017.49<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1541-1672\" target=\"_blank\">1541-1672<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7933925\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7933925\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Manufacturing+Analytics+and+Industrial+Internet+of+Things&rft.jtitle=IEEE+Intelligent+Systems&rft.aulast=Lade&rft.aufirst=Prasanth&rft.au=Lade%2C%26%2332%3BPrasanth&rft.au=Ghosh%2C%26%2332%3BRumi&rft.au=Srinivasan%2C%26%2332%3BSoundar&rft.date=1+May+2017&rft.volume=32&rft.issue=3&rft.pages=74%E2%80%9379&rft_id=info:doi\/10.1109%2FMIS.2017.49&rft.issn=1541-1672&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7933925%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-62\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-62\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Z\u00fcfle, Marwin; Moog, Felix; Lesch, Veronika; Krupitzer, Christian; Kounev, Samuel (1 July 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0019057821003773\" target=\"_blank\">\"A machine learning-based workflow for automatic detection of anomalies in machine tools\"<\/a> (in en). <i>ISA Transactions<\/i>: S0019057821003773. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.isatra.2021.07.010\" target=\"_blank\">10.1016\/j.isatra.2021.07.010<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0019057821003773\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0019057821003773<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+machine+learning-based+workflow+for+automatic+detection+of+anomalies+in+machine+tools&rft.jtitle=ISA+Transactions&rft.aulast=Z%C3%BCfle&rft.aufirst=Marwin&rft.au=Z%C3%BCfle%2C%26%2332%3BMarwin&rft.au=Moog%2C%26%2332%3BFelix&rft.au=Lesch%2C%26%2332%3BVeronika&rft.au=Krupitzer%2C%26%2332%3BChristian&rft.au=Kounev%2C%26%2332%3BSamuel&rft.date=1+July+2021&rft.pages=S0019057821003773&rft_id=info:doi\/10.1016%2Fj.isatra.2021.07.010&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0019057821003773&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-63\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-63\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zuefle, Marwin; Bauer, Andre; Lesch, Veronika; Krupitzer, Christian; Herbst, Nikolas; Kounev, Samuel; Curtef, Valentin (1 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8831197\/\" target=\"_blank\">\"Autonomic Forecasting Method Selection: Examination and Ways Ahead\"<\/a>. <i>2019 IEEE International Conference on Autonomic Computing (ICAC)<\/i> (Umea, Sweden: IEEE): 167\u2013176. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FICAC.2019.00028\" target=\"_blank\">10.1109\/ICAC.2019.00028<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-7281-2411-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8831197\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8831197\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Autonomic+Forecasting+Method+Selection%3A+Examination+and+Ways+Ahead&rft.jtitle=2019+IEEE+International+Conference+on+Autonomic+Computing+%28ICAC%29&rft.aulast=Zuefle&rft.aufirst=Marwin&rft.au=Zuefle%2C%26%2332%3BMarwin&rft.au=Bauer%2C%26%2332%3BAndre&rft.au=Lesch%2C%26%2332%3BVeronika&rft.au=Krupitzer%2C%26%2332%3BChristian&rft.au=Herbst%2C%26%2332%3BNikolas&rft.au=Kounev%2C%26%2332%3BSamuel&rft.au=Curtef%2C%26%2332%3BValentin&rft.date=1+June+2019&rft.pages=167%E2%80%93176&rft.place=Umea%2C+Sweden&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FICAC.2019.00028&rft.isbn=978-1-7281-2411-7&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8831197%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-64\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-64\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zhang, Yuanyuan; Harman, Mark; Ochoa, Gabriela; Ruhe, Guenther; Brinkkemper, Sjaak (5 June 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3196831\" target=\"_blank\">\"An Empirical Study of Meta- and Hyper-Heuristic Search for Multi-Objective Release Planning\"<\/a> (in en). <i>ACM Transactions on Software Engineering and Methodology<\/i> <b>27<\/b> (1): 1\u201332. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3196831\" target=\"_blank\">10.1145\/3196831<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1049-331X\" target=\"_blank\">1049-331X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3196831\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3196831<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=An+Empirical+Study+of+Meta-+and+Hyper-Heuristic+Search+for+Multi-Objective+Release+Planning&rft.jtitle=ACM+Transactions+on+Software+Engineering+and+Methodology&rft.aulast=Zhang&rft.aufirst=Yuanyuan&rft.au=Zhang%2C%26%2332%3BYuanyuan&rft.au=Harman%2C%26%2332%3BMark&rft.au=Ochoa%2C%26%2332%3BGabriela&rft.au=Ruhe%2C%26%2332%3BGuenther&rft.au=Brinkkemper%2C%26%2332%3BSjaak&rft.date=5+June+2018&rft.volume=27&rft.issue=1&rft.pages=1%E2%80%9332&rft_id=info:doi\/10.1145%2F3196831&rft.issn=1049-331X&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3196831&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-65\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-65\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zhong, Ray; Xu, Xun; Wang, Lihui (16 October 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.emerald.com\/insight\/content\/doi\/10.1108\/IMDS-09-2016-0391\/full\/html\" target=\"_blank\">\"Food supply chain management: systems, implementations, and future research\"<\/a> (in en). <i>Industrial Management & Data Systems<\/i> <b>117<\/b> (9): 2085\u20132114. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1108%2FIMDS-09-2016-0391\" target=\"_blank\">10.1108\/IMDS-09-2016-0391<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0263-5577\" target=\"_blank\">0263-5577<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.emerald.com\/insight\/content\/doi\/10.1108\/IMDS-09-2016-0391\/full\/html\" target=\"_blank\">https:\/\/www.emerald.com\/insight\/content\/doi\/10.1108\/IMDS-09-2016-0391\/full\/html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Food+supply+chain+management%3A+systems%2C+implementations%2C+and+future+research&rft.jtitle=Industrial+Management+%26+Data+Systems&rft.aulast=Zhong&rft.aufirst=Ray&rft.au=Zhong%2C%26%2332%3BRay&rft.au=Xu%2C%26%2332%3BXun&rft.au=Wang%2C%26%2332%3BLihui&rft.date=16+October+2017&rft.volume=117&rft.issue=9&rft.pages=2085%E2%80%932114&rft_id=info:doi\/10.1108%2FIMDS-09-2016-0391&rft.issn=0263-5577&rft_id=https%3A%2F%2Fwww.emerald.com%2Finsight%2Fcontent%2Fdoi%2F10.1108%2FIMDS-09-2016-0391%2Ffull%2Fhtml&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Verdouw, C. 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Guizani, Mohsen; Mohammadi, Mehdi; Aledhari, Mohammed; Ayyash, Moussa (24\/2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7123563\/\" target=\"_blank\">\"Internet of Things: A Survey on Enabling Technologies, Protocols, and Applications\"<\/a>. <i>IEEE Communications Surveys & Tutorials<\/i> <b>17<\/b> (4): 2347\u20132376. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FCOMST.2015.2444095\" target=\"_blank\">10.1109\/COMST.2015.2444095<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1553-877X\" target=\"_blank\">1553-877X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7123563\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/7123563\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+Things%3A+A+Survey+on+Enabling+Technologies%2C+Protocols%2C+and+Applications&rft.jtitle=IEEE+Communications+Surveys+%26+Tutorials&rft.aulast=Al-Fuqaha&rft.aufirst=Ala&rft.au=Al-Fuqaha%2C%26%2332%3BAla&rft.au=Guizani%2C%26%2332%3BMohsen&rft.au=Mohammadi%2C%26%2332%3BMehdi&rft.au=Aledhari%2C%26%2332%3BMohammed&rft.au=Ayyash%2C%26%2332%3BMoussa&rft.date=24%2F2015&rft.volume=17&rft.issue=4&rft.pages=2347%E2%80%932376&rft_id=info:doi\/10.1109%2FCOMST.2015.2444095&rft.issn=1553-877X&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7123563%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-69\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-69\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Javed, Farhana; Afzal, Muhamamd Khalil; Sharif, Muhammad; Kim, Byung-Seo (23\/2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8320780\/\" target=\"_blank\">\"Internet of Things (IoT) Operating Systems Support, Networking Technologies, Applications, and Challenges: A Comparative Review\"<\/a>. <i>IEEE Communications Surveys & Tutorials<\/i> <b>20<\/b> (3): 2062\u20132100. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FCOMST.2018.2817685\" target=\"_blank\">10.1109\/COMST.2018.2817685<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1553-877X\" target=\"_blank\">1553-877X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8320780\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8320780\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+Things+%28IoT%29+Operating+Systems+Support%2C+Networking+Technologies%2C+Applications%2C+and+Challenges%3A+A+Comparative+Review&rft.jtitle=IEEE+Communications+Surveys+%26+Tutorials&rft.aulast=Javed&rft.aufirst=Farhana&rft.au=Javed%2C%26%2332%3BFarhana&rft.au=Afzal%2C%26%2332%3BMuhamamd+Khalil&rft.au=Sharif%2C%26%2332%3BMuhammad&rft.au=Kim%2C%26%2332%3BByung-Seo&rft.date=23%2F2018&rft.volume=20&rft.issue=3&rft.pages=2062%E2%80%932100&rft_id=info:doi\/10.1109%2FCOMST.2018.2817685&rft.issn=1553-877X&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8320780%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-70\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-70\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Triantafyllou, Anna; Sarigiannidis, Panagiotis; Lagkas, Thomas D. (13 September 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hindawi.com\/journals\/wcmc\/2018\/5349894\/\" target=\"_blank\">\"Network Protocols, Schemes, and Mechanisms for Internet of Things (IoT): Features, Open Challenges, and Trends\"<\/a> (in en). <i>Wireless Communications and Mobile Computing<\/i> <b>2018<\/b>: 1\u201324. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1155%2F2018%2F5349894\" target=\"_blank\">10.1155\/2018\/5349894<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1530-8669\" target=\"_blank\">1530-8669<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hindawi.com\/journals\/wcmc\/2018\/5349894\/\" target=\"_blank\">https:\/\/www.hindawi.com\/journals\/wcmc\/2018\/5349894\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Network+Protocols%2C+Schemes%2C+and+Mechanisms+for+Internet+of+Things+%28IoT%29%3A+Features%2C+Open+Challenges%2C+and+Trends&rft.jtitle=Wireless+Communications+and+Mobile+Computing&rft.aulast=Triantafyllou&rft.aufirst=Anna&rft.au=Triantafyllou%2C%26%2332%3BAnna&rft.au=Sarigiannidis%2C%26%2332%3BPanagiotis&rft.au=Lagkas%2C%26%2332%3BThomas+D.&rft.date=13+September+2018&rft.volume=2018&rft.pages=1%E2%80%9324&rft_id=info:doi\/10.1155%2F2018%2F5349894&rft.issn=1530-8669&rft_id=https%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fwcmc%2F2018%2F5349894%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-71\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-71\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ben-Daya, Mohamed; Hassini, Elkafi; Bahroun, Zied (29 August 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/00207543.2017.1402140\" target=\"_blank\">\"Internet of things and supply chain management: a literature review\"<\/a> (in en). <i>International Journal of Production Research<\/i> <b>57<\/b> (15-16): 4719\u20134742. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F00207543.2017.1402140\" target=\"_blank\">10.1080\/00207543.2017.1402140<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0020-7543\" target=\"_blank\">0020-7543<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/00207543.2017.1402140\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/00207543.2017.1402140<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Internet+of+things+and+supply+chain+management%3A+a+literature+review&rft.jtitle=International+Journal+of+Production+Research&rft.aulast=Ben-Daya&rft.aufirst=Mohamed&rft.au=Ben-Daya%2C%26%2332%3BMohamed&rft.au=Hassini%2C%26%2332%3BElkafi&rft.au=Bahroun%2C%26%2332%3BZied&rft.date=29+August+2019&rft.volume=57&rft.issue=15-16&rft.pages=4719%E2%80%934742&rft_id=info:doi\/10.1080%2F00207543.2017.1402140&rft.issn=0020-7543&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F00207543.2017.1402140&rfr_id=info:sid\/en.wikipedia.org:Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation and updates to spelling and grammar. In some cases important information was missing from the references, and that information was added. The authors did not provide citations for the \"World Scientists'\" papers; citations were added for this version.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628174158\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.730 seconds\nReal time usage: 1.153 seconds\nPreprocessor visited node count: 68856\/1000000\nPost\u2010expand include size: 598444\/2097152 bytes\nTemplate argument size: 185395\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 174688\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 665.614 1 -total\n 89.07% 592.893 1 Template:Reflist\n 70.37% 468.376 71 Template:Citation\/core\n 58.05% 386.366 57 Template:Cite_journal\n 11.17% 74.338 61 Template:Date\n 7.45% 49.620 125 Template:Citation\/identifier\n 6.52% 43.370 5 Template:Cite_web\n 6.17% 41.066 5 Template:Cite_book\n 5.29% 35.212 4 Template:Citation\n 4.57% 30.430 1 Template:Infobox_journal_article\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13102-0!canonical and timestamp 20220628174157 and revision id 47060. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape\">https:\/\/www.limswiki.org\/index.php\/Journal:Food_informatics:_Review_of_the_current_state-of-the-art,_revised_definition,_and_classification_into_the_research_landscape<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","7d0d518d42d836f46cc21938cfd66d37_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/93\/Fig1_Krupitzer_Foods21_10-11.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/df\/Fig2_Krupitzer_Foods21_10-11.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/9d\/Fig3_Krupitzer_Foods21_10-11.png"],"7d0d518d42d836f46cc21938cfd66d37_timestamp":1656439832,"da7b86c02e387ab4edff0524bbe2a563_type":"article","da7b86c02e387ab4edff0524bbe2a563_title":"A roadmap for LIMS at NIST Material Measurement Laboratory (Greene et al. 2022)","da7b86c02e387ab4edff0524bbe2a563_url":"https:\/\/www.limswiki.org\/index.php\/Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory","da7b86c02e387ab4edff0524bbe2a563_plaintext":"\n\nJournal:A roadmap for LIMS at NIST Material Measurement LaboratoryFrom LIMSWikiJump to navigationJump to searchFull article title\n \nA roadmap for LIMS at NIST Material Measurement LaboratoryAuthor(s)\n \nGreene, Gretchen; Ragland, Jared; Trautt, Zachary; Lau, June; Plante, Raymond; Taillon, Joshua; Creuziger, Adam; Becker, Chandler; Bennett, Joseph; Blonder, Niksa; Borsuk, Lisa; Campbell, Carelyn; Friss, Adam; Hale, Lucas; Halter, Michael; Hanisch, Robert; Hardin, Gary; Levine, Lyle; Maragh, Samantha; Miller, Sierra; Muzny, Christopher; Newrock, Marcus; Perkins, John; Plant, Anne; Ravel, Bruce; Ross, David; Scott, John H.; Szakal, Chris; Tona, Alessandro; Vallone, PeterAuthor affiliation(s)\n \nNational Institute of Standards and TechnologyYear published\n \n2022Volume and issue\n \nNIST Technical Note 2216Page(s)\n \ni\u2013iii, 1\u201317DOI\n \n10.6028\/NIST.TN.2216Distribution license\n \nPublic domainWebsite\n \nhttps:\/\/www.nist.gov\/publications\/roadmap-lims-nist-material-measurement-laboratoryDownload\n \nhttps:\/\/tsapps.nist.gov\/publication\/get_pdf.cfm?pub_id=934610 (PDF)\n\nContents \n\n1 Foreword \n2 Abstract \n3 Introduction \n4 Roadmap objectives \n\n4.1 Challenges \n\n\n5 MML LIMS stakeholders \n\n5.1 External solutions and partnering \n\n\n6 Implementation of the roadmap \n\n6.1 System level solutions \n6.2 LIMS tiers \n\n6.2.1 Tier 1: On-demand resources \n6.2.2 Tier 2: Data science and services \n6.2.3 Tier 3: Discipline science \n\n\n6.3 Supporting services \n6.4 Infrastructure resources for LIMS \n6.5 Community standards and best practices \n\n\n7 LIMS architecture \n\n7.1 Capabilities of LIMS \n7.2 LIMS components \n7.3 Research workflows \n7.4 LIMS networked architecture \n\n\n8 Metrics and qualitative measures \n9 Conclusion \n10 Footnotes \n11 Acronyms and initialisms \n12 Acknowledgements \n13 References \n14 Notes \n\n\n\nForeword \nOver the past decade, emerging technology in laboratory and computational science has changed the landscape for research by accelerating the production, processing, and exchange of data. The NIST Material Measurement Laboratory community recognizes that to keep pace with the transformation of measurement science to a digital paradigm, it is essential to implement laboratory information management systems (LIMS). Effective introduction of LIMS early in the research life cycle provides direct support for planning and execution of experiments and accelerating research productivity. From this perspective, LIMS are not passive entities with isolated interaction, but rather key resources supporting collaboration, scientific integrity, and transfer of knowledge over time. They serve as a delivery system for organizational contributions to the broader federated data community, supporting both controlled and open access, determined by the sensitivity of the research. \nThe overall goal of a successful LIMS is to empower a research community by establishing common tools providing access to laboratory data resources. Modern LIMS should therefore provide several core functions and touchpoints:\n\nWorkflow management \u2013 A research workflow describes steps to be performed to derive results. These patterns serve as a prescription for LIMS to control the progression of data\nand associated services or tools. Automation of a workflow simplifies the transfer of information through defined interfaces from a network of systems.\n\nRepository of data \u2013 Effective storage and retrieval of data (raw and derived)\u2014including associated metadata, data products, calibration, software, logs, etc.\u2014facilitates data discovery, processing, collaboration, and dissemination.\nCreation of data products and tools \u2013 A LIMS should support storage and processing of raw data, leading to products which can be shared and consumed. Examples would include sample data, instrument-generated data, and algorithms generating defined outputs. Inclusion of data models provides context and structure, and machine learning (ML) integration may generate related data which could be combined into more comprehensive data models. Tools may include visualization, evaluation, and analysis packages offering users advanced capabilities for their research projects.\nOrganization of data for search and retrieval \u2013 Tools and interfaces give users access to sophisticated searches of data holdings and efficient mechanisms for data transfer in standardized formats. Searching should extend to domain or project-specific semantics, be coupled closely with related data, and go beyond individual research projects to include super-searches (e.g., use-case-driven interoperability between LIMS).\nLong-lived, stable, and agile structures \u2013 LIMS require institutional and architectural sustainability for long baseline research and curatorship. Technology tends to change faster than the practical lifetime of research programs, so paths must exist for maintaining IT infrastructure and introducing faster and more complex processes.\nStandards and best practices \u2013 LIMS benefit from standardization to support collaborations among research communities and make data workflows efficient and affordable. Community buy-in for standards and best practices is an essential part of LIMS, and organizational shared expertise naturally serves as a means for coordination and adaptation of standards.\nUser involvement \u2013 In all the core functions listed above, it is critical to involve the subject matter experts from the beginning. LIMS should establish a working team that explicitly includes representatives from the end user community.\nAbstract \nInstrumentation generates data faster and in greater quantity than ever before, and inter-laboratory research is in historic demand domestically and internationally to stimulate economic innovation. Strategic mission needs of the NIST Material Measurement Laboratory (MML) to support a wide array of research disciplines therefore compel our organization to adopt advanced strategies for research data management. Laboratory information management systems (LIMS) provide a framework for managing data from the outset of the research life cycle, delivering new capabilities for machine learning (ML), data analysis, collaboration, and dissemination. This roadmap describes our current understanding and strategy for adapting our research workflows for LIMS throughout MML by embracing the use of standards and best practices from data science communities. The NIST research data cyber-infrastructure complements these goals for MML by providing a secure environment to host LIMS solutions. Additionally, integration of scientific workflows requires ongoing collaboration to bridge organizational LIMS with external scientific communities. Thus, MML LIMS will evolve over time in synergy with the technology and experimental environments, delivering new science. LIMS will broaden our mission impact through adoption of the FAIR Data Principles. \nKeywords: data, laboratory information management systems, experimental data, research data, research workflows \n\nIntroduction \nBeginning late 2019, MML initiated as part of its strategic plan the development of \"next-generation\" data and informatics with a focus on LIMS as a key resource to support research data and science. This effort was complemented by initiatives for enhancing data management planning and data systems infrastructure. The first year\u2019s groundwork established common needs for both individual researchers and teams to engage more readily with LIMS, with a goal of building greater capacity for interaction and use of data. A vision for LIMS was written to convey the purpose of these collective efforts: \n\n\u201cLaboratory information management systems will provide MML scientists a practical means for repeatability, traceability, reproducibility, efficiency, and compliance of research, serving as a beacon to both intramural and extramural community stakeholders.\u201d\nThe MML approach to implementing LIMS started with defining goals for specific division research laboratory projects and established a cross-divisional Community of Interest (COI) group for sharing solutions, services, practices, and challenges. Comprehensive LIMS solutions have been successfully implemented in several NIST laboratories. Several shared resources have successfully demonstrated use of LIMS components including repository platforms, a standard persistent identifier service, a centralized research data storage with networked data transfer nodes, and data transfer services, in addition to expertise in data modeling and semantics. These resources, along with community best practices, contribute to a basic LIMS architecture for research. \nA system view and architecture model provide the foundation for planned future outcomes. In this roadmap, we define a set of research-oriented LIMS capabilities which serves to guide implementation along with components to deliver these capabilities. More detailed guidance for use of specific LIMS resources is available internally to NIST and where possible shared on external repository websites. It is also anticipated that LIMS implementation will provide an important contribution to the goals of NIST program areas such as artificial intelligence (AI), biosystems, chemical informatics, additive manufacturing, and the materials science areas which spearheaded early innovation in data systems through the Materials Genome Initiative. \n\nRoadmap objectives \nThis roadmap provides a framework for manifesting the MML LIMS vision and outlines the key objectives highlighted by the MML LIMS COI project goals. These are grouped into near- and long-term objectives for MML LIMS prioritization. These objectives, along with broader community efforts, will strengthen the NIST data-as-an-asset[1] strategic approach to research. More comprehensive goals such as the development of a \"digital twin\"[2] will enable models to probe the measurement science space to further analyze the physics and gain understanding, leading to new science. \nNear-term objectives include:\n\nEstablish a LIMS COI for MML (as of this writing, already in place)\nDevelop pilot LIMS solutions for targeted research workflows (as of this writing, several solutions already piloted and deployed for laboratory operations)\nDesign tiered LIMS architectures to support a range of research workflow implementations\nEstablish core infrastructure services to support LIMS\nDevelop data acquisition and experimental activity capture solutions\nDeploy key functional support services such as a Handle.Net service (supports persistent identifiers) and data transfer service (see the later subsection on supporting services)\nPrototype and exchange LIMS components as a basis for shared resources (e.g., repository platforms for experimental activity; instrumentation; samples; extract, transform, and load [ETL])\nEstablish best practices in digital object management to support standards and community practice\nLong-term objectives include:\n\nEstablish best practices for development and implementation of data models and semantics\nDeploy prioritized LIMS end-to-end solutions (achieving multi-component level functionality)\nDevelop use-case-driven solutions for cross-laboratory LIMS interconnectivity\nProvide on-demand system-level LIMS resources for research teams at NIST for rapid engagement\nDevelop automated workflow integration between LIMS and computational platforms (e.g., high-performance computing [HPC], ML, and analysis applications like SciServer)\nDevelop integration between LIMS and public data access systems\nEstablish methodology for building and applying \"digital twin\" models\nProvide NIST leadership a strategy for adoption and implementation of LIMS to promote innovative data-driven science\nChallenges \nWithin the MML LIMS COI exchange forum, lessons learned and shared by early adopters of LIMS highlighted several key challenges. These will be factored into data management plans for implementation and extended to the broader MML community, which relies on either operation of LIMS or end-usage LIMS outputs. \nOne common challenge with instrumentation data is generation of vendor-proprietary output formats. A repository for sharing data format exchange software tools is a good example of a solution benefiting LIMS by supporting the need to transform vendor data into more consumable open data formats for downstream analysis and computation. A prototype repository was created by the Office of Data and Informatics (ODI) with a few extractor tools, and efforts are underway to explore how this may achieve wider utility. Community repositories such as Bio-Formats and MaterialsIO are examples of resources which support tools for conversions of third-party data into open data models. These community-oriented solutions successfully demonstrate methods to lower the barrier for LIMS through shared software. \nAnother challenge is finding appropriately skilled labor resources required for domain-specific engineering LIMS workflows. This is a common barrier to LIMS prioritization for research organizations. Integrating data structures requires close collaboration between domain and data science subject matter experts (SMEs) for modeling and mapping of multiple source data to repository storage. \nIntegration or migration of legacy systems and bespoke tools with next-generation LIMS architecture presents another challenge, especially for those with limited resources supporting maintenance. Legacy systems commonly lack sustainability due to factors such as end of funding support or unavailable expertise. \nData provenance is commonly required for sample tracking and traceability across laboratory processes (e.g., sample transformations, generation of parts, or inter-laboratory sample exchange). The latter is a challenge for inter-laboratory study because data management systems (including LIMS) are most commonly not standard or normalized. Supporting common data exchange protocols and chain of custody workflows will be an ongoing design consideration for interoperability, including concepts such as data trust and integrity. \nAnother common challenge is operational security compliance for IT infrastructure. NIST adheres to CIS Controls (Critical Security Controls,) and as LIMS architectures rely on networked systems, this translates to requirements for vigilant monitoring of service and platform deployments to ensure organizational security.\n\nMML LIMS stakeholders \nMML LIMS has a number of stakeholders with differing needs and priorities. ODI and research project leads work with all stakeholder categories, balancing goals to develop options that provide the best overall benefit. Stakeholders include:\n\nResearch community: Each research discipline area involves a community benefiting from the generation and exchange of data outcomes.\nMML Laboratory Office: The MML Lab Office ensures support of the NIST organizational mission through the productivity achieved from the use of LIMS.\nProgram funding sources: Funding for strategic initiatives and research priorities for NIST and MML address both internal and external stakeholder needs and account for LIMS resources.\nCollaborative partners: Critical stakeholders help foster research innovation and science through exchange of LIMS data and software products. A key benefit to LIMS is the ability to support collaboration through exchange and access to data, data products, software, and related resources.\nExternal solutions and partnering \nWorking with the external community has resulted in a more robust MML LIMS knowledge base, benefiting from partnerships with external researchers during LIMS development and implementation, commercial procurement, and collaboration. Several organizational partners have contributed to MML efforts, including the National Research Energy Laboratory[3], Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Air Force Research Laboratory, 3M Corporation, NASA, University of Illinois - Champaign, and national forensic crime labs in collaboration with the National Institute of Justice.[4] Many NIST strategic research areas rely on collaborative data engagement; as such, having a LIMS with capabilities for supporting external access is important in many cases. \nCollaboration with external partners may involve co-development of a LIMS platform system (or component), adoption of a community LIMS, shared access to data\/code, or support for commercial vendor solution customization. Such collaborations often include harmonizing requirements and goals to inform the design, architecture, and engineering of a solution. Open-source solutions often provide more mechanisms supporting the complexity of many research workflows through their flexible configuration, customization, and independent software enhancements. A few examples of such solutions include ORNL DataFed[5], SynBioHub, BNL\u2019s BlueSky platform[6], and SciServer. While these may require engineering expertise to fit within the NIST infrastructure, each adds meaningful user capabilities. \nAs one example, NIST synchrotron beamline stations at the BNL National Synchrotron Light Source II (NSLS-II) Facility have implemented BlueSky in partnership with BNL\u2019s Data Science and Systems Integration (DSSI) group.\nSeveral solutions have also been developed by partnering within NIST, and both are highly customized to the research requirements of their respective user groups. They include: \n\nthe Nexus Electron Microscopy LIMS (NexusLIMS[7]) workflow based on the Configurable Data Repository System (CDCS), a NIST-developed open platform, and\na LIMS supporting real-time biosystem cell line sample tracking LIMS with a custom Excel application used for experimental activity capture.\nA few commercial solutions[a] were adopted in part or in full. In one successful example, the NIST Center for Automotive Lightweighting (NCAL) successfully implemented the commercial platform Ansys Granta. Other community and vendor solutions have been and continue to be evaluated for pilot use, such as 4CeeD[8], the Tadabase no-code solution, the Benchling cloud platform, Microsoft platforms, and others. Due to the challenging nature of customized research workflows and complexity in the secure integration with government networked infrastructure, commercial solutions may pose additional cost and skillset requirements for successful adaptation into the laboratory working environment. In most cases at NIST, use case development leads to the adoption of hybrid solutions. Closed-source solutions widely adopted in the scientific community (e.g., Globus) provide unique and robust capabilities that are difficult to recreate. In the instance of Globus, the linkage to several research community services and best practices like GridFTP, linked identity management with institutions authentication including InCommon, a Python software development kit (SDK), and multi-platform storage connections provide high value and ease of adoption. \n\nImplementation of the roadmap \nSystem level solutions \nA LIMS, as we define it, is a system of components which delivers the capabilities for the early stages of a research life cycle.[9] It is widely recognized there is no singular LIMS solution that ranges across all disciplines of research, yet shared components (and data assets) provide greater economy of scale and consistent usage across the organization and beyond. A LIMS design implements research workflow requirements and provides context for assembling an architecture supporting component integration to produce desired outcomes. Off-the-Shelf (OTS) LIMS solutions are often challenging to adopt, primarily due to the limitations in both configuration and customization of components to match workflows. Monolithic solutions have demonstrated challenges whether they are homegrown or OTS by constraining interfaces between components. Workflow flexibility, orchestration, and evolution can be managed with lower risk[10] to overall performance when using service-oriented solutions. Therefore, implementations may vary as to which components are used and in which sequence to support the required research workflow. A tiered model ranging from basic components and plug-in architecture to instantiation of more complex data models with computational support can lower the barrier for entry. Given this context and the goal of flexibility, a few commonly used LIMS workflow components provide critical functionality. \n\nLIMS tiers \nRequirements for building or deploying LIMS are dependent upon the complexity of the research workflow and project needs. In the consideration of the system, a basic three-tiered model serves as a general guide for capabilities mapping and implementation, to level of effort (Fig. 1). As with many aspects of LIMS, this model may have variations in the strata depending on the optimal architecture for achieving desired outcomes. \n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. LIMS three-tiered model for implementation\n\n\n\nTier 1: On-demand resources \nTier 1 is primarily reliant on infrastructure and support services and can be readily adopted with available \u201con-demand\u201d resources, meaning those resources that exist and can be provisioned for use upon request. The main functions for Tier 1 LIMS include data acquisition, near-line instrument data collection, sample tracking, and data movement\u2014possibly automated\u2014to a storage location, ideally with access for processing and analysis. Tier 1 LIMS support unstructured data and may provide more flexibility for researchers to experiment with data structures, formats, and tuning for workflow. \n\nTier 2: Data science and services \nTier 2 integrates research workflow design, including data structuring, formatting, metadata, and possible integration to a data repository solution. The Tier 2 LIMS also requires a greater level of effort and engagement between a research SME and data science engineers for design, installation, and operational configuration. \n\nTier 3: Discipline science \nThe Tier 3 LIMS require the highest level of commitment and collaboration between the research SME and a data science expert to factor in all the functionality for more complex workflows. This might involve functionality such as computational system integration, support for external client tools through an application programming interface (API), and semantic modeling to factor in community adoption for data consumption. An example of a Tier 3 LIMS would include data generated from multiple instruments, each with variable processes, interconnected to computational tools and applications to produce data products, with dependencies on analytical requirements for external interoperability. Both the MML NexusLIMS and Granta NCAL systems are examples of Tier 3. \n\nSupporting services \nCommon services support LIMS at various touch points throughout the research data workflow. These may be considered part of the infrastructure, i.e., they are underlying services shared and configured to support more than one stage of a LIMS workflow. However, by nature, they often require a contextual prescription for how they interface with a LIMS workflow of component. Examples of these key support services include: \n\nData transfer services: manual, automation, and tools for file movement between storage locations\nHandle service: generates and resolves a standard persistent identifier (PID) known as a Handle\nRepository systems: OTS solutions or well-established and supported repository platforms (e.g., CDCS, Cordra, GitLab, GitHub) and open-source solutions supporting customization for (meta)data\nContainerized deployments: Docker, Kubernetes, virtual machine (VM) or cloud services supporting deployments of LIMS applications and tools\nSolutions brokering: Documentation and communications, including instructional guides (\u201cplaybooks\u201d) and consultation for design and use of LIMS systems, services, and components\nInfrastructure resources for LIMS \nOrganizationally MML and NIST both provide infrastructure-as-a-service (IAAS) for networking, storage, and compute resources. These systems may be requested through internal NIST IT services and are readily available. \nAs part of the MML Data and Informatics strategic plan, both network and storage have been significantly expanded to support higher bandwidth for data transfer between laboratory instruments and storage (see Fig. 2). Data space allocations are designed to be flexible and can be established on request for cross-organizational projects, research teams, and instrument dedicated endpoints. Several network-attached storage (NAS) solutions have been implemented to support both localized (data collection nodes) and central data storage (CDS; a dedicated MML Research Data storage array). Additionally, the NIST Amazon Web Service (AWS) cloud environment is available and integrated with the NIST VPN (virtual private network) providing both storage and compute on demand. \nA research equipment network (REN) is used to manage pass through and routing between instrument laboratory equipment and data storage. Network configuration via the REN ensures that instrument-control computers are protected and isolated as needed for secure operations. Higher speed network backbones and a Science DMZ[11] is currently in a planning phase to provide higher throughputs and secured zones for operating with LIMS architectures. \n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. MML LIMS data plumbing model for harvesting instrumental raw data\n\n\n\nCurrent infrastructure resources include DCN, NAS, CDS, AWS, and local research data storage, as well as enki, AWS, SciServer, and HPC computational resources. Meanwhile, efforts are ongoing to integrate the CIS Controls into the infrastructure and expand capabilities in support of LIMS. Security for government research networks is a top priority for NIST, and all LIMS deployments must adhere to cybersecurity controls and processes for monitoring and managing access. This critical infrastructure element requires coordination between LIMS developers and IT security offices to ensure systems are protected and compliant with CIS including monitoring, security patching, and notification of problems for mitigation. In developing a plan to implement LIMS, resource needs to complete security assessment and authorization should be taken into consideration. \n\nCommunity standards and best practices \nSeveral standards and best practices in the research data community are key to building an effective LIMS workspace. While we list a few concepts core to LIMS and examples of use, these are only a small subset in the growing field of data science. Standards and best practices will continue to evolve, requiring resources for maintenance, expansion, community engagement, and user training, though one goal of a successful LIMS implementation is to minimize these burdens for end users. Examples of data standards and practices used with LIMS are found in Table 1.\n\n\n\n\n\n\n\nTable 1. Data standards and practices used with LIMS\n\n\nCommunity standard\/practice\n\nExamples of use\n\n\nPersistent identifiers\n\nDOIs, ORCIDs, ARKid, Handles\n\n\nOpen-source code\n\nUSNISTGOV GitHub (ETL pipelines, libraries, tools)\n\n\nFAIR (findable, accessible, interoperable, reusable) Data Principles[12]\n\nGo-Fair.org, FAIR Maturity Model[13]\n\n\nSemantic standards\n\nDCAT, Schema.org, DataCite, LinkedData, discipline-specific taxonomy, ontological\n\n\nStandardized communications network protocols\n\nRESTful API or Open API, e.g., Swagger Docs\n\n\n\nLIMS architecture \nCapabilities of LIMS \nLIMS helps a researcher by providing capabilities in an integrated way. These capabilities are delivered by one or more of the system components and serve as drivers for LIMS requirements. Common data-oriented functions, such as sample tracking, from the user perspective might also be more readily identified in terms of the capabilities. These may take on slightly different naming conventions and forms across implementations, yet in general they can be described in the context of the function they support within research environments. Capabilities may be mapped into the design architecture through implementation of modular components, as shown in Fig. 3. For external vendor and community open LIMS platforms or sub-components, understanding how and where in the system these capabilities are supported is also key to evaluating their compatibility with research workflows. \nCore capabilities generally fall into one of several categories. A few example aspects supported by each category are provided. \n\nData generation: provenance of data, software descriptions and custom code, instrument configuration, data acquisition descriptions\nDigital information management: data models, data formats and reformatting, file and data set access, persistent identifier resolution, curation, sample tracking\nData ingestion: absorption of data, attachment of metadata, digital transformations, support for combinations of structured and non-structured data sources\nData archiving: long term preservation, automated backup, user permission access controls, life cycle maintenance\nProcessing and analysis: instrument and model calibration records, data pipelines for computation of derived or final results, visualization and reporting tools\nData publishing and sharing: table or figure preparation, organization, crossholdings search, data as a service\nDigital asset movement: internal and external sharing, migration between platforms, exports to other platforms, life cycle management, and other capabilities that support capture and organization of data from equipment, preservation and recovery of data, tracking of samples, automated conversion of data to open formats, linking of information between systems, data querying for download, and countless others as needs evolve\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. LIMS components grouped by major functional category\n\n\n\nLIMS components \nThe architecture of LIMS is built with a variety of functional components (Fig. 3), which may be implemented using different platform services, tools, and interfaces. They are shown here grouped into a set of four functional categories (generation, persistence, communication, and consumption & distribution), which are also illustrated in the LIMS networked architecture of Fig. 6 (discussed later). Systems engineering factors into capabilities, components, and research requirements to build out an integrated LIMS such as the sample workflow model illustrated in Fig. 4. The model shows examples of data generation: instruments, electronic laboratory notebook (ELN)[14], or simulations, which are managed by intake to repository and file storage to support processing, analysis, and user search and access. \n\r\n\n\n\n\n\n\n\n\n\n\nFigure 4. A basic LIMS functional workflow model\n\n\n\nResearch workflows \nRequirements for each research discipline may be unique and require customized workflows. There are many common patterns, though each instrument and component implementation may have a unique interface for the input and output. It is critical when defining workflows to incorporate the perspective of experimentalists (or theoreticians and computational scientists) such that key inputs and outputs are captured in the correct sequence and factor into the human interaction dependencies and touchpoints. Several common themes include activity capture, management and recall of varied data, availability of infrastructure and resource skills, and iterative data planning to improve upon practice. One approach is to define the native workflow (perhaps through a white-boarding exercise) to identify the principle experimental attributes, e.g., instrument, calendar (time), sample preparation and characterization, laboratory notes and observations, and processes. Another exercise complementary to the research workflow is the definition of downstream data queries which SMEs would routinely use. The emerging theme of \u201cdecision science\u201d has been introduced as the concept which helps use-case-driven design to factor in what questions (query) will the LIMS support through access to holdings\/services\/tools. These queries motivate the process of analyzing, describing, and defining workflows. Furthermore, they provide scientifically motivated context for LIMS design such that the granularity of structured data and operational utility of the system will provide appropriate functionality for analytical tools. \nExamples of research workflow are illustrated in Fig. 5, showing how native workflows serve as use cases to identify which LIMS components are required to support specific capabilities.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 5. Assorted research workflows in native model representations\n\n\n\nLIMS networked architecture \nAn end-to-end architecture workflow view with networked functionality is shown in Fig. 6. The data progresses from generation through persistence via communication and leads to resulting consumption and distribution. This illustrates at a conceptual level a generalized workflow with networked systems. The operational requirements for an end-to-end architecture to support scientific application requires infrastructure reliability, performance, reference \u201cplaybooks\u201d for developers, and consistent availability of microservices which provide the flexibility for integration and functionality. \n\r\n\n\n\n\n\n\n\n\n\n\nFigure 6. LIMS networked architecture concept with four stages of operation\n\n\n\nThe supporting LIMS infrastructure takes into consideration the supporting services and sources of information and is critical in providing the foundation for applications. Sub-LIMS\u2014i.e., specialized systems such as freezer systems and inventory & tracking systems\u2014also need to be accounted for, in particular those which will continue to involve manual inputs and operations. The \u201cpeople\u201d resources for LIMS, shared infrastructure, and specialized systems are also critical resources for building and maintaining an environment for successful operation.\n\nMetrics and qualitative measures \nAs important as the establishing and vetting of the vision, strategic goals, and operating principles outlined here is the establishment of a set of metrics that can be used internally and externally to quantify how well NIST MML LIMS efforts are progressing. These metrics include:\n\nLIMS usage statistics: MML and NIST are beginning the process of collecting statistics on usage and impact of data and software systems. These are expected to be useful for project implementation as well as for all activities in which MML promotes the benefits of data-driven research. To achieve this, LIMS efforts will require supporting systems for sharing usage of instrumentation and technology in MML.\nHigh science impact capabilities: While we cannot guarantee publication or adoption in high-impact science areas, we should be able to demonstrate the potential for such results to be produced. Metrics should focus on data products, features, and processes that increase the potential for high-impact science. Peer-reviewed papers, data publications, and industry impact measurements will be used to demonstrate this measure.\nCollaborative activities and capabilities: As a major focus for our future, tracking the number and extent of collaborative activities will be important. Tracking should include quality and cost effectiveness assessments.\nCost, schedule, and scope targets for milestones: These metrics will be used for demonstrating value, as well as for highlighting potential efficiency areas.\nConclusion \nIn the MML research environment, a wide array of applications and digital tools are adopted to conduct both experimental and theoretical measurement science. We have embarked upon a new mission space for data management and sharing which we believe will significantly enhance the scientific return on investment in our laboratory. Adoption of LIMS provides a modern approach toward this goal by embedding data and software systems supporting research workflows and capturing information in a manner compatible with the FAIR Data Principles.[12] In this roadmap, we introduce important concepts for the design and implementation of a LIMS. The benefits of a LIMS are already beginning to demonstrate their value to science through more efficient access to data for analysis over time. Our next-generation LIMS will provide standards for interoperability and collaboration, further enabling scientific investigation spanning across experimental groups. With proper LIMS design in place, solutions will evolve in tandem with research domain knowledge, providing an essential resource to stimulate scientific innovation. \n\nFootnotes \n\n\n\u2191 Any mention of commercial products is for information only; it does not imply recommendation or endorsement by NIST. \n\n\nAcronyms and initialisms \nAFRL: Air Force Research Laboratory\nAI: artificial intelligence\nARKid: Archival Resource Key identifiers\nAPI: application programming interface\nAWS: Amazon Web Services\nBNL: Brookhaven National Laboratory\nCDCS: Configurable Data Curation System\nCDS: central data storage\nCIS: Critical Security\nCOI: community of interest\nDCAT: Data Catalog Vocabulary\nDCN: data compute node\nDOI: digital object identifier\nDSSI: Data Science and Systems Integration\nELN: electronic laboratory notebook\nEM: environmental monitor\nESNET: Energy Sciences Network\nETL: extract, transform, and load\nFAIR: findable, accessible, interoperable, and reusable\nFTP: File Transfer Protocol\nHPC: high-performance computing\nIaaS: infrastructure as a service\nIC: instrument controller\nIT: information technology\nLIMS: laboratory information management system\nMI: monitored instrumentation\nML: machine learning\nMML: Material Measurement Laboratory\nNAS: network-attached storage\nNASA: National Aeronautics and Space Administration\nNCAL: NIST Center for Automotive Lightweighting\nNIST: National Institute of Standards and Technology\nNREL: National Renewable Energy Laboratory\nNSLS-II: National Synchrotron Light Source-II\nODI: Office of Data and Informatics (in MML, NIST)\nORCID: Open Researcher and Contributor IDentifier\nORNL: Oak Ridge National Laboratory\nOTS: off-the-shelf\nPID: persistent identifier\nREN: Research Equipment Network\nREST: representational state transfer\nSDK: software development kit\nSME: subject matter expert\nVM: virtual machine\nVPN: virtual private network\n\nAcknowledgements \nThe authors would like to thank the numerous internal and external collaborators who have shared their knowledge, experience, and access to LIMS solutions and tools. The Configurable Data Curation System project team within the NIST Information Technology Laboratory Software and Systems Division has devoted considerable time and effort to design and implementation for several of the solutions described. The NIST Office of Information Systems Management, Research Services Office has been a key collaborator for design, deployment, and operations within the NIST infrastructure. \n\nReferences \n\n\n\u2191 \"Resources\". Federal Data Strategy: Leveraging Data as a Strategic Asset. GSA Technology Transformation Services. https:\/\/strategy.data.gov\/resources\/ . Retrieved April 2022 .   \n \n\n\u2191 Knapp, G.L.; Mukherjee, T.; Zuback, J.S.; Wei, H.L.; Palmer, T.A.; De, A.; DebRoy, T. (1 August 2017). \"Building blocks for a digital twin of additive manufacturing\" (in en). Acta Materialia 135: 390\u2013399. doi:10.1016\/j.actamat.2017.06.039. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359645417305141 .   \n \n\n\u2191 Talley, Kevin R.; White, Robert; Wunder, Nick; Eash, Matthew; Schwarting, Marcus; Evenson, Dave; Perkins, John D.; Tumas, William et al. (1 December 2021). \"Research data infrastructure for high-throughput experimental materials science\" (in en). Patterns 2 (12): 100373. doi:10.1016\/j.patter.2021.100373. PMC PMC8672147. PMID 34950901. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S266638992100235X .   \n \n\n\u2191 Bollinger, K.; Salyards, J.; Satcher, R. et al. (1 August 2020). [https:\/\/nij.ojp.gov\/library\/publications\/landscape-study-laboratory-information-management-systems-forensic-crime \"A Landscape Study of Laboratory Information Management\nSystems (LIMS) for Forensic Crime Laboratories\"]. National Institute of Justice Forensic Technology Center of Excellence. https:\/\/nij.ojp.gov\/library\/publications\/landscape-study-laboratory-information-management-systems-forensic-crime . Retrieved April 2022 .   \n \n\n\u2191 Stansberry, Dale; Somnath, Suhas; Breet, Jessica; Shutt, Gregory; Shankar, Mallikarjun (7 April 2020). \"DataFed: Towards Reproducible Research via Federated Data Management\". arXiv:2004.03710 [cs]. http:\/\/arxiv.org\/abs\/2004.03710 .   \n \n\n\u2191 Arkilic, A.; Allan, D. B.; Caswell, T.A.; Li, L.; Lauer, K.; Abeykoon, S. (4 March 2017). \"Towards Integrated Facility-Wide Data Acquisition and Analysis at NSLS-II\" (in en). Synchrotron Radiation News 30 (2): 44\u201345. doi:10.1080\/08940886.2017.1289810. ISSN 0894-0886. https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/08940886.2017.1289810 .   \n \n\n\u2191 Taillon, Joshua A.; Bina, Thomas F.; Plante, Raymond L.; Newrock, Marcus W.; Greene, Gretchen R.; Lau, June W. (1 June 2021). \"NexusLIMS: A Laboratory Information Management System for Shared-Use Electron Microscopy Facilities\" (in en). Microscopy and Microanalysis 27 (3): 511\u2013527. doi:10.1017\/S1431927621000222. ISSN 1431-9276. PMC PMC8551308. PMID 33908340. https:\/\/www.cambridge.org\/core\/product\/identifier\/S1431927621000222\/type\/journal_article .   \n \n\n\u2191 Lau, June W.; Devers, Rachel F.; Newrock, Marcus; Greene, Gretchen (17 December 2019). \"Laboratory Information Management Systems for Electron Microscopy: Evaluation of the 4CeeD Data Curation Platform\" (in en). Journal of Research of the National Institute of Standards and Technology 124: 124034. doi:10.6028\/jres.124.034. ISSN 2165-7254. PMC PMC7351567. PMID 34877182. https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/124\/jres.124.034.pdf .   \n \n\n\u2191 \"Research Data Management\". UC Santa Cruz University Library. https:\/\/guides.library.ucsc.edu\/datamanagement\/ . Retrieved April 2022 .   \n \n\n\u2191 Hopson, M.; McFadden, V.; Refoy, R. et al. (September 2020). \"De-risking Government Technology: Federal Agency Field Guide\". 18F, General Services Administration. https:\/\/derisking-guide.18f.gov\/federal-field-guide\/ . Retrieved April 2022 .   \n \n\n\u2191 Dart, Eli; Rotman, Lauren; Tierney, Brian; Hester, Mary; Zurawski, Jason (2014). \"The Science DMZ: A Network Design Pattern for Data-Intensive Science\" (in en). Scientific Programming. doi:10.3233\/spr-140382. https:\/\/www.hindawi.com\/journals\/sp\/2014\/701405\/ .   \n \n\n\u2191 12.0 12.1 Wilkinson, Mark D.; Dumontier, Michel; Aalbersberg, IJsbrand Jan; Appleton, Gabrielle; Axton, Myles; Baak, Arie; Blomberg, Niklas; Boiten, Jan-Willem et al. (1 December 2016). \"The FAIR Guiding Principles for scientific data management and stewardship\" (in en). Scientific Data 3 (1): 160018. doi:10.1038\/sdata.2016.18. ISSN 2052-4463. PMC PMC4792175. PMID 26978244. http:\/\/www.nature.com\/articles\/sdata201618 .   \n \n\n\u2191 Wilkinson, Mark D.; Dumontier, Michel; Sansone, Susanna-Assunta; Bonino da Silva Santos, Luiz Olavo; Prieto, Mario; Batista, Dominique; McQuilton, Peter; Kuhn, Tobias et al. (1 December 2019). \"Evaluating FAIR maturity through a scalable, automated, community-governed framework\" (in en). Scientific Data 6 (1): 174. doi:10.1038\/s41597-019-0184-5. ISSN 2052-4463. PMC PMC6754447. PMID 31541130. http:\/\/www.nature.com\/articles\/s41597-019-0184-5 .   \n \n\n\u2191 Gates, Richard S.; McLean, Mark J.; Osborn, William A. (1 December 2015). \"Smart Electronic Laboratory Notebooks for the NIST Research Environment\" (in en). Journal of Research of the National Institute of Standards and Technology 120: 293. doi:10.6028\/jres.120.018. ISSN 2165-7254. PMC PMC4730679. PMID 26958447. https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/120\/jres.120.018.pdf .   \n \n\n\nNotes \nThis document falls in the U.S. public domain and is republished courtesy of the National Institute of Standards and Technology. This presentation is faithful to the original, with only a few minor changes to presentation, spelling, and grammar. The original document mislabels the figures; they are corrected in this version. A few external links were also added or corrected. The original uses numbers for footnotes, but this wiki uses letters, by design. Citations 12 and 13 are inadvertently reversed in the original and were swapped to their correct places for this version.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\">https:\/\/www.limswiki.org\/index.php\/Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on laboratory informaticsLIMSwiki journal articles on softwareNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 9 May 2022, at 22:20.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 157 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","da7b86c02e387ab4edff0524bbe2a563_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory rootpage-Journal_A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:A roadmap for LIMS at NIST Material Measurement Laboratory<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Foreword\">Foreword<\/span><\/h2>\n<p>Over the past decade, emerging technology in <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> and computational science has changed the landscape for research by accelerating the production, processing, and exchange of data. The NIST Material Measurement Laboratory community recognizes that to keep pace with the transformation of measurement science to a digital paradigm, it is essential to implement <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management systems<\/a> (LIMS). Effective introduction of LIMS early in the research life cycle provides direct support for planning and execution of experiments and accelerating research productivity. From this perspective, LIMS are not passive entities with isolated interaction, but rather key resources supporting collaboration, scientific integrity, and transfer of knowledge over time. They serve as a delivery system for organizational contributions to the broader federated data community, supporting both controlled and open access, determined by the sensitivity of the research. \n<\/p><p>The overall goal of a successful LIMS is to empower a research community by establishing common tools providing access to laboratory data resources. Modern LIMS should therefore provide several core functions and touchpoints:\n<\/p>\n<ul><li><i>Workflow management<\/i> \u2013 A research <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> describes steps to be performed to derive results. These patterns serve as a prescription for LIMS to control the progression of data<\/li><\/ul>\n<p>and associated services or tools. <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_automation\" title=\"Laboratory automation\" class=\"wiki-link\" data-key=\"0061880849aeaca05f8aa27ae171f331\">Automation<\/a> of a workflow simplifies the transfer of <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> through defined interfaces from a network of systems.\n<\/p>\n<ul><li><i>Repository of data<\/i> \u2013 Effective storage and retrieval of data (raw and derived)\u2014including associated <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" title=\"Metadata\" class=\"wiki-link\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">metadata<\/a>, data products, calibration, software, logs, etc.\u2014facilitates data discovery, processing, collaboration, and dissemination.<\/li><\/ul>\n<ul><li><i>Creation of data products and tools<\/i> \u2013 A LIMS should support storage and processing of raw data, leading to products which can be shared and consumed. Examples would include <a href=\"https:\/\/www.limswiki.org\/index.php\/Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"7f8cd41a077a88d02370c02a3ba3d9d6\">sample<\/a> data, instrument-generated data, and algorithms generating defined outputs. Inclusion of data models provides context and structure, and <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> (ML) integration may generate related data which could be combined into more comprehensive data models. Tools may include <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_visualization\" title=\"Data visualization\" class=\"wiki-link\" data-key=\"4a3b86cba74bc7bb7471aa3fc2fcccc3\">visualization<\/a>, evaluation, and analysis packages offering users advanced capabilities for their research projects.<\/li><\/ul>\n<ul><li><i>Organization of data for search and retrieval<\/i> \u2013 Tools and interfaces give users access to sophisticated searches of data holdings and efficient mechanisms for data transfer in standardized formats. Searching should extend to domain or project-specific semantics, be coupled closely with related data, and go beyond individual research projects to include super-searches (e.g., use-case-driven interoperability between LIMS).<\/li><\/ul>\n<ul><li><i>Long-lived, stable, and agile structures<\/i> \u2013 LIMS require institutional and architectural sustainability for long baseline research and curatorship. Technology tends to change faster than the practical lifetime of research programs, so paths must exist for maintaining IT infrastructure and introducing faster and more complex processes.<\/li><\/ul>\n<ul><li><i>Standards and best practices<\/i> \u2013 LIMS benefit from standardization to support collaborations among research communities and make data workflows efficient and affordable. Community buy-in for standards and best practices is an essential part of LIMS, and organizational shared expertise naturally serves as a means for coordination and adaptation of standards.<\/li><\/ul>\n<ul><li><i>User involvement<\/i> \u2013 In all the core functions listed above, it is critical to involve the subject matter experts from the beginning. LIMS should establish a working team that explicitly includes representatives from the end user community.<\/li><\/ul>\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Instrumentation generates data faster and in greater quantity than ever before, and inter-laboratory research is in historic demand domestically and internationally to stimulate economic innovation. Strategic mission needs of the NIST Material Measurement Laboratory (MML) to support a wide array of research disciplines therefore compel our organization to adopt advanced strategies for research <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">data management<\/a>. Laboratory information management systems (LIMS) provide a framework for managing data from the outset of the research life cycle, delivering new capabilities for machine learning (ML), data analysis, collaboration, and dissemination. This roadmap describes our current understanding and strategy for adapting our research workflows for LIMS throughout MML by embracing the use of standards and best practices from data science communities. The NIST research data cyber-infrastructure complements these goals for MML by providing a secure environment to host LIMS solutions. Additionally, integration of scientific workflows requires ongoing collaboration to bridge organizational LIMS with external scientific communities. Thus, MML LIMS will evolve over time in synergy with the technology and experimental environments, delivering new science. LIMS will broaden our mission impact through adoption of the <a href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_FAIR_Guiding_Principles_for_scientific_data_management_and_stewardship\" title=\"Journal:The FAIR Guiding Principles for scientific data management and stewardship\" class=\"wiki-link\" data-key=\"e5903ddcc7734415af1d91fcd258da90\">FAIR Data Principles<\/a>. \n<\/p><p><b>Keywords<\/b>: data, laboratory information management systems, experimental data, research data, research workflows \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Beginning late 2019, MML initiated as part of its strategic plan the development of \"next-generation\" data and <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics_(academic_field)\" title=\"Informatics (academic field)\" class=\"wiki-link\" data-key=\"0391318826a5d9f9a1a1bcc88394739f\">informatics<\/a> with a focus on LIMS as a key resource to support research data and science. This effort was complemented by initiatives for enhancing data management planning and data systems infrastructure. The first year\u2019s groundwork established common needs for both individual researchers and teams to engage more readily with LIMS, with a goal of building greater capacity for interaction and use of data. A vision for LIMS was written to convey the purpose of these collective efforts: \n<\/p>\n<blockquote><p>\u201cLaboratory information management systems will provide MML scientists a practical means for repeatability, traceability, reproducibility, efficiency, and compliance of research, serving as a beacon to both intramural and extramural community stakeholders.\u201d<\/p><\/blockquote>\n<p>The MML approach to implementing LIMS started with defining goals for specific division research laboratory projects and established a cross-divisional Community of Interest (COI) group for sharing solutions, services, practices, and challenges. Comprehensive LIMS solutions have been successfully implemented in several NIST laboratories. Several shared resources have successfully demonstrated use of LIMS components including repository platforms, a standard persistent identifier service, a centralized research data storage with networked data transfer nodes, and data transfer services, in addition to expertise in data modeling and semantics. These resources, along with community best practices, contribute to a basic LIMS architecture for research. \n<\/p><p>A system view and architecture model provide the foundation for planned future outcomes. In this roadmap, we define a set of research-oriented LIMS capabilities which serves to guide implementation along with components to deliver these capabilities. More detailed guidance for use of specific LIMS resources is available internally to NIST and where possible shared on external repository websites. It is also anticipated that LIMS implementation will provide an important contribution to the goals of NIST program areas such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI), biosystems, <a href=\"https:\/\/www.limswiki.org\/index.php\/Chemical_informatics\" title=\"Chemical informatics\" class=\"wiki-link\" data-key=\"f351334854570f46a1227e6e952840c1\">chemical informatics<\/a>, additive manufacturing, and the materials science areas which spearheaded early innovation in data systems through the <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nist.gov\/mgi\" target=\"_blank\">Materials Genome Initiative<\/a>. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Roadmap_objectives\">Roadmap objectives<\/span><\/h2>\n<p>This roadmap provides a framework for manifesting the MML LIMS vision and outlines the key objectives highlighted by the MML LIMS COI project goals. These are grouped into near- and long-term objectives for MML LIMS prioritization. These objectives, along with broader community efforts, will strengthen the NIST data-as-an-asset<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup> strategic approach to research. More comprehensive goals such as the development of a \"digital twin\"<sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup> will enable models to probe the measurement science space to further analyze the physics and gain understanding, leading to new science. \n<\/p><p>Near-term objectives include:\n<\/p>\n<ul><li>Establish a LIMS COI for MML (as of this writing, already in place)<\/li>\n<li>Develop pilot LIMS solutions for targeted research workflows (as of this writing, several solutions already piloted and deployed for laboratory operations)<\/li>\n<li>Design tiered LIMS architectures to support a range of research workflow implementations<\/li>\n<li>Establish core infrastructure services to support LIMS<\/li>\n<li>Develop data acquisition and experimental activity capture solutions<\/li>\n<li>Deploy key functional support services such as a <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/handle.net\/\" target=\"_blank\">Handle.Net service<\/a> (supports persistent identifiers) and data transfer service (see the later subsection on supporting services)<\/li>\n<li>Prototype and exchange LIMS components as a basis for shared resources (e.g., repository platforms for experimental activity; instrumentation; samples; extract, transform, and load [ETL])<\/li>\n<li>Establish best practices in digital object management to support standards and community practice<\/li><\/ul>\n<p>Long-term objectives include:\n<\/p>\n<ul><li>Establish best practices for development and implementation of data models and semantics<\/li>\n<li>Deploy prioritized LIMS end-to-end solutions (achieving multi-component level functionality)<\/li>\n<li>Develop use-case-driven solutions for cross-laboratory LIMS interconnectivity<\/li>\n<li>Provide on-demand system-level LIMS resources for research teams at NIST for rapid engagement<\/li>\n<li>Develop automated workflow integration between LIMS and computational platforms (e.g., high-performance computing [HPC], ML, and analysis applications like <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciserver.org\/\" target=\"_blank\">SciServer<\/a>)<\/li>\n<li>Develop integration between LIMS and public data access systems<\/li>\n<li>Establish methodology for building and applying \"digital twin\" models<\/li>\n<li>Provide NIST leadership a strategy for adoption and implementation of LIMS to promote innovative data-driven science<\/li><\/ul>\n<h3><span class=\"mw-headline\" id=\"Challenges\">Challenges<\/span><\/h3>\n<p>Within the MML LIMS COI exchange forum, lessons learned and shared by early adopters of LIMS highlighted several key challenges. These will be factored into data management plans for implementation and extended to the broader MML community, which relies on either operation of LIMS or end-usage LIMS outputs. \n<\/p><p>One common challenge with instrumentation data is generation of vendor-proprietary output formats. A repository for sharing data format exchange software tools is a good example of a solution benefiting LIMS by supporting the need to transform vendor data into more consumable open data formats for downstream analysis and computation. A prototype repository was created by the Office of Data and Informatics (ODI) with a few extractor tools, and efforts are underway to explore how this may achieve wider utility. Community repositories such as <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/docs.openmicroscopy.org\/bio-formats\/6.7.0\/index.html\" target=\"_blank\">Bio-Formats<\/a> and <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/github.com\/materials-data-facility\/MaterialsIO\" target=\"_blank\">MaterialsIO<\/a> are examples of resources which support tools for conversions of third-party data into open data models. These community-oriented solutions successfully demonstrate methods to lower the barrier for LIMS through shared software. \n<\/p><p>Another challenge is finding appropriately skilled labor resources required for domain-specific engineering LIMS workflows. This is a common barrier to LIMS prioritization for research organizations. Integrating data structures requires close collaboration between domain and data science subject matter experts (SMEs) for modeling and mapping of multiple source data to repository storage. \n<\/p><p>Integration or migration of legacy systems and bespoke tools with next-generation LIMS architecture presents another challenge, especially for those with limited resources supporting maintenance. Legacy systems commonly lack sustainability due to factors such as end of funding support or unavailable expertise. \n<\/p><p>Data provenance is commonly required for sample tracking and traceability across laboratory processes (e.g., sample transformations, generation of parts, or inter-laboratory sample exchange). The latter is a challenge for inter-laboratory study because data management systems (including LIMS) are most commonly not standard or normalized. Supporting common <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_exchange\" title=\"Data exchange\" class=\"wiki-link\" data-key=\"7f41f95d4835a37b958fa9e870357f66\">data exchange<\/a> protocols and <a href=\"https:\/\/www.limswiki.org\/index.php\/Chain_of_custody\" title=\"Chain of custody\" class=\"wiki-link\" data-key=\"6ba04fe2bb1c8375e133455821aa3894\">chain of custody<\/a> workflows will be an ongoing design consideration for interoperability, including concepts such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_integrity\" title=\"Data integrity\" class=\"wiki-link\" data-key=\"382a9bb77ee3e36bb3b37c79ed813167\">data trust and integrity<\/a>. \n<\/p><p>Another common challenge is operational security compliance for IT infrastructure. NIST adheres to CIS Controls (Critical Security Controls,) and as LIMS architectures rely on networked systems, this translates to requirements for vigilant monitoring of service and platform deployments to ensure organizational security.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"MML_LIMS_stakeholders\">MML LIMS stakeholders<\/span><\/h2>\n<p>MML LIMS has a number of stakeholders with differing needs and priorities. ODI and research project leads work with all stakeholder categories, balancing goals to develop options that provide the best overall benefit. Stakeholders include:\n<\/p>\n<ul><li>Research community: Each research discipline area involves a community benefiting from the generation and exchange of data outcomes.<\/li>\n<li>MML Laboratory Office: The MML Lab Office ensures support of the NIST organizational mission through the productivity achieved from the use of LIMS.<\/li>\n<li>Program funding sources: Funding for strategic initiatives and research priorities for NIST and MML address both internal and external stakeholder needs and account for LIMS resources.<\/li>\n<li>Collaborative partners: Critical stakeholders help foster research innovation and science through exchange of LIMS data and software products. A key benefit to LIMS is the ability to support collaboration through exchange and access to data, data products, software, and related resources.<\/li><\/ul>\n<h3><span class=\"mw-headline\" id=\"External_solutions_and_partnering\">External solutions and partnering<\/span><\/h3>\n<p>Working with the external community has resulted in a more robust MML LIMS knowledge base, benefiting from partnerships with external researchers during LIMS development and implementation, commercial procurement, and collaboration. Several organizational partners have contributed to MML efforts, including the National Research Energy Laboratory<sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup>, Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Air Force Research Laboratory, 3M Corporation, NASA, University of Illinois - Champaign, and national <a href=\"https:\/\/www.limswiki.org\/index.php\/Forensic_laboratory\" class=\"mw-redirect wiki-link\" title=\"Forensic laboratory\" data-key=\"dabef2566b55c1f13b395543b47ae81e\">forensic crime labs<\/a> in collaboration with the National Institute of Justice.<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> Many NIST strategic research areas rely on collaborative data engagement; as such, having a LIMS with capabilities for supporting external access is important in many cases. \n<\/p><p>Collaboration with external partners may involve co-development of a LIMS platform system (or component), adoption of a community LIMS, shared access to data\/code, or support for commercial vendor solution customization. Such collaborations often include harmonizing requirements and goals to inform the design, architecture, and engineering of a solution. Open-source solutions often provide more mechanisms supporting the complexity of many research workflows through their flexible configuration, customization, and independent software enhancements. A few examples of such solutions include ORNL DataFed<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup>, <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/synbiohub.org\/\" target=\"_blank\">SynBioHub<\/a>, BNL\u2019s BlueSky platform<sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup>, and SciServer. While these may require engineering expertise to fit within the NIST infrastructure, each adds meaningful user capabilities. \n<\/p><p>As one example, NIST synchrotron beamline stations at the BNL National Synchrotron Light Source II (NSLS-II) Facility have implemented BlueSky in partnership with BNL\u2019s Data Science and Systems Integration (DSSI) group.\n<\/p><p>Several solutions have also been developed by partnering within NIST, and both are highly customized to the research requirements of their respective user groups. They include: \n<\/p>\n<ol><li>the Nexus Electron Microscopy LIMS (NexusLIMS<sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup>) workflow based on the <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nist.gov\/programs-projects\/configurable-data-curation-system-cdcs\" target=\"_blank\">Configurable Data Repository System<\/a> (CDCS), a NIST-developed open platform, and<\/li>\n<li>a LIMS supporting real-time biosystem cell line sample tracking LIMS with a custom Excel application used for experimental activity capture.<\/li><\/ol>\n<p>A few commercial solutions<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[a]<\/a><\/sup> were adopted in part or in full. In one successful example, the NIST Center for Automotive Lightweighting (NCAL) successfully implemented the commercial platform Ansys Granta. Other community and vendor solutions have been and continue to be evaluated for pilot use, such as 4CeeD<sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[8]<\/a><\/sup>, the <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/tadabase.io\/\" target=\"_blank\">Tadabase<\/a> no-code solution, the <a href=\"https:\/\/www.limswiki.org\/index.php\/Benchling,_Inc.\" title=\"Benchling, Inc.\" class=\"wiki-link\" data-key=\"67634090ee7d17da2ed0d3748a65379d\">Benchling<\/a> cloud platform, Microsoft platforms, and others. Due to the challenging nature of customized research workflows and complexity in the secure integration with government networked infrastructure, commercial solutions may pose additional cost and skillset requirements for successful adaptation into the laboratory working environment. In most cases at NIST, use case development leads to the adoption of hybrid solutions. Closed-source solutions widely adopted in the scientific community (e.g., <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.globus.org\/\" target=\"_blank\">Globus<\/a>) provide unique and robust capabilities that are difficult to recreate. In the instance of Globus, the linkage to several research community services and best practices like GridFTP, linked identity management with institutions authentication including <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/incommon.org\/\" target=\"_blank\">InCommon<\/a>, a Python software development kit (SDK), and multi-platform storage connections provide high value and ease of adoption. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Implementation_of_the_roadmap\">Implementation of the roadmap<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"System_level_solutions\">System level solutions<\/span><\/h3>\n<p>A LIMS, as we define it, is a system of components which delivers the capabilities for the early stages of a research life cycle.<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[9]<\/a><\/sup> It is widely recognized there is no singular LIMS solution that ranges across all disciplines of research, yet shared components (and data assets) provide greater economy of scale and consistent usage across the organization and beyond. A LIMS design implements research workflow requirements and provides context for assembling an architecture supporting component integration to produce desired outcomes. Off-the-Shelf (OTS) LIMS solutions are often challenging to adopt, primarily due to the limitations in both configuration and customization of components to match workflows. Monolithic solutions have demonstrated challenges whether they are homegrown or OTS by constraining interfaces between components. Workflow flexibility, orchestration, and evolution can be managed with lower risk<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[10]<\/a><\/sup> to overall performance when using service-oriented solutions. Therefore, implementations may vary as to which components are used and in which sequence to support the required research workflow. A tiered model ranging from basic components and plug-in architecture to instantiation of more complex data models with computational support can lower the barrier for entry. Given this context and the goal of flexibility, a few commonly used LIMS workflow components provide critical functionality. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"LIMS_tiers\">LIMS tiers<\/span><\/h3>\n<p>Requirements for building or deploying LIMS are dependent upon the complexity of the research workflow and project needs. In the consideration of the system, a basic three-tiered model serves as a general guide for capabilities mapping and implementation, to level of effort (Fig. 1). As with many aspects of LIMS, this model may have variations in the strata depending on the optimal architecture for achieving desired outcomes. \n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"bc5faf9498677fc72c05bb8e79810482\"><img alt=\"Fig1 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d9\/Fig1_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> LIMS three-tiered model for implementation<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h4><span class=\"mw-headline\" id=\"Tier_1:_On-demand_resources\">Tier 1: On-demand resources<\/span><\/h4>\n<p>Tier 1 is primarily reliant on infrastructure and support services and can be readily adopted with available \u201con-demand\u201d resources, meaning those resources that exist and can be provisioned for use upon request. The main functions for Tier 1 LIMS include data acquisition, near-line instrument data collection, sample tracking, and data movement\u2014possibly automated\u2014to a storage location, ideally with access for processing and analysis. Tier 1 LIMS support unstructured data and may provide more flexibility for researchers to experiment with data structures, formats, and tuning for workflow. \n<\/p>\n<h4><span class=\"mw-headline\" id=\"Tier_2:_Data_science_and_services\">Tier 2: Data science and services<\/span><\/h4>\n<p>Tier 2 integrates research workflow design, including data structuring, formatting, metadata, and possible integration to a data repository solution. The Tier 2 LIMS also requires a greater level of effort and engagement between a research SME and data science engineers for design, installation, and operational configuration. \n<\/p>\n<h4><span class=\"mw-headline\" id=\"Tier_3:_Discipline_science\">Tier 3: Discipline science<\/span><\/h4>\n<p>The Tier 3 LIMS require the highest level of commitment and collaboration between the research SME and a data science expert to factor in all the functionality for more complex workflows. This might involve functionality such as computational system integration, support for external client tools through an <a href=\"https:\/\/www.limswiki.org\/index.php\/Application_programming_interface\" title=\"Application programming interface\" class=\"wiki-link\" data-key=\"36fc319869eba4613cb0854b421b0934\">application programming interface<\/a> (API), and semantic modeling to factor in community adoption for data consumption. An example of a Tier 3 LIMS would include data generated from multiple instruments, each with variable processes, interconnected to computational tools and applications to produce data products, with dependencies on analytical requirements for external interoperability. Both the MML NexusLIMS and Granta NCAL systems are examples of Tier 3. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Supporting_services\">Supporting services<\/span><\/h3>\n<p>Common services support LIMS at various touch points throughout the research data workflow. These may be considered part of the infrastructure, i.e., they are underlying services shared and configured to support more than one stage of a LIMS workflow. However, by nature, they often require a contextual prescription for how they interface with a LIMS workflow of component. Examples of these key support services include: \n<\/p>\n<ul><li>Data transfer services: manual, automation, and tools for file movement between storage locations<\/li>\n<li>Handle service: generates and resolves a standard persistent identifier (PID) known as a Handle<\/li>\n<li>Repository systems: OTS solutions or well-established and supported repository platforms (e.g., CDCS, <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.cordra.org\/\" target=\"_blank\">Cordra<\/a>, GitLab, GitHub) and open-source solutions supporting customization for (meta)data<\/li>\n<li>Containerized deployments: Docker, Kubernetes, virtual machine (VM) or cloud services supporting deployments of LIMS applications and tools<\/li>\n<li>Solutions brokering: Documentation and communications, including instructional guides (\u201cplaybooks\u201d) and consultation for design and use of LIMS systems, services, and components<\/li><\/ul>\n<h3><span class=\"mw-headline\" id=\"Infrastructure_resources_for_LIMS\">Infrastructure resources for LIMS<\/span><\/h3>\n<p>Organizationally MML and NIST both provide infrastructure-as-a-service (IAAS) for networking, storage, and compute resources. These systems may be requested through internal NIST IT services and are readily available. \n<\/p><p>As part of the MML Data and Informatics strategic plan, both network and storage have been significantly expanded to support higher bandwidth for data transfer between laboratory instruments and storage (see Fig. 2). Data space allocations are designed to be flexible and can be established on request for cross-organizational projects, research teams, and instrument dedicated endpoints. Several network-attached storage (NAS) solutions have been implemented to support both localized (data collection nodes) and central data storage (CDS; a dedicated MML Research Data storage array). Additionally, the NIST Amazon Web Service (AWS) cloud environment is available and integrated with the NIST VPN (virtual private network) providing both storage and compute on demand. \n<\/p><p>A research equipment network (REN) is used to manage pass through and routing between instrument laboratory equipment and data storage. Network configuration via the REN ensures that instrument-control computers are protected and isolated as needed for secure operations. Higher speed network backbones and a Science DMZ<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[11]<\/a><\/sup> is currently in a planning phase to provide higher throughputs and secured zones for operating with LIMS architectures. \n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"b86d983811ed7129786f726a659114bc\"><img alt=\"Fig2 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/83\/Fig2_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> MML LIMS data plumbing model for harvesting instrumental raw data<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Current infrastructure resources include DCN, NAS, CDS, AWS, and local research data storage, as well as <i><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nist.gov\/programs-projects\/computation-platform-aiml\" target=\"_blank\">enki<\/a><\/i>, AWS, SciServer, and HPC computational resources. Meanwhile, efforts are ongoing to integrate the CIS Controls into the infrastructure and expand capabilities in support of LIMS. Security for government research networks is a top priority for NIST, and all LIMS deployments must adhere to <a href=\"https:\/\/www.limswiki.org\/index.php\/Cybersecurity\" class=\"mw-redirect wiki-link\" title=\"Cybersecurity\" data-key=\"ba653dc2a1384e5f9f6ac9dc1a740109\">cybersecurity<\/a> controls and processes for monitoring and managing access. This critical infrastructure element requires coordination between LIMS developers and IT security offices to ensure systems are protected and compliant with CIS including monitoring, security patching, and notification of problems for mitigation. In developing a plan to implement LIMS, resource needs to complete security assessment and authorization should be taken into consideration. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Community_standards_and_best_practices\">Community standards and best practices<\/span><\/h3>\n<p>Several standards and best practices in the research data community are key to building an effective LIMS workspace. While we list a few concepts core to LIMS and examples of use, these are only a small subset in the growing field of data science. Standards and best practices will continue to evolve, requiring resources for maintenance, expansion, community engagement, and user training, though one goal of a successful LIMS implementation is to minimize these burdens for end users. Examples of data standards and practices used with LIMS are found in Table 1.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Data standards and practices used with LIMS\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Community standard\/practice\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Examples of use\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Persistent identifiers\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">DOIs, ORCIDs, <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arks.org\/\" target=\"_blank\">ARKid<\/a>, Handles\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Open-source code\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">USNISTGOV GitHub (ETL pipelines, libraries, tools)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">FAIR (findable, accessible, interoperable, reusable) Data Principles<sup id=\"rdp-ebb-cite_ref-:0_13-0\" class=\"reference\"><a href=\"#cite_note-:0-13\">[12]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Go-Fair.org, FAIR Maturity Model<sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[13]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Semantic standards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">DCAT, Schema.org, DataCite, LinkedData, discipline-specific taxonomy, ontological\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Standardized communications network protocols\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">RESTful API or Open API, e.g., Swagger Docs\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"LIMS_architecture\">LIMS architecture<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Capabilities_of_LIMS\">Capabilities of LIMS<\/span><\/h3>\n<p>LIMS helps a researcher by providing capabilities in an integrated way. These capabilities are delivered by one or more of the system components and serve as drivers for LIMS requirements. Common data-oriented functions, such as sample tracking, from the user perspective might also be more readily identified in terms of the capabilities. These may take on slightly different naming conventions and forms across implementations, yet in general they can be described in the context of the function they support within research environments. Capabilities may be mapped into the design architecture through implementation of modular components, as shown in Fig. 3. For external vendor and community open LIMS platforms or sub-components, understanding how and where in the system these capabilities are supported is also key to evaluating their compatibility with research workflows. \n<\/p><p>Core capabilities generally fall into one of several categories. A few example aspects supported by each category are provided. \n<\/p>\n<ul><li><b>Data generation<\/b>: provenance of data, software descriptions and custom code, instrument configuration, data acquisition descriptions<\/li>\n<li><b>Digital information management<\/b>: data models, data formats and reformatting, file and data set access, persistent identifier resolution, curation, sample tracking<\/li>\n<li><b>Data ingestion<\/b>: absorption of data, attachment of metadata, digital transformations, support for combinations of structured and non-structured data sources<\/li>\n<li><b>Data archiving<\/b>: long term preservation, automated backup, user permission access controls, life cycle maintenance<\/li>\n<li><b>Processing and analysis<\/b>: instrument and model calibration records, data pipelines for computation of derived or final results, visualization and reporting tools<\/li>\n<li><b>Data publishing and sharing<\/b>: table or figure preparation, organization, crossholdings search, data as a service<\/li>\n<li><b>Digital asset movement<\/b>: internal and external sharing, migration between platforms, exports to other platforms, life cycle management, and other capabilities that support capture and organization of data from equipment, preservation and recovery of data, tracking of samples, automated conversion of data to open formats, linking of information between systems, data querying for download, and countless others as needs evolve<\/li><\/ul>\n<p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"c172433ae83ab85eadd5937e826c06a1\"><img alt=\"Fig3 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cc\/Fig3_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> LIMS components grouped by major functional category<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"LIMS_components\">LIMS components<\/span><\/h3>\n<p>The architecture of LIMS is built with a variety of functional components (Fig. 3), which may be implemented using different platform services, tools, and interfaces. They are shown here grouped into a set of four functional categories (generation, persistence, communication, and consumption & distribution), which are also illustrated in the LIMS networked architecture of Fig. 6 (discussed later). Systems engineering factors into capabilities, components, and research requirements to build out an integrated LIMS such as the sample workflow model illustrated in Fig. 4. The model shows examples of data generation: instruments, <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_laboratory_notebook\" title=\"Electronic laboratory notebook\" class=\"wiki-link\" data-key=\"a9fbbd5e0807980106763fab31f1e72f\">electronic laboratory notebook<\/a> (ELN)<sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[14]<\/a><\/sup>, or simulations, which are managed by intake to repository and file storage to support processing, analysis, and user search and access. \n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"c3bc73bc38e63b6f9aa2ca45be874cf6\"><img alt=\"Fig4 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6f\/Fig4_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 4.<\/b> A basic LIMS functional workflow model<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Research_workflows\">Research workflows<\/span><\/h3>\n<p>Requirements for each research discipline may be unique and require customized workflows. There are many common patterns, though each instrument and component implementation may have a unique interface for the input and output. It is critical when defining workflows to incorporate the perspective of experimentalists (or theoreticians and computational scientists) such that key inputs and outputs are captured in the correct sequence and factor into the human interaction dependencies and touchpoints. Several common themes include activity capture, management and recall of varied data, availability of infrastructure and resource skills, and iterative data planning to improve upon practice. One approach is to define the native workflow (perhaps through a white-boarding exercise) to identify the principle experimental attributes, e.g., instrument, calendar (time), sample preparation and characterization, laboratory notes and observations, and processes. Another exercise complementary to the research workflow is the definition of downstream data queries which SMEs would routinely use. The emerging theme of \u201cdecision science\u201d has been introduced as the concept which helps use-case-driven design to factor in what questions (query) will the LIMS support through access to holdings\/services\/tools. These queries motivate the process of analyzing, describing, and defining workflows. Furthermore, they provide scientifically motivated context for LIMS design such that the granularity of structured data and operational utility of the system will provide appropriate functionality for analytical tools. \n<\/p><p>Examples of research workflow are illustrated in Fig. 5, showing how native workflows serve as use cases to identify which LIMS components are required to support specific capabilities.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"fa0b9eccac443ed07ddcda5ce5647deb\"><img alt=\"Fig5 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6d\/Fig5_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 5.<\/b> Assorted research workflows in native model representations<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"LIMS_networked_architecture\">LIMS networked architecture<\/span><\/h3>\n<p>An end-to-end architecture workflow view with networked functionality is shown in Fig. 6. The data progresses from generation through persistence via communication and leads to resulting consumption and distribution. This illustrates at a conceptual level a generalized workflow with networked systems. The operational requirements for an end-to-end architecture to support scientific application requires infrastructure reliability, performance, reference \u201cplaybooks\u201d for developers, and consistent availability of microservices which provide the flexibility for integration and functionality. \n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Green_NIST221-22.png\" class=\"image wiki-link\" data-key=\"28f9b1c3a0e0592052950bbe8f4e6b1f\"><img alt=\"Fig6 Green NIST221-22.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f3\/Fig6_Green_NIST221-22.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 6.<\/b> LIMS networked architecture concept with four stages of operation<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The supporting LIMS infrastructure takes into consideration the supporting services and sources of information and is critical in providing the foundation for applications. Sub-LIMS\u2014i.e., specialized systems such as freezer systems and inventory & tracking systems\u2014also need to be accounted for, in particular those which will continue to involve manual inputs and operations. The \u201cpeople\u201d resources for LIMS, shared infrastructure, and specialized systems are also critical resources for building and maintaining an environment for successful operation.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Metrics_and_qualitative_measures\">Metrics and qualitative measures<\/span><\/h2>\n<p>As important as the establishing and vetting of the vision, strategic goals, and operating principles outlined here is the establishment of a set of metrics that can be used internally and externally to quantify how well NIST MML LIMS efforts are progressing. These metrics include:\n<\/p>\n<ul><li><b>LIMS usage statistics<\/b>: MML and NIST are beginning the process of collecting statistics on usage and impact of data and software systems. These are expected to be useful for project implementation as well as for all activities in which MML promotes the benefits of data-driven research. To achieve this, LIMS efforts will require supporting systems for sharing usage of instrumentation and technology in MML.<\/li>\n<li><b>High science impact capabilities<\/b>: While we cannot guarantee publication or adoption in high-impact science areas, we should be able to demonstrate the potential for such results to be produced. Metrics should focus on data products, features, and processes that increase the potential for high-impact science. Peer-reviewed papers, data publications, and industry impact measurements will be used to demonstrate this measure.<\/li>\n<li><b>Collaborative activities and capabilities<\/b>: As a major focus for our future, tracking the number and extent of collaborative activities will be important. Tracking should include quality and cost effectiveness assessments.<\/li>\n<li><b>Cost, schedule, and scope targets for milestones<\/b>: These metrics will be used for demonstrating value, as well as for highlighting potential efficiency areas.<\/li><\/ul>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>In the MML research environment, a wide array of applications and digital tools are adopted to conduct both experimental and theoretical measurement science. We have embarked upon a new mission space for data management and sharing which we believe will significantly enhance the scientific return on investment in our laboratory. Adoption of LIMS provides a modern approach toward this goal by embedding data and software systems supporting research workflows and capturing information in a manner compatible with the FAIR Data Principles.<sup id=\"rdp-ebb-cite_ref-:0_13-1\" class=\"reference\"><a href=\"#cite_note-:0-13\">[12]<\/a><\/sup> In this roadmap, we introduce important concepts for the design and implementation of a LIMS. The benefits of a LIMS are already beginning to demonstrate their value to science through more efficient access to data for analysis over time. Our next-generation LIMS will provide standards for interoperability and collaboration, further enabling scientific investigation spanning across experimental groups. With proper LIMS design in place, solutions will evolve in tandem with research domain knowledge, providing an essential resource to stimulate scientific innovation. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Footnotes\">Footnotes<\/span><\/h2>\n<div class=\"reflist\" style=\"list-style-type: lower-alpha;\">\n<div class=\"mw-references-wrap\"><ol class=\"references\">\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\">Any mention of commercial products is for information only; it does not imply recommendation or endorsement by NIST.<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Acronyms_and_initialisms\">Acronyms and initialisms<\/span><\/h2>\n<p><b>AFRL<\/b>: Air Force Research Laboratory\n<\/p><p><b>AI<\/b>: artificial intelligence\n<\/p><p><b>ARKid<\/b>: Archival Resource Key identifiers\n<\/p><p><b>API<\/b>: application programming interface\n<\/p><p><b>AWS<\/b>: Amazon Web Services\n<\/p><p><b>BNL<\/b>: Brookhaven National Laboratory\n<\/p><p><b>CDCS<\/b>: Configurable Data Curation System\n<\/p><p><b>CDS<\/b>: central data storage\n<\/p><p><b>CIS<\/b>: Critical Security\n<\/p><p><b>COI<\/b>: community of interest\n<\/p><p><b>DCAT<\/b>: Data Catalog Vocabulary\n<\/p><p><b>DCN<\/b>: data compute node\n<\/p><p><b>DOI<\/b>: digital object identifier\n<\/p><p><b>DSSI<\/b>: Data Science and Systems Integration\n<\/p><p><b>ELN<\/b>: electronic laboratory notebook\n<\/p><p><b>EM<\/b>: environmental monitor\n<\/p><p><b>ESNET<\/b>: Energy Sciences Network\n<\/p><p><b>ETL<\/b>: extract, transform, and load\n<\/p><p><b>FAIR<\/b>: findable, accessible, interoperable, and reusable\n<\/p><p><b>FTP<\/b>: File Transfer Protocol\n<\/p><p><b>HPC<\/b>: high-performance computing\n<\/p><p><b>IaaS<\/b>: infrastructure as a service\n<\/p><p><b>IC<\/b>: instrument controller\n<\/p><p><b>IT<\/b>: information technology\n<\/p><p><b>LIMS<\/b>: laboratory information management system\n<\/p><p><b>MI<\/b>: monitored instrumentation\n<\/p><p><b>ML<\/b>: machine learning\n<\/p><p><b>MML<\/b>: Material Measurement Laboratory\n<\/p><p><b>NAS<\/b>: network-attached storage\n<\/p><p><b>NASA<\/b>: National Aeronautics and Space Administration\n<\/p><p><b>NCAL<\/b>: NIST Center for Automotive Lightweighting\n<\/p><p><b>NIST<\/b>: National Institute of Standards and Technology\n<\/p><p><b>NREL<\/b>: National Renewable Energy Laboratory\n<\/p><p><b>NSLS-II<\/b>: National Synchrotron Light Source-II\n<\/p><p><b>ODI<\/b>: Office of Data and Informatics (in MML, NIST)\n<\/p><p><b>ORCID<\/b>: Open Researcher and Contributor IDentifier\n<\/p><p><b>ORNL<\/b>: Oak Ridge National Laboratory\n<\/p><p><b>OTS<\/b>: off-the-shelf\n<\/p><p><b>PID<\/b>: persistent identifier\n<\/p><p><b>REN<\/b>: Research Equipment Network\n<\/p><p><b>REST<\/b>: representational state transfer\n<\/p><p><b>SDK<\/b>: software development kit\n<\/p><p><b>SME<\/b>: subject matter expert\n<\/p><p><b>VM<\/b>: virtual machine\n<\/p><p><b>VPN<\/b>: virtual private network\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The authors would like to thank the numerous internal and external collaborators who have shared their knowledge, experience, and access to LIMS solutions and tools. The Configurable Data Curation System project team within the NIST Information Technology Laboratory Software and Systems Division has devoted considerable time and effort to design and implementation for several of the solutions described. The NIST Office of Information Systems Management, Research Services Office has been a key collaborator for design, deployment, and operations within the NIST infrastructure. \n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/strategy.data.gov\/resources\/\" target=\"_blank\">\"Resources\"<\/a>. <i>Federal Data Strategy: Leveraging Data as a Strategic Asset<\/i>. 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Devers, Rachel F.; Newrock, Marcus; Greene, Gretchen (17 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/124\/jres.124.034.pdf\" target=\"_blank\">\"Laboratory Information Management Systems for Electron Microscopy: Evaluation of the 4CeeD Data Curation Platform\"<\/a> (in en). <i>Journal of Research of the National Institute of Standards and Technology<\/i> <b>124<\/b>: 124034. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.6028%2Fjres.124.034\" target=\"_blank\">10.6028\/jres.124.034<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2165-7254\" target=\"_blank\">2165-7254<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7351567\/\" target=\"_blank\">PMC7351567<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34877182\" target=\"_blank\">34877182<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/124\/jres.124.034.pdf\" target=\"_blank\">https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/124\/jres.124.034.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Laboratory+Information+Management+Systems+for+Electron+Microscopy%3A+Evaluation+of+the+4CeeD+Data+Curation+Platform&rft.jtitle=Journal+of+Research+of+the+National+Institute+of+Standards+and+Technology&rft.aulast=Lau&rft.aufirst=June+W.&rft.au=Lau%2C%26%2332%3BJune+W.&rft.au=Devers%2C%26%2332%3BRachel+F.&rft.au=Newrock%2C%26%2332%3BMarcus&rft.au=Greene%2C%26%2332%3BGretchen&rft.date=17+December+2019&rft.volume=124&rft.pages=124034&rft_id=info:doi\/10.6028%2Fjres.124.034&rft.issn=2165-7254&rft_id=info:pmc\/PMC7351567&rft_id=info:pmid\/34877182&rft_id=https%3A%2F%2Fnvlpubs.nist.gov%2Fnistpubs%2Fjres%2F124%2Fjres.124.034.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/guides.library.ucsc.edu\/datamanagement\/\" target=\"_blank\">\"Research Data Management\"<\/a>. UC Santa Cruz University Library<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/guides.library.ucsc.edu\/datamanagement\/\" target=\"_blank\">https:\/\/guides.library.ucsc.edu\/datamanagement\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved April 2022<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Research+Data+Management&rft.atitle=&rft.pub=UC+Santa+Cruz+University+Library&rft_id=https%3A%2F%2Fguides.library.ucsc.edu%2Fdatamanagement%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Hopson, M.; McFadden, V.; Refoy, R. et al. 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Retrieved April 2022<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=De-risking+Government+Technology%3A+Federal+Agency+Field+Guide&rft.atitle=&rft.aulast=Hopson%2C+M.%3B+McFadden%2C+V.%3B+Refoy%2C+R.+et+al.&rft.au=Hopson%2C+M.%3B+McFadden%2C+V.%3B+Refoy%2C+R.+et+al.&rft.date=September+2020&rft.pub=18F%2C+General+Services+Administration&rft_id=https%3A%2F%2Fderisking-guide.18f.gov%2Ffederal-field-guide%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Dart, Eli; Rotman, Lauren; Tierney, Brian; Hester, Mary; Zurawski, Jason (2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hindawi.com\/journals\/sp\/2014\/701405\/\" target=\"_blank\">\"The Science DMZ: A Network Design Pattern for Data-Intensive Science\"<\/a> (in en). <i>Scientific Programming<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3233%2Fspr-140382\" target=\"_blank\">10.3233\/spr-140382<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hindawi.com\/journals\/sp\/2014\/701405\/\" target=\"_blank\">https:\/\/www.hindawi.com\/journals\/sp\/2014\/701405\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+Science+DMZ%3A+A+Network+Design+Pattern+for+Data-Intensive+Science&rft.atitle=Scientific+Programming&rft.aulast=Dart&rft.aufirst=Eli&rft.au=Dart%2C%26%2332%3BEli&rft.au=Rotman%2C%26%2332%3BLauren&rft.au=Tierney%2C%26%2332%3BBrian&rft.au=Hester%2C%26%2332%3BMary&rft.au=Zurawski%2C%26%2332%3BJason&rft.date=2014&rft_id=info:doi\/10.3233%2Fspr-140382&rft_id=https%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fsp%2F2014%2F701405%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_13-0\">12.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_13-1\">12.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wilkinson, Mark D.; 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Dumontier, Michel; Sansone, Susanna-Assunta; Bonino da Silva Santos, Luiz Olavo; Prieto, Mario; Batista, Dominique; McQuilton, Peter; Kuhn, Tobias <i>et al.<\/i> (1 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41597-019-0184-5\" target=\"_blank\">\"Evaluating FAIR maturity through a scalable, automated, community-governed framework\"<\/a> (in en). <i>Scientific Data<\/i> <b>6<\/b> (1): 174. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41597-019-0184-5\" target=\"_blank\">10.1038\/s41597-019-0184-5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2052-4463\" target=\"_blank\">2052-4463<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6754447\/\" target=\"_blank\">PMC6754447<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31541130\" target=\"_blank\">31541130<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41597-019-0184-5\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41597-019-0184-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Evaluating+FAIR+maturity+through+a+scalable%2C+automated%2C+community-governed+framework&rft.jtitle=Scientific+Data&rft.aulast=Wilkinson&rft.aufirst=Mark+D.&rft.au=Wilkinson%2C%26%2332%3BMark+D.&rft.au=Dumontier%2C%26%2332%3BMichel&rft.au=Sansone%2C%26%2332%3BSusanna-Assunta&rft.au=Bonino+da+Silva+Santos%2C%26%2332%3BLuiz+Olavo&rft.au=Prieto%2C%26%2332%3BMario&rft.au=Batista%2C%26%2332%3BDominique&rft.au=McQuilton%2C%26%2332%3BPeter&rft.au=Kuhn%2C%26%2332%3BTobias&rft.au=Rocca-Serra%2C%26%2332%3BPhilippe&rft.date=1+December+2019&rft.volume=6&rft.issue=1&rft.pages=174&rft_id=info:doi\/10.1038%2Fs41597-019-0184-5&rft.issn=2052-4463&rft_id=info:pmc\/PMC6754447&rft_id=info:pmid\/31541130&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41597-019-0184-5&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gates, Richard S.; McLean, Mark J.; Osborn, William A. (1 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/120\/jres.120.018.pdf\" target=\"_blank\">\"Smart Electronic Laboratory Notebooks for the NIST Research Environment\"<\/a> (in en). <i>Journal of Research of the National Institute of Standards and Technology<\/i> <b>120<\/b>: 293. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.6028%2Fjres.120.018\" target=\"_blank\">10.6028\/jres.120.018<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2165-7254\" target=\"_blank\">2165-7254<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4730679\/\" target=\"_blank\">PMC4730679<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26958447\" target=\"_blank\">26958447<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/120\/jres.120.018.pdf\" target=\"_blank\">https:\/\/nvlpubs.nist.gov\/nistpubs\/jres\/120\/jres.120.018.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Smart+Electronic+Laboratory+Notebooks+for+the+NIST+Research+Environment&rft.jtitle=Journal+of+Research+of+the+National+Institute+of+Standards+and+Technology&rft.aulast=Gates&rft.aufirst=Richard+S.&rft.au=Gates%2C%26%2332%3BRichard+S.&rft.au=McLean%2C%26%2332%3BMark+J.&rft.au=Osborn%2C%26%2332%3BWilliam+A.&rft.date=1+December+2015&rft.volume=120&rft.pages=293&rft_id=info:doi\/10.6028%2Fjres.120.018&rft.issn=2165-7254&rft_id=info:pmc\/PMC4730679&rft_id=info:pmid\/26958447&rft_id=https%3A%2F%2Fnvlpubs.nist.gov%2Fnistpubs%2Fjres%2F120%2Fjres.120.018.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This document falls in the U.S. public domain and is republished courtesy of the National Institute of Standards and Technology. This presentation is faithful to the original, with only a few minor changes to presentation, spelling, and grammar. The original document mislabels the figures; they are corrected in this version. A few external links were also added or corrected. The original uses numbers for footnotes, but this wiki uses letters, by design. Citations 12 and 13 are inadvertently reversed in the original and were swapped to their correct places for this version.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628175032\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.254 seconds\nReal time usage: 0.636 seconds\nPreprocessor visited node count: 15811\/1000000\nPost\u2010expand include size: 133208\/2097152 bytes\nTemplate argument size: 42334\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 33795\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 203.953 1 -total\n 74.73% 152.414 2 Template:Reflist\n 56.33% 114.892 14 Template:Citation\/core\n 42.38% 86.433 9 Template:Cite_journal\n 20.53% 41.863 5 Template:Cite_web\n 14.63% 29.831 1 Template:Infobox_journal_article\n 13.14% 26.795 1 Template:Infobox\n 9.04% 18.427 12 Template:Date\n 8.10% 16.525 27 Template:Citation\/identifier\n 6.17% 12.574 80 Template:Infobox\/row\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13234-0!canonical and timestamp 20220628175031 and revision id 47734. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory\">https:\/\/www.limswiki.org\/index.php\/Journal:A_roadmap_for_LIMS_at_NIST_Material_Measurement_Laboratory<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","da7b86c02e387ab4edff0524bbe2a563_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d9\/Fig1_Green_NIST221-22.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/83\/Fig2_Green_NIST221-22.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cc\/Fig3_Green_NIST221-22.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6f\/Fig4_Green_NIST221-22.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6d\/Fig5_Green_NIST221-22.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f3\/Fig6_Green_NIST221-22.png"],"da7b86c02e387ab4edff0524bbe2a563_timestamp":1656439831,"97ebdae24d5298692e56e4a9d01fa0cb_type":"article","97ebdae24d5298692e56e4a9d01fa0cb_title":"Design of a data management reference architecture for sustainable agriculture (Giray and Catal 2021)","97ebdae24d5298692e56e4a9d01fa0cb_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture","97ebdae24d5298692e56e4a9d01fa0cb_plaintext":"\n\nJournal:Design of a data management reference architecture for sustainable agricultureFrom LIMSWikiJump to navigationJump to searchFull article title\n \nDesign of a data management reference architecture for sustainable agricultureJournal\n \nSustainabilityAuthor(s)\n \nGiray, G\u00f6rkem; Catal, CagatayAuthor affiliation(s)\n \nIndependent researcher, Qatar UniversityPrimary contact\n \nEmail: gorkemgiray at gmail dot comYear published\n \n2021Volume and issue\n \n13(13)Article #\n \n7309DOI\n \n10.3390\/su13137309ISSN\n \n2071-1050Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2071-1050\/13\/13\/7309\/htmDownload\n \nhttps:\/\/www.mdpi.com\/2071-1050\/13\/13\/7309\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Research method \n4 Problem definition \n5 Solution design and artifact description \n\n5.1 Related reference architecture studies \n5.2 Domain scoping \n5.3 Domain modeling \n5.4 Reference architecture design \n\n\n6 Validation \n\n6.1 Components of the data management reference architecture \n\n\n7 Discussion and caveats \n8 Conclusions and future work \n9 Acknowledgements \n\n9.1 Author contributions \n9.2 Funding \n9.3 Conflicts of interest \n\n\n10 References \n11 Notes \n\n\n\nAbstract \nEffective and efficient data management is crucial for smart farming and precision agriculture. To realize operational efficiency, full automation, and high productivity in agricultural systems, different kinds of data are collected from operational systems using different sensors, stored in different systems, and processed using advanced techniques, such as machine learning and deep learning. Due to the complexity of data management operations, a data management reference architecture is required. While there are different initiatives to design data management reference architectures, a data management reference architecture for sustainable agriculture is missing. In this study, we follow domain scoping, domain modeling, and reference architecture design stages to design the reference architecture for sustainable agriculture. Four case studies were performed to demonstrate the applicability of the reference architecture. This study shows that the proposed data management reference architecture is practical and effective for sustainable agriculture.\nKeywords: sustainability, agriculture, sustainable agriculture, data management, reference architecture, design science research\n\nIntroduction \nThe increase in food demand and its associated large ecological footprint call for action in agricultural production.[1] Inputs and assets should be optimized, and long-term ecological impacts should be assessed for sustainable agriculture. Decision-making processes on optimization and assessment need data on several inputs, outputs, and external factors. To this end, various systems have been developed for data acquisition and management to enable precision agriculture.[1] Precision agriculture refers to the application of technologies and principles for improving crop performance and environmental sustainability.[2] Smart farming extends precision agriculture and enhances decision-making capabilities by using recent technologies for smart sensing, monitoring, analysis, planning, and control.[1] Data to be acquired are enhanced by context, situation, and location awareness.[1] Real-time sensors are utilized to collect various data, and real-time actuators are used to fine-tune production parameters instantly.\nIn the late 2000s, Murakami et al.[3] and Steinberger et al.[4] pointed out a need for data storage and a processing platform for agricultural production. They utilized web services to send and receive data from a central web application. That web application received, stored, and processed data, and it provided the required outputs to its users or any other system. Similarly, S\u00f8rensen et al.[5] listed several data processing use cases to assist farmers\u2019 decision-making processes. More recently, technologies such as the internet of things (IoT) make digital data acquisition, and hence smart farming, possible.[6] In recent years, many studies have been performed in the fields of smart farming and precision agriculture.[7][8][9][10][11][12][13] At the heart of many of those studies is Industry 4.0, which acts as a transformative force on smart farming processes. Industry 4.0-related technologies\u2014namely IoT, big data, edge computing, 3D printing, augmented reality, collaborative robotics, data science, cloud computing, cyber-physical systems, digital twins, cybersecurity, and real-time optimization\u2014are increasingly integrated into different parts of modern agricultural systems.[14]\nTo realize operational efficiency, full automation, and high productivity in these systems, different types of data are collected from operational systems using different sensors, stored in big data systems, and processed using machine learning and deep learning approaches. Traditional data management techniques and systems are not sufficient to deal with this scale of data, and as such, big data infrastructures and systems have been designed and implemented. To manage the complexity of this big data, many different aspects of data must be considered during the design of these systems. Different data management reference architectures have been designed to date.[15][16][17] To the best of our knowledge, none of these studies have focused on sustainable agriculture. There exist several practices for sustainable agriculture that can protect the environment, improve soil fertility, and increase natural resources. It is known that agriculture can affect soil erosion, water quality, human health, and pollination services.[18] As such, sustainable agriculture is crucial to minimize the negative effects of agricultural production. Sustainable agriculture requires an iterative process because each actor in the system has a different responsibility, and the success of this process is highly dependent on the success of each actor.\nThe goal of this study is to present a data management reference architecture for supporting smart farming, sustainable agriculture, and other domains. The study builds on the recent developments in data management and processing, i.e., big data, machine learning, and data lakes. We designed a data management reference architecture for sustainable agriculture and evaluated it using several case studies. Domain scoping, domain modeling, and reference architecture design stages were followed to create the reference architecture. Based on the reference architecture, we can design different application architectures. During the validation stage of this study, using different case studies obtained from the literature, we have shown the applicability of our reference architecture as a novel data management reference architecture for sustainable agriculture.\nThe structure of this paper follows the outline proposed by Gregor & Hevner[19] for design science research. The next section summarizes the research method adopted in this study, followed by the definition and structuring of the problem by analyzing the existing literature. We then present the related reference architecture studies and explain the solution design process and the reference architecture obtained. That is followed by the evaluation of the reference architecture by deriving application architectures from it based on some requirements from the sustainable agriculture domain. The penultimate section discusses the results, and the final section provides conclusions and plans of future work.\n\nResearch method \nThe design science research (DSR) method proposed by Hevner et al.[20] was followed in this study. DSR is a problem-solving paradigm and seeks to create artifacts through which information systems can be effectively and efficiently engineered.[20] These artifacts are designed to interact with a problem context to improve something in that context.[21]\nThe activities and the artifacts span two significant dimensions, i.e., problem-solution and theory-practice dimensions.[22] Figure 1 shows the research method used in this study. The first step was the identification of some problem instances occurring in practice and sharing similar aspects. These problem instances were analyzed, and a problem statement was formed using theoretical concepts from the literature. A conceptual solution, i.e., an artifact or artifacts, was designed by following a systematic approach. Domain analysis was used to derive and represent domain knowledge to be used for solution design. Domain analysis involved domain scoping and domain modeling activities.[23] Domain scoping refers to the identification of relevant knowledge sources to derive the key concepts of the solution.[24] To this end, several searches were conducted on the Scopus database using different search strings. Domain modeling aims at unifying and representing the domain knowledge obtained from relevant sources. The feature model was used to represent the output of domain modeling.[25] A reference architecture was designed as a conceptual solution.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 The research method used in this study, which involves the main steps of design science research (DSR), i.e., problem definition, solution design, and validation. The iterative nature of the research method was neglected for the sake of simplicity.\n\n\n\nTo evaluate the reference architecture, requirements were specified using recent literature on sustainable agriculture.[26][27][28][29][30] Based on these requirements, a concrete application architecture was derived using the reference architecture.\nIn accordance with DSR and the research method described here, the following sections describe problem definition, design of a solution, and the evaluation of the solution.\n\nProblem definition \nThis study was motivated by three use cases involving different data management requirements to support sustainable agriculture. The following three use cases were used for understanding and conceptualizing the problem:\n\nCase 1: Satellite images (e.g., Sentinel-2 data) can be obtained from a data provider. These images can be processed to derive plant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content during the growing season.[31] Afterward, the current growth status and development of cultivated crops at each location in the field can be deduced.[32] This information can be used for site-specific plant protection and fertilization measures[33], which support sustainable agriculture.\nCase 2: Harvested crop volume can be quantified and recorded in real time using numerous sensors.[34] Various parameters such as \"quantity per hectare\" and \"flow\" can be calculated, and crop productivity maps can be built.[34] Farmers can use these maps to optimize inputs such as fertilizers, pesticides, and seeding rates, resulting in an increase in yields.[35]\nCase 3: Machinery process data such as speed, angle, pressure, and flow rate can be obtained through sensors in tractors and equipment.[4] Machine, worker, field, and time slot data can be stored, and basic statistics like minimum, maximum, and standard deviation can be computed.[4] As a result, automated documentation of the production process and site-specific work can be attained.[4]\nTable 1 summarizes the above-mentioned cases from a data management perspective. Similar to many cases in various domains, at a high level, digital data are produced and fed to a software system to be processed and stored. Such a system can be designated a data management platform and produce outputs that can lead to better business outcomes. As per the first case, satellite images can be processed via computer vision algorithms to drive plant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content, which can in turn be used to track the current growth status of cultivated crops and support decision-making activities.\n\n\n\n\n\n\n\nTable 1. A summary of the three cases presented above from a data management perspective\n\n\n\nData input\n\nData processing\n\nData output\n\nOutcome\n\n\nSatellite images\n\nDerive plant parameters via computer vision algorithms\n\nPlant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content\n\nTrack current growth status and development of cultivated crop at each location\n\n\nHarvested crops volume via sensors\n\nBuild crop productivity maps\n\nVarious parameters such as \"quantity per hectare\" and \"flow\" on the map\n\nUse such maps to optimize inputs such as fertilizers, pesticides, and seeding rates in order to increase yields\n\n\nMachinery process data via sensors\n\nCompute statistics\n\nMachine, worker, field, and time slot data, along with basic statistics such as minimum, maximum, and standard deviation\n\nAttain automated documentation of the production process and site-specific work\n\n\n\nSolution design and artifact description \nThis section starts with a summary of related reference architecture studies and then presents the three steps of the solution design phase, namely domain scoping, domain modeling, and reference architecture design.\n\nRelated reference architecture studies \nBefore presenting our reference architecture, we discuss the available reference architectures in the literature. First, while Nikkil\u00e4 et al.[36] and Kaloxylos et al.[37] presented architectural aspects of Farm Management Information Systems (FMISs), they did not propose a reference architecture, which limited the utility of their research for our purposes. However, Tummers et al.[17] designed a reference architecture for FMISs. They first identified the stakeholders and their concerns. Afterward, a feature model for FMISs was created. The reference architecture was designed and represented via context and decomposition views. Three case studies were performed to show the applicability of the proposed reference architecture.\nK\u00f6ksal & Tekinerdogan[6] proposed a reference architecture for IoT-based FMISs. They proposed an architecture design method and showed that the approach is practical and effective. Their architecture included data acquisition, data processing, data visualization, system management, and external services. Each main feature consisted of several sub-features. For instance, the data processing feature involved sub-features like image\/video processing, data mining, decision support, and data logging. They used decomposition, layered, and deployment views to document the reference architecture. For deriving a concrete FMIS architecture, their reference architecture can thus be used.\nKruize et al.[38] proposed a reference architecture for farm software ecosystems. Farm software ecosystems aim to fulfill the needs of several actors in the smart farming domain. In that respect, their scope is much wider compared to FMISs. The farm software ecosystem reference architecture mainly focused on the problem of bringing various software and hardware components together to form a platform for multiple actors.\nTo the best of our knowledge, there is no other study that presents a data management reference architecture for sustainable agriculture. Although some of the previous studies mention several data-related components, a complete architectural view of managing data for sustainable agriculture was missing. As such, our reference architecture study aims to fill this research gap.\n\r\n\n\nDomain scoping \nThe Scopus database was used as the knowledge source for domain scoping. To identify the search keywords, it was crucial to understand the recent factors driving reference architectures for data management. The concept of \"big data\" has emerged to highlight challenges of data management, including volume, velocity, and variety.[39] Machine learning is another hot research topic, which tries to acquire knowledge by extracting patterns from raw data[40][41] and solve problems using this knowledge. The concept of a \"data lake\" is another to have recently emerged, which addresses the shortcomings of data warehouses. A data lake can be defined as a data management platform that allows the storing of both structured and unstructured data, unlike data warehouses that handle only structured data. This type of platform is designed to enable big data processing, real time analytics, and machine learning. \nBased on these recent trends, four search strings were used to form the initial paper pool. The phrase \u201creference architecture\u201d was combined with four phrases representing the recent trends in data processing for sustainable agriculture (i.e., \"data management,\" \"big data,\" \"machine learning,\" and \"data lake\"). The search keywords were kept general to have a high recall and relatively low precision. Although this required more effort from the authors, obtaining a broader initial set of papers decreased the possibility of missing relevant studies.\nThe database search on Scopus was conducted in February 2021. No criterion was set for the publication date. A total number of 270 papers was obtained for the pool of candidate papers. All the results were combined in an Excel sheet, which included useful information about the papers such as title, abstract, keywords, and publication date, which are used in further steps.\nTo identify the relevant papers for designing a reference architecture, we applied the exclusion criteria to the papers obtained from Scopus. Those papers that were duplicated, not written in English, or lacking full text were filtered out. The papers involving a reference architecture to process data in any business domain were included. Seven papers included a reference architecture for data processing, along with the essential components.\nThe data extraction phase followed the selection of relevant papers. The components of the data processing architecture listed in the papers were extracted and recorded in an Excel sheet. These components were unified by reading the definitions presented in the papers. Table 2 shows the unified list of the components and the source papers where each component was identified.\n\n\n\n\n\n\n\nTable 2. The unified list of components identified in the literature\n\n\nComponent\n\nNadal et al.[15]\n\nDayal et al.[42]\n\nSuriarachchi and Plale[43]\n\nRao et al.[44]\n\nSang et al.[45]\n\nArass et al.[46]\n\nP\u00e4\u00e4kk\u00f6nen and Pakkala[47]\n\n\nIngestion\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\nInformation extraction\n\n\n\n\n\n\n\n\n\n\n\n\n\n\u2713\n\n\nData quality management\n\n\n\n\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\nIntegration\n\n\n\n\u2713\n\n\n\n\u2713\n\n\n\n\u2713\n\n\u2713\n\n\nAnalysis\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\nStorage\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\u2713\n\n\nSecurity\/Privacy\n\n\n\n\n\n\n\n\u2713\n\n\n\n\u2713\n\n\n\n\nMetadata management\n\n\u2713\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nReplication\/Archiving\n\n\n\n\n\n\n\n\n\n\u2713\n\n\u2713\n\n\u2713\n\n\n\nAll the papers address three main components that deal with collecting data from various sources (i.e., acquisition), processing data to provide some value to data consumers (i.e., analysis), and addressing persist data (i.e., storage). P\u00e4\u00e4kk\u00f6nen and Pakkala[47] identified information extraction as a component to extract structured data from unstructured and semi-structured data, such as email or images. Data quality management is another vital component to handle data quality problems. Data received from various sources should be integrated for further analysis. Security and privacy components are used to protect data from unauthorized data and for proper handling of personal data. Metadata management refers to the creation and storage of metadata to document the meaning of data. The replication component ensures redundant storage of data sources to provide better data availability in case of technical problems, and the archiving component is responsible for storing cold data for future possible needs.\n\nDomain modeling \nFeature modeling is one of the approaches to represent domain knowledge in a reusable format.[24][25] Figure 2 shows the feature model, which is derived from the unified list of components presented in Table 2. A feature diagram can include mandatory and optional features. Three components identified by all papers are treated as mandatory features. The remaining features are optional and can be used depending on business requirements.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 The feature model for data management in the sustainable agriculture domain\n\n\n\nData need to be onboarded to a data platform for further processing and storage, a process referred to as the ETL (extract, transform, and load) process in traditional data warehousing architectures.[48] Such architectures possess a pre-defined data schema and data are loaded based on this schema. Data ingestion refers to the process of transferring data from providers to a platform for further processing.[49] The umbrella term for such processes is \"data acquisition.\" Data can be acquired in batches at regular intervals or in real time (or in near real time) as streams. A component acquiring data streams should be able to handle data with high velocity.[50]\nInformation extraction is intended for obtaining useful information from unstructured and semi-structured data.[51] Unstructured and semi-structured data may include natural language text, image, audio, and video. Several tasks performed under information extraction include classification, named entity recognition, relationship extraction, and structure extraction.[16][48][52] Named entity recognition (i.e., named entity identification) aims at identifying and classifying named entities in unstructured or semi-structured texts into predefined categories such as a person, organization, or location. For instance, Gangadharan and Gupta[53] extracted names of crops, soil types, crop diseases, pathogen names, and fertilizers from documents on agriculture. Relation extraction is the task of detecting and classifying predefined types of associations among recognized entities.[52] For example, relationships among crop diseases and locations can be extracted. The sub-features for information extraction can be expanded depending on domain-specific requirements.\nData quality management refers to handling data quality problems that may arise due to several reasons[48], including missing, incorrect, unusable, or redundant data.[54] To address these main data quality problems, missing data can be completed, incorrect data can be corrected, unusable data can be transformed, and redundant data can be cleaned.\nIn general, data management platforms acquire data from multiple sources that usually involve differences in data models, schemas, and data semantics.[55] Data integration aims at combining heterogeneous data and providing a unified view of these data.[56] One technique for data integration is schema mapping, which refers to conveying the data schemas of multiple data sources into one global common schema.[57]\nData are analyzed to obtain some value from them. Results of analysis may provide insights to users and constitute some intermediate output for further processing.[48] Stream analysis encompasses the timely processing of flowing data and generates required outputs. For instance, an environmental monitoring system can process raw data coming from sensor networks to identify critical cases.[58] On the contrary, batch analysis is conducted on static datasets.[59] Data mining and machine learning, including deep learning algorithms, may be utilized to produce deeper analyses.[60][61]\nStorage is a feature supporting other features and refers to the temporary and persistent storage of data. To manage the increased volume, velocity, and variety of data[39], different types of data stores are released. Therefore, the storage feature involves various database management systems (e.g., Microsoft SQL Server, Oracle, PostgreSQL, or MongoDB) implementing different data models such as relational or nonrelational (or NoSQL).\nThe security and privacy feature addresses authentication and authorization, access tracking, and data anonymization.[48] Several standards, guidelines, and mechanisms can affect the realization of this feature, such as data encryption standards and mechanisms, access guidelines, and remote access standards.[62]\nMetadata management is related to planning, implementation, and control activities to enable access to metadata.[62] This feature mainly involves capabilities related to collecting and integrating metadata from diverse sources and providing a standard way to access these metadata.[62]\nThe replication feature manages the storage of the same data on multiple storage devices.[62] While having replicated instances of data support remain highly available, data consistency may become an issue to deal with. The archiving feature addresses the movement of infrequently used data onto media with a lower retrieval performance.[62]\n\nReference architecture design \nBased on the abstraction derived from the three cases presented prior, Figure 3 shows the context diagram of a data management system. The context diagram shows the overall purpose of the system and its interfaces with the external environment.[63] At a very high level, some data providers send data to a data management system. These may be humans entering data through a graphical user interface (GUI) or external systems providing input data to be processed. Data obtained from data providers are stored, processed, and served to data consumers based on their requirements.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 3 The context diagram for a data management system to conceptualize the cases identified in the sustainable agriculture domain\n\n\n\nFigure 4 shows the decomposition view of the data management reference architecture proposed for data processing.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 4 Decomposition view of the data management reference architecture\n\n\n\nAcquisition components are responsible for onboarding data to the data management platform for further processing. Useful information such as named entities and relations can be extracted from the acquired data. Quality problems can be resolved by completing, correcting, transforming, and cleaning the acquired data to obtain more accurate results from analyses. The data obtained from various sources need to be integrated to end up with better and richer insights. Various components can be used to analyze data to support decision-making. The storage component handles different modes of storing data. The security and privacy component is needed to protect data from unauthorized access. Data on the description of acquired data, are handled by the metadata management component. Replication may be needed for high availability. An archive component is usually required to manage the process of archiving unused historical data.\nThe next section presents how an application architecture can be derived from the reference architecture based on the requirements in sustainable agriculture.\n\nValidation \nTo evaluate the reference architecture, a set of requirements was extracted from recent papers on sustainable agriculture.[26][27][28][29][30] The high-level requirements address issues on crop yield prediction[27], irrigation management[28], real time variable-rate fertilization[30], and exotic animal infectious diseases monitoring.[26] These diverse high-level requirements address various data management aspects in sustainable architecture.\nSustainability is a long-term, high-level goal involving several aspects and sub-goals. Generally, there is a gap between software requirements and sustainability goals. While software requirements tend to be more tangible, sustainability goals tend to be more intangible. Therefore, a tangible decomposition of sustainability and the ability to map it to concrete software requirements are required to monitor the achievement of sustainability goals.[64]\nPenzenstadler and Femmer proposed a reference model to show the dimensions of sustainability (i.e., individual, social, economic, environmental, and technical) and map them to high-level software requirements.[65] Figure 5 shows the high-level software requirements obtained from the literature and how they are mapped in the sustainability model proposed by Penzenstadler & Femmer.[64][65]\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 5 The requirements obtained from the literature on sustainable agriculture. The requirements are mapped to sustainability dimensions using the sustainability model proposed by Penzenstadler & Femmer.[64][65]\n\n\n\nThe goal of sustainability has several dimensions such as economic and environmental. There are moral and natural goods that are perceived as an expression of a specific dimension.[64] Long-term profit and healthy environment are two examples of values contributing to economic and environmental dimensions, respectively. Indicators are qualitative or quantitative metrics that express a specific degree or score regarding a value.[64] Consumption amounts of resources, water, agricultural pesticide, and weedicide are examples of indicators. Activities are measures taken to contribute to values[64] and can have different levels of granularities, which are associated with each other. Lower-level activities such as crop phenotypic monitoring, shown in Figure 5, can contribute to a higher-level activity such as variable-rate fertilization management. Lower-level leaf activities, such as predicting crop yield, shown in Figure 5, can be treated as the high-level software requirements (e.g., high-level use cases or epics) against which one or more system features are developed. \n\nComponents of the data management reference architecture \nThe components of the data management reference architecture used to realize each high-level software requirement are described as follows.\nCrop yield prediction is an essential task for growers and farmers to decide on what and when to grow.[66] However, it is extremely challenging due to numerous complex factors.[67] To overcome this challenge, researchers started to use machine learning algorithms to predict crop yield based on various input variables.[27] Mohsen et al.[27] suggest using weather, soil, plant population, and planting process data. These historical data are extracted from various sources such as surveys[68][69] and stored (acquisition: batch). Unusable data such as rows with missing values are removed (cleaning) and some of the values are normalized (transformation). The data obtained from different sources are combined (integration). Several machine learning models are built through experimentation (machine learning: model development). One of the obtained machine learning models that exhibits a satisfactory performance is deployed (machine learning: model deployment). The performance of the deployed model should be monitored for a possible performance degradation.[70][71] When the performance does not meet expectations, a new machine learning model should be trained and deployed.\nWireless sensor networks using IoT technologies can be utilized for irrigation management.[28] Sensors can measure real-time environmental data such as soil moisture in predefined periods and send these data to the data storage over the internet (acquisition: stream).[72] A weather forecast can be obtained from a data provider (acquisition: batch) to manage irrigation by considering the conditions that affect the irrigation process, such as rain or strong winds.[72] The measurement and forecast data are combined (integration) by considering time dimension, i.e., data obtained from different sources must fit into the same temporal window.[73] Based on the combined data, irrigation decisions can be drawn based on predefined rules[28] or a prediction model (machine learning).[73] The data on this decision can be sent to an actuator to control irrigation.\nCrop phenotypic information can be used to enable real-time variable-rate fertilization.[74][75] The predictors of phenotypic information involve crop three-dimensional size, biomass, and vegetation index, as well as other indicators.[30] These data can be acquired using aviation-based[76][77] and ground-based[78] approaches. Data obtained through sensors mounted to unmanned aerial vehicles (UAVs)[79], or ground-based phenotypic platforms with a series of sensors and a GPS[80][81] can be ingested into a data management platform (acquisition: stream). To obtain accurate predictions of crop phenotypic information, it is necessary to combine multi-source sensor data such as color, depth, and spectral data with environmental and crop physiology data[30] (integration) and develop machine learning models (machine learning: model development). Those models need to be deployed (machine learning: model deployment) and used for real time variable-rate fertilization. As a result, improvements in the level of fertilizer utilization efficiency enable environmental and economic sustainability benefits by maximizing crop output and minimizing fertilizer input.[30]\nExotic animal infectious diseases are considerable threats to global health security and economic stability.[26][82] One of the vital sources for detecting signals of disease is online news platforms. Data can be collected from platforms such as Google News (acquisition: batch) and stored for further analysis (storage). The named entities such as location, date, disease, hosts, and number of cases can be extracted using Natural Language Processing (NLP) techniques[26] (information extraction: named entity recognition). In addition, predefined types of relationships among the recognized entities can be detected (information extraction: relation extraction). As an example, the sentence \u201c12 pigs have been infected by African swine fever in Poland\u201d can provide the following entities[26]: number of cases = 12; host = pig; disease = African swine fever; location = Poland.\nTable 3 shows the functionalities extracted from the three problem cases (PC) and the four validation cases (VC). Figure 6 presents how these functionalities are mapped to the components of the reference architecture proposed in this study.\n\n\n\n\n\n\n\nTable 3. The functionalities in the problem cases (PC) and validation cases (VC)\n\n\nCase\n\n#\n\nFunctionality\n\n\nPC1\n\nPC1.1\n\nObtain and store satellite images\n\n\nPC1.2\n\nProcess images to derive plant parameters, such as leaf area index (LAI), biomass, and chlorophyll content\n\n\nPC1.3\n\nDeduce the current growth status and development of cultivated crops at each location in the field\n\n\nPC2\n\nPC2.1\n\nObtain and store harvested crop volume in real time using sensors\n\n\nPC2.2\n\nCalculate parameters such as quantity per hectare and flow and build crop productivity maps\n\n\nPC3\n\nPC3.1\n\nObtain and store machinery process data such as speed, angle, pressure, and flow rate through sensors in tractors\n\n\nPC3.2\n\nCompute basic figures such as minimum, maximum, standard deviation and produce documentation of the production process\n\n\nVC1\n\nVC1.1\n\nAcquire and store historical data on weather, soil, plant population, and planting process\n\n\nVC1.2\n\nRemove unusable data and normalize the remaining data\n\n\nVC1.3\n\nCombine data on weather, soil, plant population, and planting process\n\n\nVC1.4\n\nBuild machine learning models and deploy the one that best satisfies requirements\n\n\nVC2\n\nVC2.1\n\nMeasure and store real time environmental data\n\n\nVC2.2\n\nObtain and store weather forecast\n\n\nVC2.3\n\nCombine measurement and forecast data\n\n\nVC2.4\n\nDecide on irrigation based on predefined rules or a prediction model\n\n\nVC3\n\nVC3.1\n\nObtain and store data, such as crop three-dimensional size, biomass, and vegetation index\n\n\nVC3.2\n\nCombine multisource sensor data, such as color, depth, and spectral data, with environmental and crop physiology data\n\n\nVC3.3\n\nBuild machine learning models and deploy the one that best satisfies requirements for real-time variable-rate fertilization\n\n\nVC4\n\nVC4.1\n\nObtain and store news from online news platforms\n\n\nVC4.2\n\nExtract named entities, such as location, date, disease, hosts, and number of cases\n\n\nVC4.3\n\nDetect predefined types of relationships among recognized entities\n\n\n\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 6 Mapping functionalities to the reference architecture components\n\n\n\nDiscussion and caveats \nThis research presents a novel data management reference architecture for sustainable agriculture using well-established architecture modeling techniques. As such, this study can pave the way for similar studies on data management reference architectures. The reference architecture was designed based on domain analysis. Other data management application architectures can be developed based on this reference architecture using variant features specified in this study.\nThe features shown in this study were obtained from peer-reviewed papers in the Scopus database. The inclusion of other databases may reveal unidentified features and the presented reference architecture may be extended accordingly. Since precision agriculture and smart farming are still evolving, new features can be integrated in the future, and data management reference architecture can be adapted. Different tools, techniques, and systems are currently developed by practitioners and researchers in smart farming, and therefore we expect to see new papers in databases that might bring new functionalities and features to the presented reference architecture. However, the presented methodology and the overall reference architecture can be easily changed to reflect the recent changes in smart farming.\nThe reference architecture is used to derive application architectures based on a multi-case study approach. For the multi-case study, there is a threat of misinterpretation of applied concepts. Although we discussed the concepts carefully and iteratively, there is a possibility that several concepts may have been interpreted differently compared to the concepts presented in the selected studies. The generalization of the presented findings must be taken with caution because different case studies may require new functionalities. While we can identify many different application scenarios in smart farming, the scenarios share some features from a data management perspective. Therefore, four case studies were shown to demonstrate the applicability of the proposed reference architecture. Other researchers can also evaluate the applicability of this architecture using different case studies in smart farming and create an application architecture for their uses.\nIt was shown that reference architecture design is useful for the agri-food domain. This study focused on sustainability; however, it can be extended to a larger context by covering other critical aspects of agriculture. For sustainable agriculture, the presented features are beneficial when designing new systems for agricultural production. Further research is needed to evaluate the applicability of the data management reference architecture for different application domains. We expect that increasingly more researchers will focus on sustainability in agriculture in the near future and develop novel models to fully address sustainability from several aspects. The advancement in machine learning and particularly deep learning techniques can also contribute to the development of novel models addressing sustainability.\n\nConclusions and future work \nIn this study, a data management reference architecture for sustainable agriculture was proposed and evaluated using different case studies. To the best of our knowledge, this is the first study that focuses on sustainability within the context of data management reference architecture. The design science research (DSR) method was applied while designing the reference architecture. Domain scoping, domain modeling, and reference architecture design stages were followed for solution design. Domain scoping was performed based on relevant papers, the domain model was represented as a feature model, and the reference architecture was built at the end of the reference architecture design stage. Three case studies were investigated from different perspectives, and the applicability of the data management reference architecture was evaluated. We consider that this research can improve the research in sustainable agriculture with respect to data management and pave the research for designing smart systems for smart farming and precision agriculture.\nAs future work, we plan to extend this study with new case studies and evaluate the applicability of the presented reference architecture for different scenarios. Another planned study involves the mapping of the reference architecture to the components of the farm management information systems and platforms used in the industry. This mapping can help us identify the possible missing components in the reference architecture. In addition, we can identify enhancement opportunities for the systems and platforms used in the industry.\n\nAcknowledgements \nAuthor contributions \nConceptualization, G.G. and C.C.; methodology, G.G.; investigation, G.G.; data curation, G.G.; validation, G.G. and C.C.; writing\u2014original draft preparation, G.G.; writing\u2014review and editing, G.G. and C.C. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis research received no external funding.\n\nConflicts of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 1.0 1.1 1.2 1.3 Wolfert, Sjaak; Goense, Daan; Sorensen, Claus Aage Gron (1 April 2014). \"A Future Internet Collaboration Platform for Safe and Healthy Food from Farm to Fork\". 2014 Annual SRII Global Conference (San Jose, CA, USA: IEEE): 266\u2013273. doi:10.1109\/SRII.2014.47. 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Computers in Industry 124: 103343. doi:10.1016\/j.compind.2020.103343. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361520305777 .   \n \n\n\u2191 25.0 25.1 Tekinerdogan, Bedir; \u00d6zt\u00fcrk, Karahan (2013), Mahmood, Zaigham; Saeed, Saqib, eds., \"Feature-Driven Design of SaaS Architectures\", Software Engineering Frameworks for the Cloud Computing Paradigm (London: Springer London): 189\u2013212, doi:10.1007\/978-1-4471-5031-2_9, ISBN 978-1-4471-5030-5, http:\/\/link.springer.com\/10.1007\/978-1-4471-5031-2_9   \n \n\n\u2191 26.0 26.1 26.2 26.3 26.4 26.5 Arsevska, Elena; Valentin, Sarah; Rabatel, Julien; de Go\u00ebr de Herv\u00e9, Jocelyn; Falala, Sylvain; Lancelot, Renaud; Roche, Mathieu (3 August 2018). D\u00f3rea, Fernanda C.. ed. \"Web monitoring of emerging animal infectious diseases integrated in the French Animal Health Epidemic Intelligence System\" (in en). PLOS ONE 13 (8): e0199960. doi:10.1371\/journal.pone.0199960. ISSN 1932-6203. PMC PMC6075742. PMID 30074992. https:\/\/dx.plos.org\/10.1371\/journal.pone.0199960 .   \n \n\n\u2191 27.0 27.1 27.2 27.3 27.4 Shahhosseini, Mohsen; Hu, Guiping; Huber, Isaiah; Archontoulis, Sotirios V. (1 December 2021). \"Coupling machine learning and crop modeling improves crop yield prediction in the US Corn Belt\" (in en). Scientific Reports 11 (1): 1606. doi:10.1038\/s41598-020-80820-1. ISSN 2045-2322. PMC PMC7810832. PMID 33452349. http:\/\/www.nature.com\/articles\/s41598-020-80820-1 .   \n \n\n\u2191 28.0 28.1 28.2 28.3 28.4 Sanjeevi, P.; Prasanna, S.; Siva Kumar, B.; Gunasekaran, G.; Alagiri, I.; Vijay Anand, R. (1 December 2020). \"Precision agriculture and farming using Internet of Things based on wireless sensor network\" (in en). Transactions on Emerging Telecommunications Technologies 31 (12): e3978. doi:10.1002\/ett.3978. ISSN 2161-3915. https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ett.3978 .   \n \n\n\u2191 29.0 29.1 Sharma, Rohit; Kamble, Sachin S.; Gunasekaran, Angappa; Kumar, Vikas; Kumar, Anil (1 July 2020). \"A systematic literature review on machine learning applications for sustainable agriculture supply chain performance\" (in en). Computers & Operations Research 119: 104926. doi:10.1016\/j.cor.2020.104926. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0305054820300435 .   \n \n\n\u2191 30.0 30.1 30.2 30.3 30.4 30.5 Shi, Yinyan; Zhu, Yang; Wang, Xiaochan; Sun, Xin; Ding, Yangfen; Cao, Wexing; Hu, Zhichao (1 December 2020). \"Progress and development on biological information of crop phenotype research applied to real-time variable-rate fertilization\" (in en). Plant Methods 16 (1): 11. doi:10.1186\/s13007-020-0559-9. ISSN 1746-4811. PMC PMC6998365. PMID 32042303. https:\/\/plantmethods.biomedcentral.com\/articles\/10.1186\/s13007-020-0559-9 .   \n \n\n\u2191 Clevers, Jan; Kooistra, Lammert; van den Brande, Marnix (25 April 2017). \"Using Sentinel-2 Data for Retrieving LAI and Leaf and Canopy Chlorophyll Content of a Potato Crop\" (in en). Remote Sensing 9 (5): 405. doi:10.3390\/rs9050405. ISSN 2072-4292. http:\/\/www.mdpi.com\/2072-4292\/9\/5\/405 .   \n \n\n\u2191 Bach, H.; Mauser, W.; Angermair, W. et al. (2010). \"An integrative approach of using satellite-based information for precision farming: TalkingFields\". Proceedings of the 61st International Astronautical Congress. http:\/\/iafastro.directory\/iac\/archive\/browse\/IAC-10\/B5\/1\/6894\/ .   \n \n\n\u2191 Bach, Heike; Mauser, Wolfram (2018), Mathieu, Pierre-Philippe; Aubrecht, Christoph, eds., \"Sustainable Agriculture and Smart Farming\" (in en), Earth Observation Open Science and Innovation (Cham: Springer International Publishing): 261\u2013269, doi:10.1007\/978-3-319-65633-5_12, ISBN 978-3-319-65632-8, http:\/\/link.springer.com\/10.1007\/978-3-319-65633-5_12   \n \n\n\u2191 34.0 34.1 Burlacu, George; Costa, Ruben; Sarraipa, Joao; Jardim-Golcalves, Ricardo; Popescu, Dan (2014), Camarinha-Matos, Luis M.; Barrento, Nuno S.; Mendon\u00e7a, Ricardo, eds., \"A Conceptual Model of Farm Management Information System for Decision Support\", Technological Innovation for Collective Awareness Systems (Berlin, Heidelberg: Springer Berlin Heidelberg) 423: 47\u201354, doi:10.1007\/978-3-642-54734-8_6, ISBN 978-3-642-54733-1, http:\/\/link.springer.com\/10.1007\/978-3-642-54734-8_6   \n \n\n\u2191 Srivastava, S. (2002). \"Space inputs for precision agriculture: scope for prototype experiments in the diverse Indian agro-ecosystems\". Proceedings of the Map Asia 2002. https:\/\/www.geospatialworld.net\/article\/space-inputs-for-precision-agriculture-scope-for-proto-type-experiments-in-the-diverse-indian-agro-ecosystems\/ .   \n \n\n\u2191 Nikkil\u00e4, Raimo; Seilonen, Ilkka; Koskinen, Kari (1 March 2010). \"Software architecture for farm management information systems in precision agriculture\" (in en). Computers and Electronics in Agriculture 70 (2): 328\u2013336. doi:10.1016\/j.compag.2009.08.013. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169909001859 .   \n \n\n\u2191 Kaloxylos, Alexandros; Groumas, Aggelos; Sarris, Vassilis; Katsikas, Lampros; Magdalinos, Panagis; Antoniou, Eleni; Politopoulou, Zoi; Wolfert, Sjaak et al. (1 January 2014). \"A cloud-based Farm Management System: Architecture and implementation\" (in en). 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ISBN 978-0-262-03561-3.   \n \n\n\u2191 Ashmore, Rob; Calinescu, Radu; Paterson, Colin (30 June 2022). \"Assuring the Machine Learning Lifecycle: Desiderata, Methods, and Challenges\" (in en). ACM Computing Surveys 54 (5): 1\u201339. doi:10.1145\/3453444. ISSN 0360-0300. https:\/\/dl.acm.org\/doi\/10.1145\/3453444 .   \n \n\n\u2191 Dayal, U.; Akatsu, M.; Gupta, C. et al. (2014). \"Expanding Global Big Data Solutions with Innovative Analytics\". Hitachi Review 63 (6): 333\u201339. https:\/\/www.hitachi.com\/rev\/archive\/2014\/r2014_06.html .   \n \n\n\u2191 Suriarachchi, Isuru; Plale, Beth (1 October 2016). \"Crossing analytics systems: A case for integrated provenance in data lakes\". 2016 IEEE 12th International Conference on e-Science (e-Science) (Baltimore, MD, USA: IEEE): 349\u2013354. doi:10.1109\/eScience.2016.7870919. 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(2007), Krogstie, John; Opdahl, Andreas Lothe; Brinkkemper, Sjaak, eds., \"Data Integration \u2014 Problems, Approaches, and Perspectives\" (in en), Conceptual Modelling in Information Systems Engineering (Berlin, Heidelberg: Springer Berlin Heidelberg): 39\u201358, doi:10.1007\/978-3-540-72677-7_3, ISBN 978-3-540-72676-0, http:\/\/link.springer.com\/10.1007\/978-3-540-72677-7_3   \n \n\n\u2191 Lenzerini, Maurizio (2002). \"Data integration: a theoretical perspective\" (in en). Proceedings of the twenty-first ACM SIGMOD-SIGACT-SIGART symposium on Principles of database systems - PODS '02 (Madison, Wisconsin: ACM Press): 233. doi:10.1145\/543613.543644. ISBN 978-1-58113-507-7. http:\/\/portal.acm.org\/citation.cfm?doid=543613.543644 .   \n \n\n\u2191 Batini, C.; Lenzerini, M.; Navathe, S. B. (11 December 1986). \"A comparative analysis of methodologies for database schema integration\" (in en). ACM Computing Surveys 18 (4): 323\u2013364. doi:10.1145\/27633.27634. 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PMID 23447014. http:\/\/www.mdpi.com\/1424-8220\/13\/3\/2830 .   \n \n\n\u2191 Sharma, L.K.; Bu, H.; Franzen, D.W.; Denton, A. (1 June 2016). \"Use of corn height measured with an acoustic sensor improves yield estimation with ground based active optical sensors\" (in en). Computers and Electronics in Agriculture 124: 254\u2013262. doi:10.1016\/j.compag.2016.04.016. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301399 .   \n \n\n\u2191 Arsevska, Elena; Roche, Mathieu; Hendrikx, Pascal; Chavernac, David; Falala, Sylvain; Lancelot, Renaud; Dufour, Barbara (1 April 2016). \"Identification of terms for detecting early signals of emerging infectious disease outbreaks on the web\" (in en). Computers and Electronics in Agriculture 123: 104\u2013115. doi:10.1016\/j.compag.2016.02.010. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916300473 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. The original citation five for S\u00f8rensen et al. had a dead URL; an alternate source was found with the same information and used for this version.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\">https:\/\/www.limswiki.org\/index.php\/Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on agricultureLIMSwiki journal articles on data management and sharingNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 9 June 2022, at 23:53.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 159 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","97ebdae24d5298692e56e4a9d01fa0cb_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Design_of_a_data_management_reference_architecture_for_sustainable_agriculture rootpage-Journal_Design_of_a_data_management_reference_architecture_for_sustainable_agriculture skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Design of a data management reference architecture for sustainable agriculture<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Effective and efficient <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">data management<\/a> is crucial for smart farming and precision agriculture. To realize operational efficiency, full automation, and high productivity in agricultural systems, different kinds of data are collected from operational systems using different sensors, stored in different systems, and processed using advanced techniques, such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> and deep learning. Due to the complexity of data management operations, a data management <a href=\"https:\/\/www.limswiki.org\/index.php\/Reference_architecture\" title=\"Reference architecture\" class=\"wiki-link\" data-key=\"abd6aa65d05f0b4151934d7eaaf5d72e\">reference architecture<\/a> is required. While there are different initiatives to design data management reference architectures, a data management reference architecture for sustainable agriculture is missing. In this study, we follow domain scoping, domain modeling, and reference architecture design stages to design the reference architecture for sustainable agriculture. Four case studies were performed to demonstrate the applicability of the reference architecture. This study shows that the proposed data management reference architecture is practical and effective for sustainable agriculture.\n<\/p><p><b>Keywords<\/b>: sustainability, agriculture, sustainable agriculture, data management, reference architecture, design science research\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>The increase in food demand and its associated large ecological footprint call for action in agricultural production.<sup id=\"rdp-ebb-cite_ref-:0_1-0\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> Inputs and assets should be optimized, and long-term ecological impacts should be assessed for sustainable agriculture. Decision-making processes on optimization and assessment need data on several inputs, outputs, and external factors. To this end, various systems have been developed for <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">data acquisition and management<\/a> to enable precision agriculture.<sup id=\"rdp-ebb-cite_ref-:0_1-1\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> Precision agriculture refers to the application of technologies and principles for improving crop performance and environmental sustainability.<sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup> Smart farming extends precision agriculture and enhances decision-making capabilities by using recent technologies for smart sensing, monitoring, analysis, planning, and control.<sup id=\"rdp-ebb-cite_ref-:0_1-2\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> Data to be acquired are enhanced by context, situation, and location awareness.<sup id=\"rdp-ebb-cite_ref-:0_1-3\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> Real-time sensors are utilized to collect various data, and real-time actuators are used to fine-tune production parameters instantly.\n<\/p><p>In the late 2000s, Murakami <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup> and Steinberger <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:1_4-0\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> pointed out a need for data storage and a processing platform for agricultural production. They utilized web services to send and receive data from a central web application. That web application received, stored, and processed data, and it provided the required outputs to its users or any other system. Similarly, S\u00f8rensen <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> listed several data processing use cases to assist farmers\u2019 decision-making processes. More recently, technologies such as the <a href=\"https:\/\/www.limswiki.org\/index.php\/Internet_of_things\" title=\"Internet of things\" class=\"wiki-link\" data-key=\"13e0b826fa1770fe4bea72e3cb942f0f\">internet of things<\/a> (IoT) make digital data acquisition, and hence smart farming, possible.<sup id=\"rdp-ebb-cite_ref-:2_6-0\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> In recent years, many studies have been performed in the fields of smart farming and precision agriculture.<sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup> At the heart of many of those studies is Industry 4.0, which acts as a transformative force on smart farming processes. Industry 4.0-related technologies\u2014namely IoT, big data, edge computing, 3D printing, augmented reality, collaborative robotics, data science, <a href=\"https:\/\/www.limswiki.org\/index.php\/Cloud_computing\" title=\"Cloud computing\" class=\"wiki-link\" data-key=\"fcfe5882eaa018d920cedb88398b604f\">cloud computing<\/a>, cyber-physical systems, digital twins, <a href=\"https:\/\/www.limswiki.org\/index.php\/Cybersecurity\" class=\"mw-redirect wiki-link\" title=\"Cybersecurity\" data-key=\"ba653dc2a1384e5f9f6ac9dc1a740109\">cybersecurity<\/a>, and real-time optimization\u2014are increasingly integrated into different parts of modern agricultural systems.<sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup>\n<\/p><p>To realize operational efficiency, full automation, and high productivity in these systems, different types of data are collected from operational systems using different sensors, stored in big data systems, and processed using <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> and deep learning approaches. Traditional data management techniques and systems are not sufficient to deal with this scale of data, and as such, big data infrastructures and systems have been designed and implemented. To manage the complexity of this big data, many different aspects of data must be considered during the design of these systems. Different data management <a href=\"https:\/\/www.limswiki.org\/index.php\/Reference_architecture\" title=\"Reference architecture\" class=\"wiki-link\" data-key=\"abd6aa65d05f0b4151934d7eaaf5d72e\">reference architectures<\/a> have been designed to date.<sup id=\"rdp-ebb-cite_ref-:3_15-0\" class=\"reference\"><a href=\"#cite_note-:3-15\">[15]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:9_16-0\" class=\"reference\"><a href=\"#cite_note-:9-16\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_17-0\" class=\"reference\"><a href=\"#cite_note-:4-17\">[17]<\/a><\/sup> To the best of our knowledge, none of these studies have focused on sustainable agriculture. There exist several practices for sustainable agriculture that can protect the environment, improve soil fertility, and increase natural resources. It is known that agriculture can affect soil erosion, water quality, human health, and pollination services.<sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup> As such, sustainable agriculture is crucial to minimize the negative effects of agricultural production. Sustainable agriculture requires an iterative process because each actor in the system has a different responsibility, and the success of this process is highly dependent on the success of each actor.\n<\/p><p>The goal of this study is to present a data management reference architecture for supporting smart farming, sustainable agriculture, and other domains. The study builds on the recent developments in data management and processing, i.e., big data, machine learning, and data lakes. We designed a data management reference architecture for sustainable agriculture and evaluated it using several case studies. Domain scoping, domain modeling, and reference architecture design stages were followed to create the reference architecture. Based on the reference architecture, we can design different application architectures. During the <a href=\"https:\/\/www.limswiki.org\/index.php\/Software_verification_and_validation\" title=\"Software verification and validation\" class=\"wiki-link\" data-key=\"14bdd953b2bde31c520ba57b1002195e\">validation<\/a> stage of this study, using different case studies obtained from the literature, we have shown the applicability of our reference architecture as a novel data management reference architecture for sustainable agriculture.\n<\/p><p>The structure of this paper follows the outline proposed by Gregor & Hevner<sup id=\"rdp-ebb-cite_ref-19\" class=\"reference\"><a href=\"#cite_note-19\">[19]<\/a><\/sup> for design science research. The next section summarizes the research method adopted in this study, followed by the definition and structuring of the problem by analyzing the existing literature. We then present the related reference architecture studies and explain the solution design process and the reference architecture obtained. That is followed by the evaluation of the reference architecture by deriving application architectures from it based on some requirements from the sustainable agriculture domain. The penultimate section discusses the results, and the final section provides conclusions and plans of future work.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Research_method\">Research method<\/span><\/h2>\n<p>The design science research (DSR) method proposed by Hevner <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:10_20-0\" class=\"reference\"><a href=\"#cite_note-:10-20\">[20]<\/a><\/sup> was followed in this study. DSR is a problem-solving paradigm and seeks to create artifacts through which <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> systems can be effectively and efficiently engineered.<sup id=\"rdp-ebb-cite_ref-:10_20-1\" class=\"reference\"><a href=\"#cite_note-:10-20\">[20]<\/a><\/sup> These artifacts are designed to interact with a problem context to improve something in that context.<sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup>\n<\/p><p>The activities and the artifacts span two significant dimensions, i.e., problem-solution and theory-practice dimensions.<sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup> Figure 1 shows the research method used in this study. The first step was the identification of some problem instances occurring in practice and sharing similar aspects. These problem instances were analyzed, and a problem statement was formed using theoretical concepts from the literature. A conceptual solution, i.e., an artifact or artifacts, was designed by following a systematic approach. Domain analysis was used to derive and represent domain knowledge to be used for solution design. Domain analysis involved domain scoping and domain modeling activities.<sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup> Domain scoping refers to the identification of relevant knowledge sources to derive the key concepts of the solution.<sup id=\"rdp-ebb-cite_ref-:5_24-0\" class=\"reference\"><a href=\"#cite_note-:5-24\">[24]<\/a><\/sup> To this end, several searches were conducted on the Scopus database using different search strings. Domain modeling aims at unifying and representing the domain knowledge obtained from relevant sources. The feature model was used to represent the output of domain modeling.<sup id=\"rdp-ebb-cite_ref-:6_25-0\" class=\"reference\"><a href=\"#cite_note-:6-25\">[25]<\/a><\/sup> A reference architecture was designed as a conceptual solution.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"505b8b519830abf6b6f75e993d6d033f\"><img alt=\"Fig1 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cf\/Fig1_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> The research method used in this study, which involves the main steps of design science research (DSR), i.e., problem definition, solution design, and validation. The iterative nature of the research method was neglected for the sake of simplicity.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>To evaluate the reference architecture, requirements were specified using recent literature on sustainable agriculture.<sup id=\"rdp-ebb-cite_ref-:11_26-0\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:12_27-0\" class=\"reference\"><a href=\"#cite_note-:12-27\">[27]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:13_28-0\" class=\"reference\"><a href=\"#cite_note-:13-28\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:14_29-0\" class=\"reference\"><a href=\"#cite_note-:14-29\">[29]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:15_30-0\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup> Based on these requirements, a concrete application architecture was derived using the reference architecture.\n<\/p><p>In accordance with DSR and the research method described here, the following sections describe problem definition, design of a solution, and the evaluation of the solution.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Problem_definition\">Problem definition<\/span><\/h2>\n<p>This study was motivated by three use cases involving different data management requirements to support sustainable agriculture. The following three use cases were used for understanding and conceptualizing the problem:\n<\/p>\n<ul><li><b>Case 1<\/b>: Satellite images (e.g., Sentinel-2 data) can be obtained from a data provider. These images can be processed to derive plant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content during the growing season.<sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup> Afterward, the current growth status and development of cultivated crops at each location in the field can be deduced.<sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup> This information can be used for site-specific plant protection and fertilization measures<sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup>, which support sustainable agriculture.<\/li><\/ul>\n<ul><li><b>Case 2<\/b>: Harvested crop volume can be quantified and recorded in real time using numerous sensors.<sup id=\"rdp-ebb-cite_ref-:7_34-0\" class=\"reference\"><a href=\"#cite_note-:7-34\">[34]<\/a><\/sup> Various parameters such as \"quantity per hectare\" and \"flow\" can be calculated, and crop productivity maps can be built.<sup id=\"rdp-ebb-cite_ref-:7_34-1\" class=\"reference\"><a href=\"#cite_note-:7-34\">[34]<\/a><\/sup> Farmers can use these maps to optimize inputs such as fertilizers, pesticides, and seeding rates, resulting in an increase in yields.<sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup><\/li><\/ul>\n<ul><li><b>Case 3<\/b>: Machinery process data such as speed, angle, pressure, and flow rate can be obtained through sensors in tractors and equipment.<sup id=\"rdp-ebb-cite_ref-:1_4-1\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> Machine, worker, field, and time slot data can be stored, and basic statistics like minimum, maximum, and standard deviation can be computed.<sup id=\"rdp-ebb-cite_ref-:1_4-2\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> As a result, automated documentation of the production process and site-specific work can be attained.<sup id=\"rdp-ebb-cite_ref-:1_4-3\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup><\/li><\/ul>\n<p>Table 1 summarizes the above-mentioned cases from a data management perspective. Similar to many cases in various domains, at a high level, digital data are produced and fed to a software system to be processed and stored. Such a system can be designated a data management platform and produce outputs that can lead to better business outcomes. As per the first case, satellite images can be processed via computer vision algorithms to drive plant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content, which can in turn be used to track the current growth status of cultivated crops and support decision-making activities.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"4\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> A summary of the three cases presented above from a data management perspective\n<\/td><\/tr>\n\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Data input\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Data processing\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Data output\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Outcome\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Satellite images\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Derive plant parameters via computer vision algorithms\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Plant parameters such as Leaf Area Index (LAI), biomass, and chlorophyll content\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Track current growth status and development of cultivated crop at each location\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Harvested crops volume via sensors\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Build crop productivity maps\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Various parameters such as \"quantity per hectare\" and \"flow\" on the map\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Use such maps to optimize inputs such as fertilizers, pesticides, and seeding rates in order to increase yields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Machinery process data via sensors\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Compute statistics\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Machine, worker, field, and time slot data, along with basic statistics such as minimum, maximum, and standard deviation\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Attain automated documentation of the production process and site-specific work\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Solution_design_and_artifact_description\">Solution design and artifact description<\/span><\/h2>\n<p>This section starts with a summary of related reference architecture studies and then presents the three steps of the solution design phase, namely domain scoping, domain modeling, and reference architecture design.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Related_reference_architecture_studies\">Related reference architecture studies<\/span><\/h3>\n<p>Before presenting our reference architecture, we discuss the available reference architectures in the literature. First, while Nikkil\u00e4 <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup> and Kaloxylos <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup> presented architectural aspects of Farm Management Information Systems (FMISs), they did not propose a reference architecture, which limited the utility of their research for our purposes. However, Tummers <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:4_17-1\" class=\"reference\"><a href=\"#cite_note-:4-17\">[17]<\/a><\/sup> designed a reference architecture for FMISs. They first identified the stakeholders and their concerns. Afterward, a feature model for FMISs was created. The reference architecture was designed and represented via context and decomposition views. Three case studies were performed to show the applicability of the proposed reference architecture.\n<\/p><p>K\u00f6ksal & Tekinerdogan<sup id=\"rdp-ebb-cite_ref-:2_6-1\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> proposed a reference architecture for IoT-based FMISs. They proposed an architecture design method and showed that the approach is practical and effective. Their architecture included data acquisition, data processing, data visualization, system management, and external services. Each main feature consisted of several sub-features. For instance, the data processing feature involved sub-features like image\/video processing, <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_mining\" title=\"Data mining\" class=\"wiki-link\" data-key=\"be09d3680fe1608addedf6f62692ee47\">data mining<\/a>, decision support, and data logging. They used decomposition, layered, and deployment views to document the reference architecture. For deriving a concrete FMIS architecture, their reference architecture can thus be used.\n<\/p><p>Kruize <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup> proposed a reference architecture for farm software ecosystems. Farm software ecosystems aim to fulfill the needs of several actors in the smart farming domain. In that respect, their scope is much wider compared to FMISs. The farm software ecosystem reference architecture mainly focused on the problem of bringing various software and hardware components together to form a platform for multiple actors.\n<\/p><p>To the best of our knowledge, there is no other study that presents a data management reference architecture for sustainable agriculture. Although some of the previous studies mention several data-related components, a complete architectural view of managing data for sustainable agriculture was missing. As such, our reference architecture study aims to fill this research gap.\n<\/p><p><br \/>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Domain_scoping\">Domain scoping<\/span><\/h3>\n<p>The Scopus database was used as the knowledge source for domain scoping. To identify the search keywords, it was crucial to understand the recent factors driving reference architectures for data management. The concept of \"big data\" has emerged to highlight challenges of data management, including volume, velocity, and variety.<sup id=\"rdp-ebb-cite_ref-:16_39-0\" class=\"reference\"><a href=\"#cite_note-:16-39\">[39]<\/a><\/sup> Machine learning is another hot research topic, which tries to acquire knowledge by extracting patterns from raw data<sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[41]<\/a><\/sup> and solve problems using this knowledge. The concept of a \"data lake\" is another to have recently emerged, which addresses the shortcomings of data warehouses. A data lake can be defined as a data management platform that allows the storing of both structured and unstructured data, unlike data warehouses that handle only structured data. This type of platform is designed to enable big data processing, real time analytics, and machine learning. \n<\/p><p>Based on these recent trends, four search strings were used to form the initial paper pool. The phrase \u201creference architecture\u201d was combined with four phrases representing the recent trends in data processing for sustainable agriculture (i.e., \"data management,\" \"big data,\" \"machine learning,\" and \"data lake\"). The search keywords were kept general to have a high recall and relatively low precision. Although this required more effort from the authors, obtaining a broader initial set of papers decreased the possibility of missing relevant studies.\n<\/p><p>The database search on Scopus was conducted in February 2021. No criterion was set for the publication date. A total number of 270 papers was obtained for the pool of candidate papers. All the results were combined in an Excel sheet, which included useful information about the papers such as title, abstract, keywords, and publication date, which are used in further steps.\n<\/p><p>To identify the relevant papers for designing a reference architecture, we applied the exclusion criteria to the papers obtained from Scopus. Those papers that were duplicated, not written in English, or lacking full text were filtered out. The papers involving a reference architecture to process data in any business domain were included. Seven papers included a reference architecture for data processing, along with the essential components.\n<\/p><p>The data extraction phase followed the selection of relevant papers. The components of the data processing architecture listed in the papers were extracted and recorded in an Excel sheet. These components were unified by reading the definitions presented in the papers. Table 2 shows the unified list of the components and the source papers where each component was identified.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> The unified list of components identified in the literature\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Component\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Nadal <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:3_15-1\" class=\"reference\"><a href=\"#cite_note-:3-15\">[15]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Dayal <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Suriarachchi and Plale<sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[43]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Rao <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Sang <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[45]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Arass <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-46\" class=\"reference\"><a href=\"#cite_note-46\">[46]<\/a><\/sup>\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">P\u00e4\u00e4kk\u00f6nen and Pakkala<sup id=\"rdp-ebb-cite_ref-:8_47-0\" class=\"reference\"><a href=\"#cite_note-:8-47\">[47]<\/a><\/sup>\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ingestion\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Information extraction\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Data quality management\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Integration\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Analysis\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Storage\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Security\/Privacy\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Metadata management\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Replication\/Archiving\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>All the papers address three main components that deal with collecting data from various sources (i.e., acquisition), processing data to provide some value to data consumers (i.e., analysis), and addressing persist data (i.e., storage). P\u00e4\u00e4kk\u00f6nen and Pakkala<sup id=\"rdp-ebb-cite_ref-:8_47-1\" class=\"reference\"><a href=\"#cite_note-:8-47\">[47]<\/a><\/sup> identified information extraction as a component to extract structured data from unstructured and semi-structured data, such as email or images. Data quality management is another vital component to handle data quality problems. Data received from various sources should be integrated for further analysis. Security and privacy components are used to protect data from unauthorized data and for proper handling of personal data. <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" title=\"Metadata\" class=\"wiki-link\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">Metadata<\/a> management refers to the creation and storage of metadata to document the meaning of data. The replication component ensures redundant storage of data sources to provide better data availability in case of technical problems, and the archiving component is responsible for storing cold data for future possible needs.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Domain_modeling\">Domain modeling<\/span><\/h3>\n<p>Feature modeling is one of the approaches to represent domain knowledge in a reusable format.<sup id=\"rdp-ebb-cite_ref-:5_24-1\" class=\"reference\"><a href=\"#cite_note-:5-24\">[24]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_25-1\" class=\"reference\"><a href=\"#cite_note-:6-25\">[25]<\/a><\/sup> Figure 2 shows the feature model, which is derived from the unified list of components presented in Table 2. A feature diagram can include mandatory and optional features. Three components identified by all papers are treated as mandatory features. The remaining features are optional and can be used depending on business requirements.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"ee6d58751059b06933c9d1356e9e7704\"><img alt=\"Fig2 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/eb\/Fig2_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> The feature model for data management in the sustainable agriculture domain<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Data need to be onboarded to a data platform for further processing and storage, a process referred to as the ETL (extract, transform, and load) process in traditional <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_warehouse\" title=\"Data warehouse\" class=\"wiki-link\" data-key=\"ca506499cdf544371c0a0d549ff0e9ee\">data warehousing<\/a> architectures.<sup id=\"rdp-ebb-cite_ref-:17_48-0\" class=\"reference\"><a href=\"#cite_note-:17-48\">[48]<\/a><\/sup> Such architectures possess a pre-defined data schema and data are loaded based on this schema. Data ingestion refers to the process of transferring data from providers to a platform for further processing.<sup id=\"rdp-ebb-cite_ref-49\" class=\"reference\"><a href=\"#cite_note-49\">[49]<\/a><\/sup> The umbrella term for such processes is \"data acquisition.\" Data can be acquired in batches at regular intervals or in real time (or in near real time) as streams. A component acquiring data streams should be able to handle data with high velocity.<sup id=\"rdp-ebb-cite_ref-50\" class=\"reference\"><a href=\"#cite_note-50\">[50]<\/a><\/sup>\n<\/p><p>Information extraction is intended for obtaining useful information from unstructured and semi-structured data.<sup id=\"rdp-ebb-cite_ref-51\" class=\"reference\"><a href=\"#cite_note-51\">[51]<\/a><\/sup> Unstructured and semi-structured data may include natural language text, image, audio, and video. Several tasks performed under information extraction include classification, named entity recognition, relationship extraction, and structure extraction.<sup id=\"rdp-ebb-cite_ref-:9_16-1\" class=\"reference\"><a href=\"#cite_note-:9-16\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:17_48-1\" class=\"reference\"><a href=\"#cite_note-:17-48\">[48]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:18_52-0\" class=\"reference\"><a href=\"#cite_note-:18-52\">[52]<\/a><\/sup> Named entity recognition (i.e., named entity identification) aims at identifying and classifying named entities in unstructured or semi-structured texts into predefined categories such as a person, organization, or location. For instance, Gangadharan and Gupta<sup id=\"rdp-ebb-cite_ref-53\" class=\"reference\"><a href=\"#cite_note-53\">[53]<\/a><\/sup> extracted names of crops, soil types, crop diseases, pathogen names, and fertilizers from documents on agriculture. Relation extraction is the task of detecting and classifying predefined types of associations among recognized entities.<sup id=\"rdp-ebb-cite_ref-:18_52-1\" class=\"reference\"><a href=\"#cite_note-:18-52\">[52]<\/a><\/sup> For example, relationships among crop diseases and locations can be extracted. The sub-features for information extraction can be expanded depending on domain-specific requirements.\n<\/p><p>Data quality management refers to handling data <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_(business)\" title=\"Quality (business)\" class=\"wiki-link\" data-key=\"c4ac43430d1c3a3a15d1255257aaea37\">quality<\/a> problems that may arise due to several reasons<sup id=\"rdp-ebb-cite_ref-:17_48-2\" class=\"reference\"><a href=\"#cite_note-:17-48\">[48]<\/a><\/sup>, including missing, incorrect, unusable, or redundant data.<sup id=\"rdp-ebb-cite_ref-54\" class=\"reference\"><a href=\"#cite_note-54\">[54]<\/a><\/sup> To address these main data quality problems, missing data can be completed, incorrect data can be corrected, unusable data can be transformed, and redundant data can be cleaned.\n<\/p><p>In general, data management platforms acquire data from multiple sources that usually involve differences in data models, schemas, and data semantics.<sup id=\"rdp-ebb-cite_ref-55\" class=\"reference\"><a href=\"#cite_note-55\">[55]<\/a><\/sup> <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_integration\" title=\"Data integration\" class=\"wiki-link\" data-key=\"fd01c635859e1d5b9583e43e31ef6718\">Data integration<\/a> aims at combining heterogeneous data and providing a unified view of these data.<sup id=\"rdp-ebb-cite_ref-56\" class=\"reference\"><a href=\"#cite_note-56\">[56]<\/a><\/sup> One technique for data integration is schema mapping, which refers to conveying the data schemas of multiple data sources into one global common schema.<sup id=\"rdp-ebb-cite_ref-57\" class=\"reference\"><a href=\"#cite_note-57\">[57]<\/a><\/sup>\n<\/p><p>Data are analyzed to obtain some value from them. Results of <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_analysis\" title=\"Data analysis\" class=\"wiki-link\" data-key=\"545c95e40ca67c9e63cd0a16042a5bd1\">analysis<\/a> may provide insights to users and constitute some intermediate output for further processing.<sup id=\"rdp-ebb-cite_ref-:17_48-3\" class=\"reference\"><a href=\"#cite_note-:17-48\">[48]<\/a><\/sup> Stream analysis encompasses the timely processing of flowing data and generates required outputs. For instance, an environmental monitoring system can process raw data coming from sensor networks to identify critical cases.<sup id=\"rdp-ebb-cite_ref-58\" class=\"reference\"><a href=\"#cite_note-58\">[58]<\/a><\/sup> On the contrary, batch analysis is conducted on static datasets.<sup id=\"rdp-ebb-cite_ref-59\" class=\"reference\"><a href=\"#cite_note-59\">[59]<\/a><\/sup> Data mining and machine learning, including deep learning algorithms, may be utilized to produce deeper analyses.<sup id=\"rdp-ebb-cite_ref-60\" class=\"reference\"><a href=\"#cite_note-60\">[60]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-61\" class=\"reference\"><a href=\"#cite_note-61\">[61]<\/a><\/sup>\n<\/p><p>Storage is a feature supporting other features and refers to the temporary and persistent storage of data. To manage the increased volume, velocity, and variety of data<sup id=\"rdp-ebb-cite_ref-:16_39-1\" class=\"reference\"><a href=\"#cite_note-:16-39\">[39]<\/a><\/sup>, different types of data stores are released. Therefore, the storage feature involves various database management systems (e.g., Microsoft SQL Server, Oracle, <a href=\"https:\/\/www.limswiki.org\/index.php\/PostgreSQL\" title=\"PostgreSQL\" class=\"wiki-link\" data-key=\"a5dd945cdcb63e2d8f7a5edb3a896d82\">PostgreSQL<\/a>, or MongoDB) implementing different data models such as relational or nonrelational (or NoSQL).\n<\/p><p>The security and privacy feature addresses authentication and authorization, access tracking, and data anonymization.<sup id=\"rdp-ebb-cite_ref-:17_48-4\" class=\"reference\"><a href=\"#cite_note-:17-48\">[48]<\/a><\/sup> Several standards, guidelines, and mechanisms can affect the realization of this feature, such as data <a href=\"https:\/\/www.limswiki.org\/index.php\/Encryption\" title=\"Encryption\" class=\"wiki-link\" data-key=\"86a503652ed5cc9d8e2b0252a480b5e1\">encryption<\/a> standards and mechanisms, access guidelines, and remote access standards.<sup id=\"rdp-ebb-cite_ref-:19_62-0\" class=\"reference\"><a href=\"#cite_note-:19-62\">[62]<\/a><\/sup>\n<\/p><p>Metadata management is related to planning, implementation, and control activities to enable access to metadata.<sup id=\"rdp-ebb-cite_ref-:19_62-1\" class=\"reference\"><a href=\"#cite_note-:19-62\">[62]<\/a><\/sup> This feature mainly involves capabilities related to collecting and integrating metadata from diverse sources and providing a standard way to access these metadata.<sup id=\"rdp-ebb-cite_ref-:19_62-2\" class=\"reference\"><a href=\"#cite_note-:19-62\">[62]<\/a><\/sup>\n<\/p><p>The replication feature manages the storage of the same data on multiple storage devices.<sup id=\"rdp-ebb-cite_ref-:19_62-3\" class=\"reference\"><a href=\"#cite_note-:19-62\">[62]<\/a><\/sup> While having replicated instances of data support remain highly available, data consistency may become an issue to deal with. The archiving feature addresses the movement of infrequently used data onto media with a lower retrieval performance.<sup id=\"rdp-ebb-cite_ref-:19_62-4\" class=\"reference\"><a href=\"#cite_note-:19-62\">[62]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Reference_architecture_design\">Reference architecture design<\/span><\/h3>\n<p>Based on the abstraction derived from the three cases presented prior, Figure 3 shows the context diagram of a data management system. The context diagram shows the overall purpose of the system and its interfaces with the external environment.<sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[63]<\/a><\/sup> At a very high level, some data providers send data to a data management system. These may be humans entering data through a graphical user interface (GUI) or external systems providing input data to be processed. Data obtained from data providers are stored, processed, and served to data consumers based on their requirements.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"d5ac8f10477284a8688f9f4c709f5aaf\"><img alt=\"Fig3 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/98\/Fig3_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 3<\/b> The context diagram for a data management system to conceptualize the cases identified in the sustainable agriculture domain<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Figure 4 shows the decomposition view of the data management reference architecture proposed for data processing.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"4e2685fd06056a8e2e0570512a60329f\"><img alt=\"Fig4 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d6\/Fig4_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 4<\/b> Decomposition view of the data management reference architecture<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Acquisition components are responsible for onboarding data to the data management platform for further processing. Useful information such as named entities and relations can be extracted from the acquired data. Quality problems can be resolved by completing, correcting, transforming, and cleaning the acquired data to obtain more accurate results from analyses. The data obtained from various sources need to be integrated to end up with better and richer insights. Various components can be used to analyze data to support decision-making. The storage component handles different modes of storing data. The security and privacy component is needed to protect data from unauthorized access. Data on the description of acquired data, are handled by the metadata management component. Replication may be needed for high availability. An archive component is usually required to manage the process of archiving unused historical data.\n<\/p><p>The next section presents how an application architecture can be derived from the reference architecture based on the requirements in sustainable agriculture.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Validation\">Validation<\/span><\/h2>\n<p>To evaluate the reference architecture, a set of requirements was extracted from recent papers on sustainable agriculture.<sup id=\"rdp-ebb-cite_ref-:11_26-1\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:12_27-1\" class=\"reference\"><a href=\"#cite_note-:12-27\">[27]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:13_28-1\" class=\"reference\"><a href=\"#cite_note-:13-28\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:14_29-1\" class=\"reference\"><a href=\"#cite_note-:14-29\">[29]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:15_30-1\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup> The high-level requirements address issues on crop yield prediction<sup id=\"rdp-ebb-cite_ref-:12_27-2\" class=\"reference\"><a href=\"#cite_note-:12-27\">[27]<\/a><\/sup>, irrigation management<sup id=\"rdp-ebb-cite_ref-:13_28-2\" class=\"reference\"><a href=\"#cite_note-:13-28\">[28]<\/a><\/sup>, real time variable-rate fertilization<sup id=\"rdp-ebb-cite_ref-:15_30-2\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup>, and exotic animal infectious diseases monitoring.<sup id=\"rdp-ebb-cite_ref-:11_26-2\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup> These diverse high-level requirements address various data management aspects in sustainable architecture.\n<\/p><p>Sustainability is a long-term, high-level goal involving several aspects and sub-goals. Generally, there is a gap between software requirements and sustainability goals. While software requirements tend to be more tangible, sustainability goals tend to be more intangible. Therefore, a tangible decomposition of sustainability and the ability to map it to concrete software requirements are required to monitor the achievement of sustainability goals.<sup id=\"rdp-ebb-cite_ref-:20_64-0\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup>\n<\/p><p>Penzenstadler and Femmer proposed a reference model to show the dimensions of sustainability (i.e., individual, social, economic, environmental, and technical) and map them to high-level software requirements.<sup id=\"rdp-ebb-cite_ref-:21_65-0\" class=\"reference\"><a href=\"#cite_note-:21-65\">[65]<\/a><\/sup> Figure 5 shows the high-level software requirements obtained from the literature and how they are mapped in the sustainability model proposed by Penzenstadler & Femmer.<sup id=\"rdp-ebb-cite_ref-:20_64-1\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:21_65-1\" class=\"reference\"><a href=\"#cite_note-:21-65\">[65]<\/a><\/sup>\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"c4440e99b3f6a22b4edcb85722de0619\"><img alt=\"Fig5 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/ab\/Fig5_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 5<\/b> The requirements obtained from the literature on sustainable agriculture. The requirements are mapped to sustainability dimensions using the sustainability model proposed by Penzenstadler & Femmer.<sup id=\"rdp-ebb-cite_ref-:20_64-2\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:21_65-2\" class=\"reference\"><a href=\"#cite_note-:21-65\">[65]<\/a><\/sup><\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The goal of sustainability has several dimensions such as economic and environmental. There are moral and natural goods that are perceived as an expression of a specific dimension.<sup id=\"rdp-ebb-cite_ref-:20_64-3\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup> Long-term profit and healthy environment are two examples of values contributing to economic and environmental dimensions, respectively. Indicators are qualitative or quantitative metrics that express a specific degree or score regarding a value.<sup id=\"rdp-ebb-cite_ref-:20_64-4\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup> Consumption amounts of resources, water, agricultural pesticide, and weedicide are examples of indicators. Activities are measures taken to contribute to values<sup id=\"rdp-ebb-cite_ref-:20_64-5\" class=\"reference\"><a href=\"#cite_note-:20-64\">[64]<\/a><\/sup> and can have different levels of granularities, which are associated with each other. Lower-level activities such as crop phenotypic monitoring, shown in Figure 5, can contribute to a higher-level activity such as variable-rate fertilization management. Lower-level leaf activities, such as predicting crop yield, shown in Figure 5, can be treated as the high-level software requirements (e.g., high-level use cases or epics) against which one or more system features are developed. \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Components_of_the_data_management_reference_architecture\">Components of the data management reference architecture<\/span><\/h3>\n<p>The components of the data management reference architecture used to realize each high-level software requirement are described as follows.\n<\/p><p>Crop yield prediction is an essential task for growers and farmers to decide on what and when to grow.<sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[66]<\/a><\/sup> However, it is extremely challenging due to numerous complex factors.<sup id=\"rdp-ebb-cite_ref-67\" class=\"reference\"><a href=\"#cite_note-67\">[67]<\/a><\/sup> To overcome this challenge, researchers started to use machine learning algorithms to predict crop yield based on various input variables.<sup id=\"rdp-ebb-cite_ref-:12_27-3\" class=\"reference\"><a href=\"#cite_note-:12-27\">[27]<\/a><\/sup> Mohsen <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:12_27-4\" class=\"reference\"><a href=\"#cite_note-:12-27\">[27]<\/a><\/sup> suggest using weather, soil, plant population, and planting process data. These historical data are extracted from various sources such as surveys<sup id=\"rdp-ebb-cite_ref-68\" class=\"reference\"><a href=\"#cite_note-68\">[68]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-69\" class=\"reference\"><a href=\"#cite_note-69\">[69]<\/a><\/sup> and stored (<i>acquisition: batch<\/i>). Unusable data such as rows with missing values are removed (<i>cleaning<\/i>) and some of the values are normalized (<i>transformation<\/i>). The data obtained from different sources are combined (<i>integration<\/i>). Several machine learning models are built through experimentation (<i>machine learning: model development<\/i>). One of the obtained machine learning models that exhibits a satisfactory performance is deployed (<i>machine learning: model deployment<\/i>). The performance of the deployed model should be monitored for a possible performance degradation.<sup id=\"rdp-ebb-cite_ref-70\" class=\"reference\"><a href=\"#cite_note-70\">[70]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-71\" class=\"reference\"><a href=\"#cite_note-71\">[71]<\/a><\/sup> When the performance does not meet expectations, a new machine learning model should be trained and deployed.\n<\/p><p>Wireless sensor networks using IoT technologies can be utilized for irrigation management.<sup id=\"rdp-ebb-cite_ref-:13_28-3\" class=\"reference\"><a href=\"#cite_note-:13-28\">[28]<\/a><\/sup> Sensors can measure real-time environmental data such as soil moisture in predefined periods and send these data to the data storage over the internet (<i>acquisition: stream<\/i>).<sup id=\"rdp-ebb-cite_ref-:22_72-0\" class=\"reference\"><a href=\"#cite_note-:22-72\">[72]<\/a><\/sup> A weather forecast can be obtained from a data provider (<i>acquisition: batch<\/i>) to manage irrigation by considering the conditions that affect the irrigation process, such as rain or strong winds.<sup id=\"rdp-ebb-cite_ref-:22_72-1\" class=\"reference\"><a href=\"#cite_note-:22-72\">[72]<\/a><\/sup> The measurement and forecast data are combined (<i>integration<\/i>) by considering time dimension, i.e., data obtained from different sources must fit into the same temporal window.<sup id=\"rdp-ebb-cite_ref-:23_73-0\" class=\"reference\"><a href=\"#cite_note-:23-73\">[73]<\/a><\/sup> Based on the combined data, irrigation decisions can be drawn based on predefined rules<sup id=\"rdp-ebb-cite_ref-:13_28-4\" class=\"reference\"><a href=\"#cite_note-:13-28\">[28]<\/a><\/sup> or a prediction model (<i>machine learning<\/i>).<sup id=\"rdp-ebb-cite_ref-:23_73-1\" class=\"reference\"><a href=\"#cite_note-:23-73\">[73]<\/a><\/sup> The data on this decision can be sent to an actuator to control irrigation.\n<\/p><p>Crop phenotypic information can be used to enable real-time variable-rate fertilization.<sup id=\"rdp-ebb-cite_ref-74\" class=\"reference\"><a href=\"#cite_note-74\">[74]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-75\" class=\"reference\"><a href=\"#cite_note-75\">[75]<\/a><\/sup> The predictors of phenotypic information involve crop three-dimensional size, biomass, and vegetation index, as well as other indicators.<sup id=\"rdp-ebb-cite_ref-:15_30-3\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup> These data can be acquired using aviation-based<sup id=\"rdp-ebb-cite_ref-76\" class=\"reference\"><a href=\"#cite_note-76\">[76]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-77\" class=\"reference\"><a href=\"#cite_note-77\">[77]<\/a><\/sup> and ground-based<sup id=\"rdp-ebb-cite_ref-78\" class=\"reference\"><a href=\"#cite_note-78\">[78]<\/a><\/sup> approaches. Data obtained through sensors mounted to unmanned aerial vehicles (UAVs)<sup id=\"rdp-ebb-cite_ref-79\" class=\"reference\"><a href=\"#cite_note-79\">[79]<\/a><\/sup>, or ground-based phenotypic platforms with a series of sensors and a GPS<sup id=\"rdp-ebb-cite_ref-80\" class=\"reference\"><a href=\"#cite_note-80\">[80]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-81\" class=\"reference\"><a href=\"#cite_note-81\">[81]<\/a><\/sup> can be ingested into a data management platform (<i>acquisition: stream<\/i>). To obtain accurate predictions of crop phenotypic information, it is necessary to combine multi-source sensor data such as color, depth, and spectral data with environmental and crop physiology data<sup id=\"rdp-ebb-cite_ref-:15_30-4\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup> (<i>integration<\/i>) and develop machine learning models (<i>machine learning: model development<\/i>). Those models need to be deployed (<i>machine learning: model deployment<\/i>) and used for real time variable-rate fertilization. As a result, improvements in the level of fertilizer utilization efficiency enable environmental and economic sustainability benefits by maximizing crop output and minimizing fertilizer input.<sup id=\"rdp-ebb-cite_ref-:15_30-5\" class=\"reference\"><a href=\"#cite_note-:15-30\">[30]<\/a><\/sup>\n<\/p><p>Exotic animal infectious diseases are considerable threats to global health security and economic stability.<sup id=\"rdp-ebb-cite_ref-:11_26-3\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-82\" class=\"reference\"><a href=\"#cite_note-82\">[82]<\/a><\/sup> One of the vital sources for detecting signals of disease is online news platforms. Data can be collected from platforms such as Google News (<i>acquisition: batch<\/i>) and stored for further analysis (<i>storage<\/i>). The named entities such as location, date, disease, hosts, and number of cases can be extracted using Natural Language Processing (NLP) techniques<sup id=\"rdp-ebb-cite_ref-:11_26-4\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup> (<i>information extraction: named entity recognition<\/i>). In addition, predefined types of relationships among the recognized entities can be detected (<i>information extraction: relation extraction<\/i>). As an example, the sentence \u201c12 pigs have been infected by African swine fever in Poland\u201d can provide the following entities<sup id=\"rdp-ebb-cite_ref-:11_26-5\" class=\"reference\"><a href=\"#cite_note-:11-26\">[26]<\/a><\/sup>: number of cases = 12; host = pig; disease = African swine fever; location = Poland.\n<\/p><p>Table 3 shows the functionalities extracted from the three problem cases (PC) and the four validation cases (VC). Figure 6 presents how these functionalities are mapped to the components of the reference architecture proposed in this study.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> The functionalities in the problem cases (PC) and validation cases (VC)\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Case\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">#\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Functionality\n<\/th><\/tr>\n<tr>\n<td rowspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC1.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store satellite images\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC1.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Process images to derive plant parameters, such as leaf area index (LAI), biomass, and chlorophyll content\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC1.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Deduce the current growth status and development of cultivated crops at each location in the field\n<\/td><\/tr>\n<tr>\n<td rowspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC2.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store harvested crop volume in real time using sensors\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC2.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Calculate parameters such as quantity per hectare and flow and build crop productivity maps\n<\/td><\/tr>\n<tr>\n<td rowspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC3.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store machinery process data such as speed, angle, pressure, and flow rate through sensors in tractors\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PC3.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Compute basic figures such as minimum, maximum, standard deviation and produce documentation of the production process\n<\/td><\/tr>\n<tr>\n<td rowspan=\"4\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC1.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Acquire and store historical data on weather, soil, plant population, and planting process\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC1.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Remove unusable data and normalize the remaining data\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC1.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Combine data on weather, soil, plant population, and planting process\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC1.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Build machine learning models and deploy the one that best satisfies requirements\n<\/td><\/tr>\n<tr>\n<td rowspan=\"4\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC2.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Measure and store real time environmental data\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC2.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store weather forecast\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC2.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Combine measurement and forecast data\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC2.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Decide on irrigation based on predefined rules or a prediction model\n<\/td><\/tr>\n<tr>\n<td rowspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC3.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store data, such as crop three-dimensional size, biomass, and vegetation index\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC3.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Combine multisource sensor data, such as color, depth, and spectral data, with environmental and crop physiology data\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC3.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Build machine learning models and deploy the one that best satisfies requirements for real-time variable-rate fertilization\n<\/td><\/tr>\n<tr>\n<td rowspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC4.1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Obtain and store news from online news platforms\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC4.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Extract named entities, such as location, date, disease, hosts, and number of cases\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">VC4.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Detect predefined types of relationships among recognized entities\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Giray_Sustain21_13-13.png\" class=\"image wiki-link\" data-key=\"ecdd26d7c69a311167c287343b97e11d\"><img alt=\"Fig6 Giray Sustain21 13-13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f5\/Fig6_Giray_Sustain21_13-13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 6<\/b> Mapping functionalities to the reference architecture components<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion_and_caveats\">Discussion and caveats<\/span><\/h2>\n<p>This research presents a novel data management reference architecture for sustainable agriculture using well-established architecture modeling techniques. As such, this study can pave the way for similar studies on data management reference architectures. The reference architecture was designed based on domain analysis. Other data management application architectures can be developed based on this reference architecture using variant features specified in this study.\n<\/p><p>The features shown in this study were obtained from peer-reviewed papers in the Scopus database. The inclusion of other databases may reveal unidentified features and the presented reference architecture may be extended accordingly. Since precision agriculture and smart farming are still evolving, new features can be integrated in the future, and data management reference architecture can be adapted. Different tools, techniques, and systems are currently developed by practitioners and researchers in smart farming, and therefore we expect to see new papers in databases that might bring new functionalities and features to the presented reference architecture. However, the presented methodology and the overall reference architecture can be easily changed to reflect the recent changes in smart farming.\n<\/p><p>The reference architecture is used to derive application architectures based on a multi-case study approach. For the multi-case study, there is a threat of misinterpretation of applied concepts. Although we discussed the concepts carefully and iteratively, there is a possibility that several concepts may have been interpreted differently compared to the concepts presented in the selected studies. The generalization of the presented findings must be taken with caution because different case studies may require new functionalities. While we can identify many different application scenarios in smart farming, the scenarios share some features from a data management perspective. Therefore, four case studies were shown to demonstrate the applicability of the proposed reference architecture. Other researchers can also evaluate the applicability of this architecture using different case studies in smart farming and create an application architecture for their uses.\n<\/p><p>It was shown that reference architecture design is useful for the agri-food domain. This study focused on sustainability; however, it can be extended to a larger context by covering other critical aspects of agriculture. For sustainable agriculture, the presented features are beneficial when designing new systems for agricultural production. Further research is needed to evaluate the applicability of the data management reference architecture for different application domains. We expect that increasingly more researchers will focus on sustainability in agriculture in the near future and develop novel models to fully address sustainability from several aspects. The advancement in machine learning and particularly deep learning techniques can also contribute to the development of novel models addressing sustainability.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions_and_future_work\">Conclusions and future work<\/span><\/h2>\n<p>In this study, a data management reference architecture for sustainable agriculture was proposed and evaluated using different case studies. To the best of our knowledge, this is the first study that focuses on sustainability within the context of data management reference architecture. The design science research (DSR) method was applied while designing the reference architecture. Domain scoping, domain modeling, and reference architecture design stages were followed for solution design. Domain scoping was performed based on relevant papers, the domain model was represented as a feature model, and the reference architecture was built at the end of the reference architecture design stage. Three case studies were investigated from different perspectives, and the applicability of the data management reference architecture was evaluated. We consider that this research can improve the research in sustainable agriculture with respect to data management and pave the research for designing smart systems for smart farming and precision agriculture.\n<\/p><p>As future work, we plan to extend this study with new case studies and evaluate the applicability of the presented reference architecture for different scenarios. Another planned study involves the mapping of the reference architecture to the components of the farm management information systems and platforms used in the industry. This mapping can help us identify the possible missing components in the reference architecture. In addition, we can identify enhancement opportunities for the systems and platforms used in the industry.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Conceptualization, G.G. and C.C.; methodology, G.G.; investigation, G.G.; data curation, G.G.; validation, G.G. and C.C.; writing\u2014original draft preparation, G.G.; writing\u2014review and editing, G.G. and C.C. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This research received no external funding.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-:0-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_1-0\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-1\">1.1<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-2\">1.2<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-3\">1.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wolfert, Sjaak; 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European Commission<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/cordis.europa.eu\/project\/id\/212117\" target=\"_blank\">https:\/\/cordis.europa.eu\/project\/id\/212117<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Integration+of+Farm+Management+Information+Systems+to+support+real-time+management+decisions+and+compliance+of+management+standards&rft.atitle=CORDIS&rft.aulast=S%C3%B8rensen%2C+C.%3B+Bilds%C3%B8e%2C+P.%3B+Fountas%2C+S.+et+al.&rft.au=S%C3%B8rensen%2C+C.%3B+Bilds%C3%B8e%2C+P.%3B+Fountas%2C+S.+et+al.&rft.date=31+May+2011&rft.pub=European+Commission&rft_id=https%3A%2F%2Fcordis.europa.eu%2Fproject%2Fid%2F212117&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_6-0\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-1\">6.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">K\u00f6ksal, \u00d6.; Tekinerdogan, B. (1 October 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11119-018-09624-8\" target=\"_blank\">\"Architecture design approach for IoT-based farm management information systems\"<\/a> (in en). <i>Precision Agriculture<\/i> <b>20<\/b> (5): 926\u2013958. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11119-018-09624-8\" target=\"_blank\">10.1007\/s11119-018-09624-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1385-2256\" target=\"_blank\">1385-2256<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11119-018-09624-8\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11119-018-09624-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Architecture+design+approach+for+IoT-based+farm+management+information+systems&rft.jtitle=Precision+Agriculture&rft.aulast=K%C3%B6ksal&rft.aufirst=%C3%96.&rft.au=K%C3%B6ksal%2C%26%2332%3B%C3%96.&rft.au=Tekinerdogan%2C%26%2332%3BB.&rft.date=1+October+2019&rft.volume=20&rft.issue=5&rft.pages=926%E2%80%93958&rft_id=info:doi\/10.1007%2Fs11119-018-09624-8&rft.issn=1385-2256&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11119-018-09624-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-7\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-7\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Groeneveld, Desir\u00e9e; Tekinerdogan, Bedir; Garousi, Vahid; Catal, Cagatay (1 August 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/link.springer.com\/10.1007\/s11119-020-09770-y\" target=\"_blank\">\"A domain-specific language framework for farm management information systems in precision agriculture\"<\/a> (in en). <i>Precision Agriculture<\/i> <b>22<\/b> (4): 1067\u20131106. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11119-020-09770-y\" target=\"_blank\">10.1007\/s11119-020-09770-y<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1385-2256\" target=\"_blank\">1385-2256<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/link.springer.com\/10.1007\/s11119-020-09770-y\" target=\"_blank\">https:\/\/link.springer.com\/10.1007\/s11119-020-09770-y<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+domain-specific+language+framework+for+farm+management+information+systems+in+precision+agriculture&rft.jtitle=Precision+Agriculture&rft.aulast=Groeneveld&rft.aufirst=Desir%C3%A9e&rft.au=Groeneveld%2C%26%2332%3BDesir%C3%A9e&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.au=Garousi%2C%26%2332%3BVahid&rft.au=Catal%2C%26%2332%3BCagatay&rft.date=1+August+2021&rft.volume=22&rft.issue=4&rft.pages=1067%E2%80%931106&rft_id=info:doi\/10.1007%2Fs11119-020-09770-y&rft.issn=1385-2256&rft_id=https%3A%2F%2Flink.springer.com%2F10.1007%2Fs11119-020-09770-y&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jin, Xue-Bo; Yu, Xing-Hong; Wang, Xiao-Yi; Bai, Yu-Ting; Su, Ting-Li; Kong, Jian-Lei (14 February 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2071-1050\/12\/4\/1433\" target=\"_blank\">\"Deep Learning Predictor for Sustainable Precision Agriculture Based on Internet of Things System\"<\/a> (in en). <i>Sustainability<\/i> <b>12<\/b> (4): 1433. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fsu12041433\" target=\"_blank\">10.3390\/su12041433<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2071-1050\" target=\"_blank\">2071-1050<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2071-1050\/12\/4\/1433\" target=\"_blank\">https:\/\/www.mdpi.com\/2071-1050\/12\/4\/1433<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Deep+Learning+Predictor+for+Sustainable+Precision+Agriculture+Based+on+Internet+of+Things+System&rft.jtitle=Sustainability&rft.aulast=Jin&rft.aufirst=Xue-Bo&rft.au=Jin%2C%26%2332%3BXue-Bo&rft.au=Yu%2C%26%2332%3BXing-Hong&rft.au=Wang%2C%26%2332%3BXiao-Yi&rft.au=Bai%2C%26%2332%3BYu-Ting&rft.au=Su%2C%26%2332%3BTing-Li&rft.au=Kong%2C%26%2332%3BJian-Lei&rft.date=14+February+2020&rft.volume=12&rft.issue=4&rft.pages=1433&rft_id=info:doi\/10.3390%2Fsu12041433&rft.issn=2071-1050&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2071-1050%2F12%2F4%2F1433&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-9\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kaya, Aydin; Keceli, Ali Seydi; Catal, Cagatay; Yalic, Hamdi Yalin; Temucin, Huseyin; Tekinerdogan, Bedir (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169918315308\" target=\"_blank\">\"Analysis of transfer learning for deep neural network based plant classification models\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>158<\/b>: 20\u201329. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2019.01.041\" target=\"_blank\">10.1016\/j.compag.2019.01.041<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169918315308\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169918315308<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+transfer+learning+for+deep+neural+network+based+plant+classification+models&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Kaya&rft.aufirst=Aydin&rft.au=Kaya%2C%26%2332%3BAydin&rft.au=Keceli%2C%26%2332%3BAli+Seydi&rft.au=Catal%2C%26%2332%3BCagatay&rft.au=Yalic%2C%26%2332%3BHamdi+Yalin&rft.au=Temucin%2C%26%2332%3BHuseyin&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.date=1+March+2019&rft.volume=158&rft.pages=20%E2%80%9329&rft_id=info:doi\/10.1016%2Fj.compag.2019.01.041&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169918315308&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Loures, Lu\u00eds; Chamizo, Alejandro; Ferreira, Paulo; Loures, Ana; Castanho, Rui; Panagopoulos, Thomas (6 May 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2071-1050\/12\/9\/3765\" target=\"_blank\">\"Assessing the Effectiveness of Precision Agriculture Management Systems in Mediterranean Small Farms\"<\/a> (in en). <i>Sustainability<\/i> <b>12<\/b> (9): 3765. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fsu12093765\" target=\"_blank\">10.3390\/su12093765<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2071-1050\" target=\"_blank\">2071-1050<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2071-1050\/12\/9\/3765\" target=\"_blank\">https:\/\/www.mdpi.com\/2071-1050\/12\/9\/3765<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Assessing+the+Effectiveness+of+Precision+Agriculture+Management+Systems+in+Mediterranean+Small+Farms&rft.jtitle=Sustainability&rft.aulast=Loures&rft.aufirst=Lu%C3%ADs&rft.au=Loures%2C%26%2332%3BLu%C3%ADs&rft.au=Chamizo%2C%26%2332%3BAlejandro&rft.au=Ferreira%2C%26%2332%3BPaulo&rft.au=Loures%2C%26%2332%3BAna&rft.au=Castanho%2C%26%2332%3BRui&rft.au=Panagopoulos%2C%26%2332%3BThomas&rft.date=6+May+2020&rft.volume=12&rft.issue=9&rft.pages=3765&rft_id=info:doi\/10.3390%2Fsu12093765&rft.issn=2071-1050&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2071-1050%2F12%2F9%2F3765&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Podlasek, Anna; Koda, Eugeniusz; Vaverkov\u00e1, Magdalena Daria (8 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1660-4601\/18\/2\/465\" target=\"_blank\">\"The Variability of Nitrogen Forms in Soils Due to Traditional and Precision Agriculture: Case Studies in Poland\"<\/a> (in en). <i>International Journal of Environmental Research and Public Health<\/i> <b>18<\/b> (2): 465. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fijerph18020465\" target=\"_blank\">10.3390\/ijerph18020465<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1660-4601\" target=\"_blank\">1660-4601<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7827450\/\" target=\"_blank\">PMC7827450<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33430097\" target=\"_blank\">33430097<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1660-4601\/18\/2\/465\" target=\"_blank\">https:\/\/www.mdpi.com\/1660-4601\/18\/2\/465<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Variability+of+Nitrogen+Forms+in+Soils+Due+to+Traditional+and+Precision+Agriculture%3A+Case+Studies+in+Poland&rft.jtitle=International+Journal+of+Environmental+Research+and+Public+Health&rft.aulast=Podlasek&rft.aufirst=Anna&rft.au=Podlasek%2C%26%2332%3BAnna&rft.au=Koda%2C%26%2332%3BEugeniusz&rft.au=Vaverkov%C3%A1%2C%26%2332%3BMagdalena+Daria&rft.date=8+January+2021&rft.volume=18&rft.issue=2&rft.pages=465&rft_id=info:doi\/10.3390%2Fijerph18020465&rft.issn=1660-4601&rft_id=info:pmc\/PMC7827450&rft_id=info:pmid\/33430097&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1660-4601%2F18%2F2%2F465&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Verdouw, Cor; Tekinerdogan, Bedir; Beulens, Adrie; Wolfert, Sjaak (1 April 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0308521X20309070\" target=\"_blank\">\"Digital twins in smart farming\"<\/a> (in en). <i>Agricultural Systems<\/i> <b>189<\/b>: 103046. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.agsy.2020.103046\" target=\"_blank\">10.1016\/j.agsy.2020.103046<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0308521X20309070\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0308521X20309070<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+twins+in+smart+farming&rft.jtitle=Agricultural+Systems&rft.aulast=Verdouw&rft.aufirst=Cor&rft.au=Verdouw%2C%26%2332%3BCor&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.au=Beulens%2C%26%2332%3BAdrie&rft.au=Wolfert%2C%26%2332%3BSjaak&rft.date=1+April+2021&rft.volume=189&rft.pages=103046&rft_id=info:doi\/10.1016%2Fj.agsy.2020.103046&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0308521X20309070&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Keceli, Ali Seydi; Catal, Cagatay; Kaya, Aydin; Tekinerdogan, Bedir (1 March 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169919312220\" target=\"_blank\">\"Development of a recurrent neural networks-based calving prediction model using activity and behavioral data\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>170<\/b>: 105285. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2020.105285\" target=\"_blank\">10.1016\/j.compag.2020.105285<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169919312220\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169919312220<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Development+of+a+recurrent+neural+networks-based+calving+prediction+model+using+activity+and+behavioral+data&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Keceli&rft.aufirst=Ali+Seydi&rft.au=Keceli%2C%26%2332%3BAli+Seydi&rft.au=Catal%2C%26%2332%3BCagatay&rft.au=Kaya%2C%26%2332%3BAydin&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.date=1+March+2020&rft.volume=170&rft.pages=105285&rft_id=info:doi\/10.1016%2Fj.compag.2020.105285&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169919312220&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Catal, Cagatay; Tekinerdogan, Bedir (2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050919311901\" target=\"_blank\">\"Aligning Education for the Life Sciences Domain to Support Digitalization and Industry 4.0\"<\/a> (in en). <i>Procedia Computer Science<\/i> <b>158<\/b>: 99\u2013106. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.procs.2019.09.032\" target=\"_blank\">10.1016\/j.procs.2019.09.032<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050919311901\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050919311901<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Aligning+Education+for+the+Life+Sciences+Domain+to+Support+Digitalization+and+Industry+4.0&rft.jtitle=Procedia+Computer+Science&rft.aulast=Catal&rft.aufirst=Cagatay&rft.au=Catal%2C%26%2332%3BCagatay&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.date=2019&rft.volume=158&rft.pages=99%E2%80%93106&rft_id=info:doi\/10.1016%2Fj.procs.2019.09.032&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1877050919311901&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-15\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_15-0\">15.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_15-1\">15.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nadal, Sergi; Herrero, Victor; Romero, Oscar; Abell\u00f3, Alberto; Franch, Xavier; Vansummeren, Stijn; Valerio, Danilo (1 October 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0950584917304287\" target=\"_blank\">\"A software reference architecture for semantic-aware Big Data systems\"<\/a> (in en). <i>Information and Software Technology<\/i> <b>90<\/b>: 75\u201392. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.infsof.2017.06.001\" target=\"_blank\">10.1016\/j.infsof.2017.06.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0950584917304287\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0950584917304287<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+software+reference+architecture+for+semantic-aware+Big+Data+systems&rft.jtitle=Information+and+Software+Technology&rft.aulast=Nadal&rft.aufirst=Sergi&rft.au=Nadal%2C%26%2332%3BSergi&rft.au=Herrero%2C%26%2332%3BVictor&rft.au=Romero%2C%26%2332%3BOscar&rft.au=Abell%C3%B3%2C%26%2332%3BAlberto&rft.au=Franch%2C%26%2332%3BXavier&rft.au=Vansummeren%2C%26%2332%3BStijn&rft.au=Valerio%2C%26%2332%3BDanilo&rft.date=1+October+2017&rft.volume=90&rft.pages=75%E2%80%9392&rft_id=info:doi\/10.1016%2Fj.infsof.2017.06.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0950584917304287&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-16\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_16-0\">16.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_16-1\">16.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFAvci_SalmaTekinerdoganAthanasiadis2017\">Avci Salma, Cigdem; Tekinerdogan, Bedir; Athanasiadis, Ioannis N. (2017), <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128054673000041\" target=\"_blank\">\"Domain-Driven Design of Big Data Systems Based on a Reference Architecture\"<\/a> (in en), <i>Software Architecture for Big Data and the Cloud<\/i> (Elsevier): 49\u201368, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fb978-0-12-805467-3.00004-1\" target=\"_blank\">10.1016\/b978-0-12-805467-3.00004-1<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-12-805467-3<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128054673000041\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128054673000041<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Domain-Driven+Design+of+Big+Data+Systems+Based+on+a+Reference+Architecture&rft.jtitle=Software+Architecture+for+Big+Data+and+the+Cloud&rft.aulast=Avci+Salma&rft.aufirst=Cigdem&rft.au=Avci+Salma%2C%26%2332%3BCigdem&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.au=Athanasiadis%2C%26%2332%3BIoannis+N.&rft.date=2017&rft.pages=49%E2%80%9368&rft.pub=Elsevier&rft_id=info:doi\/10.1016%2Fb978-0-12-805467-3.00004-1&rft.isbn=978-0-12-805467-3&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FB9780128054673000041&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-17\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_17-0\">17.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_17-1\">17.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tummers, J.; Kassahun, A.; Tekinerdogan, B. (1 February 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/link.springer.com\/10.1007\/s11119-020-09728-0\" target=\"_blank\">\"Reference architecture design for farm management information systems: a multi-case study approach\"<\/a> (in en). <i>Precision Agriculture<\/i> <b>22<\/b> (1): 22\u201350. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11119-020-09728-0\" target=\"_blank\">10.1007\/s11119-020-09728-0<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1385-2256\" target=\"_blank\">1385-2256<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/link.springer.com\/10.1007\/s11119-020-09728-0\" target=\"_blank\">https:\/\/link.springer.com\/10.1007\/s11119-020-09728-0<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reference+architecture+design+for+farm+management+information+systems%3A+a+multi-case+study+approach&rft.jtitle=Precision+Agriculture&rft.aulast=Tummers&rft.aufirst=J.&rft.au=Tummers%2C%26%2332%3BJ.&rft.au=Kassahun%2C%26%2332%3BA.&rft.au=Tekinerdogan%2C%26%2332%3BB.&rft.date=1+February+2021&rft.volume=22&rft.issue=1&rft.pages=22%E2%80%9350&rft_id=info:doi\/10.1007%2Fs11119-020-09728-0&rft.issn=1385-2256&rft_id=https%3A%2F%2Flink.springer.com%2F10.1007%2Fs11119-020-09728-0&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">DeLonge, Marcia S.; Miles, Albie; Carlisle, Liz (1 January 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1462901115300812\" target=\"_blank\">\"Investing in the transition to sustainable agriculture\"<\/a> (in en). <i>Environmental Science & Policy<\/i> <b>55<\/b>: 266\u2013273. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.envsci.2015.09.013\" target=\"_blank\">10.1016\/j.envsci.2015.09.013<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1462901115300812\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1462901115300812<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Investing+in+the+transition+to+sustainable+agriculture&rft.jtitle=Environmental+Science+%26+Policy&rft.aulast=DeLonge&rft.aufirst=Marcia+S.&rft.au=DeLonge%2C%26%2332%3BMarcia+S.&rft.au=Miles%2C%26%2332%3BAlbie&rft.au=Carlisle%2C%26%2332%3BLiz&rft.date=1+January+2016&rft.volume=55&rft.pages=266%E2%80%93273&rft_id=info:doi\/10.1016%2Fj.envsci.2015.09.013&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1462901115300812&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-19\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gregor, Shirley; Hevner, Alan R. (2 February 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.25300\/MISQ\/2013\/37.2.01\" target=\"_blank\">\"Positioning and Presenting Design Science Research for Maximum Impact\"<\/a>. <i>MIS Quarterly<\/i> <b>37<\/b> (2): 337\u2013355. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.25300%2Fmisq%2F2013%2F37.2.01\" target=\"_blank\">10.25300\/misq\/2013\/37.2.01<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0276-7783\" target=\"_blank\">0276-7783<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.25300\/MISQ\/2013\/37.2.01\" target=\"_blank\">https:\/\/doi.org\/10.25300\/MISQ\/2013\/37.2.01<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Positioning+and+Presenting+Design+Science+Research+for+Maximum+Impact&rft.jtitle=MIS+Quarterly&rft.aulast=Gregor&rft.aufirst=Shirley&rft.au=Gregor%2C%26%2332%3BShirley&rft.au=Hevner%2C%26%2332%3BAlan+R.&rft.date=2+February+2013&rft.volume=37&rft.issue=2&rft.pages=337%E2%80%93355&rft_id=info:doi\/10.25300%2Fmisq%2F2013%2F37.2.01&rft.issn=0276-7783&rft_id=https%3A%2F%2Fdoi.org%2F10.25300%2FMISQ%2F2013%2F37.2.01&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-20\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_20-0\">20.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_20-1\">20.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hevner; March; Park; Ram (2004). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.jstor.org\/stable\/10.2307\/25148625\" target=\"_blank\">\"Design Science in Information Systems Research\"<\/a>. <i>MIS Quarterly<\/i> <b>28<\/b> (1): 75\u2013105. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2307%2F25148625\" target=\"_blank\">10.2307\/25148625<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.jstor.org\/stable\/10.2307\/25148625\" target=\"_blank\">https:\/\/www.jstor.org\/stable\/10.2307\/25148625<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Design+Science+in+Information+Systems+Research&rft.jtitle=MIS+Quarterly&rft.aulast=Hevner&rft.au=Hevner&rft.au=March&rft.au=Park&rft.au=Ram&rft.date=2004&rft.volume=28&rft.issue=1&rft.pages=75%E2%80%93105&rft_id=info:doi\/10.2307%2F25148625&rft_id=https%3A%2F%2Fwww.jstor.org%2Fstable%2F10.2307%2F25148625&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Wieringa, Roel J. (2014). <i>Design Science Methodology for Information Systems and Software Engineering<\/i> (1st ed. 2014 ed.). Berlin, Heidelberg: Springer Berlin Heidelberg : Imprint: Springer. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-662-43839-8.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Design+Science+Methodology+for+Information+Systems+and+Software+Engineering&rft.aulast=Wieringa&rft.aufirst=Roel+J.&rft.au=Wieringa%2C%26%2332%3BRoel+J.&rft.date=2014&rft.edition=1st+ed.+2014&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg+%3A+Imprint%3A+Springer&rft.isbn=978-3-662-43839-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFRunesonEngstr.C3.B6mStorey2020\">Runeson, Per; Engstr\u00f6m, Emelie; Storey, Margaret-Anne (2020), Felderer, Michael; Travassos, Guilherme Horta, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-030-32489-6_5\" target=\"_blank\">\"The Design Science Paradigm as a Frame for Empirical Software Engineering\"<\/a> (in en), <i>Contemporary Empirical Methods in Software Engineering<\/i> (Cham: Springer International Publishing): 127\u2013147, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-030-32489-6_5\" target=\"_blank\">10.1007\/978-3-030-32489-6_5<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-030-32488-9<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-030-32489-6_5\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-030-32489-6_5<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Design+Science+Paradigm+as+a+Frame+for+Empirical+Software+Engineering&rft.jtitle=Contemporary+Empirical+Methods+in+Software+Engineering&rft.aulast=Runeson&rft.aufirst=Per&rft.au=Runeson%2C%26%2332%3BPer&rft.au=Engstr%C3%B6m%2C%26%2332%3BEmelie&rft.au=Storey%2C%26%2332%3BMargaret-Anne&rft.date=2020&rft.pages=127%E2%80%93147&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-030-32489-6_5&rft.isbn=978-3-030-32488-9&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-030-32489-6_5&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Koksal, Omer; Tekinerdogan, Bedir (1 June 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/8039061\/\" target=\"_blank\">\"Feature-Driven Domain Analysis of Session Layer Protocols of Internet of Things\"<\/a>. <i>2017 IEEE International Congress on Internet of Things (ICIOT)<\/i> (Honolulu, HI, USA: IEEE): 105\u2013112. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FIEEE.ICIOT.2017.19\" target=\"_blank\">10.1109\/IEEE.ICIOT.2017.19<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5386-2011-3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/8039061\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/8039061\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Feature-Driven+Domain+Analysis+of+Session+Layer+Protocols+of+Internet+of+Things&rft.jtitle=2017+IEEE+International+Congress+on+Internet+of+Things+%28ICIOT%29&rft.aulast=Koksal&rft.aufirst=Omer&rft.au=Koksal%2C%26%2332%3BOmer&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.date=1+June+2017&rft.pages=105%E2%80%93112&rft.place=Honolulu%2C+HI%2C+USA&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FIEEE.ICIOT.2017.19&rft.isbn=978-1-5386-2011-3&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8039061%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-24\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_24-0\">24.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_24-1\">24.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">van Geest, Maarten; Tekinerdogan, Bedir; Catal, Cagatay (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361520305777\" target=\"_blank\">\"Design of a reference architecture for developing smart warehouses in industry 4.0\"<\/a> (in en). <i>Computers in Industry<\/i> <b>124<\/b>: 103343. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compind.2020.103343\" target=\"_blank\">10.1016\/j.compind.2020.103343<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361520305777\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361520305777<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Design+of+a+reference+architecture+for+developing+smart+warehouses+in+industry+4.0&rft.jtitle=Computers+in+Industry&rft.aulast=van+Geest&rft.aufirst=Maarten&rft.au=van+Geest%2C%26%2332%3BMaarten&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.au=Catal%2C%26%2332%3BCagatay&rft.date=1+January+2021&rft.volume=124&rft.pages=103343&rft_id=info:doi\/10.1016%2Fj.compind.2020.103343&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0166361520305777&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-25\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_25-0\">25.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_25-1\">25.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFTekinerdogan.C3.96zt.C3.BCrk2013\">Tekinerdogan, Bedir; \u00d6zt\u00fcrk, Karahan (2013), Mahmood, Zaigham; Saeed, Saqib, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-1-4471-5031-2_9\" target=\"_blank\">\"Feature-Driven Design of SaaS Architectures\"<\/a>, <i>Software Engineering Frameworks for the Cloud Computing Paradigm<\/i> (London: Springer London): 189\u2013212, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-1-4471-5031-2_9\" target=\"_blank\">10.1007\/978-1-4471-5031-2_9<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4471-5030-5<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-1-4471-5031-2_9\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-1-4471-5031-2_9<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Feature-Driven+Design+of+SaaS+Architectures&rft.jtitle=Software+Engineering+Frameworks+for+the+Cloud+Computing+Paradigm&rft.aulast=Tekinerdogan&rft.aufirst=Bedir&rft.au=Tekinerdogan%2C%26%2332%3BBedir&rft.au=%C3%96zt%C3%BCrk%2C%26%2332%3BKarahan&rft.date=2013&rft.pages=189%E2%80%93212&rft.place=London&rft.pub=Springer+London&rft_id=info:doi\/10.1007%2F978-1-4471-5031-2_9&rft.isbn=978-1-4471-5030-5&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-1-4471-5031-2_9&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-26\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_26-0\">26.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_26-1\">26.1<\/a><\/sup> <sup><a href=\"#cite_ref-:11_26-2\">26.2<\/a><\/sup> <sup><a href=\"#cite_ref-:11_26-3\">26.3<\/a><\/sup> <sup><a href=\"#cite_ref-:11_26-4\">26.4<\/a><\/sup> <sup><a href=\"#cite_ref-:11_26-5\">26.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Arsevska, Elena; Valentin, Sarah; Rabatel, Julien; de Go\u00ebr de Herv\u00e9, Jocelyn; Falala, Sylvain; Lancelot, Renaud; Roche, Mathieu (3 August 2018). D\u00f3rea, Fernanda C.. ed. <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dx.plos.org\/10.1371\/journal.pone.0199960\" target=\"_blank\">\"Web monitoring of emerging animal infectious diseases integrated in the French Animal Health Epidemic Intelligence System\"<\/a> (in en). <i>PLOS ONE<\/i> <b>13<\/b> (8): e0199960. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1371%2Fjournal.pone.0199960\" target=\"_blank\">10.1371\/journal.pone.0199960<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1932-6203\" target=\"_blank\">1932-6203<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6075742\/\" target=\"_blank\">PMC6075742<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30074992\" target=\"_blank\">30074992<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dx.plos.org\/10.1371\/journal.pone.0199960\" target=\"_blank\">https:\/\/dx.plos.org\/10.1371\/journal.pone.0199960<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Web+monitoring+of+emerging+animal+infectious+diseases+integrated+in+the+French+Animal+Health+Epidemic+Intelligence+System&rft.jtitle=PLOS+ONE&rft.aulast=Arsevska&rft.aufirst=Elena&rft.au=Arsevska%2C%26%2332%3BElena&rft.au=Valentin%2C%26%2332%3BSarah&rft.au=Rabatel%2C%26%2332%3BJulien&rft.au=de+Go%C3%ABr+de+Herv%C3%A9%2C%26%2332%3BJocelyn&rft.au=Falala%2C%26%2332%3BSylvain&rft.au=Lancelot%2C%26%2332%3BRenaud&rft.au=Roche%2C%26%2332%3BMathieu&rft.date=3+August+2018&rft.volume=13&rft.issue=8&rft.pages=e0199960&rft_id=info:doi\/10.1371%2Fjournal.pone.0199960&rft.issn=1932-6203&rft_id=info:pmc\/PMC6075742&rft_id=info:pmid\/30074992&rft_id=https%3A%2F%2Fdx.plos.org%2F10.1371%2Fjournal.pone.0199960&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-27\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_27-0\">27.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_27-1\">27.1<\/a><\/sup> <sup><a href=\"#cite_ref-:12_27-2\">27.2<\/a><\/sup> <sup><a href=\"#cite_ref-:12_27-3\">27.3<\/a><\/sup> <sup><a href=\"#cite_ref-:12_27-4\">27.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shahhosseini, Mohsen; Hu, Guiping; Huber, Isaiah; Archontoulis, Sotirios V. (1 December 2021). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41598-020-80820-1\" target=\"_blank\">\"Coupling machine learning and crop modeling improves crop yield prediction in the US Corn Belt\"<\/a> (in en). <i>Scientific Reports<\/i> <b>11<\/b> (1): 1606. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41598-020-80820-1\" target=\"_blank\">10.1038\/s41598-020-80820-1<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2045-2322\" target=\"_blank\">2045-2322<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7810832\/\" target=\"_blank\">PMC7810832<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33452349\" target=\"_blank\">33452349<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41598-020-80820-1\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41598-020-80820-1<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Coupling+machine+learning+and+crop+modeling+improves+crop+yield+prediction+in+the+US+Corn+Belt&rft.jtitle=Scientific+Reports&rft.aulast=Shahhosseini&rft.aufirst=Mohsen&rft.au=Shahhosseini%2C%26%2332%3BMohsen&rft.au=Hu%2C%26%2332%3BGuiping&rft.au=Huber%2C%26%2332%3BIsaiah&rft.au=Archontoulis%2C%26%2332%3BSotirios+V.&rft.date=1+December+2021&rft.volume=11&rft.issue=1&rft.pages=1606&rft_id=info:doi\/10.1038%2Fs41598-020-80820-1&rft.issn=2045-2322&rft_id=info:pmc\/PMC7810832&rft_id=info:pmid\/33452349&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41598-020-80820-1&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:13-28\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:13_28-0\">28.0<\/a><\/sup> <sup><a href=\"#cite_ref-:13_28-1\">28.1<\/a><\/sup> <sup><a href=\"#cite_ref-:13_28-2\">28.2<\/a><\/sup> <sup><a href=\"#cite_ref-:13_28-3\">28.3<\/a><\/sup> <sup><a href=\"#cite_ref-:13_28-4\">28.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sanjeevi, P.; Prasanna, S.; Siva Kumar, B.; Gunasekaran, G.; Alagiri, I.; Vijay Anand, R. (1 December 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ett.3978\" target=\"_blank\">\"Precision agriculture and farming using Internet of Things based on wireless sensor network\"<\/a> (in en). <i>Transactions on Emerging Telecommunications Technologies<\/i> <b>31<\/b> (12): e3978. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fett.3978\" target=\"_blank\">10.1002\/ett.3978<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2161-3915\" target=\"_blank\">2161-3915<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ett.3978\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ett.3978<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Precision+agriculture+and+farming+using+Internet+of+Things+based+on+wireless+sensor+network&rft.jtitle=Transactions+on+Emerging+Telecommunications+Technologies&rft.aulast=Sanjeevi&rft.aufirst=P.&rft.au=Sanjeevi%2C%26%2332%3BP.&rft.au=Prasanna%2C%26%2332%3BS.&rft.au=Siva+Kumar%2C%26%2332%3BB.&rft.au=Gunasekaran%2C%26%2332%3BG.&rft.au=Alagiri%2C%26%2332%3BI.&rft.au=Vijay+Anand%2C%26%2332%3BR.&rft.date=1+December+2020&rft.volume=31&rft.issue=12&rft.pages=e3978&rft_id=info:doi\/10.1002%2Fett.3978&rft.issn=2161-3915&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fett.3978&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:14-29\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:14_29-0\">29.0<\/a><\/sup> <sup><a href=\"#cite_ref-:14_29-1\">29.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sharma, Rohit; Kamble, Sachin S.; Gunasekaran, Angappa; Kumar, Vikas; Kumar, Anil (1 July 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0305054820300435\" target=\"_blank\">\"A systematic literature review on machine learning applications for sustainable agriculture supply chain performance\"<\/a> (in en). <i>Computers & Operations Research<\/i> <b>119<\/b>: 104926. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.cor.2020.104926\" target=\"_blank\">10.1016\/j.cor.2020.104926<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0305054820300435\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0305054820300435<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+systematic+literature+review+on+machine+learning+applications+for+sustainable+agriculture+supply+chain+performance&rft.jtitle=Computers+%26+Operations+Research&rft.aulast=Sharma&rft.aufirst=Rohit&rft.au=Sharma%2C%26%2332%3BRohit&rft.au=Kamble%2C%26%2332%3BSachin+S.&rft.au=Gunasekaran%2C%26%2332%3BAngappa&rft.au=Kumar%2C%26%2332%3BVikas&rft.au=Kumar%2C%26%2332%3BAnil&rft.date=1+July+2020&rft.volume=119&rft.pages=104926&rft_id=info:doi\/10.1016%2Fj.cor.2020.104926&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0305054820300435&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:15-30\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:15_30-0\">30.0<\/a><\/sup> <sup><a href=\"#cite_ref-:15_30-1\">30.1<\/a><\/sup> <sup><a href=\"#cite_ref-:15_30-2\">30.2<\/a><\/sup> <sup><a href=\"#cite_ref-:15_30-3\">30.3<\/a><\/sup> <sup><a href=\"#cite_ref-:15_30-4\">30.4<\/a><\/sup> <sup><a href=\"#cite_ref-:15_30-5\">30.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shi, Yinyan; Zhu, Yang; Wang, Xiaochan; Sun, Xin; Ding, Yangfen; Cao, Wexing; Hu, Zhichao (1 December 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/plantmethods.biomedcentral.com\/articles\/10.1186\/s13007-020-0559-9\" target=\"_blank\">\"Progress and development on biological information of crop phenotype research applied to real-time variable-rate fertilization\"<\/a> (in en). <i>Plant Methods<\/i> <b>16<\/b> (1): 11. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fs13007-020-0559-9\" target=\"_blank\">10.1186\/s13007-020-0559-9<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1746-4811\" target=\"_blank\">1746-4811<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6998365\/\" target=\"_blank\">PMC6998365<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32042303\" target=\"_blank\">32042303<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/plantmethods.biomedcentral.com\/articles\/10.1186\/s13007-020-0559-9\" target=\"_blank\">https:\/\/plantmethods.biomedcentral.com\/articles\/10.1186\/s13007-020-0559-9<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Progress+and+development+on+biological+information+of+crop+phenotype+research+applied+to+real-time+variable-rate+fertilization&rft.jtitle=Plant+Methods&rft.aulast=Shi&rft.aufirst=Yinyan&rft.au=Shi%2C%26%2332%3BYinyan&rft.au=Zhu%2C%26%2332%3BYang&rft.au=Wang%2C%26%2332%3BXiaochan&rft.au=Sun%2C%26%2332%3BXin&rft.au=Ding%2C%26%2332%3BYangfen&rft.au=Cao%2C%26%2332%3BWexing&rft.au=Hu%2C%26%2332%3BZhichao&rft.date=1+December+2020&rft.volume=16&rft.issue=1&rft.pages=11&rft_id=info:doi\/10.1186%2Fs13007-020-0559-9&rft.issn=1746-4811&rft_id=info:pmc\/PMC6998365&rft_id=info:pmid\/32042303&rft_id=https%3A%2F%2Fplantmethods.biomedcentral.com%2Farticles%2F10.1186%2Fs13007-020-0559-9&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Clevers, Jan; Kooistra, Lammert; van den Brande, Marnix (25 April 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.mdpi.com\/2072-4292\/9\/5\/405\" target=\"_blank\">\"Using Sentinel-2 Data for Retrieving LAI and Leaf and Canopy Chlorophyll Content of a Potato Crop\"<\/a> (in en). <i>Remote Sensing<\/i> <b>9<\/b> (5): 405. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Frs9050405\" target=\"_blank\">10.3390\/rs9050405<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2072-4292\" target=\"_blank\">2072-4292<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.mdpi.com\/2072-4292\/9\/5\/405\" target=\"_blank\">http:\/\/www.mdpi.com\/2072-4292\/9\/5\/405<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Using+Sentinel-2+Data+for+Retrieving+LAI+and+Leaf+and+Canopy+Chlorophyll+Content+of+a+Potato+Crop&rft.jtitle=Remote+Sensing&rft.aulast=Clevers&rft.aufirst=Jan&rft.au=Clevers%2C%26%2332%3BJan&rft.au=Kooistra%2C%26%2332%3BLammert&rft.au=van+den+Brande%2C%26%2332%3BMarnix&rft.date=25+April+2017&rft.volume=9&rft.issue=5&rft.pages=405&rft_id=info:doi\/10.3390%2Frs9050405&rft.issn=2072-4292&rft_id=http%3A%2F%2Fwww.mdpi.com%2F2072-4292%2F9%2F5%2F405&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-32\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bach, H.; Mauser, W.; Angermair, W. et al. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/iafastro.directory\/iac\/archive\/browse\/IAC-10\/B5\/1\/6894\/\" target=\"_blank\">\"An integrative approach of using satellite-based information for precision farming: TalkingFields\"<\/a>. <i>Proceedings of the 61st International Astronautical Congress<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/iafastro.directory\/iac\/archive\/browse\/IAC-10\/B5\/1\/6894\/\" target=\"_blank\">http:\/\/iafastro.directory\/iac\/archive\/browse\/IAC-10\/B5\/1\/6894\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=An+integrative+approach+of+using+satellite-based+information+for+precision+farming%3A+TalkingFields&rft.jtitle=Proceedings+of+the+61st+International+Astronautical+Congress&rft.aulast=Bach%2C+H.%3B+Mauser%2C+W.%3B+Angermair%2C+W.+et+al.&rft.au=Bach%2C+H.%3B+Mauser%2C+W.%3B+Angermair%2C+W.+et+al.&rft.date=2010&rft_id=http%3A%2F%2Fiafastro.directory%2Fiac%2Farchive%2Fbrowse%2FIAC-10%2FB5%2F1%2F6894%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-33\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFBachMauser2018\">Bach, Heike; Mauser, Wolfram (2018), Mathieu, Pierre-Philippe; Aubrecht, Christoph, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-65633-5_12\" target=\"_blank\">\"Sustainable Agriculture and Smart Farming\"<\/a> (in en), <i>Earth Observation Open Science and Innovation<\/i> (Cham: Springer International Publishing): 261\u2013269, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-65633-5_12\" target=\"_blank\">10.1007\/978-3-319-65633-5_12<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-65632-8<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-65633-5_12\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-65633-5_12<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Sustainable+Agriculture+and+Smart+Farming&rft.jtitle=Earth+Observation+Open+Science+and+Innovation&rft.aulast=Bach&rft.aufirst=Heike&rft.au=Bach%2C%26%2332%3BHeike&rft.au=Mauser%2C%26%2332%3BWolfram&rft.date=2018&rft.pages=261%E2%80%93269&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-65633-5_12&rft.isbn=978-3-319-65632-8&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-65633-5_12&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-34\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_34-0\">34.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_34-1\">34.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFBurlacuCostaSarraipaJardim-Golcalves2014\">Burlacu, George; Costa, Ruben; Sarraipa, Joao; Jardim-Golcalves, Ricardo; Popescu, Dan (2014), Camarinha-Matos, Luis M.; Barrento, Nuno S.; Mendon\u00e7a, Ricardo, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-54734-8_6\" target=\"_blank\">\"A Conceptual Model of Farm Management Information System for Decision Support\"<\/a>, <i>Technological Innovation for Collective Awareness Systems<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>423<\/b>: 47\u201354, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-642-54734-8_6\" target=\"_blank\">10.1007\/978-3-642-54734-8_6<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-642-54733-1<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-54734-8_6\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-642-54734-8_6<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Conceptual+Model+of+Farm+Management+Information+System+for+Decision+Support&rft.jtitle=Technological+Innovation+for+Collective+Awareness+Systems&rft.aulast=Burlacu&rft.aufirst=George&rft.au=Burlacu%2C%26%2332%3BGeorge&rft.au=Costa%2C%26%2332%3BRuben&rft.au=Sarraipa%2C%26%2332%3BJoao&rft.au=Jardim-Golcalves%2C%26%2332%3BRicardo&rft.au=Popescu%2C%26%2332%3BDan&rft.date=2014&rft.volume=423&rft.pages=47%E2%80%9354&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-642-54734-8_6&rft.isbn=978-3-642-54733-1&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-642-54734-8_6&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Srivastava, S. (2002). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.geospatialworld.net\/article\/space-inputs-for-precision-agriculture-scope-for-proto-type-experiments-in-the-diverse-indian-agro-ecosystems\/\" target=\"_blank\">\"Space inputs for precision agriculture: scope for prototype experiments in the diverse Indian agro-ecosystems\"<\/a>. <i>Proceedings of the Map Asia 2002<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.geospatialworld.net\/article\/space-inputs-for-precision-agriculture-scope-for-proto-type-experiments-in-the-diverse-indian-agro-ecosystems\/\" target=\"_blank\">https:\/\/www.geospatialworld.net\/article\/space-inputs-for-precision-agriculture-scope-for-proto-type-experiments-in-the-diverse-indian-agro-ecosystems\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Space+inputs+for+precision+agriculture%3A+scope+for+prototype+experiments+in+the+diverse+Indian+agro-ecosystems&rft.atitle=Proceedings+of+the+Map+Asia+2002&rft.aulast=Srivastava%2C+S.&rft.au=Srivastava%2C+S.&rft.date=2002&rft_id=https%3A%2F%2Fwww.geospatialworld.net%2Farticle%2Fspace-inputs-for-precision-agriculture-scope-for-proto-type-experiments-in-the-diverse-indian-agro-ecosystems%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nikkil\u00e4, Raimo; Seilonen, Ilkka; Koskinen, Kari (1 March 2010). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169909001859\" target=\"_blank\">\"Software architecture for farm management information systems in precision agriculture\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>70<\/b> (2): 328\u2013336. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2009.08.013\" target=\"_blank\">10.1016\/j.compag.2009.08.013<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169909001859\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169909001859<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Software+architecture+for+farm+management+information+systems+in+precision+agriculture&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Nikkil%C3%A4&rft.aufirst=Raimo&rft.au=Nikkil%C3%A4%2C%26%2332%3BRaimo&rft.au=Seilonen%2C%26%2332%3BIlkka&rft.au=Koskinen%2C%26%2332%3BKari&rft.date=1+March+2010&rft.volume=70&rft.issue=2&rft.pages=328%E2%80%93336&rft_id=info:doi\/10.1016%2Fj.compag.2009.08.013&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169909001859&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kaloxylos, Alexandros; Groumas, Aggelos; Sarris, Vassilis; Katsikas, Lampros; Magdalinos, Panagis; Antoniou, Eleni; Politopoulou, Zoi; Wolfert, Sjaak <i>et al.<\/i> (1 January 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169913002846\" target=\"_blank\">\"A cloud-based Farm Management System: Architecture and implementation\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>100<\/b>: 168\u2013179. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2013.11.014\" target=\"_blank\">10.1016\/j.compag.2013.11.014<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169913002846\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169913002846<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+cloud-based+Farm+Management+System%3A+Architecture+and+implementation&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Kaloxylos&rft.aufirst=Alexandros&rft.au=Kaloxylos%2C%26%2332%3BAlexandros&rft.au=Groumas%2C%26%2332%3BAggelos&rft.au=Sarris%2C%26%2332%3BVassilis&rft.au=Katsikas%2C%26%2332%3BLampros&rft.au=Magdalinos%2C%26%2332%3BPanagis&rft.au=Antoniou%2C%26%2332%3BEleni&rft.au=Politopoulou%2C%26%2332%3BZoi&rft.au=Wolfert%2C%26%2332%3BSjaak&rft.au=Brewster%2C%26%2332%3BChristopher&rft.date=1+January+2014&rft.volume=100&rft.pages=168%E2%80%93179&rft_id=info:doi\/10.1016%2Fj.compag.2013.11.014&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169913002846&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kruize, J.W.; Wolfert, J.; Scholten, H.; Verdouw, C.N.; Kassahun, A.; Beulens, A.J.M. (1 July 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301296\" target=\"_blank\">\"A reference architecture for Farm Software Ecosystems\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>125<\/b>: 12\u201328. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2016.04.011\" target=\"_blank\">10.1016\/j.compag.2016.04.011<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301296\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301296<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+reference+architecture+for+Farm+Software+Ecosystems&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Kruize&rft.aufirst=J.W.&rft.au=Kruize%2C%26%2332%3BJ.W.&rft.au=Wolfert%2C%26%2332%3BJ.&rft.au=Scholten%2C%26%2332%3BH.&rft.au=Verdouw%2C%26%2332%3BC.N.&rft.au=Kassahun%2C%26%2332%3BA.&rft.au=Beulens%2C%26%2332%3BA.J.M.&rft.date=1+July+2016&rft.volume=125&rft.pages=12%E2%80%9328&rft_id=info:doi\/10.1016%2Fj.compag.2016.04.011&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169916301296&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:16-39\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:16_39-0\">39.0<\/a><\/sup> <sup><a href=\"#cite_ref-:16_39-1\">39.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">McAfee, A.; Brynjolffsson, E. (October 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/hbr.org\/2012\/10\/big-data-the-management-revolution\" target=\"_blank\">\"Big Data: The Management Revolution\"<\/a>. <i>Harvard Business Review<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/hbr.org\/2012\/10\/big-data-the-management-revolution\" target=\"_blank\">https:\/\/hbr.org\/2012\/10\/big-data-the-management-revolution<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Big+Data%3A+The+Management+Revolution&rft.atitle=Harvard+Business+Review&rft.aulast=McAfee%2C+A.%3B+Brynjolffsson%2C+E.&rft.au=McAfee%2C+A.%3B+Brynjolffsson%2C+E.&rft.date=October+2012&rft_id=https%3A%2F%2Fhbr.org%2F2012%2F10%2Fbig-data-the-management-revolution&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Goodfellow, Ian; Bengio, Yoshua; Courville, Aaron (2016). <i>Deep learning<\/i>. Adaptive computation and machine learning. Cambridge, Massachusetts: The MIT Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-262-03561-3.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Deep+learning&rft.aulast=Goodfellow&rft.aufirst=Ian&rft.au=Goodfellow%2C%26%2332%3BIan&rft.au=Bengio%2C%26%2332%3BYoshua&rft.au=Courville%2C%26%2332%3BAaron&rft.date=2016&rft.series=Adaptive+computation+and+machine+learning&rft.place=Cambridge%2C+Massachusetts&rft.pub=The+MIT+Press&rft.isbn=978-0-262-03561-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ashmore, Rob; Calinescu, Radu; Paterson, Colin (30 June 2022). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3453444\" target=\"_blank\">\"Assuring the Machine Learning Lifecycle: Desiderata, Methods, and Challenges\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>54<\/b> (5): 1\u201339. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3453444\" target=\"_blank\">10.1145\/3453444<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3453444\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3453444<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Assuring+the+Machine+Learning+Lifecycle%3A+Desiderata%2C+Methods%2C+and+Challenges&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Ashmore&rft.aufirst=Rob&rft.au=Ashmore%2C%26%2332%3BRob&rft.au=Calinescu%2C%26%2332%3BRadu&rft.au=Paterson%2C%26%2332%3BColin&rft.date=30+June+2022&rft.volume=54&rft.issue=5&rft.pages=1%E2%80%9339&rft_id=info:doi\/10.1145%2F3453444&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3453444&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Dayal, U.; Akatsu, M.; Gupta, C. et al. (2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hitachi.com\/rev\/archive\/2014\/r2014_06.html\" target=\"_blank\">\"Expanding Global Big Data Solutions with Innovative Analytics\"<\/a>. <i>Hitachi Review<\/i> <b>63<\/b> (6): 333\u201339<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hitachi.com\/rev\/archive\/2014\/r2014_06.html\" target=\"_blank\">https:\/\/www.hitachi.com\/rev\/archive\/2014\/r2014_06.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Expanding+Global+Big+Data+Solutions+with+Innovative+Analytics&rft.jtitle=Hitachi+Review&rft.aulast=Dayal%2C+U.%3B+Akatsu%2C+M.%3B+Gupta%2C+C.+et+al.&rft.au=Dayal%2C+U.%3B+Akatsu%2C+M.%3B+Gupta%2C+C.+et+al.&rft.date=2014&rft.volume=63&rft.issue=6&rft.pages=333%E2%80%9339&rft_id=https%3A%2F%2Fwww.hitachi.com%2Frev%2Farchive%2F2014%2Fr2014_06.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Suriarachchi, Isuru; Plale, Beth (1 October 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7870919\/\" target=\"_blank\">\"Crossing analytics systems: A case for integrated provenance in data lakes\"<\/a>. <i>2016 IEEE 12th International Conference on e-Science (e-Science)<\/i> (Baltimore, MD, USA: IEEE): 349\u2013354. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FeScience.2016.7870919\" target=\"_blank\">10.1109\/eScience.2016.7870919<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5090-4273-9<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7870919\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7870919\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Crossing+analytics+systems%3A+A+case+for+integrated+provenance+in+data+lakes&rft.jtitle=2016+IEEE+12th+International+Conference+on+e-Science+%28e-Science%29&rft.aulast=Suriarachchi&rft.aufirst=Isuru&rft.au=Suriarachchi%2C%26%2332%3BIsuru&rft.au=Plale%2C%26%2332%3BBeth&rft.date=1+October+2016&rft.pages=349%E2%80%93354&rft.place=Baltimore%2C+MD%2C+USA&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FeScience.2016.7870919&rft.isbn=978-1-5090-4273-9&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7870919%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFRaoJiangYangPeng2017\">Rao, Wei; Jiang, Jing; Yang, Ming; Peng, Wei; Zhou, Aihua (2017), Li, Kang; Xue, Yusheng; Cui, Shumei <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-10-6364-0_22\" target=\"_blank\">\"Research on Energy Interconnection Oriented Big Data Sharing Platform Reference Architecture\"<\/a>, <i>Advanced Computational Methods in Energy, Power, Electric Vehicles, and Their Integration<\/i> (Singapore: Springer Singapore) <b>763<\/b>: 217\u2013225, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-981-10-6364-0_22\" target=\"_blank\">10.1007\/978-981-10-6364-0_22<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-981-10-6363-3<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-10-6364-0_22\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-981-10-6364-0_22<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+on+Energy+Interconnection+Oriented+Big+Data+Sharing+Platform+Reference+Architecture&rft.jtitle=Advanced+Computational+Methods+in+Energy%2C+Power%2C+Electric+Vehicles%2C+and+Their+Integration&rft.aulast=Rao&rft.aufirst=Wei&rft.au=Rao%2C%26%2332%3BWei&rft.au=Jiang%2C%26%2332%3BJing&rft.au=Yang%2C%26%2332%3BMing&rft.au=Peng%2C%26%2332%3BWei&rft.au=Zhou%2C%26%2332%3BAihua&rft.date=2017&rft.volume=763&rft.pages=217%E2%80%93225&rft.place=Singapore&rft.pub=Springer+Singapore&rft_id=info:doi\/10.1007%2F978-981-10-6364-0_22&rft.isbn=978-981-10-6363-3&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-981-10-6364-0_22&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFSangXude_Vrieze2017\">Sang, Go Muan; Xu, Lai; de Vrieze, Paul (2017), Camarinha-Matos, Luis M.; Afsarmanesh, Hamideh; Fornasiero, Rosanna, eds., <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/link.springer.com\/10.1007\/978-3-319-65151-4_23\" target=\"_blank\">\"Simplifying Big Data Analytics Systems with a Reference Architecture\"<\/a> (in en), <i>Collaboration in a Data-Rich World<\/i> (Cham: Springer International Publishing) <b>506<\/b>: 242\u2013249, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-65151-4_23\" target=\"_blank\">10.1007\/978-3-319-65151-4_23<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-65150-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/link.springer.com\/10.1007\/978-3-319-65151-4_23\" target=\"_blank\">https:\/\/link.springer.com\/10.1007\/978-3-319-65151-4_23<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Simplifying+Big+Data+Analytics+Systems+with+a+Reference+Architecture&rft.jtitle=Collaboration+in+a+Data-Rich+World&rft.aulast=Sang&rft.aufirst=Go+Muan&rft.au=Sang%2C%26%2332%3BGo+Muan&rft.au=Xu%2C%26%2332%3BLai&rft.au=de+Vrieze%2C%26%2332%3BPaul&rft.date=2017&rft.volume=506&rft.pages=242%E2%80%93249&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-65151-4_23&rft.isbn=978-3-319-65150-7&rft_id=https%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-65151-4_23&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-46\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-46\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Arass, M.E.; Ouazzani-Touhami, K.; Souissi, N. (25 August 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.warse.org\/IJATCSE\/static\/pdf\/file\/ijatcse215942020.pdf\" target=\"_blank\">\"Data Life Cycle: Towards a Reference Architecture\"<\/a>. <i>International Journal of Advanced Trends in Computer Science and Engineering<\/i> <b>9<\/b> (4): 5645\u20135653. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.30534%2Fijatcse%2F2020%2F215942020\" target=\"_blank\">10.30534\/ijatcse\/2020\/215942020<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.warse.org\/IJATCSE\/static\/pdf\/file\/ijatcse215942020.pdf\" target=\"_blank\">http:\/\/www.warse.org\/IJATCSE\/static\/pdf\/file\/ijatcse215942020.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Data+Life+Cycle%3A+Towards+a+Reference+Architecture&rft.jtitle=International+Journal+of+Advanced+Trends+in+Computer+Science+and+Engineering&rft.aulast=Arass%2C+M.E.%3B+Ouazzani-Touhami%2C+K.%3B+Souissi%2C+N.&rft.au=Arass%2C+M.E.%3B+Ouazzani-Touhami%2C+K.%3B+Souissi%2C+N.&rft.date=25+August+2020&rft.volume=9&rft.issue=4&rft.pages=5645%E2%80%935653&rft_id=info:doi\/10.30534%2Fijatcse%2F2020%2F215942020&rft_id=http%3A%2F%2Fwww.warse.org%2FIJATCSE%2Fstatic%2Fpdf%2Ffile%2Fijatcse215942020.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-47\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_47-0\">47.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_47-1\">47.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">P\u00e4\u00e4kk\u00f6nen, P.; Pakkala, D. (1 December 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-020-00303-y\" target=\"_blank\">\"Extending reference architecture of big data systems towards machine learning in edge computing environments\"<\/a> (in en). <i>Journal of Big Data<\/i> <b>7<\/b> (1): 25. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fs40537-020-00303-y\" target=\"_blank\">10.1186\/s40537-020-00303-y<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2196-1115\" target=\"_blank\">2196-1115<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-020-00303-y\" target=\"_blank\">https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-020-00303-y<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Extending+reference+architecture+of+big+data+systems+towards+machine+learning+in+edge+computing+environments&rft.jtitle=Journal+of+Big+Data&rft.aulast=P%C3%A4%C3%A4kk%C3%B6nen&rft.aufirst=P.&rft.au=P%C3%A4%C3%A4kk%C3%B6nen%2C%26%2332%3BP.&rft.au=Pakkala%2C%26%2332%3BD.&rft.date=1+December+2020&rft.volume=7&rft.issue=1&rft.pages=25&rft_id=info:doi\/10.1186%2Fs40537-020-00303-y&rft.issn=2196-1115&rft_id=https%3A%2F%2Fjournalofbigdata.springeropen.com%2Farticles%2F10.1186%2Fs40537-020-00303-y&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:17-48\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:17_48-0\">48.0<\/a><\/sup> <sup><a href=\"#cite_ref-:17_48-1\">48.1<\/a><\/sup> <sup><a href=\"#cite_ref-:17_48-2\">48.2<\/a><\/sup> <sup><a href=\"#cite_ref-:17_48-3\">48.3<\/a><\/sup> <sup><a href=\"#cite_ref-:17_48-4\">48.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Maier, M. (31 October 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/research.tue.nl\/en\/studentTheses\/towards-a-big-data-reference-architecture\" target=\"_blank\">\"Towards a big data reference architecture\"<\/a>. Eindhoven University of Technology<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/research.tue.nl\/en\/studentTheses\/towards-a-big-data-reference-architecture\" target=\"_blank\">https:\/\/research.tue.nl\/en\/studentTheses\/towards-a-big-data-reference-architecture<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Towards+a+big+data+reference+architecture&rft.atitle=&rft.aulast=Maier%2C+M.&rft.au=Maier%2C+M.&rft.date=31+October+2013&rft.pub=Eindhoven+University+of+Technology&rft_id=https%3A%2F%2Fresearch.tue.nl%2Fen%2FstudentTheses%2Ftowards-a-big-data-reference-architecture&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-49\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-49\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Meehan, J.; Aslantas, C.; Zdonik, S. et al. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dblp.org\/db\/conf\/cidr\/cidr2017.html\" target=\"_blank\">\"Data Ingestion for the Connected World\"<\/a>. <i>Proceedings of the 8th Biennial Conference on Innovative Data Systems Research<\/i>: 1\u201311<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dblp.org\/db\/conf\/cidr\/cidr2017.html\" target=\"_blank\">https:\/\/dblp.org\/db\/conf\/cidr\/cidr2017.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Data+Ingestion+for+the+Connected+World&rft.jtitle=Proceedings+of+the+8th+Biennial+Conference+on+Innovative+Data+Systems+Research&rft.aulast=Meehan%2C+J.%3B+Aslantas%2C+C.%3B+Zdonik%2C+S.+et+al.&rft.au=Meehan%2C+J.%3B+Aslantas%2C+C.%3B+Zdonik%2C+S.+et+al.&rft.date=2017&rft.pages=1%E2%80%9311&rft_id=https%3A%2F%2Fdblp.org%2Fdb%2Fconf%2Fcidr%2Fcidr2017.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-50\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-50\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Stonebraker, Michael; Madden, Sam; Dubey, Pradeep (1 May 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1145\/2481528.2481537\" target=\"_blank\">\"Intel \"big data\" science and technology center vision and execution plan\"<\/a>. <i>ACM SIGMOD Record<\/i> <b>42<\/b> (1): 44\u201349. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2481528.2481537\" target=\"_blank\">10.1145\/2481528.2481537<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0163-5808\" target=\"_blank\">0163-5808<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1145\/2481528.2481537\" target=\"_blank\">https:\/\/doi.org\/10.1145\/2481528.2481537<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Intel+%22big+data%22+science+and+technology+center+vision+and+execution+plan&rft.jtitle=ACM+SIGMOD+Record&rft.aulast=Stonebraker&rft.aufirst=Michael&rft.au=Stonebraker%2C%26%2332%3BMichael&rft.au=Madden%2C%26%2332%3BSam&rft.au=Dubey%2C%26%2332%3BPradeep&rft.date=1+May+2013&rft.volume=42&rft.issue=1&rft.pages=44%E2%80%9349&rft_id=info:doi\/10.1145%2F2481528.2481537&rft.issn=0163-5808&rft_id=https%3A%2F%2Fdoi.org%2F10.1145%2F2481528.2481537&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-51\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-51\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Adnan, Kiran; Akbar, Rehan (1 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-019-0254-8\" target=\"_blank\">\"An analytical study of information extraction from unstructured and multidimensional big data\"<\/a> (in en). <i>Journal of Big Data<\/i> <b>6<\/b> (1): 91. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fs40537-019-0254-8\" target=\"_blank\">10.1186\/s40537-019-0254-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2196-1115\" target=\"_blank\">2196-1115<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-019-0254-8\" target=\"_blank\">https:\/\/journalofbigdata.springeropen.com\/articles\/10.1186\/s40537-019-0254-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=An+analytical+study+of+information+extraction+from+unstructured+and+multidimensional+big+data&rft.jtitle=Journal+of+Big+Data&rft.aulast=Adnan&rft.aufirst=Kiran&rft.au=Adnan%2C%26%2332%3BKiran&rft.au=Akbar%2C%26%2332%3BRehan&rft.date=1+December+2019&rft.volume=6&rft.issue=1&rft.pages=91&rft_id=info:doi\/10.1186%2Fs40537-019-0254-8&rft.issn=2196-1115&rft_id=https%3A%2F%2Fjournalofbigdata.springeropen.com%2Farticles%2F10.1186%2Fs40537-019-0254-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:18-52\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:18_52-0\">52.0<\/a><\/sup> <sup><a href=\"#cite_ref-:18_52-1\">52.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Singh, Sonit (2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1807.02383\" target=\"_blank\">\"Natural Language Processing for Information Extraction\"<\/a>. <i>arXiv<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.48550%2FARXIV.1807.02383\" target=\"_blank\">10.48550\/ARXIV.1807.02383<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1807.02383\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1807.02383<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Natural+Language+Processing+for+Information+Extraction&rft.jtitle=arXiv&rft.aulast=Singh&rft.aufirst=Sonit&rft.au=Singh%2C%26%2332%3BSonit&rft.date=2018&rft_id=info:doi\/10.48550%2FARXIV.1807.02383&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1807.02383&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-53\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-53\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gangadharan, Veena; Gupta, Deepa (2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050920311224\" target=\"_blank\">\"Recognizing Named Entities in Agriculture Documents using LDA based Topic Modelling Techniques\"<\/a> (in en). <i>Procedia Computer Science<\/i> <b>171<\/b>: 1337\u20131345. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.procs.2020.04.143\" target=\"_blank\">10.1016\/j.procs.2020.04.143<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050920311224\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1877050920311224<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Recognizing+Named+Entities+in+Agriculture+Documents+using+LDA+based+Topic+Modelling+Techniques&rft.jtitle=Procedia+Computer+Science&rft.aulast=Gangadharan&rft.aufirst=Veena&rft.au=Gangadharan%2C%26%2332%3BVeena&rft.au=Gupta%2C%26%2332%3BDeepa&rft.date=2020&rft.volume=171&rft.pages=1337%E2%80%931345&rft_id=info:doi\/10.1016%2Fj.procs.2020.04.143&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1877050920311224&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-54\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-54\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Oliveira, P.; Rodrigues, F.; Henriques, P.R. (2005). <a rel=\"nofollow\" class=\"external text\" href=\"#OliveiraRH05\">\"A Formal Definition of Data Quality Problems\"<\/a>. <i>Proceedings of ICIQ 2005<\/i><span class=\"printonly\">. <a rel=\"nofollow\" class=\"external free\" href=\"#OliveiraRH05\">https:\/\/dblp.uni-trier.de\/db\/conf\/iq\/iq2005.html#OliveiraRH05<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Formal+Definition+of+Data+Quality+Problems&rft.jtitle=Proceedings+of+ICIQ+2005&rft.aulast=Oliveira%2C+P.%3B+Rodrigues%2C+F.%3B+Henriques%2C+P.R.&rft.au=Oliveira%2C+P.%3B+Rodrigues%2C+F.%3B+Henriques%2C+P.R.&rft.date=2005&rft_id=https%3A%2F%2Fdblp.uni-trier.de%2Fdb%2Fconf%2Fiq%2Fiq2005.html%23OliveiraRH05&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-55\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-55\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFZieglerDittrich2007\">Ziegler, Patrick; Dittrich, Klaus R. (2007), Krogstie, John; Opdahl, Andreas Lothe; Brinkkemper, Sjaak, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-72677-7_3\" target=\"_blank\">\"Data Integration \u2014 Problems, Approaches, and Perspectives\"<\/a> (in en), <i>Conceptual Modelling in Information Systems Engineering<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg): 39\u201358, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-540-72677-7_3\" target=\"_blank\">10.1007\/978-3-540-72677-7_3<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-540-72676-0<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-72677-7_3\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-540-72677-7_3<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Data+Integration+%E2%80%94+Problems%2C+Approaches%2C+and+Perspectives&rft.jtitle=Conceptual+Modelling+in+Information+Systems+Engineering&rft.aulast=Ziegler&rft.aufirst=Patrick&rft.au=Ziegler%2C%26%2332%3BPatrick&rft.au=Dittrich%2C%26%2332%3BKlaus+R.&rft.date=2007&rft.pages=39%E2%80%9358&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-540-72677-7_3&rft.isbn=978-3-540-72676-0&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-540-72677-7_3&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-56\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-56\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lenzerini, Maurizio (2002). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=543613.543644\" target=\"_blank\">\"Data integration: a theoretical perspective\"<\/a> (in en). <i>Proceedings of the twenty-first ACM SIGMOD-SIGACT-SIGART symposium on Principles of database systems - PODS '02<\/i> (Madison, Wisconsin: ACM Press): 233. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F543613.543644\" target=\"_blank\">10.1145\/543613.543644<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-58113-507-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=543613.543644\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=543613.543644<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Data+integration%3A+a+theoretical+perspective&rft.jtitle=Proceedings+of+the+twenty-first+ACM+SIGMOD-SIGACT-SIGART+symposium+on+Principles+of+database+systems++-+PODS+%2702&rft.aulast=Lenzerini&rft.aufirst=Maurizio&rft.au=Lenzerini%2C%26%2332%3BMaurizio&rft.date=2002&rft.pages=233&rft.place=Madison%2C+Wisconsin&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F543613.543644&rft.isbn=978-1-58113-507-7&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D543613.543644&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-57\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-57\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Batini, C.; Lenzerini, M.; Navathe, S. B. (11 December 1986). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/27633.27634\" target=\"_blank\">\"A comparative analysis of methodologies for database schema integration\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>18<\/b> (4): 323\u2013364. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F27633.27634\" target=\"_blank\">10.1145\/27633.27634<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/27633.27634\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/27633.27634<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+comparative+analysis+of+methodologies+for+database+schema+integration&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Batini&rft.aufirst=C.&rft.au=Batini%2C%26%2332%3BC.&rft.au=Lenzerini%2C%26%2332%3BM.&rft.au=Navathe%2C%26%2332%3BS.+B.&rft.date=11+December+1986&rft.volume=18&rft.issue=4&rft.pages=323%E2%80%93364&rft_id=info:doi\/10.1145%2F27633.27634&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F27633.27634&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-58\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-58\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cugola, Gianpaolo; Margara, Alessandro (1 June 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2187671.2187677\" target=\"_blank\">\"Processing flows of information: From data stream to complex event processing\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>44<\/b> (3): 1\u201362. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2187671.2187677\" target=\"_blank\">10.1145\/2187671.2187677<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2187671.2187677\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/2187671.2187677<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Processing+flows+of+information%3A+From+data+stream+to+complex+event+processing&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Cugola&rft.aufirst=Gianpaolo&rft.au=Cugola%2C%26%2332%3BGianpaolo&rft.au=Margara%2C%26%2332%3BAlessandro&rft.date=1+June+2012&rft.volume=44&rft.issue=3&rft.pages=1%E2%80%9362&rft_id=info:doi\/10.1145%2F2187671.2187677&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F2187671.2187677&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-59\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-59\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Carbone, P.; Katsifodimos, A.; Ewen, S. et al. (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/sites.computer.org\/debull\/A15dec\/issue1.htm\" target=\"_blank\">\"Apache Flink: Stream and Batch Processing in a Single Engine\"<\/a>. <i>Bulletin of the Technical Committee on Data Engineering<\/i> <b>38<\/b> (4): 28\u201338<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/sites.computer.org\/debull\/A15dec\/issue1.htm\" target=\"_blank\">http:\/\/sites.computer.org\/debull\/A15dec\/issue1.htm<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Apache+Flink%3A+Stream+and+Batch+Processing+in+a+Single+Engine&rft.jtitle=Bulletin+of+the+Technical+Committee+on+Data+Engineering&rft.aulast=Carbone%2C+P.%3B+Katsifodimos%2C+A.%3B+Ewen%2C+S.+et+al.&rft.au=Carbone%2C+P.%3B+Katsifodimos%2C+A.%3B+Ewen%2C+S.+et+al.&rft.date=2015&rft.volume=38&rft.issue=4&rft.pages=28%E2%80%9338&rft_id=http%3A%2F%2Fsites.computer.org%2Fdebull%2FA15dec%2Fissue1.htm&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-60\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-60\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Begoli, Edmon (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2361999.2362039\" target=\"_blank\">\"A short survey on the state of the art in architectures and platforms for large scale data analysis and knowledge discovery from data\"<\/a> (in en). <i>Proceedings of the WICSA\/ECSA 2012 Companion Volume on - WICSA\/ECSA '12<\/i> (Helsinki, Finland: ACM Press): 177. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2361999.2362039\" target=\"_blank\">10.1145\/2361999.2362039<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-1568-5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2361999.2362039\" target=\"_blank\">http:\/\/dl.acm.org\/citation.cfm?doid=2361999.2362039<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+short+survey+on+the+state+of+the+art+in+architectures+and+platforms+for+large+scale+data+analysis+and+knowledge+discovery+from+data&rft.jtitle=Proceedings+of+the+WICSA%2FECSA+2012+Companion+Volume+on+-+WICSA%2FECSA+%2712&rft.aulast=Begoli&rft.aufirst=Edmon&rft.au=Begoli%2C%26%2332%3BEdmon&rft.date=2012&rft.pages=177&rft.place=Helsinki%2C+Finland&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F2361999.2362039&rft.isbn=978-1-4503-1568-5&rft_id=http%3A%2F%2Fdl.acm.org%2Fcitation.cfm%3Fdoid%3D2361999.2362039&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-61\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-61\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chen, Jinchuan; Chen, Yueguo; Du, Xiaoyong; Li, Cuiping; Lu, Jiaheng; Zhao, Suyun; Zhou, Xuan (1 April 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11704-013-3903-7\" target=\"_blank\">\"Big data challenge: a data management perspective\"<\/a> (in en). <i>Frontiers of Computer Science<\/i> <b>7<\/b> (2): 157\u2013164. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11704-013-3903-7\" target=\"_blank\">10.1007\/s11704-013-3903-7<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2095-2228\" target=\"_blank\">2095-2228<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11704-013-3903-7\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11704-013-3903-7<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+data+challenge%3A+a+data+management+perspective&rft.jtitle=Frontiers+of+Computer+Science&rft.aulast=Chen&rft.aufirst=Jinchuan&rft.au=Chen%2C%26%2332%3BJinchuan&rft.au=Chen%2C%26%2332%3BYueguo&rft.au=Du%2C%26%2332%3BXiaoyong&rft.au=Li%2C%26%2332%3BCuiping&rft.au=Lu%2C%26%2332%3BJiaheng&rft.au=Zhao%2C%26%2332%3BSuyun&rft.au=Zhou%2C%26%2332%3BXuan&rft.date=1+April+2013&rft.volume=7&rft.issue=2&rft.pages=157%E2%80%93164&rft_id=info:doi\/10.1007%2Fs11704-013-3903-7&rft.issn=2095-2228&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11704-013-3903-7&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:19-62\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:19_62-0\">62.0<\/a><\/sup> <sup><a href=\"#cite_ref-:19_62-1\">62.1<\/a><\/sup> <sup><a href=\"#cite_ref-:19_62-2\">62.2<\/a><\/sup> <sup><a href=\"#cite_ref-:19_62-3\">62.3<\/a><\/sup> <sup><a href=\"#cite_ref-:19_62-4\">62.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Henderson, Deborah; Earley, Susan; Data Administration Management Association, eds. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1012690183\" target=\"_blank\"><i>DAMA-DMBOK: data management body of knowledge<\/i><\/a> (Second edition ed.). Basking Ridge, New Jersey: Technics Publications. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-63462-236-3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/1012690183\" target=\"_blank\">1012690183<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1012690183\" target=\"_blank\">https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1012690183<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=DAMA-DMBOK%3A+data+management+body+of+knowledge&rft.date=2017&rft.edition=Second+edition&rft.place=Basking+Ridge%2C+New+Jersey&rft.pub=Technics+Publications&rft.isbn=978-1-63462-236-3&rft_id=info:oclcnum\/1012690183&rft_id=https%3A%2F%2Fwww.worldcat.org%2Ftitle%2Fmediawiki%2Foclc%2F1012690183&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-63\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-63\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kim, Cheol-Han; Weston, R.H.; Hodgson, A.; Lee, Kyung-Huy (1 January 2003). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361502001458\" target=\"_blank\">\"The complementary use of IDEF and UML modelling approaches\"<\/a> (in en). <i>Computers in Industry<\/i> <b>50<\/b> (1): 35\u201356. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0166-3615%2802%2900145-8\" target=\"_blank\">10.1016\/S0166-3615(02)00145-8<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361502001458\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166361502001458<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+complementary+use+of+IDEF+and+UML+modelling+approaches&rft.jtitle=Computers+in+Industry&rft.aulast=Kim&rft.aufirst=Cheol-Han&rft.au=Kim%2C%26%2332%3BCheol-Han&rft.au=Weston%2C%26%2332%3BR.H.&rft.au=Hodgson%2C%26%2332%3BA.&rft.au=Lee%2C%26%2332%3BKyung-Huy&rft.date=1+January+2003&rft.volume=50&rft.issue=1&rft.pages=35%E2%80%9356&rft_id=info:doi\/10.1016%2FS0166-3615%2802%2900145-8&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0166361502001458&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:20-64\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:20_64-0\">64.0<\/a><\/sup> <sup><a href=\"#cite_ref-:20_64-1\">64.1<\/a><\/sup> <sup><a href=\"#cite_ref-:20_64-2\">64.2<\/a><\/sup> <sup><a href=\"#cite_ref-:20_64-3\">64.3<\/a><\/sup> <sup><a href=\"#cite_ref-:20_64-4\">64.4<\/a><\/sup> <sup><a href=\"#cite_ref-:20_64-5\">64.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Penzenstadler, B.; Femmer, H. (26 November 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/mediatum.ub.tum.de\/attfile\/1121449\/hd2\/incoming\/2012-Nov\/561736.pdf\" target=\"_blank\">\"A Generic Model for Sustainability\"<\/a> (PDF). Technische Universitat<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/mediatum.ub.tum.de\/attfile\/1121449\/hd2\/incoming\/2012-Nov\/561736.pdf\" target=\"_blank\">https:\/\/mediatum.ub.tum.de\/attfile\/1121449\/hd2\/incoming\/2012-Nov\/561736.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=A+Generic+Model+for+Sustainability&rft.atitle=&rft.aulast=Penzenstadler%2C+B.%3B+Femmer%2C+H.&rft.au=Penzenstadler%2C+B.%3B+Femmer%2C+H.&rft.date=26+November+2012&rft.pub=Technische+Universitat&rft_id=https%3A%2F%2Fmediatum.ub.tum.de%2Fattfile%2F1121449%2Fhd2%2Fincoming%2F2012-Nov%2F561736.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:21-65\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:21_65-0\">65.0<\/a><\/sup> <sup><a href=\"#cite_ref-:21_65-1\">65.1<\/a><\/sup> <sup><a href=\"#cite_ref-:21_65-2\">65.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Penzenstadler, Birgit; Femmer, Henning (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2451605.2451609\" target=\"_blank\">\"A generic model for sustainability with process- and product-specific instances\"<\/a> (in en). <i>Proceedings of the 2013 workshop on Green in\/by software engineering - GIBSE '13<\/i> (Fukuoka, Japan: ACM Press): 3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2451605.2451609\" target=\"_blank\">10.1145\/2451605.2451609<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-1866-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/dl.acm.org\/citation.cfm?doid=2451605.2451609\" target=\"_blank\">http:\/\/dl.acm.org\/citation.cfm?doid=2451605.2451609<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+generic+model+for+sustainability+with+process-+and+product-specific+instances&rft.jtitle=Proceedings+of+the+2013+workshop+on+Green+in%2Fby+software+engineering+-+GIBSE+%2713&rft.aulast=Penzenstadler&rft.aufirst=Birgit&rft.au=Penzenstadler%2C%26%2332%3BBirgit&rft.au=Femmer%2C%26%2332%3BHenning&rft.date=2013&rft.pages=3&rft.place=Fukuoka%2C+Japan&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F2451605.2451609&rft.isbn=978-1-4503-1866-2&rft_id=http%3A%2F%2Fdl.acm.org%2Fcitation.cfm%3Fdoid%3D2451605.2451609&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">van Klompenburg, Thomas; Kassahun, Ayalew; Catal, Cagatay (1 October 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169920302301\" target=\"_blank\">\"Crop yield prediction using machine learning: A systematic literature review\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>177<\/b>: 105709. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2020.105709\" target=\"_blank\">10.1016\/j.compag.2020.105709<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169920302301\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169920302301<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Crop+yield+prediction+using+machine+learning%3A+A+systematic+literature+review&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=van+Klompenburg&rft.aufirst=Thomas&rft.au=van+Klompenburg%2C%26%2332%3BThomas&rft.au=Kassahun%2C%26%2332%3BAyalew&rft.au=Catal%2C%26%2332%3BCagatay&rft.date=1+October+2020&rft.volume=177&rft.pages=105709&rft_id=info:doi\/10.1016%2Fj.compag.2020.105709&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169920302301&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-67\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-67\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Khaki, Saeed; Wang, Lizhi (22 May 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00621\/full\" target=\"_blank\">\"Crop Yield Prediction Using Deep Neural Networks\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>10<\/b>: 621. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2019.00621\" target=\"_blank\">10.3389\/fpls.2019.00621<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6540942\/\" target=\"_blank\">PMC6540942<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31191564\" target=\"_blank\">31191564<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00621\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00621\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Crop+Yield+Prediction+Using+Deep+Neural+Networks&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Khaki&rft.aufirst=Saeed&rft.au=Khaki%2C%26%2332%3BSaeed&rft.au=Wang%2C%26%2332%3BLizhi&rft.date=22+May+2019&rft.volume=10&rft.pages=621&rft_id=info:doi\/10.3389%2Ffpls.2019.00621&rft.issn=1664-462X&rft_id=info:pmc\/PMC6540942&rft_id=info:pmid\/31191564&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2019.00621%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-68\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-68\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">U.S. Department of Agriculture (17 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/data.nal.usda.gov\/dataset\/natural-resources-conservation-service-web-soil-survey\" target=\"_blank\">\"Natural Resources Conservation Service Web Soil Survey\"<\/a>. <i>Ag Data Commons<\/i>. U.S. Department of Agriculture<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/data.nal.usda.gov\/dataset\/natural-resources-conservation-service-web-soil-survey\" target=\"_blank\">https:\/\/data.nal.usda.gov\/dataset\/natural-resources-conservation-service-web-soil-survey<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 23 April 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Natural+Resources+Conservation+Service+Web+Soil+Survey&rft.atitle=Ag+Data+Commons&rft.aulast=U.S.+Department+of+Agriculture&rft.au=U.S.+Department+of+Agriculture&rft.date=17+December+2015&rft.pub=U.S.+Department+of+Agriculture&rft_id=https%3A%2F%2Fdata.nal.usda.gov%2Fdataset%2Fnatural-resources-conservation-service-web-soil-survey&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-69\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-69\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">National Agricultural Statistics Service (2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nass.usda.gov\/Surveys\/\" target=\"_blank\">\"Surveys\"<\/a>. U.S. Department of Agriculture<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nass.usda.gov\/Surveys\/\" target=\"_blank\">https:\/\/www.nass.usda.gov\/Surveys\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Surveys&rft.atitle=&rft.aulast=National+Agricultural+Statistics+Service&rft.au=National+Agricultural+Statistics+Service&rft.date=2019&rft.pub=U.S.+Department+of+Agriculture&rft_id=https%3A%2F%2Fwww.nass.usda.gov%2FSurveys%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-70\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-70\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wan, Zhiyuan; Xia, Xin; Lo, David; Murphy, Gail C. (2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8812912\/\" target=\"_blank\">\"How does Machine Learning Change Software Development Practices?\"<\/a>. <i>IEEE Transactions on Software Engineering<\/i>: 1\u20131. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTSE.2019.2937083\" target=\"_blank\">10.1109\/TSE.2019.2937083<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0098-5589\" target=\"_blank\">0098-5589<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8812912\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8812912\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=How+does+Machine+Learning+Change+Software+Development+Practices%3F&rft.jtitle=IEEE+Transactions+on+Software+Engineering&rft.aulast=Wan&rft.aufirst=Zhiyuan&rft.au=Wan%2C%26%2332%3BZhiyuan&rft.au=Xia%2C%26%2332%3BXin&rft.au=Lo%2C%26%2332%3BDavid&rft.au=Murphy%2C%26%2332%3BGail+C.&rft.date=2020&rft.pages=1%E2%80%931&rft_id=info:doi\/10.1109%2FTSE.2019.2937083&rft.issn=0098-5589&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8812912%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-71\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-71\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yokoyama, Haruki (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8712157\/\" target=\"_blank\">\"Machine Learning System Architectural Pattern for Improving Operational Stability\"<\/a>. <i>2019 IEEE International Conference on Software Architecture Companion (ICSA-C)<\/i> (Hamburg, Germany: IEEE): 267\u2013274. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FICSA-C.2019.00055\" target=\"_blank\">10.1109\/ICSA-C.2019.00055<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-7281-1876-5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8712157\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8712157\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Machine+Learning+System+Architectural+Pattern+for+Improving+Operational+Stability&rft.jtitle=2019+IEEE+International+Conference+on+Software+Architecture+Companion+%28ICSA-C%29&rft.aulast=Yokoyama&rft.aufirst=Haruki&rft.au=Yokoyama%2C%26%2332%3BHaruki&rft.date=1+March+2019&rft.pages=267%E2%80%93274&rft.place=Hamburg%2C+Germany&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FICSA-C.2019.00055&rft.isbn=978-1-7281-1876-5&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8712157%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:22-72\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:22_72-0\">72.0<\/a><\/sup> <sup><a href=\"#cite_ref-:22_72-1\">72.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gl\u00f3ria, Andr\u00e9; Dionisio, Carolina; Sim\u00f5es, Gon\u00e7alo; Cardoso, Jo\u00e3o; Sebasti\u00e3o, Pedro (4 March 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1424-8220\/20\/5\/1402\" target=\"_blank\">\"Water Management for Sustainable Irrigation Systems Using Internet-of-Things\"<\/a> (in en). <i>Sensors<\/i> <b>20<\/b> (5): 1402. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fs20051402\" target=\"_blank\">10.3390\/s20051402<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1424-8220\" target=\"_blank\">1424-8220<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7085535\/\" target=\"_blank\">PMC7085535<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32143482\" target=\"_blank\">32143482<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1424-8220\/20\/5\/1402\" target=\"_blank\">https:\/\/www.mdpi.com\/1424-8220\/20\/5\/1402<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Water+Management+for+Sustainable+Irrigation+Systems+Using+Internet-of-Things&rft.jtitle=Sensors&rft.aulast=Gl%C3%B3ria&rft.aufirst=Andr%C3%A9&rft.au=Gl%C3%B3ria%2C%26%2332%3BAndr%C3%A9&rft.au=Dionisio%2C%26%2332%3BCarolina&rft.au=Sim%C3%B5es%2C%26%2332%3BGon%C3%A7alo&rft.au=Cardoso%2C%26%2332%3BJo%C3%A3o&rft.au=Sebasti%C3%A3o%2C%26%2332%3BPedro&rft.date=4+March+2020&rft.volume=20&rft.issue=5&rft.pages=1402&rft_id=info:doi\/10.3390%2Fs20051402&rft.issn=1424-8220&rft_id=info:pmc\/PMC7085535&rft_id=info:pmid\/32143482&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1424-8220%2F20%2F5%2F1402&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:23-73\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:23_73-0\">73.0<\/a><\/sup> <sup><a href=\"#cite_ref-:23_73-1\">73.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">G. S. Campos, Nidia; Rocha, Atslands R.; Gondim, Rubens; Coelho da Silva, Ticiana L.; Gomes, Danielo G. (29 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1424-8220\/20\/1\/190\" target=\"_blank\">\"Smart & Green: An Internet-of-Things Framework for Smart Irrigation\"<\/a> (in en). <i>Sensors<\/i> <b>20<\/b> (1): 190. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fs20010190\" target=\"_blank\">10.3390\/s20010190<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1424-8220\" target=\"_blank\">1424-8220<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6983084\/\" target=\"_blank\">PMC6983084<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31905749\" target=\"_blank\">31905749<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1424-8220\/20\/1\/190\" target=\"_blank\">https:\/\/www.mdpi.com\/1424-8220\/20\/1\/190<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Smart+%26+Green%3A+An+Internet-of-Things+Framework+for+Smart+Irrigation&rft.jtitle=Sensors&rft.aulast=G.+S.+Campos&rft.aufirst=Nidia&rft.au=G.+S.+Campos%2C%26%2332%3BNidia&rft.au=Rocha%2C%26%2332%3BAtslands+R.&rft.au=Gondim%2C%26%2332%3BRubens&rft.au=Coelho+da+Silva%2C%26%2332%3BTiciana+L.&rft.au=Gomes%2C%26%2332%3BDanielo+G.&rft.date=29+December+2019&rft.volume=20&rft.issue=1&rft.pages=190&rft_id=info:doi\/10.3390%2Fs20010190&rft.issn=1424-8220&rft_id=info:pmc\/PMC6983084&rft_id=info:pmid\/31905749&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1424-8220%2F20%2F1%2F190&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-74\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-74\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">\u6c6a\u5c0f\u65f5; \u9648\u6ee1; \u5b59\u56fd\u7965; \u5f20\u745c; \u7ae0\u6c38\u5e74; Xiaochan, Wang; Man, Chen; Guoxiang, Sun <i>et al.<\/i> (11 November 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.tcsae.org\/nygcxb\/article\/abstract\/2015Z213\" target=\"_blank\">\"\u51ac\u5c0f\u9ea6\u53d8\u91cf\u65bd\u80a5\u673a\u63a7\u5236\u7cfb\u7edf\u7684\u8bbe\u8ba1\u4e0e\u8bd5\u9a8c\"<\/a>. <i>\u519c\u4e1a\u5de5\u7a0b\u5b66\u62a5<\/i> <b>31<\/b> (Z2): 88\u201392. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.11975%2Fj.issn.1002-6819.2015.z2.013\" target=\"_blank\">10.11975\/j.issn.1002-6819.2015.z2.013<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.tcsae.org\/nygcxb\/article\/abstract\/2015Z213\" target=\"_blank\">http:\/\/www.tcsae.org\/nygcxb\/article\/abstract\/2015Z213<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%E5%86%AC%E5%B0%8F%E9%BA%A6%E5%8F%98%E9%87%8F%E6%96%BD%E8%82%A5%E6%9C%BA%E6%8E%A7%E5%88%B6%E7%B3%BB%E7%BB%9F%E7%9A%84%E8%AE%BE%E8%AE%A1%E4%B8%8E%E8%AF%95%E9%AA%8C&rft.jtitle=%E5%86%9C%E4%B8%9A%E5%B7%A5%E7%A8%8B%E5%AD%A6%E6%8A%A5&rft.aulast=%E6%B1%AA%E5%B0%8F%E6%97%B5&rft.au=%E6%B1%AA%E5%B0%8F%E6%97%B5&rft.au=%E9%99%88%E6%BB%A1&rft.au=%E5%AD%99%E5%9B%BD%E7%A5%A5&rft.au=%E5%BC%A0%E7%91%9C&rft.au=%E7%AB%A0%E6%B0%B8%E5%B9%B4&rft.au=Xiaochan%2C%26%2332%3BWang&rft.au=Man%2C%26%2332%3BChen&rft.au=Guoxiang%2C%26%2332%3BSun&rft.au=Yu%2C%26%2332%3BZhang&rft.date=11+November+2015&rft.volume=31&rft.issue=Z2&rft.pages=88%E2%80%9392&rft_id=info:doi\/10.11975%2Fj.issn.1002-6819.2015.z2.013&rft_id=http%3A%2F%2Fwww.tcsae.org%2Fnygcxb%2Farticle%2Fabstract%2F2015Z213&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-75\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-75\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yinyan, Shi; Man, Chen; Xiaochan, Wang; Odhiambo, Morice Oluoch; Weimin, Ding (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169917311213\" target=\"_blank\">\"Numerical simulation of spreading performance and distribution pattern of centrifugal variable-rate fertilizer applicator based on DEM software\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>144<\/b>: 249\u2013259. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2017.12.015\" target=\"_blank\">10.1016\/j.compag.2017.12.015<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169917311213\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169917311213<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Numerical+simulation+of+spreading+performance+and+distribution+pattern+of+centrifugal+variable-rate+fertilizer+applicator+based+on+DEM+software&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Yinyan&rft.aufirst=Shi&rft.au=Yinyan%2C%26%2332%3BShi&rft.au=Man%2C%26%2332%3BChen&rft.au=Xiaochan%2C%26%2332%3BWang&rft.au=Odhiambo%2C%26%2332%3BMorice+Oluoch&rft.au=Weimin%2C%26%2332%3BDing&rft.date=1+January+2018&rft.volume=144&rft.pages=249%E2%80%93259&rft_id=info:doi\/10.1016%2Fj.compag.2017.12.015&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169917311213&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-76\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-76\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Boegh, Eva; Soegaard, H.; Broge, N.; Hasager, C.B.; Jensen, N.O.; Schelde, K.; Thomsen, A. (1 August 2002). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003442570100342X\" target=\"_blank\">\"Airborne multispectral data for quantifying leaf area index, nitrogen concentration, and photosynthetic efficiency in agriculture\"<\/a> (in en). <i>Remote Sensing of Environment<\/i> <b>81<\/b> (2-3): 179\u2013193. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0034-4257%2801%2900342-X\" target=\"_blank\">10.1016\/S0034-4257(01)00342-X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003442570100342X\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003442570100342X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Airborne+multispectral+data+for+quantifying+leaf+area+index%2C+nitrogen+concentration%2C+and+photosynthetic+efficiency+in+agriculture&rft.jtitle=Remote+Sensing+of+Environment&rft.aulast=Boegh&rft.aufirst=Eva&rft.au=Boegh%2C%26%2332%3BEva&rft.au=Soegaard%2C%26%2332%3BH.&rft.au=Broge%2C%26%2332%3BN.&rft.au=Hasager%2C%26%2332%3BC.B.&rft.au=Jensen%2C%26%2332%3BN.O.&rft.au=Schelde%2C%26%2332%3BK.&rft.au=Thomsen%2C%26%2332%3BA.&rft.date=1+August+2002&rft.volume=81&rft.issue=2-3&rft.pages=179%E2%80%93193&rft_id=info:doi\/10.1016%2FS0034-4257%2801%2900342-X&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS003442570100342X&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-77\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-77\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Deery, David M.; Rebetzke, Greg J.; Jimenez-Berni, Jose A.; James, Richard A.; Condon, Anthony G.; Bovill, William D.; Hutchinson, Paul; Scarrow, Jamie <i>et al.<\/i> (6 December 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fpls.2016.01808\/full\" target=\"_blank\">\"Methodology for High-Throughput Field Phenotyping of Canopy Temperature Using Airborne Thermography\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>7<\/b>: 1808. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2016.01808\" target=\"_blank\">10.3389\/fpls.2016.01808<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5138222\/\" target=\"_blank\">PMC5138222<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27999580\" target=\"_blank\">27999580<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fpls.2016.01808\/full\" target=\"_blank\">http:\/\/journal.frontiersin.org\/article\/10.3389\/fpls.2016.01808\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Methodology+for+High-Throughput+Field+Phenotyping+of+Canopy+Temperature+Using+Airborne+Thermography&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Deery&rft.aufirst=David+M.&rft.au=Deery%2C%26%2332%3BDavid+M.&rft.au=Rebetzke%2C%26%2332%3BGreg+J.&rft.au=Jimenez-Berni%2C%26%2332%3BJose+A.&rft.au=James%2C%26%2332%3BRichard+A.&rft.au=Condon%2C%26%2332%3BAnthony+G.&rft.au=Bovill%2C%26%2332%3BWilliam+D.&rft.au=Hutchinson%2C%26%2332%3BPaul&rft.au=Scarrow%2C%26%2332%3BJamie&rft.au=Davy%2C%26%2332%3BRobert&rft.date=6+December+2016&rft.volume=7&rft.pages=1808&rft_id=info:doi\/10.3389%2Ffpls.2016.01808&rft.issn=1664-462X&rft_id=info:pmc\/PMC5138222&rft_id=info:pmid\/27999580&rft_id=http%3A%2F%2Fjournal.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2016.01808%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-78\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-78\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Qinghua, G.; Weicai, Y.; Fangfang, W. et al. (2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.cnki.net\/kcms\/doi\/10.16418\/j.issn.1000-3045.2018.09.007.html\" target=\"_blank\">\"\u9ad8\u901a\u91cf\u4f5c\u7269\u8868\u578b\u76d1\u6d4b:\u80b2\u79cd\u548c\u7cbe\u51c6\u519c\u4e1a\u53d1\u5c55\u7684\u52a0\u901f\u5668 - \u4e2d\u56fd\u77e5\u7f51\"<\/a>. <i>Bulletin of Chinese Academy of Sciences (Chinese Version)<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.16418%2Fj.issn.1000-3045.2018.09.007\" target=\"_blank\">10.16418\/j.issn.1000-3045.2018.09.007<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.cnki.net\/kcms\/doi\/10.16418\/j.issn.1000-3045.2018.09.007.html\" target=\"_blank\">https:\/\/www.cnki.net\/kcms\/doi\/10.16418\/j.issn.1000-3045.2018.09.007.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=%E9%AB%98%E9%80%9A%E9%87%8F%E4%BD%9C%E7%89%A9%E8%A1%A8%E5%9E%8B%E7%9B%91%E6%B5%8B%3A%E8%82%B2%E7%A7%8D%E5%92%8C%E7%B2%BE%E5%87%86%E5%86%9C%E4%B8%9A%E5%8F%91%E5%B1%95%E7%9A%84%E5%8A%A0%E9%80%9F%E5%99%A8+-+%E4%B8%AD%E5%9B%BD%E7%9F%A5%E7%BD%91&rft.atitle=Bulletin+of+Chinese+Academy+of+Sciences+%28Chinese+Version%29&rft.aulast=Qinghua%2C+G.%3B+Weicai%2C+Y.%3B+Fangfang%2C+W.+et+al.&rft.au=Qinghua%2C+G.%3B+Weicai%2C+Y.%3B+Fangfang%2C+W.+et+al.&rft.date=2018&rft_id=info:doi\/10.16418%2Fj.issn.1000-3045.2018.09.007&rft_id=https%3A%2F%2Fwww.cnki.net%2Fkcms%2Fdoi%2F10.16418%2Fj.issn.1000-3045.2018.09.007.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-79\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-79\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tian, M.; Ban, S.; Chang, Q. et al. (2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ingentaconnect.com\/content\/tcsae\/tcsae\/2016\/00000032\/00000021\/art00014\" target=\"_blank\">\"Use of hyperspectral images from UAV-based imaging spectroradiometer to estimate cotton leaf area index\"<\/a>. <i>Transactions of the Chinese Society of Agricultural Engineering<\/i> <b>32<\/b> (21): 102\u2013108<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ingentaconnect.com\/content\/tcsae\/tcsae\/2016\/00000032\/00000021\/art00014\" target=\"_blank\">https:\/\/www.ingentaconnect.com\/content\/tcsae\/tcsae\/2016\/00000032\/00000021\/art00014<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Use+of+hyperspectral+images+from+UAV-based+imaging+spectroradiometer+to+estimate+cotton+leaf+area+index&rft.jtitle=Transactions+of+the+Chinese+Society+of+Agricultural+Engineering&rft.aulast=Tian%2C+M.%3B+Ban%2C+S.%3B+Chang%2C+Q.+et+al.&rft.au=Tian%2C+M.%3B+Ban%2C+S.%3B+Chang%2C+Q.+et+al.&rft.date=2016&rft.volume=32&rft.issue=21&rft.pages=102%E2%80%93108&rft_id=https%3A%2F%2Fwww.ingentaconnect.com%2Fcontent%2Ftcsae%2Ftcsae%2F2016%2F00000032%2F00000021%2Fart00014&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-80\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-80\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Busemeyer, Lucas; Mentrup, Daniel; M\u00f6ller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans; Reif, Jochen <i>et al.<\/i> (27 February 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.mdpi.com\/1424-8220\/13\/3\/2830\" target=\"_blank\">\"BreedVision \u2014 A Multi-Sensor Platform for Non-Destructive Field-Based Phenotyping in Plant Breeding\"<\/a> (in en). <i>Sensors<\/i> <b>13<\/b> (3): 2830\u20132847. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fs130302830\" target=\"_blank\">10.3390\/s130302830<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1424-8220\" target=\"_blank\">1424-8220<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3658717\/\" target=\"_blank\">PMC3658717<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23447014\" target=\"_blank\">23447014<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.mdpi.com\/1424-8220\/13\/3\/2830\" target=\"_blank\">http:\/\/www.mdpi.com\/1424-8220\/13\/3\/2830<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=BreedVision+%E2%80%94+A+Multi-Sensor+Platform+for+Non-Destructive+Field-Based+Phenotyping+in+Plant+Breeding&rft.jtitle=Sensors&rft.aulast=Busemeyer&rft.aufirst=Lucas&rft.au=Busemeyer%2C%26%2332%3BLucas&rft.au=Mentrup%2C%26%2332%3BDaniel&rft.au=M%C3%B6ller%2C%26%2332%3BKim&rft.au=Wunder%2C%26%2332%3BErik&rft.au=Alheit%2C%26%2332%3BKatharina&rft.au=Hahn%2C%26%2332%3BVolker&rft.au=Maurer%2C%26%2332%3BHans&rft.au=Reif%2C%26%2332%3BJochen&rft.au=W%C3%BCrschum%2C%26%2332%3BTobias&rft.date=27+February+2013&rft.volume=13&rft.issue=3&rft.pages=2830%E2%80%932847&rft_id=info:doi\/10.3390%2Fs130302830&rft.issn=1424-8220&rft_id=info:pmc\/PMC3658717&rft_id=info:pmid\/23447014&rft_id=http%3A%2F%2Fwww.mdpi.com%2F1424-8220%2F13%2F3%2F2830&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-81\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-81\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sharma, L.K.; Bu, H.; Franzen, D.W.; Denton, A. (1 June 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301399\" target=\"_blank\">\"Use of corn height measured with an acoustic sensor improves yield estimation with ground based active optical sensors\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>124<\/b>: 254\u2013262. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2016.04.016\" target=\"_blank\">10.1016\/j.compag.2016.04.016<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301399\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916301399<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Use+of+corn+height+measured+with+an+acoustic+sensor+improves+yield+estimation+with+ground+based+active+optical+sensors&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Sharma&rft.aufirst=L.K.&rft.au=Sharma%2C%26%2332%3BL.K.&rft.au=Bu%2C%26%2332%3BH.&rft.au=Franzen%2C%26%2332%3BD.W.&rft.au=Denton%2C%26%2332%3BA.&rft.date=1+June+2016&rft.volume=124&rft.pages=254%E2%80%93262&rft_id=info:doi\/10.1016%2Fj.compag.2016.04.016&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169916301399&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-82\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-82\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Arsevska, Elena; Roche, Mathieu; Hendrikx, Pascal; Chavernac, David; Falala, Sylvain; Lancelot, Renaud; Dufour, Barbara (1 April 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916300473\" target=\"_blank\">\"Identification of terms for detecting early signals of emerging infectious disease outbreaks on the web\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>123<\/b>: 104\u2013115. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2016.02.010\" target=\"_blank\">10.1016\/j.compag.2016.02.010<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916300473\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169916300473<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+terms+for+detecting+early+signals+of+emerging+infectious+disease+outbreaks+on+the+web&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Arsevska&rft.aufirst=Elena&rft.au=Arsevska%2C%26%2332%3BElena&rft.au=Roche%2C%26%2332%3BMathieu&rft.au=Hendrikx%2C%26%2332%3BPascal&rft.au=Chavernac%2C%26%2332%3BDavid&rft.au=Falala%2C%26%2332%3BSylvain&rft.au=Lancelot%2C%26%2332%3BRenaud&rft.au=Dufour%2C%26%2332%3BBarbara&rft.date=1+April+2016&rft.volume=123&rft.pages=104%E2%80%93115&rft_id=info:doi\/10.1016%2Fj.compag.2016.02.010&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169916300473&rfr_id=info:sid\/en.wikipedia.org:Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. The original citation five for S\u00f8rensen <i>et al.<\/i> had a dead URL; an alternate source was found with the same information and used for this version.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628181030\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.807 seconds\nReal time usage: 1.614 seconds\nPreprocessor visited node count: 79150\/1000000\nPost\u2010expand include size: 666594\/2097152 bytes\nTemplate argument size: 208538\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 193951\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 702.112 1 -total\n 89.94% 631.471 1 Template:Reflist\n 73.00% 512.541 82 Template:Citation\/core\n 59.62% 418.623 62 Template:Cite_journal\n 11.76% 82.546 75 Template:Date\n 9.32% 65.469 9 Template:Citation\n 7.20% 50.558 129 Template:Citation\/identifier\n 6.43% 45.171 8 Template:Cite_web\n 3.34% 23.425 1 Template:Infobox_journal_article\n 2.96% 20.807 3 Template:Cite_book\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13349-0!canonical and timestamp 20220628181029 and revision id 48245. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture\">https:\/\/www.limswiki.org\/index.php\/Journal:Design_of_a_data_management_reference_architecture_for_sustainable_agriculture<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","97ebdae24d5298692e56e4a9d01fa0cb_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cf\/Fig1_Giray_Sustain21_13-13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/eb\/Fig2_Giray_Sustain21_13-13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/98\/Fig3_Giray_Sustain21_13-13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/d6\/Fig4_Giray_Sustain21_13-13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/ab\/Fig5_Giray_Sustain21_13-13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f5\/Fig6_Giray_Sustain21_13-13.png"],"97ebdae24d5298692e56e4a9d01fa0cb_timestamp":1656439828,"843741d77f4c16c82c818d163a13b06e_type":"article","843741d77f4c16c82c818d163a13b06e_title":"Fueling clinical and translational research in Appalachia: Informatics platform approach (Cecchetti et al. 2020)","843741d77f4c16c82c818d163a13b06e_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach","843741d77f4c16c82c818d163a13b06e_plaintext":"\n\nJournal:Fueling clinical and translational research in Appalachia: Informatics platform approachFrom LIMSWikiJump to navigationJump to searchFull article title\n \nFueling clinical and translational research in Appalachia: Informatics platform approachJournal\n \nJMIR Medical InformaticsAuthor(s)\n \nCecchetti, Alfred A.; Bhardwaj, Niharika; Murughiyan, Usha; Kothakapu, Gouthami; Sundaram, UmaAuthor affiliation(s)\n \nJoan C. Edwards School of Medicine at Marshall UniversityPrimary contact\n \nEmail: cecchetti at marshall dot eduEditors\n \nEysenbach, G.Year published\n \n2020Volume and issue\n \n8(10)Article #\n \ne17962DOI\n \n10.2196\/17962ISSN\n \n2291-9694Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/medinform.jmir.org\/2020\/10\/e17962\/Download\n \nhttps:\/\/medinform.jmir.org\/2020\/10\/e17962\/PDF (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n\n2.1 Background: Unique challenges in Appalachia \n2.2 Why an informatics platform? \n\n\n3 Methods \n\n3.1 Multi-institutional data storage: The Appalachian Clinical and Translational Science Institute-Clinical Data Warehouse \n3.2 Data validation \n3.3 Augmenting the CDW using REDCap \n3.4 Visualization \n3.5 Modeling (statistics and machine learning) \n3.6 Evaluation \n3.7 Security, privacy, and the informatics committee \n3.8 Team building \n\n\n4 Results \n5 Discussion \n\n5.1 Utility of the AIP \n5.2 Ongoing projects and future directions \n\n\n6 Conclusions \n7 Abbreviations, acronyms, and initialisms \n8 Acknowledgements \n\n8.1 Funding \n8.2 Conflicts of interest \n\n\n9 References \n10 Notes \n\n\n\nAbstract \nBackground: The Appalachian population is distinct, not just culturally and geographically but also in its healthcare needs, facing the most health care disparities in the United States. To meet these unique demands, Appalachian medical centers need an arsenal of analytics and data science tools with the foundation of a centralized data warehouse to transform healthcare data into actionable clinical interventions. However, this is an especially challenging task given the fragmented state of medical data within Appalachia and the need for integration of other types of data such as environmental, social, and economic with medical data.\nObjective: This paper aims to present the structure and process of the development of an integrated platform at a midlevel Appalachian academic medical center, along with its initial uses.\nMethods: The Appalachian Informatics Platform (AIP) was developed by the Appalachian Clinical and Translational Science Institute\u2019s Division of Clinical Informatics and consists of four major components: a centralized clinical data warehouse, modeling (statistical and machine learning), visualization, and model evaluation. Data from different clinical systems, billing systems, and state- or national-level data sets were integrated into a centralized data warehouse. The platform supports research efforts by enabling curation and analysis of data using the different components, as appropriate.\nResults: The AIP is functional and has supported several research efforts since its implementation for a variety of purposes, such as increasing knowledge of the pathophysiology of diseases, risk identification, risk prediction, and healthcare resource utilization research and estimation of the economic impact of diseases.\nConclusions: The platform provides an inexpensive yet seamless way to translate clinical and translational research ideas into clinical applications for regions similar to Appalachia that have limited resources and a largely rural population.\nKeywords: Appalachian region, medical informatics, health care disparities, electronic health records, data warehousing, data mining, data visualization, machine learning, data science \n\nIntroduction \nBackground: Unique challenges in Appalachia \nAppalachia, with its predominantly rural communities, is known to have one of the worst sets of healthcare outcomes in the United States. This is especially true of southern and central rural Appalachia, which face some of the most severe health disparities in the nation.[1] Over the years, the gap in the overall health between Appalachia and the nation as a whole has continued to grow.[2][3] To close this gap, it is critical to identify the cause of these disparities and direct efforts toward developing necessary interventions to address them.\nSuch an effort necessitates the adoption of modern technologies such as a centralized research data warehouse to house all data necessary to obtain a comprehensive picture of the health of the Appalachian population before analysis to gain actionable insights can be performed. A centralized data warehouse, once considered strictly a business tool, has evolved into an important instrument for cost containment, tracking of patient outcomes, providing clinical decision support at the point of care, improving prognostic accuracy, and facilitating research.[4] Thus, rural academic medical centers have moved toward implementing data warehouse systems that feed analytical systems for research needs.[5] This entails (1) the integration of data from different types of medical settings (i.e., multi-institutional) such as hospitals, clinics, and specialty centers; (2) linkage of financial data with clinical data, a well-established practice proven to be pivotal to high-quality care and great economic outcomes[6][7]; and (3) integration of other determinants of health such as environmental[8], social[9], and spiritual factors[10] to create longitudinal health records across the care continuum.\nHowever, there are challenges in creating a multi-institutional data warehouse.[11] Electronic health records (EHRs) do not easily interact with one another due to the use of nonstandard terminologies and difficulty in understanding the flow of information. Additionally, significant differences exist between rural and urban health systems.[12][13][14][15][16] Unlike their urban counterparts, healthcare data in Appalachia are typically fragmented, existing in silos within dissimilar databases, registries, data collections, and departmental systems. With innovations in medical technology, the list of data sources continues to grow, producing unprecedented amounts of data from all aspects of care, including diagnosis, medication, procedures, laboratory testing, imaging, and patient self-monitoring.[17][18][19][20][21] To complicate matters, the overall health and health behaviors of Appalachians are strongly affected by Appalachia\u2019s unique culture, geography, and health system issues.[22][23][24] Consequently, Appalachian academic medical centers face the complex challenge of collecting, organizing, standardizing, and analyzing these enormous quantities of heterogeneous data originating from a wide variety of sources to address the unmet needs of the population they serve.\n\n Why an informatics platform? \nData integration and interoperability have been shown to be key to unlocking these data for data analytics, enabling the development of novel patient management strategies for rural hospitals[25][26] and translational research that leads to new approaches at the bedside for prevention, diagnosis, and treatment of disease, which are essential to improving the health of a population.[27][28][29] Data analytics, once the domain of the statistician, has now become an equal partner in clinical research and research operations.[30][31] Following the data explosion, data analytics increasingly involves the use of visual analytics tools such as Tableau (Tableau Software Inc.) and Power BI (Microsoft Corp.) to explore data easily and in a self-service fashion and to clearly and effectively communicate complex ideas[32], especially to those members of the medical community who might not have an intimate understanding of the underlying data. Furthermore, machine learning is gaining importance, especially in the area of predictive analytics, to improve the practice of medicine and to infer potentially innovative risk factors.[28][33][34][35]\nHowever, these applications (e.g., data warehouse, data analytics, statistical analysis, machine learning, visual analytics) are generally uncoordinated without any overarching governance. Thus, we developed an informatics platform\u2014that is, a suite of interconnected, coordinated applications hosted within an operational environment[36]\u2014called the Appalachian Informatics Platform (AIP), in West Virginia (the only state located entirely in Appalachia) that facilitates interoperable access to integrated information, data visualization, and data analytics, thereby functioning as an excellent basis for clinical and translational research to improve health care.\nThe goal of this study is to describe the structure and process of development of the AIP and demonstrate its value in supporting clinical and translational research.\n\nMethods \nThe AIP (Figure 1) is composed of four major components: (1) a multi-institutional data storage or clinical data warehouse (CDW); (2) modeling tools (statistical and machine learning); (3) visualization tools; and (4) evaluation tools. Each of these components is described in detail in separate sections.\nThe CDW forms an integral part of the AIP. It also contains embedded data analytics (modeling and evaluation) and interactive visualization tools (e.g., Tableau, Power BI). Together, these enable the analysis of Appalachian health information to speed up the transition of translational research ideas into clinical practice.\nThe CDW serves as a secure source of quality data for descriptive, diagnostic, predictive, and prescriptive analytics for research and operational needs. The visual analytics tools enable an initial exploratory analysis of the processed data and the interactive presentation of analytical findings for further analysis and review. Depending on the use case, data can be analyzed using statistical modeling via external (e.g., SPSS [IBM Corp], Stata [StataCorp]) or integrated (e.g., R [R Foundation for Statistical Computing], Python [Python Software Foundation] in SQL [Structured Query Language]) applications or machine learning modeling. The performance of the resulting models was evaluated using appropriate metrics. Once trained and evaluated, machine learning models can be deployed and stored in the CDW for future use if needed. Furthermore, the stored machine learning models can be continuously evaluated and improved as more data are generated.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 Appalachian Informatics Platform (AIP)\n\n\n\nThe informatics committee governs the access to and utilization of AIP and ensures adherence to security and privacy rules. In addition, team-building activities are also incorporated into our clinical informatics model to foster the development of an effective clinical informatics team.\n\nMulti-institutional data storage: The Appalachian Clinical and Translational Science Institute-Clinical Data Warehouse \nThe Appalachian Clinical and Translational Science Institute (ACTSI)\u2019s Division of Clinical Informatics solicited buy-in from different entities\u2014namely Cabell-Huntington Hospital (CHH), Edwards Comprehensive Cancer Institute (ECCC), Marshall Health (MH) practice plan, and Marshall University Joan C. Edwards School of Medicine (MU JCESOM)\u2014to build the Appalachian Clinical and Translational Science Institute-Clinical Data Warehouse (ACTSI-CDW) in West Virginia. An agreement was created between these entities that provided access to both financial and clinical data.\nThe multi-institutional CDW contains more than nine years of billing and clinical data. It comprises relational tables and dimension and fact tables (Online Analytical Processing [OLAP] cube), which enable secure data storage and data access. Designed from the start to facilitate information flow, the CDW can send out a stream of near real-time data that can be used for any authorized research purpose. Documentation includes a data dictionary and flowcharts. Flowcharts follow the patient from admission (or appointment, if outpatient) to discharge (or exit, if outpatient). The data dictionary contains the standardized and source field names, descriptions, and properties, along with the associated metadata for the data contained within the data warehouse. For instance, (1) the entry of a patient into any medical service (admission or appointment) was combined with the single term encounter, and (2) a higher level of precision was introduced by separating patient age into two variables: current age or the age when the procedure was performed.\nThe CDW process is based on an older data warehouse process developed at the University of Pittsburgh.[37] The process is as follows:\n\nData dictionaries are created by recording institutional source field names and field properties and linking them to the standardized CDW names and properties found within the CDW databases. Descriptions of each field (source and CDW) are included.\nIndividual institutional flowcharts show the workflow of the data and the location of the people responsible for the quality of the data, which are also used for quality control purposes.\nAt present, the CDW contains data from six institutional software packages hosted in various parts of the country (e.g., Cerner data from Kansas City, Missouri; McKesson data from North Druid Hills, Georgia; etc.). The data are exported in a standard format (i.e., ASCII flat file, XML, etc.) and transferred through secure file transfer protocol (e.g., Cerberus [Cerberus, LLC]) to the CDW Development server.\nThe data are integrated into the Microsoft SQL databases using Microsoft SQL Server Integration Services (SSIS), a graphical tool that extracts, transforms, and loads (ETL) the data to target schemas that will be used to contain the target data objects: relational tables, dimensions, and cubes. ETL systems enable a smooth migration from one system to another irrespective of the underlying storage system.\nConformed dimensions were developed, and patient linkages using various methods (e.g., simple heuristics)[38] were also available and made at this time.\nAt present, a transactional grain fact table has been developed, but other fact tables will be created as needed.\nThe CDW contains internal structured billing and EHR data (i.e., demographics, encounter details, vitals, medications, procedures, diagnoses, orders, immunizations, laboratory and imaging results, date and time, payee, and provider). It also contains unstructured EHR data (e.g., H&P, admission notes, discharge summaries, other clinical notes). These data are received from MH, CHH, and MU JCESOM\u2019s ECCC, as well as from other outside institutions. In addition, non-EHR data are incorporated using REDCap.\nUnstructured data are analyzed using text analytics tools, and classification variables based on text mining are incorporated into the CDW.\nThe data structure (OLAP cubes and relational tables), once checked and verified, is transferred from the secure development server to the secure production server for use.\nVarious security measures (e.g., IP and password restrictions) are in place to prevent unauthorized use.\nThe CDW structure, which stores multi-institutional medical information, can now provide data for both operational and research analytical model development (statistical or machine learning) using very simple de-identified interfaces (e.g., Excel [Microsoft Corp]) or more complex interactive tools (e.g., R, Tableau, Power BI, etc.). Within the CDW, the data can be manipulated, cleaned, and prepared before the analysis as needed.\nStructured and unstructured data currently exist within the CDW. Image and BioSample data will soon be incorporated (like the Pittsburgh model), but the full design has not been finalized yet. An Honest Broker person assumes control of sample shipping and receiving.\nStandard operating procedures (SOPs) have been developed for administrative and technical areas.\nThe Health Insurance Portability and Accountability Act (HIPAA) guidelines are followed, and protocol to protect patient information has also been implemented.\nThe CDW is contained within a Microsoft SQL database that can interact with outside objects using other electronic methods such as SignalR, a software library for Microsoft ASP.NET that allows server code to send asynchronous notifications to client-side web applications, and SqlDependency, an object that represents a query notification dependency between an application and an instance of SQL server. Objects such as these provide the ability for the data warehouse to interact in real time with the outside regional population using the newest technologies such as Microsoft Machine Learning Server with embedded R or Python procedure coding.\n\nData validation \nThe information derived from multiple data sources can have inconsistencies and missing values because of their heterogeneous nature, which requires correction.[39][40][41][42] Thus, for each research study, clinical and translational researchers using the data warehouse are required to verify a random sample (calculated on the basis of the size of the study population) of all extracted study data are directly verified at the original data source to ensure data accuracy and validity. Identified errors or omissions are transmitted back to the host systems for correction or inclusion.\n\nAugmenting the CDW using REDCap \nFor certain studies, data available in the CDW may not be precise enough or include variables needed to perform this study. For such studies, data can be augmented using data capture tools. One such tool is the Research Electronic Data Capture, or REDCap, a workflow methodology and software solution designed for the rapid development and deployment of electronic data capture tools to support clinical and translational research.[43][44][45]\nOur institution has deployed and maintains 2 REDCap servers: secure (located under institutional firewall) and global (outside the firewall). The secure REDCap system is used for storing data considered protected health information (PHI) under HIPAA. The global system, on the other hand, is used to store de-identified or non-PHI data. These data are then transferred to and stored within the multi-institutional data warehouse. This method of augmenting the information pulled from the existing source systems provides research-grade data from outside sources that are normally not contained within a data warehouse.\n\nVisualization \nVisualization of information is an excellent method of providing knowledge that can be easily understood by any member of the health care discipline. Within the informatics platform, Tableau provides interactive drill-down and drill-up capabilities for specific projects.\nTableau is a visual analytics tool that provides an interactive method of exploring multidimensional data, optimized from the data warehouse and OLAP data sources. Tableau, using either indexed relational tables or a data cube, can perform associated operations such as slice, dice, roll-up, and drill-down on the data, providing detailed interactive visual overlays that range from the lowest grain of the data to high-level representations of the data. Tableau charts, graphs, filters, and maps can provide visualization of the various subgroups of interest using a storyboard approach that presents a specific question followed by an interactive dashboard that explores that question in detail. The use of visual elements such as logos, pictograms, icons, or pictures into the dashboards, in association with the subgroups, provides easy-to-reference image aids that provide clarity and understanding of complex information. The data warehouse provides the drill-down, drill-up and slice and dice capability, whereas the hub design connects both financial and clinical data to provide a full picture.\nThe developed interactive dashboards are securely shared with users within a department or a team, as needed, through the use of Tableau Server.[46]\n\n Modeling (statistics and machine learning) \nThe modeling component of the informatics platform supports the construction of tailored regional models (statistical or machine learning) to understand and predict disease and other medical events within this region. EHR is primarily a billing system, research only being a secondary function and, thus, is heterogeneous, incomplete, and noisy[25], leading to unrepresentative samples, selection bias, and misclassification.[47] During the modeling process, these issues are eliminated or minimized.\nTo assist in modeling, software packages such as SPSS and Stata, as well as embedded open-source machine learning programs (e.g., R, Python) are used. This enables faster and easier development of classification, regression, and clustering algorithms for research use. In addition, we utilize products such as Microsoft\u2019s LINQ to electronically gather information and directly incorporate that information into the CDW.\n\nEvaluation \nDuring the modeling process, evaluation of the data set as it relates to the regional population is carried out. Local experts native to this region are asked to evaluate the model from a clinical as well as a financial standpoint. Poverty is endemic within the Appalachian population, and a model that suggests the use of a very expensive medication or procedure over an older but less expensive medication or procedure is unlikely to be used.[48] Thus, the model must take into account whether the patient has the means and access to the recommended medication or procedure.[49] In addition, the willingness of Appalachian medical institutions and health care providers to follow the model\u2019s suggestions must also be evaluated.\nOnce developed, the models were tuned and tested. Location, time of treatment, outside temperature, and other contributory factors available within the CDW were employed to fine-tune the models, as applicable. The performance of the models was measured using the R programming environment using measures such as area under curve, sensitivity, specificity, F1 score, precision, recall, etc.\n\n Security, privacy, and the informatics committee \nData access and usage are permitted only as described in the mutual agreement between the three institutions and are subject to internal security and privacy rules. All data requests must follow the standard operating procedure built on the basis of mutual multi-institutional agreement. Foremost, the researcher must have appropriate credentials and authorization to be able to request for data. If the researcher is authorized to make requests, he or she must obtain the IRB approval for his or her proposed study and submit the IRB proposal and supporting documentation for review by the informatics committee. The informatics committee, independent of the IRB, reviews all requests for data from the data warehouse to ensure compliance with the agreement. If the research project is approved, the research team designated members are scheduled for the de-identified data extraction process.\n\nTeam building \nIntegral to the informatics platform is team building that builds upon previous work.[37] To facilitate effective team meetings and inter-professional collaboration (local and global) without the need or expense of constant travel, a permanent clinical informatics conference room with a fixed connected computer, an uninterruptable power supply (UPS), a smart board, a camera, and a speaker system, along with a video conferencing system (Zoom) connectivity, was built. This ensures adequate communication among all those involved (i.e., team members, users, leadership, etc.) and access to resources that would otherwise be unavailable.\n\nResults \nSince the implementation of the platform, several studies have been conducted. Each study listed below was approved by the informatics committee, and the de-identified data and platform tools were made available securely to the research team.\nTo evaluate the functionality and value of this platform, we first analyzed the aggregated data of Medicaid-insured patients across different health systems using the interconnected applications within the platform for population health management. Relevant data were extracted from the CDW, followed by exploratory analysis using a Tableau dashboard. Due to the isolated nature of the study population, regional variables such as distance from the CHH and weather conditions (i.e., temperature) were also included. Errors and missing values were identified using the dashboard, and data were subsequently cleaned and prepared. Using these clean data, the regional population was classified into three spend categories: low cost, acute, and persistent subgroups on the basis of the charges accrued. Next, the Charlson Comorbidity Index (CCI) was incorporated into the CDW to predict mortality risk within one year of hospitalization for patients with comorbid conditions within each spend category (Table 1).[50][51] \n\n\n\n\n\n\n\nTable 1. The 10-year mortality risk predicted using the Charlson Comorbidity Index\n\n\n\nMortality risk\n\nDeceased, n (%)\n\nAlive, n (%)\n\n\nHigh-risk\n\n896 (0.80)\n\n8,102 (7.20)\n\n\nLow-risk\n\n616 (0.55)\n\n102,905 (91.46)\n\n\n\nOf these categories, the persistent group had the largest percentage of patients with a high risk of mortality, followed by acute and low cost after excluding the deceased patients (persistent: 898\/1247, 72.01%; acute: 2074\/6946, 29.86%; low cost: 5130\/102,814, 4.99%). The CCI was not very sensitive in predicting the risk of mortality but was very specific and accurate (sensitivity: 896\/1512, 59.26%; specificity: 102,905\/111,007, 92.7%; accuracy: 103,801\/112,519, 92.25%). The effect of distance and weather on the CCI needs further investigation that is being conducted. Adjustments are being made to this standard national index to incorporate other Appalachian characteristics that could improve the sensitivity of this risk scoring system.\nAs such, the platform has been utilized for a variety of purposes such as increasing knowledge of the pathophysiology of diseases, risk identification, risk prediction, health care resource utilization research, and estimation of the economic impact of diseases to enable data-driven clinical decisions, leading to improved clinical outcomes. Table 2 contains a list of studies conducted so far.\n\n\n\n\n\n\n\nTable 2. Studies conducted using the Appalachian Informatics Platform\n\n\nDiagnostic accuracy improvement studies\n\n\nAlbumin Level as a Risk Marker and Predictor of Peripartum Cardiomyopathy[52]\n\n\nClinical Determinants of Myocardial Injury, Detectable and Serial Troponin Levels Among Patients With Hypertensive Crisis[53]\n\n\nIs Fever a Red Flag for Secondary Bacterial Pneumonia During RSV Bronchiolitis[54]\n\n\nMetabolic Syndrome: Are Current Colon Cancer Screening Guidelines Enough in a Rural Population?[55]\n\n\nUtilization of Appalachian Clinical and Translational Science Institute Data Warehouse to More Accurately Predict Disease Processes Important for Central Appalachia[56]\n\n\nResource utilization and financial impact research studies\n\n\nAnalysis of Benzodiazepine Prescription Practices in Elderly Appalachians with Dementia Via the Appalachian Informatics Platform: Longitudinal Study[57]\n\n\nHospital Emergency Department Visits For Non-Traumatic Oral Health Conditions[58]\n\n\nStudies to understand disease pathophysiology\n\n\nSerum Calcium Homeostasis and Volume Dynamics in Alzheimer\u2019s Disease and Diabetes Mellitus-2[59]\n\n\n\nFive studies utilized the platform for risk identification and risk prediction to improve diagnostic accuracy.[52][53][54][55][56] Sundaram et al.[56] demonstrated the value of ACTSI-CDW as a primary source to improve the diagnosis of metabolic syndrome, a diagnosis highly relevant to the Central Appalachian population. The researchers discovered that utilizing billing codes alone severely underestimated the number of patients with metabolic syndrome by a factor of more than 10, as compared with looking at specific criteria that determine this diagnosis.[56] Another study assessed the relationship between metabolic syndrome and colorectal cancer and found that patients with metabolic syndrome, especially those with insulin resistance, were more likely to have colorectal cancer, indicating the probable need for earlier screening for colorectal cancer in these patients.[55] Elmore et al.[54] examined the role of fever in predicting the development of secondary bacterial pneumonia in children with RSV and other viral illnesses. They found that febrile children were two to eight times (RSV, 47\/78 vs 27\/100; other bronchiolitis, 54\/83 vs 7\/88) more likely to have secondary bacterial pneumonia compared with afebrile children and, thus, may need to be aggressively evaluated to enable early diagnosis and treatment.[54] Amro et al.[52] studied the relationship between hypoalbuminemia and peripartum cardiomyopathy and noted that lower albumin levels were significantly associated with peripartum cardiomyopathy (P<.001; odds ratio 0.033, 95% CI 0.034-0.865) and could potentially be used as a risk marker for it. Acosta et al.[53] used data from the ACTSI-CDW to identify risk factors (lower BMI, before CHF, and prior use of aspirin) that predict myocardial injury, detectable troponin, and increase in serial troponin levels in patients with hypertensive crisis.\nFerdjallah et al.[59] analyzed the data from the ACTSI-CDW to understand how Alzheimer disease and diabetes mellitus affect serum calcium homeostasis and extracellular fluid volume. They observed that acute changes in serum calcium were significantly correlated with changes in extracellular fluid volume in both disease states.[59]\nThe platform has also been applied in two studies to assess resource utilization (e.g., emergency room, medications, etc.) and the financial impact of the disease. For instance, Bhardwaj et al.[57] utilized the platform to identify the problems associated with benzodiazepine use in geriatric patients within the health system, such as a higher number of emergency room visits and charges in geriatric patients with dementia plus at least one BZD prescription. In another study[58] that aimed to measure the volume and cost of emergency room use for these conditions and identify the factors that predict such use, the researchers built a dashboard (Figure 2) to easily explore and analyze relevant data on non-traumatic dental conditions that led to emergency room visits and to report the key findings of the study. The authors[58] observed that emergency room visits by uninsured patients were four times more likely and those by Medicaid insured two times more likely to be for dental problems than Medicare-insured patients.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 Tableau dashboard displaying patterns and trends in charges for non-traumatic dental ER visits at Cabell Huntington Hospital between 2010 and 2018. ER: emergency room.\n\n\n\nDiscussion \nUtility of the AIP \nThe AIP has supported several research projects involving the use of different components of the platform, depending on project needs. The studies described reported findings that are seldom reported in this region, enhanced our knowledge of pathophysiology and risk factors, and helped estimate and analyze resource utilization and economic burden of certain diseases within Appalachia using minimal resources (i.e., a small IT team and a relatively inexpensive platform).\nBefore the implementation of the platform, many research studies that followed the patient across multiple care settings or involved analysis of big data were not possible due to the unavailability of technical and economic resources owing to a lack of buy-in from rural health care organizations. As the data existed in silos, there was a lack of standardization and normalization, which resulted in major data inconsistencies. Studies conducted using these disjointed data sets often used unrepresentative small biased samples and had low statistical power and quality.\nThe introduction of the platform has helped address these issues. It is now easier to pinpoint and correct errors and\/or missing values and understand the distribution of data using visual analysis tools. Further, the time needed to conduct these studies from start to finish has been greatly reduced owing to the availability of all applications necessary to complete the study within the platform. This has been specifically useful because many researchers do not have the technical skills needed to perform complex and advanced data analysis, especially on larger data sets.\nThe paper also revealed that national models do not necessarily perform well when applied to the Appalachian population. The AIP allows for seamless integration of regional variables into the national model, which may improve the performance of these models. For each of the top 10 causes of death in West Virginia in 2017, per the Centers for Disease Control and Prevention[60], a machine learning algorithm was used to predict outcomes on a national level: heart disease[61][62], cancer[63][64], accidents[65][66], respiratory disease[67][68], stroke[69][70], diabetes[71][72], Alzheimer disease[73][74], pneumonia[75][76], kidney disease[77][78], and suicide.[79][80] Each of these cited models could be modified to fit the characteristics of the Appalachian population, especially those characteristics that make this region different in terms of geography, economy, education, and culture from the rest of the United States. The development of these regional models could help rural health general practitioners tackle complex medical conditions without the need for an expensive specialized health care provider nearby.[46]\nWe hope that this paper will help other rural health care organizations that serve underserved populations, such as ours, realize the value and ease of using an informatics platform to conduct research and improve care for their patients despite limited resources.\n\nOngoing projects and future directions \nAt present, a model that utilizes embedded data analytics to monitor the side effects of certain types of cancer by ingesting de-identified statements in the regional variety of English language from patients within this region[81][82] is under development. This model could be used to analyze patient responses at a certain point in time for a cross-sectional study or continuously in real time for a long-term longitudinal study to identify the patients in need of care before their scheduled follow-up visit. The ongoing results from this model would be sent to their health care providers for appropriate actions. In case of an emergency, patient-designated community support networks such as religious or other support groups may be intimated to bring the patient to the emergency department so that the patient can receive timely care.\nWe plan to expand upon our unified informatics platform to integrate programming applications for the development of state-of-the-art applications targeted specifically toward the unmet health care needs of the Appalachian population.\n\nConclusions \nThis paper establishes the value of the Appalachian Informatics Platform (AIP) in enabling seamless and secure data access, model development through an analytics engine to explore novel and unexpected hypotheses, and simple yet effective communication of all findings via interactive visualization.\nThe relatively inexpensive nature of such a platform coupled with its demonstrated advantages will hopefully encourage small and midsized rural academic centers, which traditionally have fewer resources than their urban counterparts, to adopt a research informatics platform within their institutions using the template described in this paper as a guide.\n\n Abbreviations, acronyms, and initialisms \nACTSI: Appalachian Clinical and Translational Science Institute\nAIP: Appalachian Informatics Platform\nCCI: Charlson Comorbidity Index\nCDW: clinical data warehouse\nCHH: Cabell-Huntington Hospital\nECCC: Edwards Comprehensive Cancer Institute\nEHR: electronic health record\nETL: extract, transform, and load\nHIPAA: Health Insurance Portability and Accountability Act\nMH: Marshall Health\nMU JCESOM: Marshall University Joan C Edwards School of Medicine\nOLAP: Online Analytical Processing\nPHI: protected health information\nSQL: structured query language\n\nAcknowledgements \nFunding \nThis work was supported by the National Institutes of Health grants DK-67420, DK-108054, and P20GM121299-01A1 and Veteran\u2019s Administration Merit Review grant BX003443-01 to US and UL1TR00011719 to PK.\n\nConflicts of interest \nNone declared.\n\nReferences \n\n\n\u2191 Krometis, Leigh-Anne; Gohlke, Julia; Kolivras, Korine; Satterwhite, Emily; Marmagas, Susan West; Marr, Linsey C. 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International Journal of Computer Sciences and Engineering 4 (7): 101\u201304. https:\/\/www.ijcseonline.org\/full_paper_view.php?paper_id=1008 .   \n \n\n\u2191 Basaia, Silvia; Agosta, Federica; Wagner, Luca; Canu, Elisa; Magnani, Giuseppe; Santangelo, Roberto; Filippi, Massimo (2019). \"Automated classification of Alzheimer's disease and mild cognitive impairment using a single MRI and deep neural networks\" (in en). NeuroImage: Clinical 21: 101645. doi:10.1016\/j.nicl.2018.101645. PMC PMC6413333. PMID 30584016. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213158218303930 .   \n \n\n\u2191 Alzheimer\u2019s Disease Neuroimaging Initiative; Lu, Donghuan; Popuri, Karteek; Ding, Gavin Weiguang; Balachandar, Rakesh; Beg, Mirza Faisal (1 December 2018). \"Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer\u2019s Disease using structural MR and FDG-PET images\" (in en). Scientific Reports 8 (1): 5697. doi:10.1038\/s41598-018-22871-z. ISSN 2045-2322. 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ISSN 0047-4045. https:\/\/www.cambridge.org\/core\/product\/identifier\/S0047404500014548\/type\/journal_article .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\">https:\/\/www.limswiki.org\/index.php\/Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on health informaticsNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 7 June 2022, at 23:03.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 130 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","843741d77f4c16c82c818d163a13b06e_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Fueling_clinical_and_translational_research_in_Appalachia_Informatics_platform_approach rootpage-Journal_Fueling_clinical_and_translational_research_in_Appalachia_Informatics_platform_approach skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Fueling clinical and translational research in Appalachia: Informatics platform approach<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background<\/b>: The Appalachian population is distinct, not just culturally and geographically but also in its healthcare needs, facing the most health care disparities in the United States. To meet these unique demands, Appalachian medical centers need an arsenal of analytics and data science tools with the foundation of a centralized <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_warehouse\" title=\"Data warehouse\" class=\"wiki-link\" data-key=\"ca506499cdf544371c0a0d549ff0e9ee\">data warehouse<\/a> to transform healthcare data into actionable clinical interventions. However, this is an especially challenging task given the fragmented state of medical data within Appalachia and the need for integration of other types of data such as environmental, social, and economic with medical data.\n<\/p><p><b>Objective<\/b>: This paper aims to present the structure and process of the development of an integrated platform at a midlevel Appalachian academic medical center, along with its initial uses.\n<\/p><p><b>Methods<\/b>: The Appalachian Informatics Platform (AIP) was developed by the Appalachian Clinical and Translational Science Institute\u2019s Division of Clinical Informatics and consists of four major components: a centralized clinical data warehouse, modeling (statistical and machine learning), visualization, and model evaluation. Data from different clinical systems, billing systems, and state- or national-level data sets were integrated into a centralized data warehouse. The platform supports research efforts by enabling curation and analysis of data using the different components, as appropriate.\n<\/p><p><b>Results<\/b>: The AIP is functional and has supported several research efforts since its implementation for a variety of purposes, such as increasing knowledge of the pathophysiology of diseases, risk identification, risk prediction, and healthcare resource utilization research and estimation of the economic impact of diseases.\n<\/p><p><b>Conclusions<\/b>: The platform provides an inexpensive yet seamless way to translate clinical and <a href=\"https:\/\/www.limswiki.org\/index.php\/Translational_research\" title=\"Translational research\" class=\"wiki-link\" data-key=\"b5462c2278492de7f21a60e40299b634\">translational research<\/a> ideas into clinical applications for regions similar to Appalachia that have limited resources and a largely rural population.\n<\/p><p><b>Keywords<\/b>: Appalachian region, medical informatics, health care disparities, electronic health records, data warehousing, data mining, data visualization, machine learning, data science \n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Background:_Unique_challenges_in_Appalachia\">Background: Unique challenges in Appalachia<\/span><\/h3>\n<p>Appalachia, with its predominantly rural communities, is known to have one of the worst sets of healthcare outcomes in the United States. This is especially true of southern and central rural Appalachia, which face some of the most severe health disparities in the nation.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup> Over the years, the gap in the overall health between Appalachia and the nation as a whole has continued to grow.<sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup> To close this gap, it is critical to identify the cause of these disparities and direct efforts toward developing necessary interventions to address them.\n<\/p><p>Such an effort necessitates the adoption of modern technologies such as a centralized research <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_warehouse\" title=\"Data warehouse\" class=\"wiki-link\" data-key=\"ca506499cdf544371c0a0d549ff0e9ee\">data warehouse<\/a> to house all data necessary to obtain a comprehensive picture of the health of the Appalachian population before analysis to gain actionable insights can be performed. A centralized data warehouse, once considered strictly a business tool, has evolved into an important instrument for cost containment, tracking of patient outcomes, providing <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_decision_support_system\" title=\"Clinical decision support system\" class=\"wiki-link\" data-key=\"095141425468d057aa977016869ca37d\">clinical decision support<\/a> at the point of care, improving prognostic accuracy, and facilitating research.<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> Thus, rural academic medical centers have moved toward implementing data warehouse systems that feed analytical systems for research needs.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> This entails (1) the integration of data from different types of medical settings (i.e., multi-institutional) such as <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospitals<\/a>, clinics, and specialty centers; (2) linkage of financial data with clinical data, a well-established practice proven to be pivotal to high-quality care and great economic outcomes<sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup>; and (3) integration of other determinants of health such as environmental<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup>, social<sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup>, and spiritual factors<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup> to create longitudinal health records across the care continuum.\n<\/p><p>However, there are challenges in creating a multi-institutional data warehouse.<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup> <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">Electronic health records<\/a> (EHRs) do not easily interact with one another due to the use of nonstandard terminologies and difficulty in understanding the flow of information. Additionally, significant differences exist between rural and urban health systems.<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[16]<\/a><\/sup> Unlike their urban counterparts, healthcare data in Appalachia are typically fragmented, existing in silos within dissimilar databases, registries, data collections, and departmental systems. With innovations in medical technology, the list of data sources continues to grow, producing unprecedented amounts of data from all aspects of care, including diagnosis, medication, procedures, <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> testing, <a href=\"https:\/\/www.limswiki.org\/index.php\/Imaging_informatics\" title=\"Imaging informatics\" class=\"wiki-link\" data-key=\"fc0ae6a154d8896767defefdb6d14d0e\">imaging<\/a>, and patient self-monitoring.<sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-19\" class=\"reference\"><a href=\"#cite_note-19\">[19]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-20\" class=\"reference\"><a href=\"#cite_note-20\">[20]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup> To complicate matters, the overall health and health behaviors of Appalachians are strongly affected by Appalachia\u2019s unique culture, geography, and health system issues.<sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup> Consequently, Appalachian academic medical centers face the complex challenge of collecting, organizing, standardizing, and analyzing these enormous quantities of heterogeneous data originating from a wide variety of sources to address the unmet needs of the population they serve.\n<\/p>\n<h3><span id=\"rdp-ebb-Why_an_informatics_platform?\"><\/span><span class=\"mw-headline\" id=\"Why_an_informatics_platform.3F\">Why an informatics platform?<\/span><\/h3>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/Data_integration\" title=\"Data integration\" class=\"wiki-link\" data-key=\"fd01c635859e1d5b9583e43e31ef6718\">Data integration<\/a> and interoperability have been shown to be key to unlocking these data for <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_analysis\" title=\"Data analysis\" class=\"wiki-link\" data-key=\"545c95e40ca67c9e63cd0a16042a5bd1\">data analytics<\/a>, enabling the development of novel patient management strategies for rural hospitals<sup id=\"rdp-ebb-cite_ref-:1_25-0\" class=\"reference\"><a href=\"#cite_note-:1-25\">[25]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup> and <a href=\"https:\/\/www.limswiki.org\/index.php\/Translational_research\" title=\"Translational research\" class=\"wiki-link\" data-key=\"b5462c2278492de7f21a60e40299b634\">translational research<\/a> that leads to new approaches at the bedside for prevention, diagnosis, and treatment of disease, which are essential to improving the health of a population.<sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:0_28-0\" class=\"reference\"><a href=\"#cite_note-:0-28\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-29\" class=\"reference\"><a href=\"#cite_note-29\">[29]<\/a><\/sup> Data analytics, once the domain of the statistician, has now become an equal partner in clinical research and research operations.<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup> Following the data explosion, data analytics increasingly involves the use of visual analytics tools such as Tableau (Tableau Software Inc.) and Power BI (Microsoft Corp.) to explore data easily and in a self-service fashion and to clearly and effectively communicate complex ideas<sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup>, especially to those members of the medical community who might not have an intimate understanding of the underlying data. Furthermore, <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> is gaining importance, especially in the area of predictive analytics, to improve the practice of medicine and to infer potentially innovative risk factors.<sup id=\"rdp-ebb-cite_ref-:0_28-1\" class=\"reference\"><a href=\"#cite_note-:0-28\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[34]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup>\n<\/p><p>However, these applications (e.g., data warehouse, data analytics, statistical analysis, machine learning, visual analytics) are generally uncoordinated without any overarching governance. Thus, we developed an <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics_(academic_field)\" title=\"Informatics (academic field)\" class=\"wiki-link\" data-key=\"0391318826a5d9f9a1a1bcc88394739f\">informatics<\/a> platform\u2014that is, a suite of interconnected, coordinated applications hosted within an operational environment<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup>\u2014called the Appalachian Informatics Platform (AIP), in West Virginia (the only state located entirely in Appalachia) that facilitates interoperable access to integrated <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_visualization\" title=\"Data visualization\" class=\"wiki-link\" data-key=\"4a3b86cba74bc7bb7471aa3fc2fcccc3\">data visualization<\/a>, and data analytics, thereby functioning as an excellent basis for clinical and translational research to improve health care.\n<\/p><p>The goal of this study is to describe the structure and process of development of the AIP and demonstrate its value in supporting clinical and translational research.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<p>The AIP (Figure 1) is composed of four major components: (1) a multi-institutional data storage or clinical data warehouse (CDW); (2) modeling tools (statistical and machine learning); (3) visualization tools; and (4) evaluation tools. Each of these components is described in detail in separate sections.\n<\/p><p>The CDW forms an integral part of the AIP. It also contains embedded data analytics (modeling and evaluation) and interactive visualization tools (e.g., Tableau, Power BI). Together, these enable the analysis of Appalachian health information to speed up the transition of translational research ideas into clinical practice.\n<\/p><p>The CDW serves as a secure source of <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality\" class=\"mw-redirect wiki-link\" title=\"Quality\" data-key=\"a944d57abb1130945915702cdbdb63df\">quality<\/a> data for descriptive, diagnostic, predictive, and prescriptive analytics for research and operational needs. The visual analytics tools enable an initial exploratory analysis of the processed data and the interactive presentation of analytical findings for further analysis and review. Depending on the use case, data can be analyzed using statistical modeling via external (e.g., SPSS [IBM Corp], Stata [StataCorp]) or integrated (e.g., <a href=\"https:\/\/www.limswiki.org\/index.php\/R_(programming_language)\" title=\"R (programming language)\" class=\"wiki-link\" data-key=\"1b0aa598f071aca4c5b4ee08d8bb2bde\">R<\/a> [R Foundation for Statistical Computing], <a href=\"https:\/\/www.limswiki.org\/index.php\/Python_(programming_language)\" title=\"Python (programming language)\" class=\"wiki-link\" data-key=\"ef6905a29cbb75d3c71e6bdf6e2915dd\">Python<\/a> [Python Software Foundation] in <a href=\"https:\/\/www.limswiki.org\/index.php\/SQL\" title=\"SQL\" class=\"wiki-link\" data-key=\"eef2f4a8c6f89c1a940da05abf1ace65\">SQL<\/a> [Structured Query Language]) applications or machine learning modeling. The performance of the resulting models was evaluated using appropriate metrics. Once trained and evaluated, machine learning models can be deployed and stored in the CDW for future use if needed. Furthermore, the stored machine learning models can be continuously evaluated and improved as more data are generated.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Cecchetti_JMIRMedInfo8_8-10.png\" class=\"image wiki-link\" data-key=\"66441f0951be994a24ab6130f88173d4\"><img alt=\"Fig1 Cecchetti JMIRMedInfo8 8-10.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/2a\/Fig1_Cecchetti_JMIRMedInfo8_8-10.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> Appalachian Informatics Platform (AIP)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The informatics committee governs the access to and utilization of AIP and ensures adherence to security and privacy rules. In addition, team-building activities are also incorporated into our <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_informatics\" class=\"mw-redirect wiki-link\" title=\"Clinical informatics\" data-key=\"bda8123083aecb94afe79afec9ae4686\">clinical informatics<\/a> model to foster the development of an effective clinical informatics team.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Multi-institutional_data_storage:_The_Appalachian_Clinical_and_Translational_Science_Institute-Clinical_Data_Warehouse\">Multi-institutional data storage: The Appalachian Clinical and Translational Science Institute-Clinical Data Warehouse<\/span><\/h3>\n<p>The Appalachian Clinical and Translational Science Institute (ACTSI)\u2019s Division of Clinical Informatics solicited buy-in from different entities\u2014namely Cabell-Huntington Hospital (CHH), Edwards Comprehensive Cancer Institute (ECCC), Marshall Health (MH) practice plan, and Marshall University Joan C. Edwards School of Medicine (MU JCESOM)\u2014to build the Appalachian Clinical and Translational Science Institute-Clinical Data Warehouse (ACTSI-CDW) in West Virginia. An agreement was created between these entities that provided access to both financial and clinical data.\n<\/p><p>The multi-institutional CDW contains more than nine years of billing and clinical data. It comprises relational tables and dimension and fact tables (Online Analytical Processing [OLAP] cube), which enable secure data storage and data access. Designed from the start to facilitate information flow, the CDW can send out a stream of near real-time data that can be used for any authorized research purpose. Documentation includes a data dictionary and flowcharts. Flowcharts follow the patient from admission (or appointment, if outpatient) to discharge (or exit, if outpatient). The data dictionary contains the standardized and source field names, descriptions, and properties, along with the associated <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" title=\"Metadata\" class=\"wiki-link\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">metadata<\/a> for the data contained within the data warehouse. For instance, (1) the entry of a patient into any medical service (admission or appointment) was combined with the single term encounter, and (2) a higher level of precision was introduced by separating patient age into two variables: current age or the age when the procedure was performed.\n<\/p><p>The CDW process is based on an older data warehouse process developed at the University of Pittsburgh.<sup id=\"rdp-ebb-cite_ref-:2_37-0\" class=\"reference\"><a href=\"#cite_note-:2-37\">[37]<\/a><\/sup> The process is as follows:\n<\/p>\n<ol><li>Data dictionaries are created by recording institutional source field names and field properties and linking them to the standardized CDW names and properties found within the CDW databases. Descriptions of each field (source and CDW) are included.<\/li>\n<li>Individual institutional flowcharts show the <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> of the data and the location of the people responsible for the quality of the data, which are also used for <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_control\" title=\"Quality control\" class=\"wiki-link\" data-key=\"1e0e0c2eb3e45aff02f5d61799821f0f\">quality control<\/a> purposes.<\/li>\n<li>At present, the CDW contains data from six institutional software packages hosted in various parts of the country (e.g., Cerner data from Kansas City, Missouri; McKesson data from North Druid Hills, Georgia; etc.). The data are exported in a standard format (i.e., ASCII flat file, XML, etc.) and transferred through secure file transfer protocol (e.g., Cerberus [Cerberus, LLC]) to the CDW Development server.<\/li>\n<li>The data are integrated into the Microsoft SQL databases using Microsoft SQL Server Integration Services (SSIS), a graphical tool that extracts, transforms, and loads (ETL) the data to target schemas that will be used to contain the target data objects: relational tables, dimensions, and cubes. ETL systems enable a smooth migration from one system to another irrespective of the underlying storage system.<\/li>\n<li>Conformed dimensions were developed, and patient linkages using various methods (e.g., simple heuristics)<sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup> were also available and made at this time.<\/li>\n<li>At present, a transactional grain fact table has been developed, but other fact tables will be created as needed.<\/li>\n<li>The CDW contains internal structured billing and EHR data (i.e., demographics, encounter details, vitals, medications, procedures, diagnoses, orders, immunizations, laboratory and imaging results, date and time, payee, and provider). It also contains unstructured EHR data (e.g., H&P, admission notes, discharge summaries, other clinical notes). These data are received from MH, CHH, and MU JCESOM\u2019s ECCC, as well as from other outside institutions. In addition, non-EHR data are incorporated using REDCap.<\/li>\n<li>Unstructured data are analyzed using text analytics tools, and classification variables based on text mining are incorporated into the CDW.<\/li>\n<li>The data structure (OLAP cubes and relational tables), once checked and verified, is transferred from the secure development server to the secure production server for use.<\/li>\n<li>Various security measures (e.g., IP and password restrictions) are in place to prevent unauthorized use.<\/li>\n<li>The CDW structure, which stores multi-institutional medical information, can now provide data for both operational and research analytical model development (statistical or machine learning) using very simple de-identified interfaces (e.g., Excel [Microsoft Corp]) or more complex interactive tools (e.g., R, Tableau, Power BI, etc.). Within the CDW, the data can be manipulated, cleaned, and prepared before the analysis as needed.<\/li>\n<li>Structured and unstructured data currently exist within the CDW. Image and BioSample data will soon be incorporated (like the Pittsburgh model), but the full design has not been finalized yet. An Honest Broker person assumes control of sample shipping and receiving.<\/li>\n<li>Standard operating procedures (SOPs) have been developed for administrative and technical areas.<\/li>\n<li>The <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Insurance_Portability_and_Accountability_Act\" title=\"Health Insurance Portability and Accountability Act\" class=\"wiki-link\" data-key=\"b70673a0117c21576016cb7498867153\">Health Insurance Portability and Accountability Act<\/a> (HIPAA) guidelines are followed, and protocol to protect patient information has also been implemented.<\/li><\/ol>\n<p>The CDW is contained within a Microsoft SQL database that can interact with outside objects using other electronic methods such as SignalR, a software library for Microsoft ASP.NET that allows server code to send asynchronous notifications to client-side web applications, and SqlDependency, an object that represents a query notification dependency between an application and an instance of SQL server. Objects such as these provide the ability for the data warehouse to interact in real time with the outside regional population using the newest technologies such as Microsoft Machine Learning Server with embedded R or Python procedure coding.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_validation\">Data validation<\/span><\/h3>\n<p>The information derived from multiple data sources can have inconsistencies and missing values because of their heterogeneous nature, which requires correction.<sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[41]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup> Thus, for each research study, clinical and translational researchers using the data warehouse are required to verify a random sample (calculated on the basis of the size of the study population) of all extracted study data are directly verified at the original data source to ensure data accuracy and validity. Identified errors or omissions are transmitted back to the host systems for correction or inclusion.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Augmenting_the_CDW_using_REDCap\">Augmenting the CDW using REDCap<\/span><\/h3>\n<p>For certain studies, data available in the CDW may not be precise enough or include variables needed to perform this study. For such studies, data can be augmented using data capture tools. One such tool is the Research Electronic Data Capture, or REDCap, a workflow methodology and software solution designed for the rapid development and deployment of electronic data capture tools to support clinical and translational research.<sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[43]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[45]<\/a><\/sup>\n<\/p><p>Our institution has deployed and maintains 2 REDCap servers: secure (located under institutional firewall) and global (outside the firewall). The secure REDCap system is used for storing data considered <a href=\"https:\/\/www.limswiki.org\/index.php\/Protected_health_information\" title=\"Protected health information\" class=\"wiki-link\" data-key=\"eca2f6661b6896668bd523e640e12499\">protected health information<\/a> (PHI) under HIPAA. The global system, on the other hand, is used to store de-identified or non-PHI data. These data are then transferred to and stored within the multi-institutional data warehouse. This method of augmenting the information pulled from the existing source systems provides research-grade data from outside sources that are normally not contained within a data warehouse.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Visualization\">Visualization<\/span><\/h3>\n<p>Visualization of information is an excellent method of providing knowledge that can be easily understood by any member of the health care discipline. Within the informatics platform, Tableau provides interactive drill-down and drill-up capabilities for specific projects.\n<\/p><p>Tableau is a visual analytics tool that provides an interactive method of exploring multidimensional data, optimized from the data warehouse and OLAP data sources. Tableau, using either indexed relational tables or a data cube, can perform associated operations such as slice, dice, roll-up, and drill-down on the data, providing detailed interactive visual overlays that range from the lowest grain of the data to high-level representations of the data. Tableau charts, graphs, filters, and maps can provide visualization of the various subgroups of interest using a storyboard approach that presents a specific question followed by an interactive dashboard that explores that question in detail. The use of visual elements such as logos, pictograms, icons, or pictures into the dashboards, in association with the subgroups, provides easy-to-reference image aids that provide clarity and understanding of complex information. The data warehouse provides the drill-down, drill-up and slice and dice capability, whereas the hub design connects both financial and clinical data to provide a full picture.\n<\/p><p>The developed interactive dashboards are securely shared with users within a department or a team, as needed, through the use of Tableau Server.<sup id=\"rdp-ebb-cite_ref-:3_46-0\" class=\"reference\"><a href=\"#cite_note-:3-46\">[46]<\/a><\/sup>\n<\/p>\n<h3><span id=\"rdp-ebb-Modeling_(statistics_and_machine_learning)\"><\/span><span class=\"mw-headline\" id=\"Modeling_.28statistics_and_machine_learning.29\">Modeling (statistics and machine learning)<\/span><\/h3>\n<p>The modeling component of the informatics platform supports the construction of tailored regional models (statistical or machine learning) to understand and predict disease and other medical events within this region. EHR is primarily a billing system, research only being a secondary function and, thus, is heterogeneous, incomplete, and noisy<sup id=\"rdp-ebb-cite_ref-:1_25-1\" class=\"reference\"><a href=\"#cite_note-:1-25\">[25]<\/a><\/sup>, leading to unrepresentative samples, selection bias, and misclassification.<sup id=\"rdp-ebb-cite_ref-47\" class=\"reference\"><a href=\"#cite_note-47\">[47]<\/a><\/sup> During the modeling process, these issues are eliminated or minimized.\n<\/p><p>To assist in modeling, software packages such as SPSS and Stata, as well as embedded open-source machine learning programs (e.g., R, Python) are used. This enables faster and easier development of classification, regression, and clustering algorithms for research use. In addition, we utilize products such as Microsoft\u2019s LINQ to electronically gather information and directly incorporate that information into the CDW.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Evaluation\">Evaluation<\/span><\/h3>\n<p>During the modeling process, evaluation of the data set as it relates to the regional population is carried out. Local experts native to this region are asked to evaluate the model from a clinical as well as a financial standpoint. Poverty is endemic within the Appalachian population, and a model that suggests the use of a very expensive medication or procedure over an older but less expensive medication or procedure is unlikely to be used.<sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[48]<\/a><\/sup> Thus, the model must take into account whether the patient has the means and access to the recommended medication or procedure.<sup id=\"rdp-ebb-cite_ref-49\" class=\"reference\"><a href=\"#cite_note-49\">[49]<\/a><\/sup> In addition, the willingness of Appalachian medical institutions and health care providers to follow the model\u2019s suggestions must also be evaluated.\n<\/p><p>Once developed, the models were tuned and tested. Location, time of treatment, outside temperature, and other contributory factors available within the CDW were employed to fine-tune the models, as applicable. The performance of the models was measured using the R programming environment using measures such as area under curve, sensitivity, specificity, F1 score, precision, recall, etc.\n<\/p>\n<h3><span id=\"rdp-ebb-Security,_privacy,_and_the_informatics_committee\"><\/span><span class=\"mw-headline\" id=\"Security.2C_privacy.2C_and_the_informatics_committee\">Security, privacy, and the informatics committee<\/span><\/h3>\n<p>Data access and usage are permitted only as described in the mutual agreement between the three institutions and are subject to internal security and privacy rules. All data requests must follow the standard operating procedure built on the basis of mutual multi-institutional agreement. Foremost, the researcher must have appropriate credentials and authorization to be able to request for data. If the researcher is authorized to make requests, he or she must obtain the IRB approval for his or her proposed study and submit the IRB proposal and supporting documentation for review by the informatics committee. The informatics committee, independent of the IRB, reviews all requests for data from the data warehouse to ensure compliance with the agreement. If the research project is approved, the research team designated members are scheduled for the de-identified data extraction process.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Team_building\">Team building<\/span><\/h3>\n<p>Integral to the informatics platform is team building that builds upon previous work.<sup id=\"rdp-ebb-cite_ref-:2_37-1\" class=\"reference\"><a href=\"#cite_note-:2-37\">[37]<\/a><\/sup> To facilitate effective team meetings and inter-professional collaboration (local and global) without the need or expense of constant travel, a permanent clinical informatics conference room with a fixed connected computer, an uninterruptable power supply (UPS), a smart board, a camera, and a speaker system, along with a video conferencing system (Zoom) connectivity, was built. This ensures adequate communication among all those involved (i.e., team members, users, leadership, etc.) and access to resources that would otherwise be unavailable.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>Since the implementation of the platform, several studies have been conducted. Each study listed below was approved by the informatics committee, and the de-identified data and platform tools were made available securely to the research team.\n<\/p><p>To evaluate the functionality and value of this platform, we first analyzed the aggregated data of Medicaid-insured patients across different health systems using the interconnected applications within the platform for population health management. Relevant data were extracted from the CDW, followed by exploratory analysis using a Tableau dashboard. Due to the isolated nature of the study population, regional variables such as distance from the CHH and weather conditions (i.e., temperature) were also included. Errors and missing values were identified using the dashboard, and data were subsequently cleaned and prepared. Using these clean data, the regional population was classified into three spend categories: low cost, acute, and persistent subgroups on the basis of the charges accrued. Next, the Charlson Comorbidity Index (CCI) was incorporated into the CDW to predict mortality risk within one year of hospitalization for patients with comorbid conditions within each spend category (Table 1).<sup id=\"rdp-ebb-cite_ref-50\" class=\"reference\"><a href=\"#cite_note-50\">[50]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-51\" class=\"reference\"><a href=\"#cite_note-51\">[51]<\/a><\/sup> \n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> The 10-year mortality risk predicted using the Charlson Comorbidity Index\n<\/td><\/tr>\n\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mortality risk\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Deceased, <i>n<\/i> (%)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Alive, <i>n<\/i> (%)\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">High-risk\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">896 (0.80)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8,102 (7.20)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Low-risk\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">616 (0.55)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">102,905 (91.46)\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Of these categories, the persistent group had the largest percentage of patients with a high risk of mortality, followed by acute and low cost after excluding the deceased patients (persistent: 898\/1247, 72.01%; acute: 2074\/6946, 29.86%; low cost: 5130\/102,814, 4.99%). The CCI was not very sensitive in predicting the risk of mortality but was very specific and accurate (sensitivity: 896\/1512, 59.26%; specificity: 102,905\/111,007, 92.7%; accuracy: 103,801\/112,519, 92.25%). The effect of distance and weather on the CCI needs further investigation that is being conducted. Adjustments are being made to this standard national index to incorporate other Appalachian characteristics that could improve the sensitivity of this risk scoring system.\n<\/p><p>As such, the platform has been utilized for a variety of purposes such as increasing knowledge of the pathophysiology of diseases, risk identification, risk prediction, health care resource utilization research, and estimation of the economic impact of diseases to enable data-driven clinical decisions, leading to improved clinical outcomes. Table 2 contains a list of studies conducted so far.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Studies conducted using the Appalachian Informatics Platform\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Diagnostic accuracy improvement studies\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Albumin Level as a Risk Marker and Predictor of Peripartum Cardiomyopathy<sup id=\"rdp-ebb-cite_ref-:4_52-0\" class=\"reference\"><a href=\"#cite_note-:4-52\">[52]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Clinical Determinants of Myocardial Injury, Detectable and Serial Troponin Levels Among Patients With Hypertensive Crisis<sup id=\"rdp-ebb-cite_ref-:5_53-0\" class=\"reference\"><a href=\"#cite_note-:5-53\">[53]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Is Fever a Red Flag for Secondary Bacterial Pneumonia During RSV Bronchiolitis<sup id=\"rdp-ebb-cite_ref-:6_54-0\" class=\"reference\"><a href=\"#cite_note-:6-54\">[54]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Metabolic Syndrome: Are Current Colon Cancer Screening Guidelines Enough in a Rural Population?<sup id=\"rdp-ebb-cite_ref-:7_55-0\" class=\"reference\"><a href=\"#cite_note-:7-55\">[55]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Utilization of Appalachian Clinical and Translational Science Institute Data Warehouse to More Accurately Predict Disease Processes Important for Central Appalachia<sup id=\"rdp-ebb-cite_ref-:8_56-0\" class=\"reference\"><a href=\"#cite_note-:8-56\">[56]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Resource utilization and financial impact research studies\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Analysis of Benzodiazepine Prescription Practices in Elderly Appalachians with Dementia Via the Appalachian Informatics Platform: Longitudinal Study<sup id=\"rdp-ebb-cite_ref-:9_57-0\" class=\"reference\"><a href=\"#cite_note-:9-57\">[57]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Hospital Emergency Department Visits For Non-Traumatic Oral Health Conditions<sup id=\"rdp-ebb-cite_ref-:10_58-0\" class=\"reference\"><a href=\"#cite_note-:10-58\">[58]<\/a><\/sup>\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Studies to understand disease pathophysiology\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Serum Calcium Homeostasis and Volume Dynamics in Alzheimer\u2019s Disease and Diabetes Mellitus-2<sup id=\"rdp-ebb-cite_ref-:11_59-0\" class=\"reference\"><a href=\"#cite_note-:11-59\">[59]<\/a><\/sup>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Five studies utilized the platform for risk identification and risk prediction to improve diagnostic accuracy.<sup id=\"rdp-ebb-cite_ref-:4_52-1\" class=\"reference\"><a href=\"#cite_note-:4-52\">[52]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_53-1\" class=\"reference\"><a href=\"#cite_note-:5-53\">[53]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_54-1\" class=\"reference\"><a href=\"#cite_note-:6-54\">[54]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:7_55-1\" class=\"reference\"><a href=\"#cite_note-:7-55\">[55]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:8_56-1\" class=\"reference\"><a href=\"#cite_note-:8-56\">[56]<\/a><\/sup> Sundaram <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:8_56-2\" class=\"reference\"><a href=\"#cite_note-:8-56\">[56]<\/a><\/sup> demonstrated the value of ACTSI-CDW as a primary source to improve the diagnosis of metabolic syndrome, a diagnosis highly relevant to the Central Appalachian population. The researchers discovered that utilizing billing codes alone severely underestimated the number of patients with metabolic syndrome by a factor of more than 10, as compared with looking at specific criteria that determine this diagnosis.<sup id=\"rdp-ebb-cite_ref-:8_56-3\" class=\"reference\"><a href=\"#cite_note-:8-56\">[56]<\/a><\/sup> Another study assessed the relationship between metabolic syndrome and colorectal cancer and found that patients with metabolic syndrome, especially those with insulin resistance, were more likely to have colorectal cancer, indicating the probable need for earlier screening for colorectal cancer in these patients.<sup id=\"rdp-ebb-cite_ref-:7_55-2\" class=\"reference\"><a href=\"#cite_note-:7-55\">[55]<\/a><\/sup> Elmore <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:6_54-2\" class=\"reference\"><a href=\"#cite_note-:6-54\">[54]<\/a><\/sup> examined the role of fever in predicting the development of secondary bacterial pneumonia in children with RSV and other viral illnesses. They found that febrile children were two to eight times (RSV, 47\/78 vs 27\/100; other bronchiolitis, 54\/83 vs 7\/88) more likely to have secondary bacterial pneumonia compared with afebrile children and, thus, may need to be aggressively evaluated to enable early diagnosis and treatment.<sup id=\"rdp-ebb-cite_ref-:6_54-3\" class=\"reference\"><a href=\"#cite_note-:6-54\">[54]<\/a><\/sup> Amro <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:4_52-2\" class=\"reference\"><a href=\"#cite_note-:4-52\">[52]<\/a><\/sup> studied the relationship between hypoalbuminemia and peripartum cardiomyopathy and noted that lower albumin levels were significantly associated with peripartum cardiomyopathy (<i>P<\/i><.001; odds ratio 0.033, 95% CI 0.034-0.865) and could potentially be used as a risk marker for it. Acosta <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:5_53-2\" class=\"reference\"><a href=\"#cite_note-:5-53\">[53]<\/a><\/sup> used data from the ACTSI-CDW to identify risk factors (lower BMI, before CHF, and prior use of aspirin) that predict myocardial injury, detectable troponin, and increase in serial troponin levels in patients with hypertensive crisis.\n<\/p><p>Ferdjallah <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:11_59-1\" class=\"reference\"><a href=\"#cite_note-:11-59\">[59]<\/a><\/sup> analyzed the data from the ACTSI-CDW to understand how Alzheimer disease and diabetes mellitus affect serum calcium homeostasis and extracellular fluid volume. They observed that acute changes in serum calcium were significantly correlated with changes in extracellular fluid volume in both disease states.<sup id=\"rdp-ebb-cite_ref-:11_59-2\" class=\"reference\"><a href=\"#cite_note-:11-59\">[59]<\/a><\/sup>\n<\/p><p>The platform has also been applied in two studies to assess resource utilization (e.g., emergency room, medications, etc.) and the financial impact of the disease. For instance, Bhardwaj <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:9_57-1\" class=\"reference\"><a href=\"#cite_note-:9-57\">[57]<\/a><\/sup> utilized the platform to identify the problems associated with benzodiazepine use in geriatric patients within the health system, such as a higher number of emergency room visits and charges in geriatric patients with dementia plus at least one BZD prescription. In another study<sup id=\"rdp-ebb-cite_ref-:10_58-1\" class=\"reference\"><a href=\"#cite_note-:10-58\">[58]<\/a><\/sup> that aimed to measure the volume and cost of emergency room use for these conditions and identify the factors that predict such use, the researchers built a dashboard (Figure 2) to easily explore and analyze relevant data on non-traumatic dental conditions that led to emergency room visits and to report the key findings of the study. The authors<sup id=\"rdp-ebb-cite_ref-:10_58-2\" class=\"reference\"><a href=\"#cite_note-:10-58\">[58]<\/a><\/sup> observed that emergency room visits by uninsured patients were four times more likely and those by Medicaid insured two times more likely to be for dental problems than Medicare-insured patients.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Cecchetti_JMIRMedInfo8_8-10.png\" class=\"image wiki-link\" data-key=\"e1ee28773ff0436bebc4ad9dba1d15d1\"><img alt=\"Fig2 Cecchetti JMIRMedInfo8 8-10.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/15\/Fig2_Cecchetti_JMIRMedInfo8_8-10.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> Tableau dashboard displaying patterns and trends in charges for non-traumatic dental ER visits at Cabell Huntington Hospital between 2010 and 2018. ER: emergency room.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Utility_of_the_AIP\">Utility of the AIP<\/span><\/h3>\n<p>The AIP has supported several research projects involving the use of different components of the platform, depending on project needs. The studies described reported findings that are seldom reported in this region, enhanced our knowledge of pathophysiology and risk factors, and helped estimate and analyze resource utilization and economic burden of certain diseases within Appalachia using minimal resources (i.e., a small IT team and a relatively inexpensive platform).\n<\/p><p>Before the implementation of the platform, many research studies that followed the patient across multiple care settings or involved analysis of big data were not possible due to the unavailability of technical and economic resources owing to a lack of buy-in from rural health care organizations. As the data existed in silos, there was a lack of standardization and normalization, which resulted in major data inconsistencies. Studies conducted using these disjointed data sets often used unrepresentative small biased samples and had low statistical power and quality.\n<\/p><p>The introduction of the platform has helped address these issues. It is now easier to pinpoint and correct errors and\/or missing values and understand the distribution of data using visual analysis tools. Further, the time needed to conduct these studies from start to finish has been greatly reduced owing to the availability of all applications necessary to complete the study within the platform. This has been specifically useful because many researchers do not have the technical skills needed to perform complex and advanced data analysis, especially on larger data sets.\n<\/p><p>The paper also revealed that national models do not necessarily perform well when applied to the Appalachian population. The AIP allows for seamless integration of regional variables into the national model, which may improve the performance of these models. For each of the top 10 causes of death in West Virginia in 2017, per the <a href=\"https:\/\/www.limswiki.org\/index.php\/Centers_for_Disease_Control_and_Prevention\" title=\"Centers for Disease Control and Prevention\" class=\"wiki-link\" data-key=\"176aa9c9513251c328d864d1e724e814\">Centers for Disease Control and Prevention<\/a><sup id=\"rdp-ebb-cite_ref-60\" class=\"reference\"><a href=\"#cite_note-60\">[60]<\/a><\/sup>, a machine learning algorithm was used to predict outcomes on a national level: heart disease<sup id=\"rdp-ebb-cite_ref-61\" class=\"reference\"><a href=\"#cite_note-61\">[61]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-62\" class=\"reference\"><a href=\"#cite_note-62\">[62]<\/a><\/sup>, cancer<sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[63]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-64\" class=\"reference\"><a href=\"#cite_note-64\">[64]<\/a><\/sup>, accidents<sup id=\"rdp-ebb-cite_ref-65\" class=\"reference\"><a href=\"#cite_note-65\">[65]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[66]<\/a><\/sup>, respiratory disease<sup id=\"rdp-ebb-cite_ref-67\" class=\"reference\"><a href=\"#cite_note-67\">[67]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-68\" class=\"reference\"><a href=\"#cite_note-68\">[68]<\/a><\/sup>, stroke<sup id=\"rdp-ebb-cite_ref-69\" class=\"reference\"><a href=\"#cite_note-69\">[69]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-70\" class=\"reference\"><a href=\"#cite_note-70\">[70]<\/a><\/sup>, diabetes<sup id=\"rdp-ebb-cite_ref-71\" class=\"reference\"><a href=\"#cite_note-71\">[71]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-72\" class=\"reference\"><a href=\"#cite_note-72\">[72]<\/a><\/sup>, Alzheimer disease<sup id=\"rdp-ebb-cite_ref-73\" class=\"reference\"><a href=\"#cite_note-73\">[73]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-74\" class=\"reference\"><a href=\"#cite_note-74\">[74]<\/a><\/sup>, pneumonia<sup id=\"rdp-ebb-cite_ref-75\" class=\"reference\"><a href=\"#cite_note-75\">[75]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-76\" class=\"reference\"><a href=\"#cite_note-76\">[76]<\/a><\/sup>, kidney disease<sup id=\"rdp-ebb-cite_ref-77\" class=\"reference\"><a href=\"#cite_note-77\">[77]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-78\" class=\"reference\"><a href=\"#cite_note-78\">[78]<\/a><\/sup>, and suicide.<sup id=\"rdp-ebb-cite_ref-79\" class=\"reference\"><a href=\"#cite_note-79\">[79]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-80\" class=\"reference\"><a href=\"#cite_note-80\">[80]<\/a><\/sup> Each of these cited models could be modified to fit the characteristics of the Appalachian population, especially those characteristics that make this region different in terms of geography, economy, education, and culture from the rest of the United States. The development of these regional models could help rural health general practitioners tackle complex medical conditions without the need for an expensive specialized health care provider nearby.<sup id=\"rdp-ebb-cite_ref-:3_46-1\" class=\"reference\"><a href=\"#cite_note-:3-46\">[46]<\/a><\/sup>\n<\/p><p>We hope that this paper will help other rural health care organizations that serve underserved populations, such as ours, realize the value and ease of using an informatics platform to conduct research and improve care for their patients despite limited resources.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Ongoing_projects_and_future_directions\">Ongoing projects and future directions<\/span><\/h3>\n<p>At present, a model that utilizes embedded data analytics to monitor the side effects of certain types of cancer by ingesting de-identified statements in the regional variety of English language from patients within this region<sup id=\"rdp-ebb-cite_ref-81\" class=\"reference\"><a href=\"#cite_note-81\">[81]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-82\" class=\"reference\"><a href=\"#cite_note-82\">[82]<\/a><\/sup> is under development. This model could be used to analyze patient responses at a certain point in time for a cross-sectional study or continuously in real time for a long-term longitudinal study to identify the patients in need of care before their scheduled follow-up visit. The ongoing results from this model would be sent to their health care providers for appropriate actions. In case of an emergency, patient-designated community support networks such as religious or other support groups may be intimated to bring the patient to the emergency department so that the patient can receive timely care.\n<\/p><p>We plan to expand upon our unified informatics platform to integrate programming applications for the development of state-of-the-art applications targeted specifically toward the unmet health care needs of the Appalachian population.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>This paper establishes the value of the Appalachian Informatics Platform (AIP) in enabling seamless and secure data access, model development through an analytics engine to explore novel and unexpected hypotheses, and simple yet effective communication of all findings via interactive visualization.\n<\/p><p>The relatively inexpensive nature of such a platform coupled with its demonstrated advantages will hopefully encourage small and midsized rural academic centers, which traditionally have fewer resources than their urban counterparts, to adopt a research informatics platform within their institutions using the template described in this paper as a guide.\n<\/p>\n<h2><span id=\"rdp-ebb-Abbreviations,_acronyms,_and_initialisms\"><\/span><span class=\"mw-headline\" id=\"Abbreviations.2C_acronyms.2C_and_initialisms\">Abbreviations, acronyms, and initialisms<\/span><\/h2>\n<p><b>ACTSI<\/b>: Appalachian Clinical and Translational Science Institute\n<\/p><p><b>AIP<\/b>: Appalachian Informatics Platform\n<\/p><p><b>CCI<\/b>: Charlson Comorbidity Index\n<\/p><p><b>CDW<\/b>: clinical data warehouse\n<\/p><p><b>CHH<\/b>: Cabell-Huntington Hospital\n<\/p><p><b>ECCC<\/b>: Edwards Comprehensive Cancer Institute\n<\/p><p><b>EHR<\/b>: electronic health record\n<\/p><p><b>ETL<\/b>: extract, transform, and load\n<\/p><p><b>HIPAA<\/b>: Health Insurance Portability and Accountability Act\n<\/p><p><b>MH<\/b>: Marshall Health\n<\/p><p><b>MU JCESOM<\/b>: Marshall University Joan C Edwards School of Medicine\n<\/p><p><b>OLAP<\/b>: Online Analytical Processing\n<\/p><p><b>PHI<\/b>: protected health information\n<\/p><p><b>SQL<\/b>: structured query language\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This work was supported by the National Institutes of Health grants DK-67420, DK-108054, and P20GM121299-01A1 and Veteran\u2019s Administration Merit Review grant BX003443-01 to US and UL1TR00011719 to PK.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h3>\n<p>None declared.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Krometis, Leigh-Anne; Gohlke, Julia; Kolivras, Korine; Satterwhite, Emily; Marmagas, Susan West; Marr, Linsey C. 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Raghupathi, Viju (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1186\/2047-2501-2-3\" target=\"_blank\">\"Big data analytics in healthcare: promise and potential\"<\/a> (in en). <i>Health Information Science and Systems<\/i> <b>2<\/b> (1): 3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F2047-2501-2-3\" target=\"_blank\">10.1186\/2047-2501-2-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2047-2501\" target=\"_blank\">2047-2501<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4341817\/\" target=\"_blank\">PMC4341817<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25825667\" target=\"_blank\">25825667<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1186\/2047-2501-2-3\" target=\"_blank\">http:\/\/link.springer.com\/10.1186\/2047-2501-2-3<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+data+analytics+in+healthcare%3A+promise+and+potential&rft.jtitle=Health+Information+Science+and+Systems&rft.aulast=Raghupathi&rft.aufirst=Wullianallur&rft.au=Raghupathi%2C%26%2332%3BWullianallur&rft.au=Raghupathi%2C%26%2332%3BViju&rft.date=1+December+2014&rft.volume=2&rft.issue=1&rft.pages=3&rft_id=info:doi\/10.1186%2F2047-2501-2-3&rft.issn=2047-2501&rft_id=info:pmc\/PMC4341817&rft_id=info:pmid\/25825667&rft_id=http%3A%2F%2Flink.springer.com%2F10.1186%2F2047-2501-2-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ahern, Melissa M.; Hendryx, Michael (1 June 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.liebertpub.com\/doi\/10.1089\/env.2008.0511\" target=\"_blank\">\"Health Disparities and Environmental Competence: A Case Study of Appalachian Coal Mining\"<\/a> (in en). <i>Environmental Justice<\/i> <b>1<\/b> (2): 81\u201386. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1089%2Fenv.2008.0511\" target=\"_blank\">10.1089\/env.2008.0511<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1939-4071\" target=\"_blank\">1939-4071<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.liebertpub.com\/doi\/10.1089\/env.2008.0511\" target=\"_blank\">http:\/\/www.liebertpub.com\/doi\/10.1089\/env.2008.0511<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Health+Disparities+and+Environmental+Competence%3A+A+Case+Study+of+Appalachian+Coal+Mining&rft.jtitle=Environmental+Justice&rft.aulast=Ahern&rft.aufirst=Melissa+M.&rft.au=Ahern%2C%26%2332%3BMelissa+M.&rft.au=Hendryx%2C%26%2332%3BMichael&rft.date=1+June+2008&rft.volume=1&rft.issue=2&rft.pages=81%E2%80%9386&rft_id=info:doi\/10.1089%2Fenv.2008.0511&rft.issn=1939-4071&rft_id=http%3A%2F%2Fwww.liebertpub.com%2Fdoi%2F10.1089%2Fenv.2008.0511&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-9\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">McCulloch, B.Jan (1 March 1995). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/0890406595900268\" target=\"_blank\">\"The relationship of family proximity and social support to the mental health of older rural adults: The Appalachian context\"<\/a> (in en). <i>Journal of Aging Studies<\/i> <b>9<\/b> (1): 65\u201381. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2F0890-4065%2895%2990026-8\" target=\"_blank\">10.1016\/0890-4065(95)90026-8<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/0890406595900268\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/0890406595900268<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+relationship+of+family+proximity+and+social+support+to+the+mental+health+of+older+rural+adults%3A+The+Appalachian+context&rft.jtitle=Journal+of+Aging+Studies&rft.aulast=McCulloch&rft.aufirst=B.Jan&rft.au=McCulloch%2C%26%2332%3BB.Jan&rft.date=1+March+1995&rft.volume=9&rft.issue=1&rft.pages=65%E2%80%9381&rft_id=info:doi\/10.1016%2F0890-4065%2895%2990026-8&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F0890406595900268&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Simpson, Mary Rado; King, Marilyn Givens; Mary Rado Simpson is a Doctoral Candidate at the College of Nursing and Marilyn Givens King is an Associate Professor at the College of Nursing and the Center for Rural Health at the University of Kentucky, Lexington, Kentucky. (1 February 1999). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1046\/j.1525-1446.1999.00041.x\" target=\"_blank\">\"\u201cGod Brought All These Churches Together\u201d: Issues in Developing Religion\u2010Health Partnerships in an Appalachian Community\"<\/a> (in en). <i>Public Health Nursing<\/i> <b>16<\/b> (1): 41\u201349. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1046%2Fj.1525-1446.1999.00041.x\" target=\"_blank\">10.1046\/j.1525-1446.1999.00041.x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0737-1209\" target=\"_blank\">0737-1209<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1046\/j.1525-1446.1999.00041.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1046\/j.1525-1446.1999.00041.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%E2%80%9CGod+Brought+All+These+Churches+Together%E2%80%9D%3A+Issues+in+Developing+Religion%E2%80%90Health+Partnerships+in+an+Appalachian+Community&rft.jtitle=Public+Health+Nursing&rft.aulast=Simpson&rft.aufirst=Mary+Rado&rft.au=Simpson%2C%26%2332%3BMary+Rado&rft.au=King%2C%26%2332%3BMarilyn+Givens&rft.au=Mary+Rado+Simpson+is+a+Doctoral+Candidate+at+the+College+of+Nursing+and+Marilyn+Givens+King+is+an+Associate+Professor+at+the+College+of+Nursing+and+the+Center+for+Rural+Health+at+the+University+of+Kentucky%2C+Lexington%2C+Kentucky.&rft.date=1+February+1999&rft.volume=16&rft.issue=1&rft.pages=41%E2%80%9349&rft_id=info:doi\/10.1046%2Fj.1525-1446.1999.00041.x&rft.issn=0737-1209&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2Fabs%2F10.1046%2Fj.1525-1446.1999.00041.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Holve, Erin; Segal, Courtney; Hamilton Lopez, Marianne (1 July 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journals.lww.com\/00005650-201207001-00006\" target=\"_blank\">\"Opportunities and Challenges for Comparative Effectiveness Research (CER) With Electronic Clinical Data: A Perspective From the EDM Forum\"<\/a> (in en). <i>Medical Care<\/i> <b>50<\/b>: S11\u2013S18. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FMLR.0b013e318258530f\" target=\"_blank\">10.1097\/MLR.0b013e318258530f<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0025-7079\" target=\"_blank\">0025-7079<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journals.lww.com\/00005650-201207001-00006\" target=\"_blank\">https:\/\/journals.lww.com\/00005650-201207001-00006<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Opportunities+and+Challenges+for+Comparative+Effectiveness+Research+%28CER%29+With+Electronic+Clinical+Data%3A+A+Perspective+From+the+EDM+Forum&rft.jtitle=Medical+Care&rft.aulast=Holve&rft.aufirst=Erin&rft.au=Holve%2C%26%2332%3BErin&rft.au=Segal%2C%26%2332%3BCourtney&rft.au=Hamilton+Lopez%2C%26%2332%3BMarianne&rft.date=1+July+2012&rft.volume=50&rft.pages=S11%E2%80%93S18&rft_id=info:doi\/10.1097%2FMLR.0b013e318258530f&rft.issn=0025-7079&rft_id=https%3A%2F%2Fjournals.lww.com%2F00005650-201207001-00006&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rabinowitz, Howard K.; Paynter, Nina P. (2 January 2002). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11754723\" target=\"_blank\">\"MSJAMA. The rural vs urban practice decision\"<\/a>. <i>JAMA<\/i> <b>287<\/b> (1): 113. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0098-7484\" target=\"_blank\">0098-7484<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11754723\" target=\"_blank\">11754723<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11754723\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/11754723<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=MSJAMA.+The+rural+vs+urban+practice+decision&rft.jtitle=JAMA&rft.aulast=Rabinowitz&rft.aufirst=Howard+K.&rft.au=Rabinowitz%2C%26%2332%3BHoward+K.&rft.au=Paynter%2C%26%2332%3BNina+P.&rft.date=2+January+2002&rft.volume=287&rft.issue=1&rft.pages=113&rft.issn=0098-7484&rft_id=info:pmid\/11754723&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F11754723&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Anderson, Allison E.; Henry, Kevin A.; Samadder, N. Jewel; Merrill, Ray M.; Kinney, Anita Y. (1 May 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1542356512014255\" target=\"_blank\">\"Rural vs Urban Residence Affects Risk-Appropriate Colorectal Cancer Screening\"<\/a> (in en). <i>Clinical Gastroenterology and Hepatology<\/i> <b>11<\/b> (5): 526\u2013533. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.cgh.2012.11.025\" target=\"_blank\">10.1016\/j.cgh.2012.11.025<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3615111\/\" target=\"_blank\">PMC3615111<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23220166\" target=\"_blank\">23220166<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1542356512014255\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1542356512014255<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Rural+vs+Urban+Residence+Affects+Risk-Appropriate+Colorectal+Cancer+Screening&rft.jtitle=Clinical+Gastroenterology+and+Hepatology&rft.aulast=Anderson&rft.aufirst=Allison+E.&rft.au=Anderson%2C%26%2332%3BAllison+E.&rft.au=Henry%2C%26%2332%3BKevin+A.&rft.au=Samadder%2C%26%2332%3BN.+Jewel&rft.au=Merrill%2C%26%2332%3BRay+M.&rft.au=Kinney%2C%26%2332%3BAnita+Y.&rft.date=1+May+2013&rft.volume=11&rft.issue=5&rft.pages=526%E2%80%93533&rft_id=info:doi\/10.1016%2Fj.cgh.2012.11.025&rft_id=info:pmc\/PMC3615111&rft_id=info:pmid\/23220166&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1542356512014255&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Reif, Susan; Whetten, Kathryn; Ostermann, Jan; Raper, James L. (1 September 2006). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/09540120600838738\" target=\"_blank\">\"Characteristics of HIV-infected adults in the Deep South and their utilization of mental health services: A rural vs. urban comparison\"<\/a> (in en). <i>AIDS Care<\/i> <b>18<\/b> (sup1): 10\u201317. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F09540120600838738\" target=\"_blank\">10.1080\/09540120600838738<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0954-0121\" target=\"_blank\">0954-0121<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/09540120600838738\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/09540120600838738<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Characteristics+of+HIV-infected+adults+in+the+Deep+South+and+their+utilization+of+mental+health+services%3A+A+rural+vs.+urban+comparison&rft.jtitle=AIDS+Care&rft.aulast=Reif&rft.aufirst=Susan&rft.au=Reif%2C%26%2332%3BSusan&rft.au=Whetten%2C%26%2332%3BKathryn&rft.au=Ostermann%2C%26%2332%3BJan&rft.au=Raper%2C%26%2332%3BJames+L.&rft.date=1+September+2006&rft.volume=18&rft.issue=sup1&rft.pages=10%E2%80%9317&rft_id=info:doi\/10.1080%2F09540120600838738&rft.issn=0954-0121&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F09540120600838738&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Shubhakaran, K.P.; Khichar, R.J. 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Hao, Yixue; Hwang, Kai; Wang, Lu; Wang, Lin (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7912315\/\" target=\"_blank\">\"Disease Prediction by Machine Learning Over Big Data From Healthcare Communities\"<\/a>. <i>IEEE Access<\/i> <b>5<\/b>: 8869\u20138879. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FACCESS.2017.2694446\" target=\"_blank\">10.1109\/ACCESS.2017.2694446<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2169-3536\" target=\"_blank\">2169-3536<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7912315\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7912315\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Disease+Prediction+by+Machine+Learning+Over+Big+Data+From+Healthcare+Communities&rft.jtitle=IEEE+Access&rft.aulast=Chen&rft.aufirst=Min&rft.au=Chen%2C%26%2332%3BMin&rft.au=Hao%2C%26%2332%3BYixue&rft.au=Hwang%2C%26%2332%3BKai&rft.au=Wang%2C%26%2332%3BLu&rft.au=Wang%2C%26%2332%3BLin&rft.date=2017&rft.volume=5&rft.pages=8869%E2%80%938879&rft_id=info:doi\/10.1109%2FACCESS.2017.2694446&rft.issn=2169-3536&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7912315%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-19\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jensen, Peter B.; Jensen, Lars J.; Brunak, S\u00f8ren (1 June 2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/nrg3208\" target=\"_blank\">\"Mining electronic health records: towards better research applications and clinical care\"<\/a> (in en). <i>Nature Reviews Genetics<\/i> <b>13<\/b> (6): 395\u2013405. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fnrg3208\" target=\"_blank\">10.1038\/nrg3208<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-0056\" target=\"_blank\">1471-0056<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/nrg3208\" target=\"_blank\">http:\/\/www.nature.com\/articles\/nrg3208<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mining+electronic+health+records%3A+towards+better+research+applications+and+clinical+care&rft.jtitle=Nature+Reviews+Genetics&rft.aulast=Jensen&rft.aufirst=Peter+B.&rft.au=Jensen%2C%26%2332%3BPeter+B.&rft.au=Jensen%2C%26%2332%3BLars+J.&rft.au=Brunak%2C%26%2332%3BS%C3%B8ren&rft.date=1+June+2012&rft.volume=13&rft.issue=6&rft.pages=395%E2%80%93405&rft_id=info:doi\/10.1038%2Fnrg3208&rft.issn=1471-0056&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fnrg3208&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-20\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wang, Yichuan; Kung, LeeAnn; Byrd, Terry Anthony (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040162516000500\" target=\"_blank\">\"Big data analytics: Understanding its capabilities and potential benefits for healthcare organizations\"<\/a> (in en). <i>Technological Forecasting and Social Change<\/i> <b>126<\/b>: 3\u201313. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.techfore.2015.12.019\" target=\"_blank\">10.1016\/j.techfore.2015.12.019<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040162516000500\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040162516000500<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+data+analytics%3A+Understanding+its+capabilities+and+potential+benefits+for+healthcare+organizations&rft.jtitle=Technological+Forecasting+and+Social+Change&rft.aulast=Wang&rft.aufirst=Yichuan&rft.au=Wang%2C%26%2332%3BYichuan&rft.au=Kung%2C%26%2332%3BLeeAnn&rft.au=Byrd%2C%26%2332%3BTerry+Anthony&rft.date=1+January+2018&rft.volume=126&rft.pages=3%E2%80%9313&rft_id=info:doi\/10.1016%2Fj.techfore.2015.12.019&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0040162516000500&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bhardwaj, Niharika; Wodajo, Bezawit; Spano, Anthony; Neal, Symaron; Coustasse, Alberto (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journals.lww.com\/00126450-201801000-00014\" target=\"_blank\">\"The Impact of Big Data on Chronic Disease Management\"<\/a> (in en). <i>The Health Care Manager<\/i> <b>37<\/b> (1): 90\u201398. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FHCM.0000000000000194\" target=\"_blank\">10.1097\/HCM.0000000000000194<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1550-512X\" target=\"_blank\">1550-512X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journals.lww.com\/00126450-201801000-00014\" target=\"_blank\">https:\/\/journals.lww.com\/00126450-201801000-00014<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Impact+of+Big+Data+on+Chronic+Disease+Management&rft.jtitle=The+Health+Care+Manager&rft.aulast=Bhardwaj&rft.aufirst=Niharika&rft.au=Bhardwaj%2C%26%2332%3BNiharika&rft.au=Wodajo%2C%26%2332%3BBezawit&rft.au=Spano%2C%26%2332%3BAnthony&rft.au=Neal%2C%26%2332%3BSymaron&rft.au=Coustasse%2C%26%2332%3BAlberto&rft.date=1+January+2018&rft.volume=37&rft.issue=1&rft.pages=90%E2%80%9398&rft_id=info:doi\/10.1097%2FHCM.0000000000000194&rft.issn=1550-512X&rft_id=https%3A%2F%2Fjournals.lww.com%2F00126450-201801000-00014&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Elam, C. (2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/docs.lib.purdue.edu\/eandc\/vol18\/iss1\/art4\/\" target=\"_blank\">\"Culture, poverty and education in Appalachian Kentucky\"<\/a>. <i>Education & Culture<\/i> <b>18<\/b> (1): 4<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/docs.lib.purdue.edu\/eandc\/vol18\/iss1\/art4\/\" target=\"_blank\">https:\/\/docs.lib.purdue.edu\/eandc\/vol18\/iss1\/art4\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Culture%2C+poverty+and+education+in+Appalachian+Kentucky&rft.jtitle=Education+%26+Culture&rft.aulast=Elam%2C+C.&rft.au=Elam%2C+C.&rft.date=2012&rft.volume=18&rft.issue=1&rft.pages=4&rft_id=https%3A%2F%2Fdocs.lib.purdue.edu%2Feandc%2Fvol18%2Fiss1%2Fart4%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Coyne, Cathy A; Demian-Popescu, Cristina; Friend, Dana (15 September 2006). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779288\/\" target=\"_blank\">\"Social and Cultural Factors Influencing Health in Southern West Virginia: A Qualitative Study\"<\/a>. <i>Preventing Chronic Disease<\/i> <b>3<\/b> (4): A124. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1545-1151\" target=\"_blank\">1545-1151<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/1779288\/\" target=\"_blank\">1779288<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16978499\" target=\"_blank\">16978499<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779288\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779288\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Social+and+Cultural+Factors+Influencing+Health+in+Southern+West+Virginia%3A+A+Qualitative+Study&rft.jtitle=Preventing+Chronic+Disease&rft.aulast=Coyne&rft.aufirst=Cathy+A&rft.au=Coyne%2C%26%2332%3BCathy+A&rft.au=Demian-Popescu%2C%26%2332%3BCristina&rft.au=Friend%2C%26%2332%3BDana&rft.date=15+September+2006&rft.volume=3&rft.issue=4&rft.pages=A124&rft.issn=1545-1151&rft_id=info:pmc\/1779288&rft_id=info:pmid\/16978499&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1779288%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Behringer, Bruce; Friedell, Gilbert H (15 September 2006). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779277\/\" target=\"_blank\">\"Appalachia: Where Place Matters in Health\"<\/a>. <i>Preventing Chronic Disease<\/i> <b>3<\/b> (4): A113. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1545-1151\" target=\"_blank\">1545-1151<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/1779277\/\" target=\"_blank\">1779277<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16978488\" target=\"_blank\">16978488<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779277\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1779277\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Appalachia%3A+Where+Place+Matters+in+Health&rft.jtitle=Preventing+Chronic+Disease&rft.aulast=Behringer&rft.aufirst=Bruce&rft.au=Behringer%2C%26%2332%3BBruce&rft.au=Friedell%2C%26%2332%3BGilbert+H&rft.date=15+September+2006&rft.volume=3&rft.issue=4&rft.pages=A113&rft.issn=1545-1151&rft_id=info:pmc\/1779277&rft_id=info:pmid\/16978488&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1779277%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-25\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_25-0\">25.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_25-1\">25.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kim, Jungyeon; Ohsfeldt, Robert L.; Gamm, Larry D.; Radcliff, Tiffany A.; Jiang, Luohua (1 June 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jrh.12193\" target=\"_blank\">\"Hospital Characteristics are Associated With Readiness to Attain Stage 2 Meaningful Use of Electronic Health Records: Readiness for Stage 2 Meaningful Use\"<\/a> (in en). <i>The Journal of Rural Health<\/i> <b>33<\/b> (3): 275\u2013283. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fjrh.12193\" target=\"_blank\">10.1111\/jrh.12193<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jrh.12193\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jrh.12193<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hospital+Characteristics+are+Associated+With+Readiness+to+Attain+Stage+2+Meaningful+Use+of+Electronic+Health+Records%3A+Readiness+for+Stage+2+Meaningful+Use&rft.jtitle=The+Journal+of+Rural+Health&rft.aulast=Kim&rft.aufirst=Jungyeon&rft.au=Kim%2C%26%2332%3BJungyeon&rft.au=Ohsfeldt%2C%26%2332%3BRobert+L.&rft.au=Gamm%2C%26%2332%3BLarry+D.&rft.au=Radcliff%2C%26%2332%3BTiffany+A.&rft.au=Jiang%2C%26%2332%3BLuohua&rft.date=1+June+2017&rft.volume=33&rft.issue=3&rft.pages=275%E2%80%93283&rft_id=info:doi\/10.1111%2Fjrh.12193&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fjrh.12193&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-26\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mason, Patricia; Mayer, Roger; Chien, Wen-Wen; Monestime, Judith (12 November 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/nsuworks.nova.edu\/tqr\/vol22\/iss11\/7\/\" target=\"_blank\">\"Overcoming Barriers to Implementing Electronic Health Records in Rural Primary Care Clinics\"<\/a> (in en). <i>The Qualitative Report<\/i> <b>22<\/b> (11): 2943\u20132955. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.46743%2F2160-3715%2F2017.2515\" target=\"_blank\">10.46743\/2160-3715\/2017.2515<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2160-3715\" target=\"_blank\">2160-3715<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/nsuworks.nova.edu\/tqr\/vol22\/iss11\/7\/\" target=\"_blank\">https:\/\/nsuworks.nova.edu\/tqr\/vol22\/iss11\/7\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Overcoming+Barriers+to+Implementing+Electronic+Health+Records+in+Rural+Primary+Care+Clinics&rft.jtitle=The+Qualitative+Report&rft.aulast=Mason&rft.aufirst=Patricia&rft.au=Mason%2C%26%2332%3BPatricia&rft.au=Mayer%2C%26%2332%3BRoger&rft.au=Chien%2C%26%2332%3BWen-Wen&rft.au=Monestime%2C%26%2332%3BJudith&rft.date=12+November+2017&rft.volume=22&rft.issue=11&rft.pages=2943%E2%80%932955&rft_id=info:doi\/10.46743%2F2160-3715%2F2017.2515&rft.issn=2160-3715&rft_id=https%3A%2F%2Fnsuworks.nova.edu%2Ftqr%2Fvol22%2Fiss11%2F7%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Woolf, Steven H. (9 January 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jama.jamanetwork.com\/article.aspx?doi=10.1001\/jama.2007.26\" target=\"_blank\">\"The Meaning of Translational Research and Why It Matters\"<\/a> (in en). <i>JAMA<\/i> <b>299<\/b> (2): 211\u201313. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1001%2Fjama.2007.26\" target=\"_blank\">10.1001\/jama.2007.26<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0098-7484\" target=\"_blank\">0098-7484<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jama.jamanetwork.com\/article.aspx?doi=10.1001\/jama.2007.26\" target=\"_blank\">http:\/\/jama.jamanetwork.com\/article.aspx?doi=10.1001\/jama.2007.26<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Meaning+of+Translational+Research+and+Why+It+Matters&rft.jtitle=JAMA&rft.aulast=Woolf&rft.aufirst=Steven+H.&rft.au=Woolf%2C%26%2332%3BSteven+H.&rft.date=9+January+2008&rft.volume=299&rft.issue=2&rft.pages=211%E2%80%9313&rft_id=info:doi\/10.1001%2Fjama.2007.26&rft.issn=0098-7484&rft_id=http%3A%2F%2Fjama.jamanetwork.com%2Farticle.aspx%3Fdoi%3D10.1001%2Fjama.2007.26&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-28\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_28-0\">28.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_28-1\">28.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">For members of the Jerusalem Trauma Outreach and Prevention Study (J-TOPS) group; Karstoft, Karen-Inge; Galatzer-Levy, Isaac R; Statnikov, Alexander; Li, Zhiguo; Shalev, Arieh Y (1 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/bmcpsychiatry.biomedcentral.com\/articles\/10.1186\/s12888-015-0399-8\" target=\"_blank\">\"Bridging a translational gap: using machine learning to improve the prediction of PTSD\"<\/a> (in en). <i>BMC Psychiatry<\/i> <b>15<\/b> (1): 30. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fs12888-015-0399-8\" target=\"_blank\">10.1186\/s12888-015-0399-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-244X\" target=\"_blank\">1471-244X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4360940\/\" target=\"_blank\">PMC4360940<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25886446\" target=\"_blank\">25886446<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/bmcpsychiatry.biomedcentral.com\/articles\/10.1186\/s12888-015-0399-8\" target=\"_blank\">http:\/\/bmcpsychiatry.biomedcentral.com\/articles\/10.1186\/s12888-015-0399-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bridging+a+translational+gap%3A+using+machine+learning+to+improve+the+prediction+of+PTSD&rft.jtitle=BMC+Psychiatry&rft.aulast=For+members+of+the+Jerusalem+Trauma+Outreach+and+Prevention+Study+%28J-TOPS%29+group&rft.au=For+members+of+the+Jerusalem+Trauma+Outreach+and+Prevention+Study+%28J-TOPS%29+group&rft.au=Karstoft%2C%26%2332%3BKaren-Inge&rft.au=Galatzer-Levy%2C%26%2332%3BIsaac+R&rft.au=Statnikov%2C%26%2332%3BAlexander&rft.au=Li%2C%26%2332%3BZhiguo&rft.au=Shalev%2C%26%2332%3BArieh+Y&rft.date=1+December+2015&rft.volume=15&rft.issue=1&rft.pages=30&rft_id=info:doi\/10.1186%2Fs12888-015-0399-8&rft.issn=1471-244X&rft_id=info:pmc\/PMC4360940&rft_id=info:pmid\/25886446&rft_id=http%3A%2F%2Fbmcpsychiatry.biomedcentral.com%2Farticles%2F10.1186%2Fs12888-015-0399-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-29\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ethier, J. -F.; 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M.; Bastiaens, H.; Andreasson, A.; Rossiter, J.; Zhao, L. <i>et al.<\/i> (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME13-02-0024\" target=\"_blank\">\"Clinical Data Integration Model: Core Interoperability Ontology for Research Using Primary Care Data\"<\/a> (in en). <i>Methods of Information in Medicine<\/i> <b>54<\/b> (01): 16\u201323. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3414%2FME13-02-0024\" target=\"_blank\">10.3414\/ME13-02-0024<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0026-1270\" target=\"_blank\">0026-1270<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME13-02-0024\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME13-02-0024<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+Data+Integration+Model%3A+Core+Interoperability+Ontology+for+Research+Using+Primary+Care+Data&rft.jtitle=Methods+of+Information+in+Medicine&rft.aulast=Ethier&rft.aufirst=J.+-F.&rft.au=Ethier%2C%26%2332%3BJ.+-F.&rft.au=Curcin%2C%26%2332%3BV.&rft.au=Barton%2C%26%2332%3BA.&rft.au=McGilchrist%2C%26%2332%3BM.+M.&rft.au=Bastiaens%2C%26%2332%3BH.&rft.au=Andreasson%2C%26%2332%3BA.&rft.au=Rossiter%2C%26%2332%3BJ.&rft.au=Zhao%2C%26%2332%3BL.&rft.au=Arvanitis%2C%26%2332%3BT.+N.&rft.date=2015&rft.volume=54&rft.issue=01&rft.pages=16%E2%80%9323&rft_id=info:doi\/10.3414%2FME13-02-0024&rft.issn=0026-1270&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.3414%2FME13-02-0024&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bates, David W.; Saria, Suchi; Ohno-Machado, Lucila; Shah, Anand; Escobar, Gabriel (1 July 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2014.0041\" target=\"_blank\">\"Big Data In Health Care: Using Analytics To Identify And Manage High-Risk And High-Cost Patients\"<\/a> (in en). <i>Health Affairs<\/i> <b>33<\/b> (7): 1123\u20131131. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1377%2Fhlthaff.2014.0041\" target=\"_blank\">10.1377\/hlthaff.2014.0041<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0278-2715\" target=\"_blank\">0278-2715<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2014.0041\" target=\"_blank\">http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2014.0041<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+Data+In+Health+Care%3A+Using+Analytics+To+Identify+And+Manage+High-Risk+And+High-Cost+Patients&rft.jtitle=Health+Affairs&rft.aulast=Bates&rft.aufirst=David+W.&rft.au=Bates%2C%26%2332%3BDavid+W.&rft.au=Saria%2C%26%2332%3BSuchi&rft.au=Ohno-Machado%2C%26%2332%3BLucila&rft.au=Shah%2C%26%2332%3BAnand&rft.au=Escobar%2C%26%2332%3BGabriel&rft.date=1+July+2014&rft.volume=33&rft.issue=7&rft.pages=1123%E2%80%931131&rft_id=info:doi\/10.1377%2Fhlthaff.2014.0041&rft.issn=0278-2715&rft_id=http%3A%2F%2Fwww.healthaffairs.org%2Fdoi%2F10.1377%2Fhlthaff.2014.0041&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Handelsman, D. 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Retrieved 28 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Applying+Business+Analytics+to+Optimize+Clinical+Research+Operations&rft.atitle=SAS+Global+Forum+2012&rft.aulast=Handelsman%2C+D.&rft.au=Handelsman%2C+D.&rft.date=2012&rft_id=https%3A%2F%2Fsupport.sas.com%2Fresources%2Fpapers%2Fproceedings12%2F171-2012.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-32\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Simpao, Allan F.; Ahumada, Luis M.; G\u00e1lvez, Jorge A.; Rehman, Mohamed A. (1 April 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-014-0045-x\" target=\"_blank\">\"A Review of Analytics and Clinical Informatics in Health Care\"<\/a> (in en). <i>Journal of Medical Systems<\/i> <b>38<\/b> (4): 45. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10916-014-0045-x\" target=\"_blank\">10.1007\/s10916-014-0045-x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0148-5598\" target=\"_blank\">0148-5598<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-014-0045-x\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10916-014-0045-x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Review+of+Analytics+and+Clinical+Informatics+in+Health+Care&rft.jtitle=Journal+of+Medical+Systems&rft.aulast=Simpao&rft.aufirst=Allan+F.&rft.au=Simpao%2C%26%2332%3BAllan+F.&rft.au=Ahumada%2C%26%2332%3BLuis+M.&rft.au=G%C3%A1lvez%2C%26%2332%3BJorge+A.&rft.au=Rehman%2C%26%2332%3BMohamed+A.&rft.date=1+April+2014&rft.volume=38&rft.issue=4&rft.pages=45&rft_id=info:doi\/10.1007%2Fs10916-014-0045-x&rft.issn=0148-5598&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10916-014-0045-x&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-33\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Iwabuchi, Sarina J.; Liddle, Peter F.; Palaniyappan, Lena (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fpsyt.2013.00095\/abstract\" target=\"_blank\">\"Clinical Utility of Machine-Learning Approaches in Schizophrenia: Improving Diagnostic Confidence for Translational Neuroimaging\"<\/a>. <i>Frontiers in Psychiatry<\/i> <b>4<\/b>: 95. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpsyt.2013.00095\" target=\"_blank\">10.3389\/fpsyt.2013.00095<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-0640\" target=\"_blank\">1664-0640<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3756305\/\" target=\"_blank\">PMC3756305<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24009589\" target=\"_blank\">24009589<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journal.frontiersin.org\/article\/10.3389\/fpsyt.2013.00095\/abstract\" target=\"_blank\">http:\/\/journal.frontiersin.org\/article\/10.3389\/fpsyt.2013.00095\/abstract<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+Utility+of+Machine-Learning+Approaches+in+Schizophrenia%3A+Improving+Diagnostic+Confidence+for+Translational+Neuroimaging&rft.jtitle=Frontiers+in+Psychiatry&rft.aulast=Iwabuchi&rft.aufirst=Sarina+J.&rft.au=Iwabuchi%2C%26%2332%3BSarina+J.&rft.au=Liddle%2C%26%2332%3BPeter+F.&rft.au=Palaniyappan%2C%26%2332%3BLena&rft.date=2013&rft.volume=4&rft.pages=95&rft_id=info:doi\/10.3389%2Ffpsyt.2013.00095&rft.issn=1664-0640&rft_id=info:pmc\/PMC3756305&rft_id=info:pmid\/24009589&rft_id=http%3A%2F%2Fjournal.frontiersin.org%2Farticle%2F10.3389%2Ffpsyt.2013.00095%2Fabstract&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-34\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Ainali, C. (28 September 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/kclpure.kcl.ac.uk\/portal\/files\/31802684\/2013_Ainali_Chrysanthi_0829730_ethesis.pdf\" target=\"_blank\">\"Machine Learning for Translational Medicine\"<\/a> (PDF). King's College London<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/kclpure.kcl.ac.uk\/portal\/files\/31802684\/2013_Ainali_Chrysanthi_0829730_ethesis.pdf\" target=\"_blank\">https:\/\/kclpure.kcl.ac.uk\/portal\/files\/31802684\/2013_Ainali_Chrysanthi_0829730_ethesis.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 28 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Machine+Learning+for+Translational+Medicine&rft.atitle=&rft.aulast=Ainali%2C+C.&rft.au=Ainali%2C+C.&rft.date=28+September+2012&rft.pub=King%27s+College+London&rft_id=https%3A%2F%2Fkclpure.kcl.ac.uk%2Fportal%2Ffiles%2F31802684%2F2013_Ainali_Chrysanthi_0829730_ethesis.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jiang, Min; Chen, Yukun; Liu, Mei; Rosenbloom, S Trent; Mani, Subramani; Denny, Joshua C; Xu, Hua (1 September 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000163\" target=\"_blank\">\"A study of machine-learning-based approaches to extract clinical entities and their assertions from discharge summaries\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>18<\/b> (5): 601\u2013606. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Famiajnl-2011-000163\" target=\"_blank\">10.1136\/amiajnl-2011-000163<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1067-5027\" target=\"_blank\">1067-5027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3168315\/\" target=\"_blank\">PMC3168315<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21508414\" target=\"_blank\">21508414<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000163\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000163<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+study+of+machine-learning-based+approaches+to+extract+clinical+entities+and+their+assertions+from+discharge+summaries&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Jiang&rft.aufirst=Min&rft.au=Jiang%2C%26%2332%3BMin&rft.au=Chen%2C%26%2332%3BYukun&rft.au=Liu%2C%26%2332%3BMei&rft.au=Rosenbloom%2C%26%2332%3BS+Trent&rft.au=Mani%2C%26%2332%3BSubramani&rft.au=Denny%2C%26%2332%3BJoshua+C&rft.au=Xu%2C%26%2332%3BHua&rft.date=1+September+2011&rft.volume=18&rft.issue=5&rft.pages=601%E2%80%93606&rft_id=info:doi\/10.1136%2Famiajnl-2011-000163&rft.issn=1067-5027&rft_id=info:pmc\/PMC3168315&rft_id=info:pmid\/21508414&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle-lookup%2Fdoi%2F10.1136%2Famiajnl-2011-000163&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sittig, Dean F.; Hazlehurst, Brian L.; Brown, Jeffrey; Murphy, Shawn; Rosenman, Marc; Tarczy-Hornoch, Peter; Wilcox, Adam B. (1 July 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journals.lww.com\/00005650-201207001-00012\" target=\"_blank\">\"A Survey of Informatics Platforms That Enable Distributed Comparative Effectiveness Research Using Multi-institutional Heterogenous Clinical Data\"<\/a> (in en). <i>Medical Care<\/i> <b>50<\/b>: S49\u2013S59. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FMLR.0b013e318259c02b\" target=\"_blank\">10.1097\/MLR.0b013e318259c02b<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0025-7079\" target=\"_blank\">0025-7079<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3415281\/\" target=\"_blank\">PMC3415281<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22692259\" target=\"_blank\">22692259<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journals.lww.com\/00005650-201207001-00012\" target=\"_blank\">https:\/\/journals.lww.com\/00005650-201207001-00012<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Survey+of+Informatics+Platforms+That+Enable+Distributed+Comparative+Effectiveness+Research+Using+Multi-institutional+Heterogenous+Clinical+Data&rft.jtitle=Medical+Care&rft.aulast=Sittig&rft.aufirst=Dean+F.&rft.au=Sittig%2C%26%2332%3BDean+F.&rft.au=Hazlehurst%2C%26%2332%3BBrian+L.&rft.au=Brown%2C%26%2332%3BJeffrey&rft.au=Murphy%2C%26%2332%3BShawn&rft.au=Rosenman%2C%26%2332%3BMarc&rft.au=Tarczy-Hornoch%2C%26%2332%3BPeter&rft.au=Wilcox%2C%26%2332%3BAdam+B.&rft.date=1+July+2012&rft.volume=50&rft.pages=S49%E2%80%93S59&rft_id=info:doi\/10.1097%2FMLR.0b013e318259c02b&rft.issn=0025-7079&rft_id=info:pmc\/PMC3415281&rft_id=info:pmid\/22692259&rft_id=https%3A%2F%2Fjournals.lww.com%2F00005650-201207001-00012&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-37\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_37-0\">37.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_37-1\">37.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cecchetti, Alfred A.; Parmanto, Bambang; Vecchio, Marcella L.; Ahmad, Sjarif; Buch, Shama; Zgheib, Nathalie K; Groark Jr., Stephen J.; Vemuganti, Anupama <i>et al.<\/i> (1 December 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1752-8062.2009.00157.x\" target=\"_blank\">\"Team Building: Electronic Management-Clinical Translational Research (eM-CTR) Systems\"<\/a> (in en). <i>Clinical and Translational Science<\/i> <b>2<\/b> (6): 449\u2013455. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1752-8062.2009.00157.x\" target=\"_blank\">10.1111\/j.1752-8062.2009.00157.x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3687802\/\" target=\"_blank\">PMC3687802<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20443940\" target=\"_blank\">20443940<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1752-8062.2009.00157.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1752-8062.2009.00157.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Team+Building%3A+Electronic+Management-Clinical+Translational+Research+%28eM-CTR%29+Systems&rft.jtitle=Clinical+and+Translational+Science&rft.aulast=Cecchetti&rft.aufirst=Alfred+A.&rft.au=Cecchetti%2C%26%2332%3BAlfred+A.&rft.au=Parmanto%2C%26%2332%3BBambang&rft.au=Vecchio%2C%26%2332%3BMarcella+L.&rft.au=Ahmad%2C%26%2332%3BSjarif&rft.au=Buch%2C%26%2332%3BShama&rft.au=Zgheib%2C%26%2332%3BNathalie+K&rft.au=Groark+Jr.%2C%26%2332%3BStephen+J.&rft.au=Vemuganti%2C%26%2332%3BAnupama&rft.au=Romkes%2C%26%2332%3BMarjorie&rft.date=1+December+2009&rft.volume=2&rft.issue=6&rft.pages=449%E2%80%93455&rft_id=info:doi\/10.1111%2Fj.1752-8062.2009.00157.x&rft_id=info:pmc\/PMC3687802&rft_id=info:pmid\/20443940&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1752-8062.2009.00157.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Weber, S. C.; Lowe, H.; Das, A.; Ferris, T. (1 June 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000329\" target=\"_blank\">\"A simple heuristic for blindfolded record linkage\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>19<\/b> (e1): e157\u2013e161. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Famiajnl-2011-000329\" target=\"_blank\">10.1136\/amiajnl-2011-000329<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1067-5027\" target=\"_blank\">1067-5027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3392854\/\" target=\"_blank\">PMC3392854<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22298567\" target=\"_blank\">22298567<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000329\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1136\/amiajnl-2011-000329<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+simple+heuristic+for+blindfolded+record+linkage&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Weber&rft.aufirst=S.+C.&rft.au=Weber%2C%26%2332%3BS.+C.&rft.au=Lowe%2C%26%2332%3BH.&rft.au=Das%2C%26%2332%3BA.&rft.au=Ferris%2C%26%2332%3BT.&rft.date=1+June+2012&rft.volume=19&rft.issue=e1&rft.pages=e157%E2%80%93e161&rft_id=info:doi\/10.1136%2Famiajnl-2011-000329&rft.issn=1067-5027&rft_id=info:pmc\/PMC3392854&rft_id=info:pmid\/22298567&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle-lookup%2Fdoi%2F10.1136%2Famiajnl-2011-000329&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Palma, G.; (17 September 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.beckershospitalreview.com\/healthcare-information-technology\/electronic-health-records-the-good-the-bad-and-the-ugly.html\" target=\"_blank\">\"Electronic Health Records: The Good, the Bad and the Ugly\"<\/a>. <i>Becker's Health IT<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.beckershospitalreview.com\/healthcare-information-technology\/electronic-health-records-the-good-the-bad-and-the-ugly.html\" target=\"_blank\">https:\/\/www.beckershospitalreview.com\/healthcare-information-technology\/electronic-health-records-the-good-the-bad-and-the-ugly.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Electronic+Health+Records%3A+The+Good%2C+the+Bad+and+the+Ugly&rft.atitle=Becker%27s+Health+IT&rft.aulast=Palma%2C+G.%3B&rft.au=Palma%2C+G.%3B&rft.date=17+September+2015&rft_id=https%3A%2F%2Fwww.beckershospitalreview.com%2Fhealthcare-information-technology%2Felectronic-health-records-the-good-the-bad-and-the-ugly.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kaufman, Kenneth R.; Hyler, Steven E. (1 May 2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.lww.com\/00131746-200505000-00008\" target=\"_blank\">\"Problems with the Electronic Medical Record in Clinical Psychiatry: A Hidden Cost:\"<\/a> (in en). <i>Journal of Psychiatric Practice<\/i> <b>11<\/b> (3): 200\u2013204. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2F00131746-200505000-00008\" target=\"_blank\">10.1097\/00131746-200505000-00008<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1538-1145\" target=\"_blank\">1538-1145<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.lww.com\/00131746-200505000-00008\" target=\"_blank\">http:\/\/journals.lww.com\/00131746-200505000-00008<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Problems+with+the+Electronic+Medical+Record+in+Clinical+Psychiatry%3A+A+Hidden+Cost%3A&rft.jtitle=Journal+of+Psychiatric+Practice&rft.aulast=Kaufman&rft.aufirst=Kenneth+R.&rft.au=Kaufman%2C%26%2332%3BKenneth+R.&rft.au=Hyler%2C%26%2332%3BSteven+E.&rft.date=1+May+2005&rft.volume=11&rft.issue=3&rft.pages=200%E2%80%93204&rft_id=info:doi\/10.1097%2F00131746-200505000-00008&rft.issn=1538-1145&rft_id=http%3A%2F%2Fjournals.lww.com%2F00131746-200505000-00008&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shin, Eric Y.; Ochuko, Patricia; Bhatt, Kunal; Howard, Brian; McGorisk, Gerard; Delaney, Linda; Langdon, Kristan; Khosravanipour, Marjan <i>et al.<\/i> (17 April 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.007762\" target=\"_blank\">\"Errors in Electronic Health Record\u2013Based Data Query of Statin Prescriptions in Patients With Coronary Artery Disease in a Large, Academic, Multispecialty Clinic Practice\"<\/a> (in en). <i>Journal of the American Heart Association<\/i> <b>7<\/b> (8): e007762. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1161%2FJAHA.117.007762\" target=\"_blank\">10.1161\/JAHA.117.007762<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2047-9980\" target=\"_blank\">2047-9980<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6015411\/\" target=\"_blank\">PMC6015411<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29650707\" target=\"_blank\">29650707<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.007762\" target=\"_blank\">https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.007762<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Errors+in+Electronic+Health+Record%E2%80%93Based+Data+Query+of+Statin+Prescriptions+in+Patients+With+Coronary+Artery+Disease+in+a+Large%2C+Academic%2C+Multispecialty+Clinic+Practice&rft.jtitle=Journal+of+the+American+Heart+Association&rft.aulast=Shin&rft.aufirst=Eric+Y.&rft.au=Shin%2C%26%2332%3BEric+Y.&rft.au=Ochuko%2C%26%2332%3BPatricia&rft.au=Bhatt%2C%26%2332%3BKunal&rft.au=Howard%2C%26%2332%3BBrian&rft.au=McGorisk%2C%26%2332%3BGerard&rft.au=Delaney%2C%26%2332%3BLinda&rft.au=Langdon%2C%26%2332%3BKristan&rft.au=Khosravanipour%2C%26%2332%3BMarjan&rft.au=Nambi%2C%26%2332%3BAndiran+A.&rft.date=17+April+2018&rft.volume=7&rft.issue=8&rft.pages=e007762&rft_id=info:doi\/10.1161%2FJAHA.117.007762&rft.issn=2047-9980&rft_id=info:pmc\/PMC6015411&rft_id=info:pmid\/29650707&rft_id=https%3A%2F%2Fwww.ahajournals.org%2Fdoi%2F10.1161%2FJAHA.117.007762&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Goodloe, Robert; Farber-Eger, Eric; Boston, Jonathan; Crawford, Dana C.; Bush, William S. (26 July 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5543370\/\" target=\"_blank\">\"Reducing Clinical Noise for Body Mass Index Measures Due to Unit and Transcription Errors in the Electronic Health Record\"<\/a>. <i>AMIA Summits on Translational Science Proceedings<\/i> <b>2017<\/b>: 102\u2013111. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-4063\" target=\"_blank\">2153-4063<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/5543370\/\" target=\"_blank\">5543370<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28815116\" target=\"_blank\">28815116<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5543370\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5543370\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reducing+Clinical+Noise+for+Body+Mass+Index+Measures+Due+to+Unit+and+Transcription+Errors+in+the+Electronic+Health+Record&rft.jtitle=AMIA+Summits+on+Translational+Science+Proceedings&rft.aulast=Goodloe&rft.aufirst=Robert&rft.au=Goodloe%2C%26%2332%3BRobert&rft.au=Farber-Eger%2C%26%2332%3BEric&rft.au=Boston%2C%26%2332%3BJonathan&rft.au=Crawford%2C%26%2332%3BDana+C.&rft.au=Bush%2C%26%2332%3BWilliam+S.&rft.date=26+July+2017&rft.volume=2017&rft.pages=102%E2%80%93111&rft.issn=2153-4063&rft_id=info:pmc\/5543370&rft_id=info:pmid\/28815116&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5543370%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Harris, Paul A.; Taylor, Robert; Thielke, Robert; Payne, Jonathon; Gonzalez, Nathaniel; Conde, Jose G. 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href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2700030\/\" target=\"_blank\">PMC2700030<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18929686\" target=\"_blank\">18929686<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046408001226\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046408001226<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+electronic+data+capture+%28REDCap%29%E2%80%94A+metadata-driven+methodology+and+workflow+process+for+providing+translational+research+informatics+support&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Harris&rft.aufirst=Paul+A.&rft.au=Harris%2C%26%2332%3BPaul+A.&rft.au=Taylor%2C%26%2332%3BRobert&rft.au=Thielke%2C%26%2332%3BRobert&rft.au=Payne%2C%26%2332%3BJonathon&rft.au=Gonzalez%2C%26%2332%3BNathaniel&rft.au=Conde%2C%26%2332%3BJose+G.&rft.date=1+April+2009&rft.volume=42&rft.issue=2&rft.pages=377%E2%80%93381&rft_id=info:doi\/10.1016%2Fj.jbi.2008.08.010&rft_id=info:pmc\/PMC2700030&rft_id=info:pmid\/18929686&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046408001226&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Harris, Paul A.; Taylor, Robert; Minor, Brenda L.; Elliott, Veida; Fernandez, Michelle; O'Neal, Lindsay; McLeod, Laura; Delacqua, Giovanni <i>et al.<\/i> (1 July 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046419301261\" target=\"_blank\">\"The REDCap consortium: Building an international community of software platform partners\"<\/a> (in en). <i>Journal of Biomedical Informatics<\/i> <b>95<\/b>: 103208. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbi.2019.103208\" target=\"_blank\">10.1016\/j.jbi.2019.103208<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7254481\/\" target=\"_blank\">PMC7254481<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31078660\" target=\"_blank\">31078660<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046419301261\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046419301261<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+REDCap+consortium%3A+Building+an+international+community+of+software+platform+partners&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Harris&rft.aufirst=Paul+A.&rft.au=Harris%2C%26%2332%3BPaul+A.&rft.au=Taylor%2C%26%2332%3BRobert&rft.au=Minor%2C%26%2332%3BBrenda+L.&rft.au=Elliott%2C%26%2332%3BVeida&rft.au=Fernandez%2C%26%2332%3BMichelle&rft.au=O%27Neal%2C%26%2332%3BLindsay&rft.au=McLeod%2C%26%2332%3BLaura&rft.au=Delacqua%2C%26%2332%3BGiovanni&rft.au=Delacqua%2C%26%2332%3BFrancesco&rft.date=1+July+2019&rft.volume=95&rft.pages=103208&rft_id=info:doi\/10.1016%2Fj.jbi.2019.103208&rft_id=info:pmc\/PMC7254481&rft_id=info:pmid\/31078660&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046419301261&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Harris, Paul A (1 July 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-13-S12-A15\" target=\"_blank\">\"Research Electronic Data Capture (REDCap) - planning, collecting and managing data for clinical and translational research\"<\/a> (in en). <i>BMC Bioinformatics<\/i> <b>13<\/b> (S12): A15, 1471\u20132105\u201313-S12-A15. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-13-S12-A15\" target=\"_blank\">10.1186\/1471-2105-13-S12-A15<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-2105\" target=\"_blank\">1471-2105<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3409058\/\" target=\"_blank\">PMC3409058<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-13-S12-A15\" target=\"_blank\">https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-13-S12-A15<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+Electronic+Data+Capture+%28REDCap%29+-+planning%2C+collecting+and+managing+data+for+clinical+and+translational+research&rft.jtitle=BMC+Bioinformatics&rft.aulast=Harris&rft.aufirst=Paul+A&rft.au=Harris%2C%26%2332%3BPaul+A&rft.date=1+July+2012&rft.volume=13&rft.issue=S12&rft.pages=A15%2C+1471%E2%80%932105%E2%80%9313-S12-A15&rft_id=info:doi\/10.1186%2F1471-2105-13-S12-A15&rft.issn=1471-2105&rft_id=info:pmc\/PMC3409058&rft_id=https%3A%2F%2Fbmcbioinformatics.biomedcentral.com%2Farticles%2F10.1186%2F1471-2105-13-S12-A15&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-46\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_46-0\">46.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_46-1\">46.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Marshall University; Cecchetti, Alfred A. (1 April 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/mds.marshall.edu\/mjm\/vol4\/iss2\/2\/\" target=\"_blank\">\"Why Introduce Machine Learning To Rural Health Care?\"<\/a>. <i>Marshall Journal of Medicine<\/i> <b>4<\/b> (2). <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.18590%2Fmjm.2018.vol4.iss2.2\" target=\"_blank\">10.18590\/mjm.2018.vol4.iss2.2<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/mds.marshall.edu\/mjm\/vol4\/iss2\/2\/\" target=\"_blank\">http:\/\/mds.marshall.edu\/mjm\/vol4\/iss2\/2\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Why+Introduce+Machine+Learning+To+Rural+Health+Care%3F&rft.jtitle=Marshall+Journal+of+Medicine&rft.aulast=Marshall+University&rft.au=Marshall+University&rft.au=Cecchetti%2C%26%2332%3BAlfred+A.&rft.date=1+April+2018&rft.volume=4&rft.issue=2&rft_id=info:doi\/10.18590%2Fmjm.2018.vol4.iss2.2&rft_id=http%3A%2F%2Fmds.marshall.edu%2Fmjm%2Fvol4%2Fiss2%2F2%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-47\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-47\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">McDonald, Helen I.; Shaw, Catriona; Thomas, Sara L.; Mansfield, Kathryn E.; Tomlinson, Laurie A.; Nitsch, Dorothea (1 November 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253816301661\" target=\"_blank\">\"Methodological challenges when carrying out research on CKD and AKI using routine electronic health records\"<\/a> (in en). <i>Kidney International<\/i> <b>90<\/b> (5): 943\u2013949. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.kint.2016.04.010\" target=\"_blank\">10.1016\/j.kint.2016.04.010<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253816301661\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253816301661<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Methodological+challenges+when+carrying+out+research+on+CKD+and+AKI+using+routine+electronic+health+records&rft.jtitle=Kidney+International&rft.aulast=McDonald&rft.aufirst=Helen+I.&rft.au=McDonald%2C%26%2332%3BHelen+I.&rft.au=Shaw%2C%26%2332%3BCatriona&rft.au=Thomas%2C%26%2332%3BSara+L.&rft.au=Mansfield%2C%26%2332%3BKathryn+E.&rft.au=Tomlinson%2C%26%2332%3BLaurie+A.&rft.au=Nitsch%2C%26%2332%3BDorothea&rft.date=1+November+2016&rft.volume=90&rft.issue=5&rft.pages=943%E2%80%93949&rft_id=info:doi\/10.1016%2Fj.kint.2016.04.010&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0085253816301661&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pierce, Carolyn; Scherra, Elizabeth (1 December 2004). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/rnojournal.binghamton.edu\/index.php\/RNO\/article\/view\/197\" target=\"_blank\">\"The Challenges of Data Collection in Rural Dwelling Samples\"<\/a>. <i>Online Journal of Rural Nursing and Health Care<\/i> <b>4<\/b> (2): 25\u201330. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.14574%2Fojrnhc.v4i2.197\" target=\"_blank\">10.14574\/ojrnhc.v4i2.197<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/rnojournal.binghamton.edu\/index.php\/RNO\/article\/view\/197\" target=\"_blank\">https:\/\/rnojournal.binghamton.edu\/index.php\/RNO\/article\/view\/197<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Challenges+of+Data+Collection+in+Rural+Dwelling+Samples&rft.jtitle=Online+Journal+of+Rural+Nursing+and+Health+Care&rft.aulast=Pierce&rft.aufirst=Carolyn&rft.au=Pierce%2C%26%2332%3BCarolyn&rft.au=Scherra%2C%26%2332%3BElizabeth&rft.date=1+December+2004&rft.volume=4&rft.issue=2&rft.pages=25%E2%80%9330&rft_id=info:doi\/10.14574%2Fojrnhc.v4i2.197&rft_id=https%3A%2F%2Frnojournal.binghamton.edu%2Findex.php%2FRNO%2Farticle%2Fview%2F197&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-49\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-49\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Verby, J E (1 November 1989). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.lww.com\/00001888-198911000-00009\" target=\"_blank\">\"Patients\u02bc and physicians\u02bc views of health in a rural area:\"<\/a> (in en). <i>Academic Medicine<\/i> <b>64<\/b> (11): 665\u20136. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2F00001888-198911000-00009\" target=\"_blank\">10.1097\/00001888-198911000-00009<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1040-2446\" target=\"_blank\">1040-2446<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.lww.com\/00001888-198911000-00009\" target=\"_blank\">http:\/\/journals.lww.com\/00001888-198911000-00009<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Patients%CA%BC+and+physicians%CA%BC+views+of+health+in+a+rural+area%3A&rft.jtitle=Academic+Medicine&rft.aulast=Verby&rft.aufirst=J+E&rft.au=Verby%2C%26%2332%3BJ+E&rft.date=1+November+1989&rft.volume=64&rft.issue=11&rft.pages=665%E2%80%936&rft_id=info:doi\/10.1097%2F00001888-198911000-00009&rft.issn=1040-2446&rft_id=http%3A%2F%2Fjournals.lww.com%2F00001888-198911000-00009&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-50\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-50\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hendryx, Michael; Ahern, Melissa M.; Nurkiewicz, Timothy R. (13 November 2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/15287390701601236\" target=\"_blank\">\"Hospitalization Patterns Associated with Appalachian Coal Mining\"<\/a> (in en). <i>Journal of Toxicology and Environmental Health, Part A<\/i> <b>70<\/b> (24): 2064\u20132070. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F15287390701601236\" target=\"_blank\">10.1080\/15287390701601236<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1528-7394\" target=\"_blank\">1528-7394<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/15287390701601236\" target=\"_blank\">http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/15287390701601236<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hospitalization+Patterns+Associated+with+Appalachian+Coal+Mining&rft.jtitle=Journal+of+Toxicology+and+Environmental+Health%2C+Part+A&rft.aulast=Hendryx&rft.aufirst=Michael&rft.au=Hendryx%2C%26%2332%3BMichael&rft.au=Ahern%2C%26%2332%3BMelissa+M.&rft.au=Nurkiewicz%2C%26%2332%3BTimothy+R.&rft.date=13+November+2007&rft.volume=70&rft.issue=24&rft.pages=2064%E2%80%932070&rft_id=info:doi\/10.1080%2F15287390701601236&rft.issn=1528-7394&rft_id=http%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Fabs%2F10.1080%2F15287390701601236&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-51\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-51\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ortmeyer, Carl E.; Costello, Joseph; Morgan, William Keith C.; Sweeker, Steve; Peterson, Martin (1 August 1974). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/00039896.1974.10666535\" target=\"_blank\">\"The Mortality of Appalachian Coal Miners, 1963 to 1971\"<\/a> (in en). <i>Archives of Environmental Health: An International Journal<\/i> <b>29<\/b> (2): 67\u201372. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F00039896.1974.10666535\" target=\"_blank\">10.1080\/00039896.1974.10666535<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-9896\" target=\"_blank\">0003-9896<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/00039896.1974.10666535\" target=\"_blank\">http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/00039896.1974.10666535<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Mortality+of+Appalachian+Coal+Miners%2C+1963+to+1971&rft.jtitle=Archives+of+Environmental+Health%3A+An+International+Journal&rft.aulast=Ortmeyer&rft.aufirst=Carl+E.&rft.au=Ortmeyer%2C%26%2332%3BCarl+E.&rft.au=Costello%2C%26%2332%3BJoseph&rft.au=Morgan%2C%26%2332%3BWilliam+Keith+C.&rft.au=Sweeker%2C%26%2332%3BSteve&rft.au=Peterson%2C%26%2332%3BMartin&rft.date=1+August+1974&rft.volume=29&rft.issue=2&rft.pages=67%E2%80%9372&rft_id=info:doi\/10.1080%2F00039896.1974.10666535&rft.issn=0003-9896&rft_id=http%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Fabs%2F10.1080%2F00039896.1974.10666535&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-52\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_52-0\">52.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_52-1\">52.1<\/a><\/sup> <sup><a href=\"#cite_ref-:4_52-2\">52.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Amro, Ahmed; Baez, Giancarlo Acosta; Koromia, George Augustine; Bhardwaj, Niharika; Aguilar, Rodrigo; El-Hamdani, Mehiar; Irfan, Affan (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0735109719314421\" target=\"_blank\">\"ALBUMIN LEVEL AS A RISK MARKER AND PREDICTOR OF PERIPARTUM CARDIOMYOPATHY\"<\/a> (in en). <i>Journal of the American College of Cardiology<\/i> <b>73<\/b> (9): 835. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0735-1097%2819%2931442-1\" target=\"_blank\">10.1016\/S0735-1097(19)31442-1<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0735109719314421\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0735109719314421<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ALBUMIN+LEVEL+AS+A+RISK+MARKER+AND+PREDICTOR+OF+PERIPARTUM+CARDIOMYOPATHY&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.aulast=Amro&rft.aufirst=Ahmed&rft.au=Amro%2C%26%2332%3BAhmed&rft.au=Baez%2C%26%2332%3BGiancarlo+Acosta&rft.au=Koromia%2C%26%2332%3BGeorge+Augustine&rft.au=Bhardwaj%2C%26%2332%3BNiharika&rft.au=Aguilar%2C%26%2332%3BRodrigo&rft.au=El-Hamdani%2C%26%2332%3BMehiar&rft.au=Irfan%2C%26%2332%3BAffan&rft.date=1+March+2019&rft.volume=73&rft.issue=9&rft.pages=835&rft_id=info:doi\/10.1016%2FS0735-1097%2819%2931442-1&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0735109719314421&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-53\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_53-0\">53.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_53-1\">53.1<\/a><\/sup> <sup><a href=\"#cite_ref-:5_53-2\">53.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Acosta, Giancarlo; Amro, Ahmed; Aguilar, Rodrigo; Abusnina, Waiel; Bhardwaj, Niharika; Koromia, George Augustine; Studeny, Mark; Irfan, Affan (27 January 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.cureus.com\/articles\/26546-clinical-determinants-of-myocardial-injury-detectable-and-serial-troponin-levels-among-patients-with-hypertensive-crisis\" target=\"_blank\">\"Clinical Determinants of Myocardial Injury, Detectable and Serial Troponin Levels among Patients with Hypertensive Crisis\"<\/a> (in en). <i>Cureus<\/i> <b>12<\/b> (1): e6787. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.7759%2Fcureus.6787\" target=\"_blank\">10.7759\/cureus.6787<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2168-8184\" target=\"_blank\">2168-8184<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7045977\/\" target=\"_blank\">PMC7045977<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32140347\" target=\"_blank\">32140347<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.cureus.com\/articles\/26546-clinical-determinants-of-myocardial-injury-detectable-and-serial-troponin-levels-among-patients-with-hypertensive-crisis\" target=\"_blank\">https:\/\/www.cureus.com\/articles\/26546-clinical-determinants-of-myocardial-injury-detectable-and-serial-troponin-levels-among-patients-with-hypertensive-crisis<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+Determinants+of+Myocardial+Injury%2C+Detectable+and+Serial+Troponin+Levels+among+Patients+with+Hypertensive+Crisis&rft.jtitle=Cureus&rft.aulast=Acosta&rft.aufirst=Giancarlo&rft.au=Acosta%2C%26%2332%3BGiancarlo&rft.au=Amro%2C%26%2332%3BAhmed&rft.au=Aguilar%2C%26%2332%3BRodrigo&rft.au=Abusnina%2C%26%2332%3BWaiel&rft.au=Bhardwaj%2C%26%2332%3BNiharika&rft.au=Koromia%2C%26%2332%3BGeorge+Augustine&rft.au=Studeny%2C%26%2332%3BMark&rft.au=Irfan%2C%26%2332%3BAffan&rft.date=27+January+2020&rft.volume=12&rft.issue=1&rft.pages=e6787&rft_id=info:doi\/10.7759%2Fcureus.6787&rft.issn=2168-8184&rft_id=info:pmc\/PMC7045977&rft_id=info:pmid\/32140347&rft_id=https%3A%2F%2Fwww.cureus.com%2Farticles%2F26546-clinical-determinants-of-myocardial-injury-detectable-and-serial-troponin-levels-among-patients-with-hypertensive-crisis&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-54\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_54-0\">54.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_54-1\">54.1<\/a><\/sup> <sup><a href=\"#cite_ref-:6_54-2\">54.2<\/a><\/sup> <sup><a href=\"#cite_ref-:6_54-3\">54.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Elmore, Dominique; Yaslam, Balfaqih; Putty, Krista; Magrane, Thomas; Abadir, Anthony; Bhatt, Saloni; Frazier, Marie; Flesher, Susan (1 January 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/2333794X19868660\" target=\"_blank\">\"Is Fever a Red Flag for Bacterial Pneumonia in Children With Viral Bronchiolitis?\"<\/a> (in en). <i>Global Pediatric Health<\/i> <b>6<\/b>: 2333794X1986866. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F2333794X19868660\" target=\"_blank\">10.1177\/2333794X19868660<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2333-794X\" target=\"_blank\">2333-794X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6686317\/\" target=\"_blank\">PMC6686317<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31431903\" target=\"_blank\">31431903<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/2333794X19868660\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/2333794X19868660<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Is+Fever+a+Red+Flag+for+Bacterial+Pneumonia+in+Children+With+Viral+Bronchiolitis%3F&rft.jtitle=Global+Pediatric+Health&rft.aulast=Elmore&rft.aufirst=Dominique&rft.au=Elmore%2C%26%2332%3BDominique&rft.au=Yaslam%2C%26%2332%3BBalfaqih&rft.au=Putty%2C%26%2332%3BKrista&rft.au=Magrane%2C%26%2332%3BThomas&rft.au=Abadir%2C%26%2332%3BAnthony&rft.au=Bhatt%2C%26%2332%3BSaloni&rft.au=Frazier%2C%26%2332%3BMarie&rft.au=Flesher%2C%26%2332%3BSusan&rft.date=1+January+2019&rft.volume=6&rft.pages=2333794X1986866&rft_id=info:doi\/10.1177%2F2333794X19868660&rft.issn=2333-794X&rft_id=info:pmc\/PMC6686317&rft_id=info:pmid\/31431903&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F2333794X19868660&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-55\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_55-0\">55.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_55-1\">55.1<\/a><\/sup> <sup><a href=\"#cite_ref-:7_55-2\">55.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bhardwaj, Niharika; Sundaram, Shanmuga; Carter, Larry E.; Cecchetti, Alfred A.; Sundaram, Uma (1 May 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508520335897\" target=\"_blank\">\"Tu1801 METABOLIC SYNDROME: ARE CURRENT COLON CANCER SCREENING GUIDELINES ENOUGH IN A RURAL POPULATION?\"<\/a> (in en). <i>Gastroenterology<\/i> <b>158<\/b> (6): S\u20131167. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0016-5085%2820%2933589-7\" target=\"_blank\">10.1016\/S0016-5085(20)33589-7<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508520335897\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508520335897<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Tu1801+METABOLIC+SYNDROME%3A+ARE+CURRENT+COLON+CANCER+SCREENING+GUIDELINES+ENOUGH+IN+A+RURAL+POPULATION%3F&rft.jtitle=Gastroenterology&rft.aulast=Bhardwaj&rft.aufirst=Niharika&rft.au=Bhardwaj%2C%26%2332%3BNiharika&rft.au=Sundaram%2C%26%2332%3BShanmuga&rft.au=Carter%2C%26%2332%3BLarry+E.&rft.au=Cecchetti%2C%26%2332%3BAlfred+A.&rft.au=Sundaram%2C%26%2332%3BUma&rft.date=1+May+2020&rft.volume=158&rft.issue=6&rft.pages=S%E2%80%931167&rft_id=info:doi\/10.1016%2FS0016-5085%2820%2933589-7&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0016508520335897&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-56\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_56-0\">56.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_56-1\">56.1<\/a><\/sup> <sup><a href=\"#cite_ref-:8_56-2\">56.2<\/a><\/sup> <sup><a href=\"#cite_ref-:8_56-3\">56.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Sundaram, S.; Bhardwaj, N.; Schafer, C. et al. (30 March 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ccts.uky.edu\/media\/913\" target=\"_blank\">\"Utilization of Appalachian Clinical and Translational Science Institute Data Warehouse to more accurately predict disease processes important for central Appalachia\"<\/a>. <i>12th Annual CCTS Spring Conference<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ccts.uky.edu\/media\/913\" target=\"_blank\">https:\/\/www.ccts.uky.edu\/media\/913<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Utilization+of+Appalachian+Clinical+and+Translational+Science+Institute+Data+Warehouse+to+more+accurately+predict+disease+processes+important+for+central+Appalachia&rft.atitle=12th+Annual+CCTS+Spring+Conference&rft.aulast=Sundaram%2C+S.%3B+Bhardwaj%2C+N.%3B+Schafer%2C+C.+et+al.&rft.au=Sundaram%2C+S.%3B+Bhardwaj%2C+N.%3B+Schafer%2C+C.+et+al.&rft.date=30+March+2017&rft_id=https%3A%2F%2Fwww.ccts.uky.edu%2Fmedia%2F913&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-57\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_57-0\">57.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_57-1\">57.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bhardwaj, Niharika; Cecchetti, Alfred A; Murughiyan, Usha; Neitch, Shirley (4 August 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/medinform.jmir.org\/2020\/8\/e18389\" target=\"_blank\">\"Analysis of Benzodiazepine Prescription Practices in Elderly Appalachians with Dementia via the Appalachian Informatics Platform: Longitudinal Study\"<\/a> (in en). <i>JMIR Medical Informatics<\/i> <b>8<\/b> (8): e18389. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2196%2F18389\" target=\"_blank\">10.2196\/18389<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2291-9694\" target=\"_blank\">2291-9694<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7435704\/\" target=\"_blank\">PMC7435704<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32749226\" target=\"_blank\">32749226<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/medinform.jmir.org\/2020\/8\/e18389\" target=\"_blank\">https:\/\/medinform.jmir.org\/2020\/8\/e18389<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+Benzodiazepine+Prescription+Practices+in+Elderly+Appalachians+with+Dementia+via+the+Appalachian+Informatics+Platform%3A+Longitudinal+Study&rft.jtitle=JMIR+Medical+Informatics&rft.aulast=Bhardwaj&rft.aufirst=Niharika&rft.au=Bhardwaj%2C%26%2332%3BNiharika&rft.au=Cecchetti%2C%26%2332%3BAlfred+A&rft.au=Murughiyan%2C%26%2332%3BUsha&rft.au=Neitch%2C%26%2332%3BShirley&rft.date=4+August+2020&rft.volume=8&rft.issue=8&rft.pages=e18389&rft_id=info:doi\/10.2196%2F18389&rft.issn=2291-9694&rft_id=info:pmc\/PMC7435704&rft_id=info:pmid\/32749226&rft_id=https%3A%2F%2Fmedinform.jmir.org%2F2020%2F8%2Fe18389&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-58\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_58-0\">58.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_58-1\">58.1<\/a><\/sup> <sup><a href=\"#cite_ref-:10_58-2\">58.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Khanna, R.; 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Retrieved 29 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Hospital+Emergency+Department+Visits+For+Non-Traumatic+Oral+Health+Conditions&rft.atitle=2018+National+Oral+Health+Conference&rft.aulast=Khanna%2C+R.%3B+Gress%2C+T.%3B+Cecchetti%2C+A.&rft.au=Khanna%2C+R.%3B+Gress%2C+T.%3B+Cecchetti%2C+A.&rft_id=https%3A%2F%2Fwww.nationaloralhealthconference.com%2Fpdfs%2F2018-poster-abstracts.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-59\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_59-0\">59.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_59-1\">59.1<\/a><\/sup> <sup><a href=\"#cite_ref-:11_59-2\">59.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Ferdjallah, M.; Driscoll, H. 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(1 March 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00432-018-2589-5\" target=\"_blank\">\"Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation\"<\/a> (in en). <i>Journal of Cancer Research and Clinical Oncology<\/i> <b>144<\/b> (3): 607\u2013615. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00432-018-2589-5\" target=\"_blank\">10.1007\/s00432-018-2589-5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0171-5216\" target=\"_blank\">0171-5216<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00432-018-2589-5\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00432-018-2589-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Decision+tree+analysis+to+stratify+risk+of+de+novo+non-melanoma+skin+cancer+following+liver+transplantation&rft.jtitle=Journal+of+Cancer+Research+and+Clinical+Oncology&rft.aulast=Tanaka&rft.aufirst=Tomohiro&rft.au=Tanaka%2C%26%2332%3BTomohiro&rft.au=Voigt%2C%26%2332%3BMichael+D.&rft.date=1+March+2018&rft.volume=144&rft.issue=3&rft.pages=607%E2%80%93615&rft_id=info:doi\/10.1007%2Fs00432-018-2589-5&rft.issn=0171-5216&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00432-018-2589-5&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-64\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-64\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Paxton, Raheem J.; Zhang, Lingfeng; Wei, Changshuai; Price, Daniel; Zhang, Fan; Courneya, Kerry S.; Kakadiaris, Ioannis A. 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Retrieved 25 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Predicting+car+accidents+in+Barcelona+using+a+Random+Forest+model&rft.atitle=&rft.aulast=Moreno+Hoyo%2C+A.&rft.au=Moreno+Hoyo%2C+A.&rft.date=January+2017&rft.pub=Universitat+Polit%C3%A8cnica+de+Catalunya&rft_id=http%3A%2F%2Fhdl.handle.net%2F2117%2F100298&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Xiaohui, J. 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China National Knowledge Infrastructure<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/en.cnki.com.cn\/Article_en\/CJFDTotal-JSYJ201603038.htm\" target=\"_blank\">http:\/\/en.cnki.com.cn\/Article_en\/CJFDTotal-JSYJ201603038.htm<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Forecast+model+of+road+traffic+accidents+based+on+LS-SVM+with+grey+correlation+analysis&rft.atitle=Applied+Research+in+Computing&rft.aulast=Xiaohui%2C+J.&rft.au=Xiaohui%2C+J.&rft.date=2016&rft.pub=China+National+Knowledge+Infrastructure&rft_id=http%3A%2F%2Fen.cnki.com.cn%2FArticle_en%2FCJFDTotal-JSYJ201603038.htm&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-67\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-67\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Khatri, Krishan L.; Tamil, Lakshman S. (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7912386\/\" target=\"_blank\">\"Early Detection of Peak Demand Days of Chronic Respiratory Diseases Emergency Department Visits Using Artificial Neural Networks\"<\/a>. <i>IEEE Journal of Biomedical and Health Informatics<\/i> <b>22<\/b> (1): 285\u2013290. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJBHI.2017.2698418\" target=\"_blank\">10.1109\/JBHI.2017.2698418<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2168-2194\" target=\"_blank\">2168-2194<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7912386\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7912386\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Early+Detection+of+Peak+Demand+Days+of+Chronic+Respiratory+Diseases+Emergency+Department+Visits+Using+Artificial+Neural+Networks&rft.jtitle=IEEE+Journal+of+Biomedical+and+Health+Informatics&rft.aulast=Khatri&rft.aufirst=Krishan+L.&rft.au=Khatri%2C%26%2332%3BKrishan+L.&rft.au=Tamil%2C%26%2332%3BLakshman+S.&rft.date=1+January+2018&rft.volume=22&rft.issue=1&rft.pages=285%E2%80%93290&rft_id=info:doi\/10.1109%2FJBHI.2017.2698418&rft.issn=2168-2194&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7912386%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-68\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-68\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Oijuela-Canon, Alvaro D.; Gomez-Cajas, Diego F.; Sepulveda-Sepulveda, Alexander (1 September 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7330461\" target=\"_blank\">\"Respiratory Diseases discrimination based on acoustic lung signals and neural networks\"<\/a>. <i>2015 20th Symposium on Signal Processing, Images and Computer Vision (STSIVA)<\/i> (Bogota, Colombia: IEEE): 1\u20136. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FSTSIVA.2015.7330461\" target=\"_blank\">10.1109\/STSIVA.2015.7330461<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4673-9461-1<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7330461\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/7330461<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Respiratory+Diseases+discrimination+based+on+acoustic+lung+signals+and+neural+networks&rft.jtitle=2015+20th+Symposium+on+Signal+Processing%2C+Images+and+Computer+Vision+%28STSIVA%29&rft.aulast=Oijuela-Canon&rft.aufirst=Alvaro+D.&rft.au=Oijuela-Canon%2C%26%2332%3BAlvaro+D.&rft.au=Gomez-Cajas%2C%26%2332%3BDiego+F.&rft.au=Sepulveda-Sepulveda%2C%26%2332%3BAlexander&rft.date=1+September+2015&rft.pages=1%E2%80%936&rft.place=Bogota%2C+Colombia&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FSTSIVA.2015.7330461&rft.isbn=978-1-4673-9461-1&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7330461&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-69\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-69\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">McKinley, Richard; H\u00e4ni, Levin; Gralla, Jan; El-Koussy, M; Bauer, S; Arnold, M; Fischer, U; Jung, S <i>et al.<\/i> (1 August 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X16674221\" target=\"_blank\">\"Fully automated stroke tissue estimation using random forest classifiers (FASTER)\"<\/a> (in en). <i>Journal of Cerebral Blood Flow & Metabolism<\/i> <b>37<\/b> (8): 2728\u20132741. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F0271678X16674221\" target=\"_blank\">10.1177\/0271678X16674221<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0271-678X\" target=\"_blank\">0271-678X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5536784\/\" target=\"_blank\">PMC5536784<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27798267\" target=\"_blank\">27798267<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X16674221\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X16674221<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Fully+automated+stroke+tissue+estimation+using+random+forest+classifiers+%28FASTER%29&rft.jtitle=Journal+of+Cerebral+Blood+Flow+%26+Metabolism&rft.aulast=McKinley&rft.aufirst=Richard&rft.au=McKinley%2C%26%2332%3BRichard&rft.au=H%C3%A4ni%2C%26%2332%3BLevin&rft.au=Gralla%2C%26%2332%3BJan&rft.au=El-Koussy%2C%26%2332%3BM&rft.au=Bauer%2C%26%2332%3BS&rft.au=Arnold%2C%26%2332%3BM&rft.au=Fischer%2C%26%2332%3BU&rft.au=Jung%2C%26%2332%3BS&rft.au=Mattmann%2C%26%2332%3BKaspar&rft.date=1+August+2017&rft.volume=37&rft.issue=8&rft.pages=2728%E2%80%932741&rft_id=info:doi\/10.1177%2F0271678X16674221&rft.issn=0271-678X&rft_id=info:pmc\/PMC5536784&rft_id=info:pmid\/27798267&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F0271678X16674221&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-70\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-70\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Chen, L.; Bentley, P.; Rueckert, D. (2015). <a rel=\"nofollow\" class=\"external text\" href=\"#page=17\">\"A novel framework for sub-acute stroke lesion segmentation based on random forest\"<\/a>. <i>Proceedings of Ischemic Stroke Lesion Segmentation<\/i>. pp. 9\u201312<span class=\"printonly\">. <a rel=\"nofollow\" class=\"external free\" href=\"#page=17\">http:\/\/www.isles-challenge.org\/ISLES2015\/pdf\/20150930_ISLES2015_Proceedings.pdf#page=17<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=A+novel+framework+for+sub-acute+stroke+lesion+segmentation+based+on+random+forest&rft.atitle=Proceedings+of+Ischemic+Stroke+Lesion+Segmentation&rft.aulast=Chen%2C+L.%3B+Bentley%2C+P.%3B+Rueckert%2C+D.&rft.au=Chen%2C+L.%3B+Bentley%2C+P.%3B+Rueckert%2C+D.&rft.date=2015&rft.pages=pp.+9%E2%80%9312&rft_id=http%3A%2F%2Fwww.isles-challenge.org%2FISLES2015%2Fpdf%2F20150930_ISLES2015_Proceedings.pdf%23page%3D17&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-71\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-71\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Xu, Weifeng; Zhang, Jianxin; Zhang, Qiang; Wei, Xiaopeng (1 February 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7972337\/\" target=\"_blank\">\"Risk prediction of type II diabetes based on random forest model\"<\/a>. <i>2017 Third International Conference on Advances in Electrical, Electronics, Information, Communication and Bio-Informatics (AEEICB)<\/i> (Chennai, India: IEEE): 382\u2013386. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FAEEICB.2017.7972337\" target=\"_blank\">10.1109\/AEEICB.2017.7972337<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5090-5434-3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7972337\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7972337\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Risk+prediction+of+type+II+diabetes+based+on+random+forest+model&rft.jtitle=2017+Third+International+Conference+on+Advances+in+Electrical%2C+Electronics%2C+Information%2C+Communication+and+Bio-Informatics+%28AEEICB%29&rft.aulast=Xu&rft.aufirst=Weifeng&rft.au=Xu%2C%26%2332%3BWeifeng&rft.au=Zhang%2C%26%2332%3BJianxin&rft.au=Zhang%2C%26%2332%3BQiang&rft.au=Wei%2C%26%2332%3BXiaopeng&rft.date=1+February+2017&rft.pages=382%E2%80%93386&rft.place=Chennai%2C+India&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FAEEICB.2017.7972337&rft.isbn=978-1-5090-5434-3&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7972337%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-72\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-72\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shukla, N.; Arora, M. (2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ijcseonline.org\/full_paper_view.php?paper_id=1008\" target=\"_blank\">\"Prediction of Diabetes Using Neural Network & Random Forest Tree\"<\/a>. <i>International Journal of Computer Sciences and Engineering<\/i> <b>4<\/b> (7): 101\u201304<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ijcseonline.org\/full_paper_view.php?paper_id=1008\" target=\"_blank\">https:\/\/www.ijcseonline.org\/full_paper_view.php?paper_id=1008<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Prediction+of+Diabetes+Using+Neural+Network+%26+Random+Forest+Tree&rft.jtitle=International+Journal+of+Computer+Sciences+and+Engineering&rft.aulast=Shukla%2C+N.%3B+Arora%2C+M.&rft.au=Shukla%2C+N.%3B+Arora%2C+M.&rft.date=2016&rft.volume=4&rft.issue=7&rft.pages=101%E2%80%9304&rft_id=https%3A%2F%2Fwww.ijcseonline.org%2Ffull_paper_view.php%3Fpaper_id%3D1008&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-73\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-73\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Basaia, Silvia; Agosta, Federica; Wagner, Luca; Canu, Elisa; Magnani, Giuseppe; Santangelo, Roberto; Filippi, Massimo (2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213158218303930\" target=\"_blank\">\"Automated classification of Alzheimer's disease and mild cognitive impairment using a single MRI and deep neural networks\"<\/a> (in en). <i>NeuroImage: Clinical<\/i> <b>21<\/b>: 101645. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.nicl.2018.101645\" target=\"_blank\">10.1016\/j.nicl.2018.101645<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6413333\/\" target=\"_blank\">PMC6413333<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30584016\" target=\"_blank\">30584016<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213158218303930\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213158218303930<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Automated+classification+of+Alzheimer%27s+disease+and+mild+cognitive+impairment+using+a+single+MRI+and+deep+neural+networks&rft.jtitle=NeuroImage%3A+Clinical&rft.aulast=Basaia&rft.aufirst=Silvia&rft.au=Basaia%2C%26%2332%3BSilvia&rft.au=Agosta%2C%26%2332%3BFederica&rft.au=Wagner%2C%26%2332%3BLuca&rft.au=Canu%2C%26%2332%3BElisa&rft.au=Magnani%2C%26%2332%3BGiuseppe&rft.au=Santangelo%2C%26%2332%3BRoberto&rft.au=Filippi%2C%26%2332%3BMassimo&rft.date=2019&rft.volume=21&rft.pages=101645&rft_id=info:doi\/10.1016%2Fj.nicl.2018.101645&rft_id=info:pmc\/PMC6413333&rft_id=info:pmid\/30584016&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213158218303930&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-74\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-74\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alzheimer\u2019s Disease Neuroimaging Initiative; Lu, Donghuan; Popuri, Karteek; Ding, Gavin Weiguang; Balachandar, Rakesh; Beg, Mirza Faisal (1 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41598-018-22871-z\" target=\"_blank\">\"Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer\u2019s Disease using structural MR and FDG-PET images\"<\/a> (in en). <i>Scientific Reports<\/i> <b>8<\/b> (1): 5697. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41598-018-22871-z\" target=\"_blank\">10.1038\/s41598-018-22871-z<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2045-2322\" target=\"_blank\">2045-2322<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5890270\/\" target=\"_blank\">PMC5890270<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29632364\" target=\"_blank\">29632364<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41598-018-22871-z\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41598-018-22871-z<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Multimodal+and+Multiscale+Deep+Neural+Networks+for+the+Early+Diagnosis+of+Alzheimer%E2%80%99s+Disease+using+structural+MR+and+FDG-PET+images&rft.jtitle=Scientific+Reports&rft.aulast=Alzheimer%E2%80%99s+Disease+Neuroimaging+Initiative&rft.au=Alzheimer%E2%80%99s+Disease+Neuroimaging+Initiative&rft.au=Lu%2C%26%2332%3BDonghuan&rft.au=Popuri%2C%26%2332%3BKarteek&rft.au=Ding%2C%26%2332%3BGavin+Weiguang&rft.au=Balachandar%2C%26%2332%3BRakesh&rft.au=Beg%2C%26%2332%3BMirza+Faisal&rft.date=1+December+2018&rft.volume=8&rft.issue=1&rft.pages=5697&rft_id=info:doi\/10.1038%2Fs41598-018-22871-z&rft.issn=2045-2322&rft_id=info:pmc\/PMC5890270&rft_id=info:pmid\/29632364&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41598-018-22871-z&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-75\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-75\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wiemken, Timothy L.; Furmanek, Stephen P.; Mattingly, William A.; Guinn, Brian E.; Cavallazzi, Rodrigo; Fernandez-Botran, Rafael; Wolf, Leslie A.; English, Connor L. <i>et al.<\/i> (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ir.library.louisville.edu\/jri\/vol1\/iss3\/10\/\" target=\"_blank\">\"Predicting 30-day mortality in hospitalized patients with community-acquired pneumonia using statistical and machine learning approaches.\"<\/a>. <i>Journal of Respiratory Infections<\/i> <b>1<\/b> (3). <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.18297%2Fjri%2Fvol1%2Fiss3%2F10%2F\" target=\"_blank\">10.18297\/jri\/vol1\/iss3\/10\/<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ir.library.louisville.edu\/jri\/vol1\/iss3\/10\/\" target=\"_blank\">http:\/\/ir.library.louisville.edu\/jri\/vol1\/iss3\/10\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Predicting+30-day+mortality+in+hospitalized+patients+with+community-acquired+pneumonia+using+statistical+and+machine+learning+approaches.&rft.jtitle=Journal+of+Respiratory+Infections&rft.aulast=Wiemken&rft.aufirst=Timothy+L.&rft.au=Wiemken%2C%26%2332%3BTimothy+L.&rft.au=Furmanek%2C%26%2332%3BStephen+P.&rft.au=Mattingly%2C%26%2332%3BWilliam+A.&rft.au=Guinn%2C%26%2332%3BBrian+E.&rft.au=Cavallazzi%2C%26%2332%3BRodrigo&rft.au=Fernandez-Botran%2C%26%2332%3BRafael&rft.au=Wolf%2C%26%2332%3BLeslie+A.&rft.au=English%2C%26%2332%3BConnor+L.&rft.au=Ramirez%2C%26%2332%3BJulio+A.&rft.date=2017&rft.volume=1&rft.issue=3&rft_id=info:doi\/10.18297%2Fjri%2Fvol1%2Fiss3%2F10%2F&rft_id=http%3A%2F%2Fir.library.louisville.edu%2Fjri%2Fvol1%2Fiss3%2F10%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-76\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-76\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Men\u00e9ndez Villanueva, R. 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The usefulness of Bayes theorem for clinical application<\/a>\"]. <i>Archivos De Bronconeumologia<\/i> <b>31<\/b> (7): 317\u2013322. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0300-2896\" target=\"_blank\">0300-2896<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/8777525\" target=\"_blank\">8777525<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/8777525\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/8777525<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%5BThe+diagnostic+evaluation+of+rapid+sputum+technics+for+Pneumococcus+in+community-acquired+pneumonia.+The+usefulness+of+Bayes+theorem+for+clinical+application%5D&rft.jtitle=Archivos+De+Bronconeumologia&rft.aulast=Men%C3%A9ndez+Villanueva&rft.aufirst=R.&rft.au=Men%C3%A9ndez+Villanueva%2C%26%2332%3BR.&rft.date=1+August+1995&rft.volume=31&rft.issue=7&rft.pages=317%E2%80%93322&rft.issn=0300-2896&rft_id=info:pmid\/8777525&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F8777525&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-77\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-77\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">B.V, Ravindra; Sriraam, N; Geetha, M (31 December 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.sciencepubco.com\/index.php\/ijet\/article\/view\/10669\" target=\"_blank\">\"Classification of non-chronic and chronic kidney disease using SVM neural networks\"<\/a>. <i>International Journal of Engineering & Technology<\/i> <b>7<\/b> (1.3): 191\u201394. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.14419%2Fijet.v7i1.3.10669\" target=\"_blank\">10.14419\/ijet.v7i1.3.10669<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2227-524X\" target=\"_blank\">2227-524X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.sciencepubco.com\/index.php\/ijet\/article\/view\/10669\" target=\"_blank\">https:\/\/www.sciencepubco.com\/index.php\/ijet\/article\/view\/10669<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Classification+of+non-chronic+and+chronic+kidney+disease+using+SVM+neural+networks&rft.jtitle=International+Journal+of+Engineering+%26+Technology&rft.aulast=B.V&rft.aufirst=Ravindra&rft.au=B.V%2C%26%2332%3BRavindra&rft.au=Sriraam%2C%26%2332%3BN&rft.au=Geetha%2C%26%2332%3BM&rft.date=31+December+2017&rft.volume=7&rft.issue=1.3&rft.pages=191%E2%80%9394&rft_id=info:doi\/10.14419%2Fijet.v7i1.3.10669&rft.issn=2227-524X&rft_id=https%3A%2F%2Fwww.sciencepubco.com%2Findex.php%2Fijet%2Farticle%2Fview%2F10669&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-78\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-78\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Annapoorani, J.C.B.; Gnanaselvam, C.R. (2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ciitresearch.org\/dl\/index.php\/aa\/article\/view\/AA012018003.\" target=\"_blank\">\"Enhancing Prediction Accuracy of Chronic Kidney Disease using Neural Networks\"<\/a>. <i>Automation and Autonomous System<\/i> <b>10<\/b> (1): 10\u201315. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.36039%2FAA012018003\" target=\"_blank\">10.36039\/AA012018003<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.ciitresearch.org\/dl\/index.php\/aa\/article\/view\/AA012018003\" target=\"_blank\">http:\/\/www.ciitresearch.org\/dl\/index.php\/aa\/article\/view\/AA012018003<\/a>.<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Enhancing+Prediction+Accuracy+of+Chronic+Kidney+Disease+using+Neural+Networks&rft.jtitle=Automation+and+Autonomous+System&rft.aulast=Annapoorani%2C+J.C.B.%3B+Gnanaselvam%2C+C.R.&rft.au=Annapoorani%2C+J.C.B.%3B+Gnanaselvam%2C+C.R.&rft.date=2018&rft.volume=10&rft.issue=1&rft.pages=10%E2%80%9315&rft_id=info:doi\/10.36039%2FAA012018003&rft_id=http%3A%2F%2Fwww.ciitresearch.org%2Fdl%2Findex.php%2Faa%2Farticle%2Fview%2FAA012018003.&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-79\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-79\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ayat, Saeed; Farahani, Hojjat A.; Aghamohamadi, Mehdi; Alian, Mahmood; Aghamohamadi, Somayeh; Kazemi, Zeynab (1 October 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00521-012-1086-z\" target=\"_blank\">\"A comparison of artificial neural networks learning algorithms in predicting tendency for suicide\"<\/a> (in en). <i>Neural Computing and Applications<\/i> <b>23<\/b> (5): 1381\u20131386. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00521-012-1086-z\" target=\"_blank\">10.1007\/s00521-012-1086-z<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0941-0643\" target=\"_blank\">0941-0643<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00521-012-1086-z\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00521-012-1086-z<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+comparison+of+artificial+neural+networks+learning+algorithms+in+predicting+tendency+for+suicide&rft.jtitle=Neural+Computing+and+Applications&rft.aulast=Ayat&rft.aufirst=Saeed&rft.au=Ayat%2C%26%2332%3BSaeed&rft.au=Farahani%2C%26%2332%3BHojjat+A.&rft.au=Aghamohamadi%2C%26%2332%3BMehdi&rft.au=Alian%2C%26%2332%3BMahmood&rft.au=Aghamohamadi%2C%26%2332%3BSomayeh&rft.au=Kazemi%2C%26%2332%3BZeynab&rft.date=1+October+2013&rft.volume=23&rft.issue=5&rft.pages=1381%E2%80%931386&rft_id=info:doi\/10.1007%2Fs00521-012-1086-z&rft.issn=0941-0643&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00521-012-1086-z&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-80\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-80\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bhat, H.S.; Goldman-Mellor, Sidra J. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1711.10057v2\" target=\"_blank\">\"Predicting Adolescent Suicide Attempts with Neural Networks\"<\/a>. <i>arXiv<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/ArXiv\" data-key=\"88fff3a9b495bb5db39730547691ced3\">arXiv<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/arxiv.org\/abs\/1711.10057v2\" target=\"_blank\">1711.10057v2<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1711.10057v2\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1711.10057v2<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Predicting+Adolescent+Suicide+Attempts+with+Neural+Networks&rft.jtitle=arXiv&rft.aulast=Bhat%2C+H.S.%3B+Goldman-Mellor%2C+Sidra+J.&rft.au=Bhat%2C+H.S.%3B+Goldman-Mellor%2C+Sidra+J.&rft.date=2017&rft_id=info:arxiv\/1711.10057v2&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1711.10057v2&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-81\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-81\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Wolfram, W.; Christian, D. (1976). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/files.eric.ed.gov\/fulltext\/ED130511.pdf\" target=\"_blank\">\"Appalachian Speech\"<\/a> (PDF). Center for Applied Linguistics<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/files.eric.ed.gov\/fulltext\/ED130511.pdf\" target=\"_blank\">https:\/\/files.eric.ed.gov\/fulltext\/ED130511.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 September 2020<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Appalachian+Speech&rft.atitle=&rft.aulast=Wolfram%2C+W.%3B+Christian%2C+D.&rft.au=Wolfram%2C+W.%3B+Christian%2C+D.&rft.date=1976&rft.pub=Center+for+Applied+Linguistics&rft_id=https%3A%2F%2Ffiles.eric.ed.gov%2Ffulltext%2FED130511.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-82\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-82\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Luhman, Reid (1 September 1990). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0047404500014548\/type\/journal_article\" target=\"_blank\">\"Appalachian English stereotypes: Language attitudes in Kentucky\"<\/a> (in en). <i>Language in Society<\/i> <b>19<\/b> (3): 331\u2013348. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1017%2FS0047404500014548\" target=\"_blank\">10.1017\/S0047404500014548<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0047-4045\" target=\"_blank\">0047-4045<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0047404500014548\/type\/journal_article\" target=\"_blank\">https:\/\/www.cambridge.org\/core\/product\/identifier\/S0047404500014548\/type\/journal_article<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Appalachian+English+stereotypes%3A+Language+attitudes+in+Kentucky&rft.jtitle=Language+in+Society&rft.aulast=Luhman&rft.aufirst=Reid&rft.au=Luhman%2C%26%2332%3BReid&rft.date=1+September+1990&rft.volume=19&rft.issue=3&rft.pages=331%E2%80%93348&rft_id=info:doi\/10.1017%2FS0047404500014548&rft.issn=0047-4045&rft_id=https%3A%2F%2Fwww.cambridge.org%2Fcore%2Fproduct%2Fidentifier%2FS0047404500014548%2Ftype%2Fjournal_article&rfr_id=info:sid\/en.wikipedia.org:Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220627215843\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.805 seconds\nReal time usage: 1.040 seconds\nPreprocessor visited node count: 81587\/1000000\nPost\u2010expand include size: 733456\/2097152 bytes\nTemplate argument size: 230599\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 204998\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 756.705 1 -total\n 90.15% 682.140 1 Template:Reflist\n 74.81% 566.086 82 Template:Citation\/core\n 66.83% 505.734 67 Template:Cite_journal\n 12.35% 93.419 77 Template:Date\n 11.08% 83.835 14 Template:Cite_web\n 8.58% 64.893 161 Template:Citation\/identifier\n 4.28% 32.421 1 Template:Infobox_journal_article\n 3.72% 28.115 1 Template:Infobox\n 2.82% 21.308 322 Template:Hide_in_print\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13343-0!canonical and timestamp 20220627215842 and revision id 48222. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach\">https:\/\/www.limswiki.org\/index.php\/Journal:Fueling_clinical_and_translational_research_in_Appalachia:_Informatics_platform_approach<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","843741d77f4c16c82c818d163a13b06e_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/2a\/Fig1_Cecchetti_JMIRMedInfo8_8-10.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/15\/Fig2_Cecchetti_JMIRMedInfo8_8-10.png"],"843741d77f4c16c82c818d163a13b06e_timestamp":1656439828,"d40238949d238978e30434ffe18aa050_type":"article","d40238949d238978e30434ffe18aa050_title":"Structure-based knowledge acquisition from electronic lab notebooks for research data provenance documentation (Schr\u00f6der et al. 2022)","d40238949d238978e30434ffe18aa050_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation","d40238949d238978e30434ffe18aa050_plaintext":"\n\nJournal:Structure-based knowledge acquisition from electronic lab notebooks for research data provenance documentationFrom LIMSWikiJump to navigationJump to searchFull article title\n \nStructure-based knowledge acquisition from electronic lab notebooks for research data provenance documentationJournal\n \nJournal of Biomedical SemanticsAuthor(s)\n \nSchr\u00f6der, Max; Staehlke, Susanne; Groth, Paul; Nebe, J. Barbara; Spors, Sascha; Kr\u00fcger, FrankAuthor affiliation(s)\n \nUniversity of Rostock, University Medical Center Rostock, University of AmsterdamPrimary contact\n \nEmail: max dot schroeder at uni-rostock dot deYear published\n \n2022Volume and issue\n \n13Article #\n \n4 (2022)DOI\n \n10.1186\/s13326-021-00257-xISSN\n \n2041-1480Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/s13326-021-00257-xDownload\n \nhttps:\/\/jbiomedsem.biomedcentral.com\/track\/pdf\/10.1186\/s13326-021-00257-x.pdf (PDF)\n\nContents \n\n1 Abstract \n2 Background \n3 Use case \n\n3.1 Biomedical wet lab experiments \n3.2 Research data provenance \n\n\n4 Related work \n5 Methods \n\n5.1 Manual model engineering \n5.2 Structure-based modelling approach \n5.3 Preparing ELN protocol template \n5.4 Bundling research data and re-use \n\n\n6 Results \n\n6.1 Manually engineered model \n6.2 Structure-based model \n6.3 ELN protocols and protocol template \n6.4 Research data bundles \n\n\n7 Discussion \n8 Conclusion \n9 Appendix \n\n9.1 Queries and answers for the W7 questions \n\n\n10 Abbreviations \n11 Footnotes \n12 Acknowledgements \n\n12.1 Author contributions \n12.2 Funding \n12.3 Availability of data and materials \n12.4 Competing interests \n\n\n13 References \n14 Notes \n\n\n\nAbstract \nBackground: Electronic laboratory notebooks (ELNs) are used to document experiments and investigations in the wet lab. Protocols in ELNs contain a detailed description of the conducted steps, including the necessary information to understand the procedure and the raised research data, as well as to reproduce the research investigation. The purpose of this study is to investigate whether such ELN protocols can be used to create semantic documentation of the provenance of research data by the use of ontologies and linked data methodologies.\nMethods: Based on an ELN protocol of a biomedical wet lab experiment, a retrospective provenance model of the raised research data describing the details of the experiment in a machine-interpretable way is manually engineered. Furthermore, an automated approach for knowledge acquisition from ELN protocols is derived from these results. This structure-based approach exploits the structure in the experiment\u2019s description\u2014such as headings, tables, and links\u2014to translate the ELN protocol into a semantic knowledge representation. To satisfy the FAIR guiding principles (making data findable, accessible, interoperable, and reuseable), a ready-to-publish bundle is created that contains the research data together with their semantic documentation.\nResults: While the manual modelling efforts serve as proof of concept by employing one protocol, the automated structure-based approach demonstrates the potential generalization with seven ELN protocols. For each of those protocols, a ready-to-publish bundle is created and, by employing the SPARQL query language, it is illustrated such that questions about the processes and the obtained research data can be answered.\nConclusions: The semantic documentation of research data obtained from the ELN protocols allows for the representation of the retrospective provenance of research data in a machine-interpretable way. Research Object Crate (RO-Crate) bundles including these models enable researchers to easily share the research data, including the corresponding documentation, as well as to search and relate the experiment to each other.\nKeywords: research data, provenance, knowledge acquisition, electronic laboratory notebooks, semantic documentation, RO-Crate, FAIR\n\nBackground \nEffective reuse of research data requires comprehensive documentation of their provenance. Beside metadata, knowledge about the generating process helps others to understand research data and allows for the reproduction of research investigations. This includes not only sources of input data, such as parameters and assumptions, but also information about instrumentation, devices, and materials. For wet lab experiments, such knowledge is increasingly documented in electronic laboratory notebooks (ELNs). The focus of these tools is on the documentation of laboratory activities that produce research data in so-called \"ELN protocols.\" In addition to this textual description, the FAIR guiding principles[1] provide general guidance on research data documentation in terms of metadata. However, they do not prescribe technical details about the implementation of such documentation.[2]\nTo foster the realization of the FAIR principles for research data produced in wet lab experiments, we aim for machine-interpretable representations of experimental documentation of the process that is the origin of the data. In other words, the provenance information about the research data\u2014including the activities and involved researchers, resources, and equipment\u2014should be semantically represented. For this purpose, we employ the frequently used[3] PROV W3C recommendation[4], which ontologically, in PROV Ontology (PROV-O), defines entities, activities, and agents, as well as their relations. In particular, according to Belhajjame et al., an entity is defined as a \u201cphysical, digital, conceptual, or other kind of thing with some fixed aspects,\"[5] an activity as \u201csomething that occurs over a period of time and acts upon or with entities; it may include consuming, processing, transforming, modifying, relocating, using, or generating entities,\u201d[5] and an agent as \u201csomething that bears some form of responsibility for an activity taking place, for the existence of an entity, or for another agent\u2019s activity.\u201d[5] With respect to wet lab experiments, all biological and chemical resources\u2014as well as not only the devices and software but also the research data itself\u2014can be seen as entities; researchers conducting the experiment are the agents, and the process of research data creation consists of activities. The semantic representation of this information as a knowledge graph (KG)[6] can be achieved by the use of modern web technologies where the terms and their relations are defined in ontologies such as PROV-O (TBox modelling), the instances are built up in the KG (ABox modelling), and other KGs can be linked in order to create an interconnected graph of semantic knowledge.\nIn this paper, we aim for an automatic extraction of information from ELN protocols in order to transfer them into a semantic representation that documents the produced research data. For this purpose, we employ the documentation of Calcium imaging (Ca-imaging) experiments, originally proposed by Staehlke et al.[7], as a running example. In particular, we use ELN protocols that document the conduction of Ca-imaging experiments in order to: (i) demonstrate the feasibility of manually transferring an ELN protocol into a semantic representation encoding the provenance of research data, (ii) automate the information extraction and modelling by exploiting the structure of an ELN protocol by means of a structure-based approach, and (iii) evaluate the proposed method by answering provenance questions from the resulting bundle of research data and the corresponding semantic model.\nHere, the term \"ELN protocol\" refers to the actual documentation of the wet lab experiment within an ELN and is different from the term \"protocol templates,\" which are used to encode instructions to be performed in order to conduct particular procedures or be published at protocols.io. While those protocol templates do encode a list of abstract instructions, they do not necessarily reflect particular research data, nor instrumentation, parameters, or other aspects to the execution-specific information. ELN protocols, in contrast, represent the documentation of the actual experiment, and the contained information is thus necessary to understand how the resulting research data was generated. This includes manufacturer-specific information about resources used in the experiment such as lot numbers.[a] Furthermore, passage numbers of the resources, the times when an activity was conducted, and the parameters used in a device, as well as the research data and the researchers conducting the experiment, are information specific to a particular experiment. Figure 1 illustrates the differences by providing an example for an ELN protocol and a protocol template.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. Excerpts of an ELN protocol that represents a particular experiment including all details such as timestamps, lot numbers as well as the research data (left) and a protocol template containing general instructions of experiments without these details (right, sourced from here.)\n\n\n\nThe work presented here is based on a preliminary investigation regarding the effectiveness of manually modeling ELN protocols by use of ontologies.[8] Here, we extend this preliminary work by discussing the potential of automatic information extraction from ELN protocols by employing structural information and discussing the differences and implications of both approaches. Moreover, while the previous work only sketched the semantic representation of the wet lab experiments, here, we focus on the generation of ready-to-publish research data bundles, including the semantic description of the origin of the research data.\n\nUse case \nTo demonstrate the feasibility of the proposed approach, a typical wet lab investigation was chosen as a use case. In the following, we introduce the use case and derive questions regarding the provenance of the corresponding research data.\n\nBiomedical wet lab experiments \nThe objective of the biomedical study was to investigate the intracellular calcium ions (Ca2+) dynamics by Calcium-imaging (Ca-imaging) under different settings.[7] In particular, two different wet lab experiments were considered: (i) an investigation of the influence of different material surface conditions on Ca2+ mobilization, and (ii) an investigation regarding the Ca2+ dynamics under the influence of electrical stimulation. Both types of experiments involve similar activities of the researchers. In particular, each experiment employs the Ca-imaging method previously established by Staehlke et al.[7] in different settings. The particular conditions, e.g., surface conditions or parameters of the electrical stimulation, are investigated within each experiment, while the order of the different variations was permuted across the experiments. That is, after a preparation phase, where all materials and devices are prepared, the same procedure, i.e., Ca-imaging, was executed for the different conditions. During the experiment, several materials and devices are employed, such as cell line passages, buffer, and microscopes.\nFor the purpose of this study, we asked the researchers to use an ELN for the documentation of their wet lab activities, resulting in eight ELN protocols: one for the first experiment and seven for the latter, representing different permutations of the sequential execution of Ca-imaging for different electrical stimulation parameters. In particular, eLabFTW (Deltablot, https:\/\/www.elabftw.net\/, v3.6.7)[9], a domain-independent ELN, was used. Figure 2 shows an excerpt of a protocol from the use case.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. ELN protocol about a Ca-imaging experiment in the eLabFTW software. It contains general information (top), the list of activities with their starting time (middle), used inventory items, and uploaded research data (bottom).\n\n\n\nELNs often provide an inventory database that allows the maintenance of materials and other research resources used during the experiments. Typically, each resource belongs to a configurable set of categories, e.g., cell lines, buffer, software, or devices. These entries in the inventory database can be linked from within the protocol when used within the corresponding experiment. Figure 3 illustrates the entry to the inventory database for the MG-63 cell line that is used in the experiments of the use case. Note that this entry is already augmented by information about ontology classes that were added during the manual model engineering process. Here, we use such ontology references but also other resource identifiers, such as Research Resource Identifiers (RRID)[10], could be used for resource reference. However, these RRIDs do not reflect different versions of the resources, e.g., when describing a software. Thus, they can be used to annotate the inventory database of the ELN similar to the ontology classes, but cannot be used on their own. Research data is attached to the ELN protocol by uploading and linking from within the textual description of the step that describes the generating activity.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. Shortened documentation of a Ca-imaging experiment in the eLabFTW ELN software. The upper part contains general information about the investigation, followed by the list of activities with their starting time. Below, used inventory items and uploaded research data are listed.\n\n\n\nIn summary, the execution of an individual experiment took about 4.5 hours, resulting from the preparation and the sequential executions of the Ca-imaging procedure under five different stimulation settings consisting of 15 steps for each. Each protocol referred to 22 inventory items in the database and between 85 and 110 data files of different types were generated. The different file types include (i) CZI files (developed by ZEISS) containing the microscope settings, recorded images, and raw measurement data; (ii) image files in JPEG format to illustrate particular excerpts from the video recordings; and (iii) raw measurements of the luminescence over time, in the form of XML encoded tabular data files. The latter two formats are exports from the CZI files. The provenance of all attached files needs to be documented.\n\nResearch data provenance \nWhen considering this use case, several questions regarding the provenance of the research data can be raised. To this end, we consider questions based on the W7 provenance model[11], that describes provenance as combinations of What, When, Where, How, Who, Which, and Why. We consider each question individually, encoding the view of a researcher that aims at re-using the research data from our use case. The questions were developed together with the domain experts and resemble actual questions that arise when considering the replication of the documented experiments.\n\nW1 Who participated in the study?\nWith respect to the provenance of research data, all researchers contributing to the creation are of interest, i.e., we expect to get a list of all researchers and their affiliations involved in an experiment.<\/dd>\nW2 Which biological and chemical resources and which equipment was used in the study?\nIn particular, we are interested in the resources and the equipment used in an experiment, including all details such as the lot number and the passage information.<\/dd>\nW3 How was a particular file created?\n\"What was the sequence of activities that led to the creation of a particular file\" is a question that might help other researchers in comprehending the data.<\/dd>\nW4 When was an activity conducted?\nThe date and the time point of a particular activity but also its duration are of interest. This information is useful for the planning of similar experiments, but also with respect to the comprehensibility of the results as the date and time point might influence them, e.g., due to weather or other environmental phenomena.<\/dd>\nW5 Why was the experiment done?\nUnderstanding why the research data was created is crucial for their comprehensibility. We take the objective of the experiment as the reason for the creation.<\/dd>\nW6 Where was the experiment conducted?\nThe location\u2014respectively. the institution where the experiment was conducted\u2014is of interest as regional characteristics might influence the data.<\/dd>\nW7 What was the order of the stimulation parameters in a particular experiment?\nThe order of the particular approaches influences the results as there might be effects from the timing of the experiments or the duration since their preparation. That means, with respect to the evaluation of the results, we are interested in this order.<\/dd>\nRelated work \nThe provenance of research data, including their research investigations, combines several research fields, ranging from general-purpose methods and standards for the documentation of provenance to specifically tailored methods and platforms for the tracking of research and other activities. In the following, we will discuss recent work within those fields and relate it to our method.\nMany methods aiming at documenting the provenance of activities have already been proposed. Here, we consider the classification of provenance information following the definition of Herschel et al.[12] and Lim et al.[13]:\n\nprospective provenance describes \u201can abstract workflow specification as a recipe for future data derivation\u201d[13];\nretrospective provenance documents a \u201cpast workflow execution and data derivation information, i.e., which tasks were performed and how data artifacts were derived\u201d[13]; and\nevolution provenance illustrates \u201cthe changes made between two versions of the input\u201d[12], or, in other words, versions of the procedure, the data, or the parameters are reflected by evolution provenance similar to version control such as that implemented by Git for source code.\nApplying those definitions to the use case at hand, prospective provenance allows the keeping track of changes of laboratory-specific operating procedures in general, while retrospective provenance allows the documenting of the actually executed sequence of activities that resulted in a particular set of research data. At last, evolution provenance allows the tracking of changes made to the actual ELN protocol or the inventory database items.\nWith respect to the research workflows to be represented by provenance modeling, two different types can be distinguished:\n\nIn-silico studies employ computational methods for the analysis of the data. Workflow systems like Taverna[14], Kepler[15], or Galaxy[16], and programming environments like Jupyter Notebook[17] have been successfully augmented to record retrospective provenance.\nWet lab experiments are courses of activities in a laboratory. While several approaches exist that describe prospective provenance[18][19] by analyzing published protocols, only limited work is done on documenting retrospective provenance for these workflows.\nMore detailed information about provenance modelling and the employed methods are provided in the literature.[3][12] Here, we are interested in providing detailed information about the origin of research data. Thus, we aim at providing retrospective provenance documentation of research data from ELN protocols documenting wet lab experiments.\nThe Smart Tea project[20] similarly aims at the semantic metadata recording for research data from within a customized ELN. The developed ELN provides a structured graphical user interface (GUI) requiring the user to provide information for predefined variables. All information is directly transferred into a linked data representation and persistently archived with a linked data server. While this approach perfectly guides users through the sequence of activities and tracks retrospective provenance at the same time, it fails to keep track of deviations from the predefined plan. Furthermore, as the documentation is directly translated into a semantic representation, additional information that was not considered before can hardly be attached to such protocols, which restricts both the expressivity of the semantic model and the user to previously known information.\nSimilar to the Smart Tea project, the PROV templating approach[21] suggests the recording of provenance information given a pre-defined provenance model. In other words, the main idea is that applications only store values for placeholders in a particular provenance model, which was shown to be more efficient than the storage of the original provenance models.[21] This solution is very efficient if a very large number of identical provenance structures with some variable information are to be stored. If, however, the application requires more flexibility in terms of the provenance structure, the template approach does not utilize this efficiency advantage. Note that provenance templates encode a semantic representation with variables, whereas protocol templates provide guidelines for experiments.\nCurcin et al.[22] use a very similar approach for the provenance modelling in diagnostic decision support systems. A more flexible approach is the use of knowledge graph cells (KGCs), proposed by Vogt et al.[23] They provide a concept for the definition of knowledge structures. In particular, rules including ABox and TBox expressions might be defined that allow the dynamic modification of the KG. Thus, KGCs might be used to specify potential semantic structures of ELN protocols without particular information inside. The application of KGCs would require a complete definition over all possible semantic representations of ELN protocols, which is infeasible.\nWith respect to the vocabulary used to semantically describe the laboratory-specific information, the EXperimental ACTions (EXACT2) ontology, together with the Natural Language Processing (NLP) framework[18], aims at the automatic extraction of knowledge from biomedical protocols for prospective provenance. Similarly, the SeMAntic RepresenTation for Experimental Protocols (SMART Protocols) ontology reuses EXACT2 to represent prospective provenance from published protocols.[19] In contrast to both approaches that represent a plan, we aim at retrospective provenance, i.e., a particular course of activities. Both approaches, however, could be used to describe prospective provenance of the underlying plan of an ELN protocol, to allow the documentation of potential deviations from the original plan. The Reproduce Microscopy Experiments (REPRODUCE-ME) ontology[24] introduces a specific vocabulary to describe retrospective provenance for microscopy experiments. Besides, the domain-independent ontologies, PROV-O and its predecessor Open Provenance Model (OPM)[25], are frequently employed as upper-level ontology for provenance documentation.[3] Furthermore, many extensions for specific applications have been proposed. The Provenance, Authoring, and Versioning (PAV) ontology, for example, proposes a mechanism for the versioning and authoring of web resources[26], and CollabPG encodes collaborations within processes.[3] With respect to the application domain of the use case, the Open Biological and Biomedical Ontology (OBO) Foundry is a community initiative aiming at the development and maintenance of ontologies in the biomedical domain.[27] The Basic Formal Ontology (BFO)[28] is the upper-level ontology that is used for each of the OBO ontologies.\nFor the retrospective provenance documentation of research data from computational workflows, several specifically tailored tools and approaches have been proposed in the literature. ProvBook[17], for instance, tracks provenance in Jupyter Notebooks that are used for literate programming. There's also Dataprov[29], a wrapper tool producing provenance information from the execution of analysis tools, and noWorkflow[30], which captures provenance information from analysis scripts such as for the programming language Python. Aside from these methods, other provenance tracking approaches known as lineage retrieval[31] or lineage tracking and workflow systems exist.[32] In general, in-silico workflow systems not only record provenance information, but at the same time they specify the involved processing steps and enable their execution possibly on a distributed system.[33] However, as these systems are limited to tackling computational analyses, their usage for the provenance of research data from wet lab experiments is difficult.\nRegarding the completeness of the documentation with respect to reproducibility, plenty of standards exist that aim at the definition of the minimum set of information required to comprehend and reproduce the research investigation for different applications. With respect to the use case at hand, the minimum information for electrical cell stimulation[34] and the Minimum Information About a Cellular Assay (MIACA)[35] provide such references for the documentation. Similarly, standard operating procedures (SOPs) or published instructions for experiments encode standards for the documentation of a particular experiment.\nWhen considering the publication or archiving of research data, metadata is important to provide additional context, enabling others (including the future self) to understand the research process and the resulting data. In particular, the FAIR guiding principles provide abstract recommendations for handling research data to enable its re-usability.[1] Together with the implementation suggestions of these guidelines[2], they provide a framework which is also applicable for research data from wet lab experiments. While both guidelines provide generic recommendations regarding research data documentation, different standards exist that provide vocabulary for their support. Several initiatives foster the development of documentation standards for research data, including the Data Documentation Initiative (DDI) that focuses on standardizing metadata for social science datasets.[36] The Dublin Core, instead, is a more general definition of 15 metadata elements for electronic resources.[37][38] Similarly, Data Catalog Vocabulary (DCAT) provides a common vocabulary for the interoperability of data catalogs[39] and, thus, also defines required metadata for research data. Additionally, domain-specific metadata standards have been developed. With respect to the use case, this includes metadata for microscopy images, such as that proposed by the RDM4mic Initiative.[40] In addition to these metadata, the information inside the data file might also be described. For this purpose, codebooks and data dictionaries are employed.[41][42] Considering a CSV file as an example, this includes information about each column such as the domain of the values and the unit of the measurements. This information is defined in a separate file that helps comprehend the raw data.\nFor the publication and archiving of this data, including the semantic documentation, several approaches have been proposed. These include bundling formats such as BagIt[43], Oxford Common File Layout (OCFL)[44], and RO-Crate[45], as well as literate programming methods such as using Jupyter Notebook to combine (parts of) research data, their analysis source code, and results, as well as their documentation. RO-Crate[45] is a mechanism that allows the bundling of resources together with their associated metadata, supporting the FAIR publication and archiving of the research data. By re-using existing vocabulary such as schema.org or PROV-O, it implements a linked data approach to enable researchers to provide all information necessary to (re-)use the described research data. This includes basic properties such as author and title of the resource, a license for publication, a description of the files, and a description of the workflow used to create those files in terms of retrospective provenance, including employed software and other equipment. In brief, a RO-Crate bundle consists of the research data file and a metadata file called ro-crate-metadata.json, which contains structured metadata about the files and the entire bundle in a JSON-LD format. While the ro-crate-metadata.json contains all information in machine interpretable way, it is accompanied by a human readable HTML representation. RO-Crate has successfully been used for the documentation of retrospective provenance of in-silico studies[46], but can, due to the flexibility of the vocabulary, also be used for retrospective provenance of wet lab experiments.\n\nMethods \nThe objective of the study was to investigate whether it is possible to create semantic documentation of the research process and the resulting research data in terms of provenance. To this end, semantic documentation was manually created by analyzing the ELN protocol. To support potential automation of the semantic model creation, based on the results of this analysis, a protocol template was designed that (i) guides researchers through the process while (ii) requiring them to provide all information necessary to comprehend the origin of the research data. The resulting protocol template was split up into a set of templates that encode steps of an experiment such as the staining or the imaging with a particular set of stimulation parameters. These sub-templates ease the re-use for new experiments, e.g., by combining them in other permutations. Based on this, researchers documented their wet lab experiments, resulting in a set of ELN protocols, each of which contains variations, such as differences in parameters, execution time, or execution order. The different protocols were then automatically analyzed, translated into a semantic model, and finally bundled into self-contained archives. The following provides a detailed description of each step.\n\nManual model engineering \nThe manual engineering process for the semantic model of the ELN protocol was comprised of iterative modelling and reviewing. Domain experts were consulted during this process in order to validate the model. The main objective of this process was to check if all information for the semantic provenance modelling are available in ELN protocols and whether they can be transferred into a semantic representation by employing existing ontologies. The aim of the resulting model was to document the provenance of the research data.\nProteg\u00e9[47] was used for model engineering. In particular, the modelling was conducted as follows:\n\nBioPortal[48] and Ontobee[49] are used to identify relevant ontologies for terms from the ELN protocol and the inventory database items.\nA set of ontologies is selected from these search results so that the coverage of terms from the ELN in a single ontology is maximized. Ontologies from the OBO Foundry[27], compatible with the BFO[28], were preferred.\nOntology classes representing inventory database items in the ELN (see Fig. 3) are added into the ELN description of the corresponding inventory database item as a reference for the semantic modelling.\nThe semantic model itself is constructed by ABox statements, i.e., the creation of instances of these classes that represent the particular entities and activities of the protocol and the inventory database. Each instance gets a unique identifier in the local namespace, reflecting the individual entity; for example, MG-63_(P25,_LOT_57840088) is used to encode passage 25 of the MG-63 cells that were delivered with the lot number 57840088 (see also Fig. 5). The specific input and output relations of the activity classes are used in order to connect the particular entities correspondingly.\nReferences to the same entities in other KGs such as Wikidata[50] are included by employing the owl:sameAs relation. This is essential for linked open data according to the five-star deployment scheme proposed by Berners-Lee.[51]\nThe following three rules were considered during iterative modelling in order to prevent the introduction of a bias from modeller and domain experts: \n\nUse ontological classes of the same granularity as the terms in the experiment documentation, e.g., \u201cwashing\u201d instead of \u201cmaterial processing.\u201d\nAvoid the introduction of new classes and attributes whenever possible (e.g., avoid TBox statements) and re-use existing ontologies.[52]\nUse only information from the ELN protocol, and do not introduce further knowledge despite the references to other KGs.\nThus, the semantic model serves as demonstrator for the inherent potential of ELN protocols.\n\nStructure-based modelling approach \nManual model engineering reveals the potential of ELN protocols for the semantic documentation of research data. However, in order to use this at large scale, a more automated approach is needed. To approach this target, the structure-based method presented here employs the textual structure in the ELN protocols, as well as basic text analysis, which is introduced in the following sections.\nConsidering the ELN protocol from the manual model, we observed that the main content is structured by:\n\nheadings and paragraphs,\ntables (table headings and body),\nenumerations and lists, and\nlinks to inventory items and research data.\nHeadings are used to structure the documentation, e.g., the general section about the experimental details, or a particular set of activities are preceded from a heading (upper and lower part in Fig. 2, respectively). In the latter case, different sets of activities in a protocol correspond to the templates we extracted, i.e., at each headline a new template was included.\nTables are used here for two different purposes. First, key-value mappings represent tables that encode general information about an experiment or inventory item, e.g., the objective of the investigation or the manufacturer of a resource. The description of inventory items mainly consists of a table of this kind (see Fig. 3). Second, lists of activities represent tables with two columns: \u201cStep\u201d and \u201cStarting time.\u201d Each row encodes an atomic activity of the experiment (see Fig. 2). Especially for the activity tables, cells include also enumerations, lists, and paragraphs which further describe the atomic activities and parameters, as well as the linking inventory items and the research data. As an example, see the last row in the activity table in Fig. 2. Note, that we assume each row defining an atomic activity that we do not split up at this stage.\nConsidering our ultimate goal of retrospective research data provenance documentation, we exploited the structure of the ELN protocol as follows:\n\nGeneral information such as the researcher conducting the experiment and the objective of the investigation are parsed from the key-value table at the beginning of the protocol. This information is added to the protocol activity using the relation qualifiedAssociation (prov:qualifiedAssociation).\nActivities described within the ELN protocol are hierarchically structured to represent different levels of granularity. The top-level activity resembles the entire experiment, while the different main sections are represented by second-level activities. Note that each main section contains an activity table. Finally, the third level represents activities from table rows of those tables.\nAll activities are augmented by inventory items mentioned in the respective description by the used (prov:used) relation.\nFor each research data file created during the investigation, a corresponding entity is created. Assuming that the mention of a file inside an activity marks the creation of this file, the activity is linked to the file using the relation wasGeneratedBy (prov:wasGeneratedBy).\nAs previously described, we do not further split up the third-level activities, i.e., complex structures such as enumerations and lists, including their order inside a step description, are taken as atomic.\nAside from the use of structural elements in the ELN, which was the base for the manual model, we identified different repeating patterns that can be exploited. For example, from the textual description of activities such as \u201cincubate 5 min in [Device] SANYO CO2 Incubator at 37\u2218C\u201d or \u201cwash cells with [Washing solution] PBS without Ca\/Mg [..],\u201d we observed the use of verb phrases indicating the activity of the step: \u201cincubate\u201d and \u201cwash,\u201d respectively. Here, we use the head verb of those phrases to assign the corresponding ontological class from a prior mapping. Similarly, information about researchers and institutions, manufacturers, file mime-types, and experiment type are included. For large scale usage, these information might also be retrieved from an organizational or research information system.\nParameters that are used in the textual description are identified by their unit, e.g., \u201c1.5 ml,\u201d \u201c5 min,\u201d and \u201c37\u2218C\u201d by employing regular expressions. They are then represented as blank nodes connected to the step using the relation has value specification (OBI_0001938) with the value as the numerical value of the parameter and the unit connected by has measurement unit label (IAO_0000039). We observed that most of the units mentioned in the protocols at hand are defined in the units ontology (UO).[53]\nAnother frequently used pattern observed in the textual description is the mixture of biological and chemical resources, e.g., \u201c89% [Culture Medium] DMEM + 10% [Serum] FCS + 1% [Antibiotic] Gentamicin\u201d. By employing the following regular expression, the contained information is extracted and transferred into a representation of activity of type creating a mixture of molecules in solution (OBI_0000685): \n\n[\\. \\d] + \\s*% <item> ('+' [\\. \\d] + \\s*% <item>) +\nDepending on the appearance of attribution notes in the corresponding contexts (e.g., \u201c(Attributed to Susanne Staehlke)\u201d), we create separate activities following the same specification. Figure 7 contains an example activity encoding the creation of the above mixture.\n\nPreparing ELN protocol template \nELN protocols encode instructions (i.e., lists of activities) to (re-)produce the particular research findings. This does not restrict researchers but rather provides a guideline based on earlier experiments. Specifically, they include parameters, timestamps, and the research data. Taking the first experiment of our study, which was documented as an ELN protocol, we derived a protocol template by marking all variable information as placeholders. Together with the domain experts, this generalization has been validated to allow the usage as a basis for new experiments. The main advantage for the researchers conducting experiments in the wet lab is that all parameters that need to be documented during the experiment are highlighted while the overall description of the process is already done. Thus, errors introduced from missing parameters or instructions are reduced. If, however, the documentation needs to be modified during the experimental execution, researchers can adjust the activities and description.\nThis protocol template might already be used for the documentation of identical experiments (including identical ordering of parameter variations). However, as the researchers in our use case permute the different parts of the experiment (i.e., the stimulation parameters in each experiment), the templates were further split up in individual steps. For the use case at hand, we identified the following four parts: (i) Preparation, (ii) Fluo-3 Staining, (iii) Ca-imaging with Stimulation, and (iv) Ca-imaging without Stimulation. Figure 4 illustrates the template for the approach using electrical stimulation. Placeholders that will be replaced with specific parameter values during an experiment are marked with orange background color. These templates can be re-combined and used to encode new experiments. A protocol template, therefore, can be interpreted as a combination of templates which themselves are combinations of activities in a textually structured description. In consequence, an ELN protocol represents a completed protocol template with actual parameters.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 4. Template transferred from an ELN protocol section by highlighting parameters (marked with orange background color). The template contains the preparation and microscoping of a sample with stimulation. Note that this template aims at supporting researchers during their documentation, but the semantic translation approach is more general.\n\n\n\nBundling research data and re-use \nThe structure-based approach automatically translates the ELN protocol into a semantic representation of the activities and resources involved in the production of the research data. In order to combine this semantic representation (i.e., the documentation) with the research data, we employ the RO-Crate format. The RO-Crate bundle consists of the semantic model in a JSON-LD file ro-crate-metadata.json, the research data files, and a human-readable copy of the original ELN protocol and the inventory item description as HTML files.\nBy using the resulting RO-Crates for our use case, we answer the raised provenance questions. Therefore, we load all semantic representations from the RO-Crates into a linked data server with a SPARQL endpoint. In this study, we use Apache Jena Fuseki (v4.1.0)[54] for this purpose.\nAn advantage of the semantic representation of the research data documentation is its machine interpretability. This enables the comparison of the experimental processes with respect to similarities and potential differences that may have influenced the final result. This includes the particular execution times, but also omitted or additional steps as well as different parameter combinations. Furthermore, influences of the order of the different parts can easily be investigated (W7).\n\nResults \nFirst, we present the details of the manually engineered semantic representation of the Ca-imaging procedure which served as (i) a proof of concept for the effectiveness of retrospective provenance documentation from ELN protocols, (ii) a basis for analysis of the ELN protocol structure, and (iii) the development of the protocol template for research guidance. Second, details of the structure-based semantic translation for the seven Ca-imaging protocols with stimulation are given. Finally, we present the results of the evaluation of the RO-Crate bundles.\n\nManually engineered model \nThe semantic representation of the Ca-imaging procedure is based on the upper-level ontology BFO. In addition, PROV-O[25] is used for retrospective provenance documentation of the experimental results. Table 1 lists the most important ontologies used in the model. For the representation, an artifact-based modelling approach was selected, where artifacts are central to the model and are used to connect activities via their corresponding input and output relations. In total, the protocol as well as the inventory items are represented in about 80 resources of 46 types connected by almost 20 distinct predicates from 13 vocabularies.\n\n\n\n\n\n\n\nTable 1. Ontologies selected for the manually engineered model. Upper rows list general ontologies, while the lower rows list domain-specific ontologies for resources and activities.\n\n\nName\n\nSource\n\nDetails\n\n\nBFO\n\nSmith et al.[28]\n\nBasic Formal Ontology\n\n\nPROV-O\n\nMoreau et al.[25]\n\nPROV Ontology\n\n\nBTO\n\nGremse et al.[55]\n\nBRENDA Tissue Ontology\n\n\nCHEBI\n\nDegtyarenko et al.[56]\n\nChemical Entities of Biological Interest Ontology\n\n\nCLO\n\nSarntivijai et al.[57]\n\nCell Line Ontology\n\n\nOBI\n\nBandrowski et al.[58]\n\nOntology for Biomedical Investigations\n\n\nFOAF\n\nBrickley and Miller[59]\n\nPeople and their web information\n\n\n\nAll inventory items that were mentioned as resources in the protocol were represented by instances of the corresponding ontology classes (ABox statements), which is exemplified in the following by use of the MG-63 cell line. The manually engineered representation, as well as the corresponding inventory database description, are illustrated in Figs. 5 and 3, respectively.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 5. Graphical representation of the manually engineered semantic model of the MG-63 cell line used in the protocol. (See Schr\u00f6der et al.[8])\n\n\n\nIn the ELN protocol, a passage with number 25 of the originally supplied MG-63 cells with lot number 57840088 was used, i.e., \u201c[Cell line] MG-63 P25 LOT 57840088\u201d.[b] This is modelled by using multiple instances of the corresponding class MG-63 cell (CLO_0007699), which are connected with the relation is_passage_of. The passage information are annotated using the attribute passage situation (CLO_0051628). Lot numbers are represented as an instance of lot number (IAO_0000132) and connected to the cell instances using the newly defined relation has_lot_number. The creation of a cell passage is attributed to a researcher using the relation wasAttributedTo (prov:wasAttributedTo). Finally, the supplier is an instance of class Organization (prov:Organization) and related to the cells using has_supplier (OBI_0000647).\nThe modelling of the ELN protocol can be summarized as the creation of instances of activity classes that require their individual input entities and often produce an output entity which serves as an input for the subsequent activity (artifact-based modelling). Examples of atomic activities and their corresponding activity classes include washing (OBI_0302888), creating a mixture of molecules in solution (OBI_0000685), or cell line cell culturing (CLO_0000000 . The relations that are used to connect the entities to the activities are modelled in the corresponding ontology and depend on the actual activity class. Additionally, these processes are also of type Activity (prov:Activity) in order to encode general provenance information.\nThis modelling approach was employed for the entire ELN protocol. However, the most interesting part when it comes to the provenance documentation of research data is the activity, which produces or uses the research data. The upper part in Fig. 6 illustrates the documentation from the ELN protocol relevant for the research data generation: the first two steps describe the creation of the data while the last step contains the details about the actual analysis.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 6. Graphical representation of the semantic model describing the data recording (see also Fig. 5). (See Schr\u00f6der et al.[8])\n\n\n\nStructure-based model \nFor the structure-based model, an activity-based modelling approach was used to resemble the textual structure of the ELN protocol. For this purpose, the model was build upon the general purpose ontologies RO-Crate, PROV-O, and BFO. In total, for the representation of the seven protocols and their corresponding inventory items, 1935 resources of 18 types connected by 36 distinct predicates from seven vocabularies were used.\nThe structural hierarchy of the activities was represented by bfo:hasPart, while the sequential order was represented by wasInformedBy (prov:wasInformedBy). Figure 7 illustrates this structure. For each activity, the general types Action, prov:Activity, and bfo:process were used. Further links to external ontologies were added by owl:sameAs, for instance \u201cwash\u201d was augmented by washing (OBI_0302888).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 7. Graphical representation of an excerpt of the semantic model that was created semi-automatically.\n\n\n\nThe RO-Crate\u2019s root data entity that describes the research data is required to be an entity of type Dataset (schema:Dataset). Thus, research data files are added to this dataset by hasPart (schema:hasPart). The connection of these file entities and the hierarchical structure of the activities is represented by wasGeneratedBy (prov:wasGeneratedBy) (see the right part of Fig. 7), when mentioned in the activities\u2019 textual description. This means that all files are included in this root data entity (via hasPart), but are not necessarily associated to the activities, if they are not mentioned.\nFollowing the RO-Crate specification, ELN inventory database items are encoded as the domain-independent type IndividualProduct as they provide contextual information. However, the ontological knowledge about the type of the biological and chemical resource was added using the relation owl:sameAs by the external references from the description in the ELN. The resulting entity is connected to the activities using used (prov:used). Resources with a specific passage or lot number are added as individual entities connected to a general entity encoding the inventory database item using the relation is_instance_of. Furthermore, attributes has_passage_number and has_lot_number are added with their corresponding information.\nSeveral mixtures are used in the ELN protocols. This information is modelled around the activity creating a mixture of molecules in solution (OBI_0000685). All resources that are used in this activity are linked by has_specified_input (OBI_0000293) and the resulting mixture entity by has_specified_output (OBI_0000299). To specify the recipe of this mixture, a material combination objective (OBI_0000686) is created and linked to the activity using achieves_planned_objective (OBI_0000417). If an attribution of this mixture is annotated in the ELN protocol, the corresponding agent is associated with the resulting mixture entity via wasAttributedTo. Note that recipes of a mixture are independent of the actual creation activity, i.e., if multiple researchers create a mixture using the same recipe, the same recipe entity is referenced, but individual activities and mixture entities are created.\nWith respect to parameters, we extracted values and units for the following types: (i) time and duration (min and ms), (ii) temperature (\u2218Celsius), (iii) frequency (Hz), and (iv) voltage (V) and represented by their corresponding classes. Specifically, the frequency and the voltage are of interest as they provide the parameters for the stimulation of the cells during the Ca-imaging approach.\n\nELN protocols and protocol template \nBy providing templates for the individual parts of the experiment (preparation, Fluo-3 staining, Ca-imaging with and without stimulation), the researchers were able to compile seven ELN protocols with different permutations of the experiment parameters. In comparison to the predefined protocol template, we observed that the researchers further modified the ELN protocol description to reflect the particular course of activities and observations conducted in the wet lab, e.g., the repetition of an experimental setting due to issues in the previous experiment or the documentation of issues during the experiment. That means the model represents such deviations from the original plan (prospective provenance) and allows for tracking the actually documented activity sequence by means of retrospective provenance.\n\nResearch data bundles \nIn summary, seven RO-Crates have been created, one for each ELN protocol of the Ca-imaging experiments with stimulation. The corresponding semantic representation was automatically created using the structure-based approach. All research data that was produced in a particular experiment, together with this semantic representation, was bundled in the RO-Crate. In order to foster readability, a copy of the ELN protocol and the inventory items' description was included in the form of HTML files. Thus, the RO-Crates contain between 110 and 135 files and are between 107 and 185 MB large. The particular ELN protocols are encoded in models of 2,174 to 2,553 triples with 15,823 triples in total. As some triples\u2014such as researchers, institutions, and resources\u2014are identical across all RO-Crates, the number of unique triples is only 13,490. The number of triples per protocol differ due to deviations in the documentation from the original plan and the number of research files.\nThe structure-based approach employs RO-Crate, PROV-O, and BFO as upper level ontologies. Especially RO-Crate and PROV-O are designed to encode provenance information about resources. Provenance information about experimenter, manufacturer, biological and chemical resources, activities, and research data are transferred by this approach into a semantic representation. To illustrate the capabilities of the resulting RO-Crate bundles, we evaluated SPARQL queries for the W7 questions in our use case. Considering the question \u201cHow was a particular file created?\u201d (W3), Fig. 8 presents the corresponding SPARQL query for a Ca-imaging approach in a particular experiment. Table 2 illustrates an excerpt of the result of this query, i.e., the sequence of activities from one experiment, providing the result to the question W3. That is, for every atomic activity within the Ca-imaging approach, the description as well as the created research data are listed in the order of the execution. Moreover, all resources and equipment (W2), as well as the parameters, are depicted as a result of the query.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 8. This SPARQL query selects (1) the ontological activity classes, (2) the research data produced, (3) the resources and equipment that is used, and (4) the parameters for each atomic activity order by their execution in a Ca-imaging approach, with stimulation from one of the use case ELN protocols that have been translated using the structure-based modelling approach.\n\n\n\n\n\n\n\n\n\nTable 2. An excerpt of the resulting output for the SPARQL query in Fig. 8.\n\n\nActivity\n\nText\n\nAct.-Class\n\nResources\n\nFiles\n\nPar.-Units\n\nPar.-Values\n\n\n[...]\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nap_1_with_stimulation\/14\n\nplace [Device] IonOptix 12 well plate chamber electrodes on plate\n\nobo:NCIT_C52253\n\nIonOptix 12 well plate chamber\n\n\n\n\n\n\n\n\nap_1_with_stimulation\/15\n\nincubate for 10min with stimulation in LSM hood: [...]\n\nobo:OMIT_0005807, obo:OBI_0001007, obo:OBI_0302893\n\nLSM780, ZEN 2011 (black edition)\n\nData\/02_Zeitserie-Stimulation_5V_7.9Hz.czi\n\nobo:UO_0000031, obo:UO_0000028, obo:UO_0000218, obo:UO_0000106\n\n5, 10, 7.9\n\n\n[...]\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nBeside queries for individual experiments, the semantic models enable the comparison of the documentation of multiple experiments. As an example, we consider the question \u201cWhat was the order of the stimulation parameters in a particular experiment?\u201d (W7) that should be answered for seven experiments. Figure 9 illustrates the query for the comparison of multiple experiments based on the order of their stimulation parameters. The corresponding results are shown in Table 3.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 9. This SPARQL query selects all experiments following the Ca-imaging procedure and collects their stimulation parameters in the order that they have been investigated.\n\n\n\n\n\n\n\n\n\nTable 3. The result for the SPARQL query in Fig. 9 illustrating a comparison of multiple experiments based on the order of their stimulation parameters.\n\n\nProtocol\n\nTitle\n\nStimulation parameters\n\n\neln1124\/protocol\n\nCa-imaging (with stimulation) 29.01.2021\n\n7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V\n\n\neln1042\/protocol\n\nCa-imaging (with stimulation)\n\n20Hz, 1V | 7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V\n\n\neln1021\/protocol\n\nCa-imaging (with stimulation)\n\n20Hz, 1V | 20Hz, 5V | 7.9Hz, 5V | 7.9Hz, 1V\n\n\neln1022\/protocol\n\nCa-imaging (with stimulation)\n\n7.9Hz, 5V | 7.9Hz, 1V | 20Hz, 1V | 20Hz, 5V | 7.9Hz, 5V\n\n\neln1023\/protocol\n\nCa-imaging (with stimulation) Failed (durch ATP Zugabe hat sich der Bildausschnitt ver\u00e4ndert)\n\n7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V\n\n\neln942\/protocol\n\nCa-imaging (with stimulation)\n\n7.9Hz, 5V | 7.9Hz, 1V | 20Hz, 1V | 20Hz, 5V\n\n\neln1071\/protocol\n\nCa-imaging (with stimulation) 22.01.2021\n\n7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V | 7.9Hz, 1V\n\n\n\nThe remaining W7 questions could also be validated based on similar queries, as shown in the appendix of this paper. Thus, the proposed approach demonstrates the feasibility of research data documentation using ELN protocols.\n\nDiscussion \nThe results of the manual modelling show that it is feasible to translate the information of an ELN protocol into a semantic representation for documentation of retrospective provenance of research data. Moreover, it has been shown that the creation of ready-to-publish bundles containing the research data, the associated metadata and the retrospective provenance documentation by using of RO-Crate enables to answer questions about the experimental procedure raising the research data. The manually engineered model implements an artifact-based modelling approach that uses ontological terms in full extent. Thus, the resulting representation mainly consists of a sequential list of activities and entities connected via their specific input and output relations. The level of granularity of the model corresponds in most cases to the terms used in the documentation, although existing ontologies not always provide the same level of detail for all terms. As an example, the terms \u201crelocate,\u201d \u201ctransfer,\u201d and \u201ctake out\u201d can be subsumed under moving of materials, but still have some distinct differences. Furthermore, when \u201ctake out\u201d is used in the context of a fridge or freezer, an ontological modelling additionally requires encoding of the warming up of the material. Thus, providing ontological definitions for these different situations requires much work in future ontological engineering.\nIn contrast to the manual model, the structure-based approach implements an activity-based modelling mechanism and does not use the specific input and output relations of an activity, but the same activities. As a result, the structure-based approach does not specify the particular role of the used entities. Furthermore, in the manually engineered model, the semantic representation of an entity that results from the sequential execution of activities is difficult without introducing TBox statements. The reason is that this entity needs to reflect the result of the particular activity sequence. In the structure-based approach, these entities need not be defined as the main part of the model consists of a hierarchy of activities, including the used resources. This allows the model to represent only the information that is actually contained in the textual description of the ELN protocol, without artificially introducing entities with properties that are the direct result of the activities.\nBeside the process documentation, the structure-based approach adds metadata about the mime type, the file size, and the checksum allowing to validate the integrity of the research data. This representation of the research data might be extended by additional metadata, which, however, would require the application of file-type-specific extraction methods (e.g., CZI files) or the researchers themselves to provide the information (e.g., in the form of data dictionaries for tabular data). Moreover, representing the research data itself in the same representation format as the metadata and the retrospective provenance documentation would enable further data integration and thus allow for automatic data analysis approaches.\nEmploying the structure-based approach at a large scale requires knowledge about the relation of terms from the textual description in the ELN to classes and attributes from ontologies. Here, we implemented this relation by a hard-coded mapping, for instance from verb phrases to ontology classes in the case of activities. This can also be achieved by use of a suggestion system for the researchers that proposes ontological classes selected from automated queries of ontological databases. Similarly, the external identifier might be augmented. The structure-based approach currently integrates the Open Researcher and Contributor ID (ORCID) and Research Organization Registry (ROR) for persons and organizations, respectively, and it also uses references to Wikidata entities. Several initiatives proposed the use of persistent identifiers for other aspects of wet lab experiments, e.g., RRIDs can be used to reference scientific resources similar to the inventory database of the ELN.[10] While using persistent identifiers, we observed two aspects that are crucial:\n\nThe granularity of the entity referenced by the identifier needs to be on the same level as that needed for the application. As an example, the organization referenced by the Research Organization Registry (ROR)[60] not reflect the particular department that the researchers are affiliated.\nThe entity referenced by the identifier needs to reflect evolution, too. Although the identifier should reference a particular version of an entity, the entity behind might change and, thus, the registry needs to encode these versions and provide corresponding identifier for each version. To the best of our knowledge, this is currently not supported by, e.g., RRIDs.\nA fine-grained solution for referencing researchers, organizations, and research projects on an institutional level might be implemented by organizational information systems.\nAnother important aspect is related to privacy protection, for instance, the names of all involved persons in an experiment. While for archival purposes the identity of all involved persons are of interest, it might not be wanted to publish all personal details with respect to privacy protection. The structured representation of the RO-Crate allows all involved persons (W1) to perform queries and thus would directly allow for easy implementation of pseudonymization via graph update operations.\nWith respect to the recent advances in information extraction, we employed basic methods. While this does not extract all information of interest, it sketches the potential benefits of automatic text analysis. By employing more sophisticated information extraction methods, for instance, training on labelled published protocols[61], this could further be improved. This is also true for the extraction of parameters and their assignment to activities, as can be seen by recently established NLP challenges such as MeasEval.[62] Moreover, disambiguating detected terms with respect to their context and linking them to the corresponding ontology classes is one of the core challenges in modern NLP.\nWith respect to the completeness of the documentation of wet lab experiments, minimal information guidelines provide a reference that can potentially be exploited to create protocol templates. In combination with the proposed structure-based approach, this would allow deployment of minimum information checklists using the Minim model[63] to enable the validation of the generated documentation.\nDuring the use of ELNs for a longer period of time, inventory database items are regularly updated, because e.g., the supplier changes and the software or the firmware of a device is updated. Evolution provenance methods can be employed to represent such changes. In order to reflect these versions also for the research data in the RO-Crate, a data storage solution with versioning is needed. Intra-consortia sharing platforms[64] can be employed for this purpose.\nOverall, we have shown that our approach is able to help generate increasingly FAIR data. The ELN Protocols captured, together with the data entries in the RO-Crate format, increase the findability of data produced in wet lab experiments, creating a binding between experiment steps and data. Likewise, the approach increases accessibility by allowing rich SPARQL queries to be formulated that combine the experiment metadata with the data itself. In terms of interoperability and reusability, the use of common ontologies allows for different experiment runs to be easily compared and documentation to be more easily generated. However, as noted by Mons et al.[65], making FAIR data is not an absolute but a spectrum where there are trade-offs in terms of ability to find and reuse and the effort in documentation. Our approach illustrates this by highlighting the differences between automated capture and manual capture. In particular, while automated capture reduces the burden in capturing FAIR data, it also means, for the time being, the decrease in the richness of the associated metadata needed for reusability. Having a target in terms of manual capture provides a valuable target for automated capture of metadata for the data produced in the wet lab.\n\nConclusion \nThe presented study investigated the feasibility of creating semantic provenance documentation for research data using ELN protocols from wet-lab experiments. ELN protocols contain specific information about an experiment such as the produced research data but also timestamps, lot and passage number as well as parameters. This is in contrast to templates that serve as general guidelines without such information.\nThe manually engineered model was used as a proof of concept for the translation of ELN protocols using a Ca-imaging experiment. In order to support researchers in the wet lab, we derived four templates encoding parts of this initial protocol that can be used to create new experiment documentation. Based on these results, a structure-based approach was implemented to translate these protocols into a semantic representation. This approach uses the structure in the description, including headings, tables, and links, as well as some basic text analysis. Furthermore, the resulting semantic model is bundled together with the research data. Potential provenance questions from the viewpoint of other researchers using these bundles have been implemented as SPARQL queries in order to evaluate the proposed methodology. We have shown that the structure-based approach, in combination with RO-Crate bundling, can be used to successfully document research data based on the description in the form of ELN protocols. Thus, these RO-Crates enable the sharing, publication, and archiving of the research data in terms of the FAIR principles.[1][2] Furthermore, in order to guide researchers during the conduction of Ca-imaging experiments, the four derived sub-templates can be combined to provide a documentation basis for new experiments.\nIntegrating the proposed approach, as well as the sketched extensions, into a comprehensive virtual research environment (VRE) would enable the tracking of the entire research process and the research data from the creation of a hypothesis to the publication of the data. In particular, the ELN can be used for the documentation of the wet lab investigation of a research project. The funding information of the research projects, including involved researchers and the consortia, can be stored in a research information system. Furthermore, the semantic representation of the protocol can be automatically synced with a linked data server, and the research data be stored in an institutional repository. The particular platforms can be connected with a semantic search interface for researchers that enables searching for similar experiments and data, as well as creating reports about experimental activities.\n\nAppendix \nQueries and answers for the W7 questions \nNote that for better readability, we shortened URIs in some of the following results, e.g., https:\/\/eln-provenance.elaine.uni-rostock.de\/942\/approach_1_with_stimulation\/1 has been shortened to ap_1_with_stimulation\/1, and http:\/\/localhost:3030\/Data\/02_Zeitserie-Stimulation_5V_7.9Hz.czi has been shortened to 02_Zeitserie-Stimulation_5V_7.9Hz.czi.\n\r\n\nW1: Who participated in the study?\n\n\n\n\n\n\n\n\n\nExperimentalist\n\nInvolved persons\n\n\nSusanne Staehlke\n\nPerson1 Anonymous, Person2 Anonymous\n\n\n\nNote that before publication, we pseudonymized some researchers with respect to privacy protection. Refer to the Discussion section for more details.\n\r\n\nW2: Which biological and chemical resources and which equipment was used in the study?\n\n\n\n\n\n\n\n\n\nActivity\n\nUsed resources\n\n# of previous steps\n\n\nap_1_with_stimulation\/1\n\nTube: 10ml\n\n0\n\n\nap_1_with_stimulation\/2\n\nPBS without Ca\/Mg\n\n1\n\n\nap_1_with_stimulation\/3\n\nEppendorf Centrifuge\n\n2\n\n\nap_1_with_stimulation\/4\n\n\n\n3\n\n\nap_1_with_stimulation\/5\n\n50% HEPES I (isotonic) + 50% HEPES II (hypotonic)\n\n4\n\n\nap_1_with_stimulation\/6\n\nFluo-3\/AM\n\n5\n\n\nap_1_with_stimulation\/7\n\nEppendorf Thermomixer C (incubation shaker)\n\n6\n\n\nap_1_with_stimulation\/8\n\nLSM780, IonOptix 12 well plate chamber, IonOptix C-Pace EM\n\n7\n\n\nap_1_with_stimulation\/9\n\nEppendorf Centrifuge\n\n8\n\n\nap_1_with_stimulation\/10\n\n\n\n9\n\n\nap_1_with_stimulation\/11\n\nHEPES I (isotonic)\n\n10\n\n\nap_1_with_stimulation\/12\n\n12 well plate, PBS without Ca\/Mg\n\n11\n\n\nap_1_with_stimulation\/13\n\nHEPES I (isotonic)\n\n12\n\n\nap_1_with_stimulation\/14\n\nIonOptix 12 well plate chamber\n\n13\n\n\nap_1_with_stimulation\/15\n\nLSM780, ZEN 2011 (black edition)\n\n14\n\n\nap_1_with_stimulation\/16\n\nIonOptix 12 well plate chamber\n\n15\n\n\nap_1_with_stimulation\/17\n\nLSM780,ATP, ZEN 2011 (black edition)\n\n16\n\n\n\n\r\n\nW3: How was a particular file created?\n\n\n\n\n\n\n\n\n\nFile\n\nActivity\n\nProtocol\n\n\nData\/02_Zeitserie-Stimulation_5V_7.9Hz.czi\n\neln942:ap_1_with_stimulation\/15\n\neln942:protocol\n\n\n\n\r\n\nW4: When was an activity conducted?\n\n\n\n\n\n\n\n\n\nActivity\n\nStarting time\n\n# of previous steps\n\n\nap_1_with_stimulation\/1\n\n09:00:00\n\n0\n\n\nap_1_with_stimulation\/2\n\nimmediately afterwards\n\n1\n\n\nap_1_with_stimulation\/3\n\n09:01:00\n\n2\n\n\nap_1_with_stimulation\/4\n\n09:06:00\n\n3\n\n\nap_1_with_stimulation\/5\n\nimmediately afterwards\n\n4\n\n\nap_1_with_stimulation\/6\n\nimmediately afterwards\n\n5\n\n\nap_1_with_stimulation\/7\n\n09:10:00\n\n6\n\n\nap_1_with_stimulation\/8\n\nimmediately afterwards\n\n7\n\n\nap_1_with_stimulation\/9\n\n09:40:00\n\n8\n\n\nap_1_with_stimulation\/10\n\n09:45:00\n\n9\n\n\nap_1_with_stimulation\/11\n\n\n\n10\n\n\nap_1_with_stimulation\/12\n\nimmediately afterwards\n\n11\n\n\nap_1_with_stimulation\/13\n\nimmediately afterwards\n\n12\n\n\nap_1_with_stimulation\/14\n\nimmediately afterwards\n\n13\n\n\nap_1_with_stimulation\/15\n\n09:50:00\n\n14\n\n\nap_1_with_stimulation\/16\n\n10:00:00\n\n15\n\n\nap_1_with_stimulation\/17\n\nimmediately afterwards\n\n16\n\n\n\n\r\n\nW5: When was the experiment done?\n\n\n\n\n\n\n\n\n\nTemplate\n\nProtocol\n\nObjective\n\n\nCa-imaging\n\neln1023\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln1021\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln942\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln1071\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln1042\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln1124\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\nCa-imaging\n\neln1022\/protocol\n\nIntracellular calcium dynamic caused by electric fields\n\n\n\n\r\n\nW6: Where was the experiment conducted?\n\n\n\n\n\n\n\n\n\nOrganization\n\n\nUniversity Medical Center Rostock\n\n\n\nNote that the granularity of external identifiers is not always sufficient, e.g., the researchers and the equipment are affiliated in the \u201cDepartment of Cell Biology,\u201d which is part of the \u201cUniversity Medical Center Rostock.\u201d See the discussion on this issue in the Discussion section.\n\nAbbreviations \nBFO: Basic Formal Ontology\nDCAT: Data Catalog Vocabulary\nDDI: Data Documentation Initiative\nELN: Electronic Laboratory Notebook\nEXACT2: EXperimental ACTions\nFAIR: Findable, Accessible, Interoperable, and Reuseable\nKG: Knowledge Graph\nKGC: Knowledge Graph Cell\nMIACA: Minimum Information About a Cellular Assay\nNLP: Natural Language Processing\nOBO: Open Biological and Biomedical Ontology\nOCFL: Oxford Common File Layout\nOPM: Open Provenance Model\nORCID: Open Researcher and Contributor ID\nPAV: Provenance, Authoring and Versioning\nPROV-O: PROV Ontology\nREPRODUCE-ME: Reproduce Microscopy Experiments\nRO-Crate: Research Object Crate\nROR: Research Organization Registry\nRRID: Research Resource Identifiers\nSMART Protocols: SeMAntic RepresenTation for Experimental Protocols\nSOP: Standard Operating Procedure\nUO: Units Ontology\nVRE: Virtual Research Environment\n\nFootnotes \n\n\n\u2191 A lot number is an identifier for a particular set of materials produced by one manufacturer. Thus, lot numbers enable to track information about the provenance of these material productions. \n\n\u2191 Note that this is not part of the inventory item description, as this aims at the general cell specification. However, the particular information for a specific experiment are part of the ELN protocol. \n\n\nAcknowledgements \nWe thank Tazin Hossain for her help with the prototypical implementation of parts of the structure-based approach.\n\nAuthor contributions \nAuthor contributions according to CRediT: MS: Conceptualization, Data curation, Methodology, Investigation, Software, Writing. SSt: Resources, Data curation. PG: Methodology, Writing. JBN: Resources, Funding acquisition. SSp: Funding acquisition, Supervision. FK: Conceptualization, Methodology, Writing, Funding acquisition, Supervision. All authors read and approved the final manuscript.\n\nFunding \nFunded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) \u2013 SFB 1270\/1 - 299150580. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results. Open Access funding enabled and organized by Projekt DEAL.\n\nAvailability of data and materials \nThe manually engineered model is published at GitHub. The results of the structure-based modelling approach and the research data are published as RO-Crates bundles. The source that builds the model based on the ELN API is available here. This study is based on the previously published data by Staehlke and Nebe.[66]\n\nCompeting interests \nThe authors declare that they have no competing interests.\n\nReferences \n\n\n\u2191 1.0 1.1 1.2 Wilkinson, Mark D.; Dumontier, Michel; Aalbersberg, IJsbrand Jan; Appleton, Gabrielle; Axton, Myles; Baak, Arie; Blomberg, Niklas; Boiten, Jan-Willem et al. (1 December 2016). \"The FAIR Guiding Principles for scientific data management and stewardship\" (in en). 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A lightweight approach to research object data packaging. doi:10.5281\/ZENODO.3250687. https:\/\/zenodo.org\/record\/3250687 .   \n \n\n\u2191 Chard, Kyle; Gaffney, Niall; Jones, Matthew B.; Kowalik, Kacper; Ludascher, Bertram; McPhillips, Timothy; Nabrzyski, Jarek; Stodden, Victoria et al. (1 September 2019). \"Application of BagIt-Serialized Research Object Bundles for Packaging and Re-Execution of Computational Analyses\". 2019 15th International Conference on eScience (eScience) (San Diego, CA, USA: IEEE): 514\u2013521. doi:10.1109\/eScience.2019.00068. ISBN 978-1-7281-2451-3. https:\/\/ieeexplore.ieee.org\/document\/9041738\/ .   \n \n\n\u2191 Musen, Mark A. (16 June 2015). \"The prot\u00e9g\u00e9 project: a look back and a look forward\" (in en). AI Matters 1 (4): 4\u201312. doi:10.1145\/2757001.2757003. ISSN 2372-3483. PMC PMC4883684. PMID 27239556. https:\/\/dl.acm.org\/doi\/10.1145\/2757001.2757003 .   \n \n\n\u2191 National Center for Biomedical Ontology (2021). \"BioPortal\". Board of Trustees of Leland Stanford Junior University. https:\/\/bioportal.bioontology.org\/ .   \n \n\n\u2191 Ong, Edison; Xiang, Zuoshuang; Zhao, Bin; Liu, Yue; Lin, Yu; Zheng, Jie; Mungall, Chris; Courtot, M\u00e9lanie et al. (4 January 2017). \"Ontobee: A linked ontology data server to support ontology term dereferencing, linkage, query and integration\". Nucleic Acids Research 45 (D1): D347\u2013D352. doi:10.1093\/nar\/gkw918. ISSN 1362-4962. PMC 5210626. PMID 27733503. https:\/\/pubmed.ncbi.nlm.nih.gov\/27733503 .   \n \n\n\u2191 Vrande\u010di\u0107, Denny; Kr\u00f6tzsch, Markus (23 September 2014). \"Wikidata: a free collaborative knowledgebase\" (in en). Communications of the ACM 57 (10): 78\u201385. doi:10.1145\/2629489. ISSN 0001-0782. https:\/\/dl.acm.org\/doi\/10.1145\/2629489 .   \n \n\n\u2191 Hyland, B.; Atemezing, G.; Pendleton, M. et al., ed. (27 June 2013). \"Linked Data Glossary\". W3C. https:\/\/dvcs.w3.org\/hg\/gld\/raw-file\/default\/glossary\/index.html .   \n \n\n\u2191 Heath, Tom; Bizer, Christian (9 February 2011). \"Linked Data: Evolving the Web into a Global Data Space\" (in en). Synthesis Lectures on the Semantic Web: Theory and Technology 1 (1): 1\u2013136. doi:10.2200\/S00334ED1V01Y201102WBE001. ISSN 2160-4711. http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00334ED1V01Y201102WBE001 .   \n \n\n\u2191 Gkoutos, G. V.; Schofield, P. N.; Hoehndorf, R. (10 October 2012). \"The Units Ontology: a tool for integrating units of measurement in science\" (in en). Database 2012 (0): bas033\u2013bas033. doi:10.1093\/database\/bas033. ISSN 1758-0463. PMC PMC3468815. PMID 23060432. https:\/\/academic.oup.com\/database\/article-lookup\/doi\/10.1093\/database\/bas033 .   \n \n\n\u2191 The Apache Software Foundation (2021). \"Apache Jena Fuseki\". https:\/\/jena.apache.org\/documentation\/fuseki2\/index.html .   \n \n\n\u2191 Gremse, M.; Chang, A.; Schomburg, I.; Grote, A.; Scheer, M.; Ebeling, C.; Schomburg, D. (1 January 2011). \"The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources\" (in en). Nucleic Acids Research 39 (Database): D507\u2013D513. doi:10.1093\/nar\/gkq968. ISSN 0305-1048. PMC PMC3013802. PMID 21030441. https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkq968 .   \n \n\n\u2191 Degtyarenko, K.; de Matos, P.; Ennis, M.; Hastings, J.; Zbinden, M.; McNaught, A.; Alcantara, R.; Darsow, M. et al. (23 December 2007). \"ChEBI: a database and ontology for chemical entities of biological interest\" (in en). Nucleic Acids Research 36 (Database): D344\u2013D350. doi:10.1093\/nar\/gkm791. ISSN 0305-1048. PMC PMC2238832. PMID 17932057. https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkm791 .   \n \n\n\u2191 Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Meehan, Terrence F; Diehl, Alexander D; Vempati, Uma D; Sch\u00fcrer, Stephan C; Pang, Chao et al. (2014). \"CLO: The cell line ontology\" (in en). Journal of Biomedical Semantics 5 (1): 37. doi:10.1186\/2041-1480-5-37. ISSN 2041-1480. PMC PMC4387853. PMID 25852852. http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-5-37 .   \n \n\n\u2191 Bandrowski, Anita; Brinkman, Ryan; Brochhausen, Mathias; Brush, Matthew H.; Bug, Bill; Chibucos, Marcus C.; Clancy, Kevin; Courtot, M\u00e9lanie et al. (29 April 2016). Xue, Yu. ed. \"The Ontology for Biomedical Investigations\" (in en). PLOS ONE 11 (4): e0154556. doi:10.1371\/journal.pone.0154556. ISSN 1932-6203. PMC PMC4851331. PMID 27128319. https:\/\/dx.plos.org\/10.1371\/journal.pone.0154556 .   \n \n\n\u2191 Brickley, D.; Miller, L. (14 January 2014). \"FOAF Vocabulary Specification 0.99\". xmlns.com. http:\/\/xmlns.com\/foaf\/spec\/ .   \n \n\n\u2191 Conlon, M. (2021). \"Research Organization Registry\". https:\/\/ror.org\/ .   \n \n\n\u2191 Kulkarni, Chaitanya; Xu, Wei; Ritter, Alan; Machiraju, Raghu (2018). \"An Annotated Corpus for Machine Reading of Instructions in Wet Lab Protocols\" (in en). Proceedings of the 2018 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies, Volume 2 (Short Papers) (New Orleans, Louisiana: Association for Computational Linguistics): 97\u2013106. doi:10.18653\/v1\/N18-2016. http:\/\/aclweb.org\/anthology\/N18-2016 .   \n \n\n\u2191 Harper, C.; Cox, J.; Daniel, R. et al. (1 February 2021). \"Welcome to MeasEval: Counts and Measurements!\". CodaLab. https:\/\/competitions.codalab.org\/competitions\/25770 .   \n \n\n\u2191 Soiland-Reyes, S.; Klyne, G. (17 October 2017). \"Minim model for defining checklists\". RO-manager on GitHub. https:\/\/github.com\/wf4ever\/ro-manager\/blob\/master\/Minim\/Minim-description.md .   \n \n\n\u2191 Schr\u00f6der, Max; LeBlanc, Hayley; Spors, Sascha; Kr\u00fcger, Frank (25 February 2020). \"Intra-consortia data sharing platforms for interdisciplinary collaborative research projects\" (in en). it - Information Technology 62 (1): 19\u201328. doi:10.1515\/itit-2019-0039. ISSN 2196-7032. https:\/\/www.degruyter.com\/document\/doi\/10.1515\/itit-2019-0039\/html .   \n \n\n\u2191 Mons, Barend; Neylon, Cameron; Velterop, Jan; Dumontier, Michel; da Silva Santos, Luiz Olavo Bonino; Wilkinson, Mark D. (7 March 2017). \"Cloudy, increasingly FAIR; revisiting the FAIR Data guiding principles for the European Open Science Cloud\". Information Services & Use 37 (1): 49\u201356. doi:10.3233\/ISU-170824. https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/ISU-170824 .   \n \n\n\u2191 Staehlke, Susanne; Nebe, J. Barbara (10 June 2021), \"Research data of Calcium Imaging after electrical stimulation\" (in en), Zenodo (Zenodo), doi:10.5281\/zenodo.4923173, https:\/\/zenodo.org\/record\/4923173 . Retrieved 2022-04-01   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. To more easily differentiate footnotes from references, the original footnotes (which were numbered) were updated to use lowercase letters. Most footnotes referencing web pages were turned into proper citations.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\">https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on laboratory informaticsLIMSwiki journal articles on researchLIMSwiki journal articles on softwareNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 1 April 2022, at 17:41.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 196 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","d40238949d238978e30434ffe18aa050_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation rootpage-Journal_Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Structure-based knowledge acquisition from electronic lab notebooks for research data provenance documentation<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background<\/b>: <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_laboratory_notebook\" title=\"Electronic laboratory notebook\" class=\"wiki-link\" data-key=\"a9fbbd5e0807980106763fab31f1e72f\">Electronic laboratory notebooks<\/a> (ELNs) are used to document experiments and investigations in the wet <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">lab<\/a>. Protocols in ELNs contain a detailed description of the conducted steps, including the necessary <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> to understand the procedure and the raised research data, as well as to reproduce the research investigation. The purpose of this study is to investigate whether such ELN protocols can be used to create <a href=\"https:\/\/en.wikipedia.org\/wiki\/Semantics\" class=\"extiw wiki-link\" title=\"wikipedia:Semantics\" data-key=\"74dfd4c30b765f279ab114a98bb29fbc\">semantic<\/a> documentation of the provenance of research data by the use of <a href=\"https:\/\/www.limswiki.org\/index.php\/Ontology_(information_science)\" title=\"Ontology (information science)\" class=\"wiki-link\" data-key=\"52d0664bde4b458e81fbc128b911a4a6\">ontologies<\/a> and linked data methodologies.\n<\/p><p><b>Methods<\/b>: Based on an ELN protocol of a biomedical wet lab experiment, a retrospective <a href=\"https:\/\/en.wikipedia.org\/wiki\/Provenance#Data_provenance\" class=\"extiw wiki-link\" title=\"wikipedia:Provenance\" data-key=\"2c706c3de8d05c53bb509656143db903\">provenance model<\/a> of the raised research data describing the details of the experiment in a machine-interpretable way is manually engineered. Furthermore, an automated approach for knowledge acquisition from ELN protocols is derived from these results. This structure-based approach exploits the structure in the experiment\u2019s description\u2014such as headings, tables, and links\u2014to translate the ELN protocol into a semantic knowledge representation. To satisfy the <a href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_FAIR_Guiding_Principles_for_scientific_data_management_and_stewardship\" title=\"Journal:The FAIR Guiding Principles for scientific data management and stewardship\" class=\"wiki-link\" data-key=\"e5903ddcc7734415af1d91fcd258da90\">FAIR guiding principles<\/a> (making data findable, accessible, interoperable, and reuseable), a ready-to-publish bundle is created that contains the research data together with their semantic documentation.\n<\/p><p><b>Results<\/b>: While the manual modelling efforts serve as proof of concept by employing one protocol, the automated structure-based approach demonstrates the potential generalization with seven ELN protocols. For each of those protocols, a ready-to-publish bundle is created and, by employing the SPARQL query language, it is illustrated such that questions about the processes and the obtained research data can be answered.\n<\/p><p><b>Conclusions<\/b>: The semantic documentation of research data obtained from the ELN protocols allows for the representation of the retrospective provenance of research data in a machine-interpretable way. Research Object Crate (RO-Crate) bundles including these models enable researchers to easily share the research data, including the corresponding documentation, as well as to search and relate the experiment to each other.\n<\/p><p><b>Keywords<\/b>: research data, provenance, knowledge acquisition, electronic laboratory notebooks, semantic documentation, RO-Crate, FAIR\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Background\">Background<\/span><\/h2>\n<p>Effective reuse of research data requires comprehensive documentation of their <a href=\"https:\/\/en.wikipedia.org\/wiki\/Provenance#Data_provenance\" class=\"extiw wiki-link\" title=\"wikipedia:Provenance\" data-key=\"2c706c3de8d05c53bb509656143db903\">provenance<\/a>. Beside <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" title=\"Metadata\" class=\"wiki-link\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">metadata<\/a>, knowledge about the generating process helps others to understand research data and allows for the reproduction of research investigations. This includes not only sources of input data, such as parameters and assumptions, but also <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> about instrumentation, devices, and materials. For wet <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">lab<\/a> experiments, such knowledge is increasingly documented in <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_laboratory_notebook\" title=\"Electronic laboratory notebook\" class=\"wiki-link\" data-key=\"a9fbbd5e0807980106763fab31f1e72f\">electronic laboratory notebooks<\/a> (ELNs). The focus of these tools is on the documentation of laboratory activities that produce research data in so-called \"ELN protocols.\" In addition to this textual description, the <a href=\"https:\/\/www.limswiki.org\/index.php\/Journal:The_FAIR_Guiding_Principles_for_scientific_data_management_and_stewardship\" title=\"Journal:The FAIR Guiding Principles for scientific data management and stewardship\" class=\"wiki-link\" data-key=\"e5903ddcc7734415af1d91fcd258da90\">FAIR guiding principles<\/a><sup id=\"rdp-ebb-cite_ref-:0_1-0\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> provide general guidance on research data documentation in terms of metadata. However, they do not prescribe technical details about the implementation of such documentation.<sup id=\"rdp-ebb-cite_ref-:1_2-0\" class=\"reference\"><a href=\"#cite_note-:1-2\">[2]<\/a><\/sup>\n<\/p><p>To foster the realization of the FAIR principles for research data produced in wet lab experiments, we aim for machine-interpretable representations of experimental documentation of the process that is the origin of the data. In other words, the provenance information about the research data\u2014including the activities and involved researchers, resources, and equipment\u2014should be <a href=\"https:\/\/en.wikipedia.org\/wiki\/Semantics\" class=\"extiw wiki-link\" title=\"wikipedia:Semantics\" data-key=\"74dfd4c30b765f279ab114a98bb29fbc\">semantically<\/a> represented. For this purpose, we employ the frequently used<sup id=\"rdp-ebb-cite_ref-:2_3-0\" class=\"reference\"><a href=\"#cite_note-:2-3\">[3]<\/a><\/sup> PROV W3C recommendation<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup>, which <a href=\"https:\/\/www.limswiki.org\/index.php\/Ontology_(information_science)\" title=\"Ontology (information science)\" class=\"wiki-link\" data-key=\"52d0664bde4b458e81fbc128b911a4a6\">ontologically<\/a>, in PROV Ontology (PROV-O), defines entities, activities, and agents, as well as their relations. In particular, according to Belhajjame <i>et al.<\/i>, an entity is defined as a \u201cphysical, digital, conceptual, or other kind of thing with some fixed aspects,\"<sup id=\"rdp-ebb-cite_ref-:3_5-0\" class=\"reference\"><a href=\"#cite_note-:3-5\">[5]<\/a><\/sup> an activity as \u201csomething that occurs over a period of time and acts upon or with entities; it may include consuming, processing, transforming, modifying, relocating, using, or generating entities,\u201d<sup id=\"rdp-ebb-cite_ref-:3_5-1\" class=\"reference\"><a href=\"#cite_note-:3-5\">[5]<\/a><\/sup> and an agent as \u201csomething that bears some form of responsibility for an activity taking place, for the existence of an entity, or for another agent\u2019s activity.\u201d<sup id=\"rdp-ebb-cite_ref-:3_5-2\" class=\"reference\"><a href=\"#cite_note-:3-5\">[5]<\/a><\/sup> With respect to wet lab experiments, all biological and chemical resources\u2014as well as not only the devices and software but also the research data itself\u2014can be seen as entities; researchers conducting the experiment are the agents, and the process of research data creation consists of activities. The semantic representation of this information as a knowledge graph (KG)<sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup> can be achieved by the use of modern web technologies where the terms and their relations are defined in ontologies such as PROV-O (TBox modelling), the instances are built up in the KG (ABox modelling), and other KGs can be linked in order to create an interconnected graph of semantic knowledge.\n<\/p><p>In this paper, we aim for an automatic extraction of information from ELN protocols in order to transfer them into a semantic representation that documents the produced research data. For this purpose, we employ the documentation of Calcium imaging (Ca-imaging) experiments, originally proposed by Staehlke <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:4_7-0\" class=\"reference\"><a href=\"#cite_note-:4-7\">[7]<\/a><\/sup>, as a running example. In particular, we use ELN protocols that document the conduction of Ca-imaging experiments in order to: (i) demonstrate the feasibility of manually transferring an ELN protocol into a semantic representation encoding the provenance of research data, (ii) automate the information extraction and modelling by exploiting the structure of an ELN protocol by means of a structure-based approach, and (iii) evaluate the proposed method by answering provenance questions from the resulting bundle of research data and the corresponding semantic model.\n<\/p><p>Here, the term \"ELN protocol\" refers to the actual documentation of the wet lab experiment within an ELN and is different from the term \"protocol templates,\" which are used to encode instructions to be performed in order to conduct particular procedures or be published at <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.protocols.io\/\" target=\"_blank\">protocols.io<\/a>. While those protocol templates do encode a list of abstract instructions, they do not necessarily reflect particular research data, nor instrumentation, parameters, or other aspects to the execution-specific information. ELN protocols, in contrast, represent the documentation of the actual experiment, and the contained information is thus necessary to understand how the resulting research data was generated. This includes manufacturer-specific information about resources used in the experiment such as lot numbers.<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[a]<\/a><\/sup> Furthermore, passage numbers of the resources, the times when an activity was conducted, and the parameters used in a device, as well as the research data and the researchers conducting the experiment, are information specific to a particular experiment. Figure 1 illustrates the differences by providing an example for an ELN protocol and a protocol template.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"863a412a4e6318d07e21c138cb7d43c0\"><img alt=\"Fig1 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/20\/Fig1_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> Excerpts of an ELN protocol that represents a particular experiment including all details such as timestamps, lot numbers as well as the research data (<b>left<\/b>) and a protocol template containing general instructions of experiments without these details (<b>right<\/b>, sourced <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.17504\/protocols.io.tqfemtn\" target=\"_blank\">from here<\/a>.)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The work presented here is based on a preliminary investigation regarding the effectiveness of manually modeling ELN protocols by use of ontologies.<sup id=\"rdp-ebb-cite_ref-:5_9-0\" class=\"reference\"><a href=\"#cite_note-:5-9\">[8]<\/a><\/sup> Here, we extend this preliminary work by discussing the potential of automatic information extraction from ELN protocols by employing structural information and discussing the differences and implications of both approaches. Moreover, while the previous work only sketched the semantic representation of the wet lab experiments, here, we focus on the generation of ready-to-publish research data bundles, including the semantic description of the origin of the research data.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Use_case\">Use case<\/span><\/h2>\n<p>To demonstrate the feasibility of the proposed approach, a typical wet lab investigation was chosen as a use case. In the following, we introduce the use case and derive questions regarding the provenance of the corresponding research data.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Biomedical_wet_lab_experiments\">Biomedical wet lab experiments<\/span><\/h3>\n<p>The objective of the biomedical study was to investigate the intracellular calcium ions (Ca<sup>2+<\/sup>) dynamics by Calcium-imaging (Ca-imaging) under different settings.<sup id=\"rdp-ebb-cite_ref-:4_7-1\" class=\"reference\"><a href=\"#cite_note-:4-7\">[7]<\/a><\/sup> In particular, two different wet lab experiments were considered: (i) an investigation of the influence of different material surface conditions on Ca<sup>2+<\/sup> mobilization, and (ii) an investigation regarding the Ca<sup>2+<\/sup> dynamics under the influence of electrical stimulation. Both types of experiments involve similar activities of the researchers. In particular, each experiment employs the Ca-imaging method previously established by Staehlke <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:4_7-2\" class=\"reference\"><a href=\"#cite_note-:4-7\">[7]<\/a><\/sup> in different settings. The particular conditions, e.g., surface conditions or parameters of the electrical stimulation, are investigated within each experiment, while the order of the different variations was permuted across the experiments. That is, after a preparation phase, where all materials and devices are prepared, the same procedure, i.e., Ca-imaging, was executed for the different conditions. During the experiment, several materials and devices are employed, such as cell line passages, buffer, and microscopes.\n<\/p><p>For the purpose of this study, we asked the researchers to use an ELN for the documentation of their wet lab activities, resulting in eight ELN protocols: one for the first experiment and seven for the latter, representing different permutations of the sequential execution of Ca-imaging for different electrical stimulation parameters. In particular, <a href=\"https:\/\/www.limswiki.org\/index.php\/ELabFTW\" title=\"ELabFTW\" class=\"wiki-link\" data-key=\"155590ac366985a7ee3cf74ade1df84a\">eLabFTW<\/a> (Deltablot, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.elabftw.net\/\" target=\"_blank\">https:\/\/www.elabftw.net\/<\/a>, v3.6.7)<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[9]<\/a><\/sup>, a domain-independent ELN, was used. Figure 2 shows an excerpt of a protocol from the use case.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"3496a6b8530a1618985f6c76011811a3\"><img alt=\"Fig2 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c8\/Fig2_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> ELN protocol about a Ca-imaging experiment in the eLabFTW software. It contains general information (<b>top<\/b>), the list of activities with their starting time (<b>middle<\/b>), used inventory items, and uploaded research data (<b>bottom<\/b>).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>ELNs often provide an inventory database that allows the maintenance of materials and other research resources used during the experiments. Typically, each resource belongs to a configurable set of categories, e.g., cell lines, buffer, software, or devices. These entries in the inventory database can be linked from within the protocol when used within the corresponding experiment. Figure 3 illustrates the entry to the inventory database for the MG-63 cell line that is used in the experiments of the use case. Note that this entry is already augmented by information about ontology classes that were added during the manual model engineering process. Here, we use such ontology references but also other resource identifiers, such as Research Resource Identifiers (RRID)<sup id=\"rdp-ebb-cite_ref-RRIDPortal_11-0\" class=\"reference\"><a href=\"#cite_note-RRIDPortal-11\">[10]<\/a><\/sup>, could be used for resource reference. However, these RRIDs do not reflect different versions of the resources, e.g., when describing a software. Thus, they can be used to annotate the inventory database of the ELN similar to the ontology classes, but cannot be used on their own. Research data is attached to the ELN protocol by uploading and linking from within the textual description of the step that describes the generating activity.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"a54a685ec8dbdd0c5318b56ea9e170a5\"><img alt=\"Fig3 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/3\/38\/Fig3_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> Shortened documentation of a Ca-imaging experiment in the eLabFTW ELN software. The upper part contains general information about the investigation, followed by the list of activities with their starting time. Below, used inventory items and uploaded research data are listed.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>In summary, the execution of an individual experiment took about 4.5 hours, resulting from the preparation and the sequential executions of the Ca-imaging procedure under five different stimulation settings consisting of 15 steps for each. Each protocol referred to 22 inventory items in the database and between 85 and 110 data files of different types were generated. The different file types include (i) CZI files (developed by ZEISS) containing the microscope settings, recorded images, and raw measurement data; (ii) image files in JPEG format to illustrate particular excerpts from the video recordings; and (iii) raw measurements of the luminescence over time, in the form of XML encoded tabular data files. The latter two formats are exports from the CZI files. The provenance of all attached files needs to be documented.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Research_data_provenance\">Research data provenance<\/span><\/h3>\n<p>When considering this use case, several questions regarding the provenance of the research data can be raised. To this end, we consider questions based on the W7 provenance model<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[11]<\/a><\/sup>, that describes provenance as combinations of What, When, Where, How, Who, Which, and Why. We consider each question individually, encoding the view of a researcher that aims at re-using the research data from our use case. The questions were developed together with the domain experts and resemble actual questions that arise when considering the replication of the documented experiments.\n<\/p>\n<dl><dd><b>W1<\/b> <i>Who<\/i> participated in the study?<\/dd><\/dl>\n<dl><dd><dl><dd>With respect to the provenance of research data, all researchers contributing to the creation are of interest, i.e., we expect to get a list of all researchers and their affiliations involved in an experiment.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W2<\/b> <i>Which<\/i> biological and chemical resources and which equipment was used in the study?<\/dd><\/dl>\n<dl><dd><dl><dd>In particular, we are interested in the resources and the equipment used in an experiment, including all details such as the lot number and the passage information.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W3<\/b> <i>How<\/i> was a particular file created?<\/dd><\/dl>\n<dl><dd><dl><dd>\"What was the sequence of activities that led to the creation of a particular file\" is a question that might help other researchers in comprehending the data.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W4<\/b> <i>When<\/i> was an activity conducted?<\/dd><\/dl>\n<dl><dd><dl><dd>The date and the time point of a particular activity but also its duration are of interest. This information is useful for the planning of similar experiments, but also with respect to the comprehensibility of the results as the date and time point might influence them, e.g., due to weather or other environmental phenomena.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W5<\/b> <i>Why<\/i> was the experiment done?<\/dd><\/dl>\n<dl><dd><dl><dd>Understanding why the research data was created is crucial for their comprehensibility. We take the objective of the experiment as the reason for the creation.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W6<\/b> <i>Where<\/i> was the experiment conducted?<\/dd><\/dl>\n<dl><dd><dl><dd>The location\u2014respectively. the institution where the experiment was conducted\u2014is of interest as regional characteristics might influence the data.<\/dd><\/dl><\/dd><\/dl>\n<dl><dd><b>W7<\/b> <i>What<\/i> was the order of the stimulation parameters in a particular experiment?<\/dd><\/dl>\n<dl><dd><dl><dd>The order of the particular approaches influences the results as there might be effects from the timing of the experiments or the duration since their preparation. That means, with respect to the evaluation of the results, we are interested in this order.<\/dd><\/dl><\/dd><\/dl>\n<h2><span class=\"mw-headline\" id=\"Related_work\">Related work<\/span><\/h2>\n<p>The provenance of research data, including their research investigations, combines several research fields, ranging from general-purpose methods and standards for the documentation of provenance to specifically tailored methods and platforms for the tracking of research and other activities. In the following, we will discuss recent work within those fields and relate it to our method.\n<\/p><p>Many methods aiming at documenting the provenance of activities have already been proposed. Here, we consider the classification of provenance information following the definition of Herschel <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:6_13-0\" class=\"reference\"><a href=\"#cite_note-:6-13\">[12]<\/a><\/sup> and Lim <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:7_14-0\" class=\"reference\"><a href=\"#cite_note-:7-14\">[13]<\/a><\/sup>:\n<\/p>\n<ol><li>prospective provenance describes \u201can abstract workflow specification as a recipe for future data derivation\u201d<sup id=\"rdp-ebb-cite_ref-:7_14-1\" class=\"reference\"><a href=\"#cite_note-:7-14\">[13]<\/a><\/sup>;<\/li>\n<li>retrospective provenance documents a \u201cpast workflow execution and data derivation information, i.e., which tasks were performed and how data artifacts were derived\u201d<sup id=\"rdp-ebb-cite_ref-:7_14-2\" class=\"reference\"><a href=\"#cite_note-:7-14\">[13]<\/a><\/sup>; and<\/li>\n<li>evolution provenance illustrates \u201cthe changes made between two versions of the input\u201d<sup id=\"rdp-ebb-cite_ref-:6_13-1\" class=\"reference\"><a href=\"#cite_note-:6-13\">[12]<\/a><\/sup>, or, in other words, versions of the procedure, the data, or the parameters are reflected by evolution provenance similar to version control such as that implemented by Git for source code.<\/li><\/ol>\n<p>Applying those definitions to the use case at hand, prospective provenance allows the keeping track of changes of laboratory-specific operating procedures in general, while retrospective provenance allows the documenting of the actually executed sequence of activities that resulted in a particular set of research data. At last, evolution provenance allows the tracking of changes made to the actual ELN protocol or the inventory database items.\n<\/p><p>With respect to the research workflows to be represented by provenance modeling, two different types can be distinguished:\n<\/p>\n<ol><li><i>In-silico<\/i> studies employ computational methods for the analysis of the data. <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">Workflow<\/a> systems like Taverna<sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[14]<\/a><\/sup>, Kepler<sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[15]<\/a><\/sup>, or <a href=\"https:\/\/www.limswiki.org\/index.php\/Galaxy_(biomedical_software)\" title=\"Galaxy (biomedical software)\" class=\"wiki-link\" data-key=\"ead5d6ebaa8d67744d2f68d454d89ce6\">Galaxy<\/a><sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[16]<\/a><\/sup>, and programming environments like <a href=\"https:\/\/www.limswiki.org\/index.php\/Jupyter_Notebook\" title=\"Jupyter Notebook\" class=\"wiki-link\" data-key=\"26fd35430c10e009a142bbab5dbf617a\">Jupyter Notebook<\/a><sup id=\"rdp-ebb-cite_ref-:8_18-0\" class=\"reference\"><a href=\"#cite_note-:8-18\">[17]<\/a><\/sup> have been successfully augmented to record retrospective provenance.<\/li>\n<li>Wet lab experiments are courses of activities in a laboratory. While several approaches exist that describe prospective provenance<sup id=\"rdp-ebb-cite_ref-:9_19-0\" class=\"reference\"><a href=\"#cite_note-:9-19\">[18]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:10_20-0\" class=\"reference\"><a href=\"#cite_note-:10-20\">[19]<\/a><\/sup> by analyzing published protocols, only limited work is done on documenting retrospective provenance for these workflows.<\/li><\/ol>\n<p>More detailed information about provenance modelling and the employed methods are provided in the literature.<sup id=\"rdp-ebb-cite_ref-:2_3-1\" class=\"reference\"><a href=\"#cite_note-:2-3\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_13-2\" class=\"reference\"><a href=\"#cite_note-:6-13\">[12]<\/a><\/sup> Here, we are interested in providing detailed information about the origin of research data. Thus, we aim at providing retrospective provenance documentation of research data from ELN protocols documenting wet lab experiments.\n<\/p><p>The Smart Tea project<sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[20]<\/a><\/sup> similarly aims at the semantic metadata recording for research data from within a customized ELN. The developed ELN provides a structured graphical user interface (GUI) requiring the user to provide information for predefined variables. All information is directly transferred into a linked data representation and persistently archived with a linked data server. While this approach perfectly guides users through the sequence of activities and tracks retrospective provenance at the same time, it fails to keep track of deviations from the predefined plan. Furthermore, as the documentation is directly translated into a semantic representation, additional information that was not considered before can hardly be attached to such protocols, which restricts both the expressivity of the semantic model and the user to previously known information.\n<\/p><p>Similar to the Smart Tea project, the PROV templating approach<sup id=\"rdp-ebb-cite_ref-:11_22-0\" class=\"reference\"><a href=\"#cite_note-:11-22\">[21]<\/a><\/sup> suggests the recording of provenance information given a pre-defined provenance model. In other words, the main idea is that applications only store values for placeholders in a particular provenance model, which was shown to be more efficient than the storage of the original provenance models.<sup id=\"rdp-ebb-cite_ref-:11_22-1\" class=\"reference\"><a href=\"#cite_note-:11-22\">[21]<\/a><\/sup> This solution is very efficient if a very large number of identical provenance structures with some variable information are to be stored. If, however, the application requires more flexibility in terms of the provenance structure, the template approach does not utilize this efficiency advantage. Note that provenance templates encode a semantic representation with variables, whereas protocol templates provide guidelines for experiments.\n<\/p><p>Curcin <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[22]<\/a><\/sup> use a very similar approach for the provenance modelling in <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_decision_support_system\" title=\"Clinical decision support system\" class=\"wiki-link\" data-key=\"095141425468d057aa977016869ca37d\">diagnostic decision support systems<\/a>. A more flexible approach is the use of knowledge graph cells (KGCs), proposed by Vogt <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[23]<\/a><\/sup> They provide a concept for the definition of knowledge structures. In particular, rules including ABox and TBox expressions might be defined that allow the dynamic modification of the KG. Thus, KGCs might be used to specify potential semantic structures of ELN protocols without particular information inside. The application of KGCs would require a complete definition over all possible semantic representations of ELN protocols, which is infeasible.\n<\/p><p>With respect to the vocabulary used to semantically describe the laboratory-specific information, the EXperimental ACTions (EXACT2) ontology, together with the Natural Language Processing (NLP) framework<sup id=\"rdp-ebb-cite_ref-:9_19-1\" class=\"reference\"><a href=\"#cite_note-:9-19\">[18]<\/a><\/sup>, aims at the automatic extraction of knowledge from biomedical protocols for prospective provenance. Similarly, the SeMAntic RepresenTation for Experimental Protocols (SMART Protocols) ontology reuses EXACT2 to represent prospective provenance from published protocols.<sup id=\"rdp-ebb-cite_ref-:10_20-1\" class=\"reference\"><a href=\"#cite_note-:10-20\">[19]<\/a><\/sup> In contrast to both approaches that represent a plan, we aim at retrospective provenance, i.e., a particular course of activities. Both approaches, however, could be used to describe prospective provenance of the underlying plan of an ELN protocol, to allow the documentation of potential deviations from the original plan. The Reproduce Microscopy Experiments (REPRODUCE-ME) ontology<sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[24]<\/a><\/sup> introduces a specific vocabulary to describe retrospective provenance for microscopy experiments. Besides, the domain-independent ontologies, PROV-O and its predecessor Open Provenance Model (OPM)<sup id=\"rdp-ebb-cite_ref-:12_26-0\" class=\"reference\"><a href=\"#cite_note-:12-26\">[25]<\/a><\/sup>, are frequently employed as upper-level ontology for provenance documentation.<sup id=\"rdp-ebb-cite_ref-:2_3-2\" class=\"reference\"><a href=\"#cite_note-:2-3\">[3]<\/a><\/sup> Furthermore, many extensions for specific applications have been proposed. The Provenance, Authoring, and Versioning (PAV) ontology, for example, proposes a mechanism for the versioning and authoring of web resources<sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[26]<\/a><\/sup>, and CollabPG encodes collaborations within processes.<sup id=\"rdp-ebb-cite_ref-:2_3-3\" class=\"reference\"><a href=\"#cite_note-:2-3\">[3]<\/a><\/sup> With respect to the application domain of the use case, the Open Biological and Biomedical Ontology (OBO) Foundry is a community initiative aiming at the development and maintenance of ontologies in the biomedical domain.<sup id=\"rdp-ebb-cite_ref-:13_28-0\" class=\"reference\"><a href=\"#cite_note-:13-28\">[27]<\/a><\/sup> The Basic Formal Ontology (BFO)<sup id=\"rdp-ebb-cite_ref-:14_29-0\" class=\"reference\"><a href=\"#cite_note-:14-29\">[28]<\/a><\/sup> is the upper-level ontology that is used for each of the OBO ontologies.\n<\/p><p>For the retrospective provenance documentation of research data from computational workflows, several specifically tailored tools and approaches have been proposed in the literature. ProvBook<sup id=\"rdp-ebb-cite_ref-:8_18-1\" class=\"reference\"><a href=\"#cite_note-:8-18\">[17]<\/a><\/sup>, for instance, tracks provenance in Jupyter Notebooks that are used for literate programming. There's also Dataprov<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[29]<\/a><\/sup>, a wrapper tool producing provenance information from the execution of analysis tools, and noWorkflow<sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[30]<\/a><\/sup>, which captures provenance information from analysis scripts such as for the programming language Python. Aside from these methods, other provenance tracking approaches known as lineage retrieval<sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[31]<\/a><\/sup> or lineage tracking and workflow systems exist.<sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[32]<\/a><\/sup> In general, <i>in-silico<\/i> workflow systems not only record provenance information, but at the same time they specify the involved processing steps and enable their execution possibly on a distributed system.<sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[33]<\/a><\/sup> However, as these systems are limited to tackling computational analyses, their usage for the provenance of research data from wet lab experiments is difficult.\n<\/p><p>Regarding the completeness of the documentation with respect to reproducibility, plenty of standards exist that aim at the definition of the minimum set of information required to comprehend and reproduce the research investigation for different applications. With respect to the use case at hand, the minimum information for electrical cell stimulation<sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[34]<\/a><\/sup> and the Minimum Information About a Cellular Assay (MIACA)<sup id=\"rdp-ebb-cite_ref-MIACA_36-0\" class=\"reference\"><a href=\"#cite_note-MIACA-36\">[35]<\/a><\/sup> provide such references for the documentation. Similarly, standard operating procedures (SOPs) or published instructions for experiments encode standards for the documentation of a particular experiment.\n<\/p><p>When considering the publication or archiving of research data, metadata is important to provide additional context, enabling others (including the future self) to understand the research process and the resulting data. In particular, the FAIR guiding principles provide abstract recommendations for handling research data to enable its re-usability.<sup id=\"rdp-ebb-cite_ref-:0_1-1\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> Together with the implementation suggestions of these guidelines<sup id=\"rdp-ebb-cite_ref-:1_2-1\" class=\"reference\"><a href=\"#cite_note-:1-2\">[2]<\/a><\/sup>, they provide a framework which is also applicable for research data from wet lab experiments. While both guidelines provide generic recommendations regarding research data documentation, different standards exist that provide vocabulary for their support. Several initiatives foster the development of documentation standards for research data, including the Data Documentation Initiative (DDI) that focuses on standardizing metadata for social science datasets.<sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[36]<\/a><\/sup> The Dublin Core, instead, is a more general definition of 15 metadata elements for electronic resources.<sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[37]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[38]<\/a><\/sup> Similarly, Data Catalog Vocabulary (DCAT) provides a common vocabulary for the interoperability of data catalogs<sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[39]<\/a><\/sup> and, thus, also defines required metadata for research data. Additionally, domain-specific metadata standards have been developed. With respect to the use case, this includes metadata for microscopy images, such as that proposed by the RDM4mic Initiative.<sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[40]<\/a><\/sup> In addition to these metadata, the information inside the data file might also be described. For this purpose, codebooks and data dictionaries are employed.<sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[41]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[42]<\/a><\/sup> Considering a CSV file as an example, this includes information about each column such as the domain of the values and the unit of the measurements. This information is defined in a separate file that helps comprehend the raw data.\n<\/p><p>For the publication and archiving of this data, including the semantic documentation, several approaches have been proposed. These include bundling formats such as BagIt<sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[43]<\/a><\/sup>, Oxford Common File Layout (OCFL)<sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[44]<\/a><\/sup>, and RO-Crate<sup id=\"rdp-ebb-cite_ref-:15_46-0\" class=\"reference\"><a href=\"#cite_note-:15-46\">[45]<\/a><\/sup>, as well as literate programming methods such as using Jupyter Notebook to combine (parts of) research data, their analysis source code, and results, as well as their documentation. RO-Crate<sup id=\"rdp-ebb-cite_ref-:15_46-1\" class=\"reference\"><a href=\"#cite_note-:15-46\">[45]<\/a><\/sup> is a mechanism that allows the bundling of resources together with their associated metadata, supporting the FAIR publication and archiving of the research data. By re-using existing vocabulary such as schema.org or PROV-O, it implements a linked data approach to enable researchers to provide all information necessary to (re-)use the described research data. This includes basic properties such as author and title of the resource, a license for publication, a description of the files, and a description of the workflow used to create those files in terms of retrospective provenance, including employed software and other equipment. In brief, a RO-Crate bundle consists of the research data file and a metadata file called <tt>ro-crate-metadata.json<\/tt>, which contains structured metadata about the files and the entire bundle in a JSON-LD format. While the <tt>ro-crate-metadata.json<\/tt> contains all information in machine interpretable way, it is accompanied by a human readable HTML representation. RO-Crate has successfully been used for the documentation of retrospective provenance of <i>in-silico<\/i> studies<sup id=\"rdp-ebb-cite_ref-47\" class=\"reference\"><a href=\"#cite_note-47\">[46]<\/a><\/sup>, but can, due to the flexibility of the vocabulary, also be used for retrospective provenance of wet lab experiments.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<p>The objective of the study was to investigate whether it is possible to create semantic documentation of the research process and the resulting research data in terms of provenance. To this end, semantic documentation was manually created by analyzing the ELN protocol. To support potential automation of the semantic model creation, based on the results of this analysis, a protocol template was designed that (i) guides researchers through the process while (ii) requiring them to provide all information necessary to comprehend the origin of the research data. The resulting protocol template was split up into a set of templates that encode steps of an experiment such as the staining or the imaging with a particular set of stimulation parameters. These sub-templates ease the re-use for new experiments, e.g., by combining them in other permutations. Based on this, researchers documented their wet lab experiments, resulting in a set of ELN protocols, each of which contains variations, such as differences in parameters, execution time, or execution order. The different protocols were then automatically analyzed, translated into a semantic model, and finally bundled into self-contained archives. The following provides a detailed description of each step.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Manual_model_engineering\">Manual model engineering<\/span><\/h3>\n<p>The manual engineering process for the semantic model of the ELN protocol was comprised of iterative modelling and reviewing. Domain experts were consulted during this process in order to validate the model. The main objective of this process was to check if all information for the semantic provenance modelling are available in ELN protocols and whether they can be transferred into a semantic representation by employing existing ontologies. The aim of the resulting model was to document the provenance of the research data.\n<\/p><p>Proteg\u00e9<sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[47]<\/a><\/sup> was used for model engineering. In particular, the modelling was conducted as follows:\n<\/p>\n<ol><li>BioPortal<sup id=\"rdp-ebb-cite_ref-BioPortal_49-0\" class=\"reference\"><a href=\"#cite_note-BioPortal-49\">[48]<\/a><\/sup> and Ontobee<sup id=\"rdp-ebb-cite_ref-50\" class=\"reference\"><a href=\"#cite_note-50\">[49]<\/a><\/sup> are used to identify relevant ontologies for terms from the ELN protocol and the inventory database items.<\/li>\n<li>A set of ontologies is selected from these search results so that the coverage of terms from the ELN in a single ontology is maximized. Ontologies from the OBO Foundry<sup id=\"rdp-ebb-cite_ref-:13_28-1\" class=\"reference\"><a href=\"#cite_note-:13-28\">[27]<\/a><\/sup>, compatible with the BFO<sup id=\"rdp-ebb-cite_ref-:14_29-1\" class=\"reference\"><a href=\"#cite_note-:14-29\">[28]<\/a><\/sup>, were preferred.<\/li>\n<li>Ontology classes representing inventory database items in the ELN (see Fig. 3) are added into the ELN description of the corresponding inventory database item as a reference for the semantic modelling.<\/li>\n<li>The semantic model itself is constructed by ABox statements, i.e., the creation of instances of these classes that represent the particular entities and activities of the protocol and the inventory database. Each instance gets a unique identifier in the local namespace, reflecting the individual entity; for example, <tt>MG-63_(P25,_LOT_57840088)<\/tt> is used to encode passage 25 of the MG-63 cells that were delivered with the lot number 57840088 (see also Fig. 5). The specific input and output relations of the activity classes are used in order to connect the particular entities correspondingly.<\/li>\n<li>References to the same entities in other KGs such as Wikidata<sup id=\"rdp-ebb-cite_ref-51\" class=\"reference\"><a href=\"#cite_note-51\">[50]<\/a><\/sup> are included by employing the <tt>owl:sameAs<\/tt> relation. This is essential for linked open data according to the five-star deployment scheme proposed by Berners-Lee.<sup id=\"rdp-ebb-cite_ref-HylandLinked13_52-0\" class=\"reference\"><a href=\"#cite_note-HylandLinked13-52\">[51]<\/a><\/sup><\/li><\/ol>\n<p>The following three rules were considered during iterative modelling in order to prevent the introduction of a bias from modeller and domain experts: \n<\/p>\n<ul><li>Use ontological classes of the same granularity as the terms in the experiment documentation, e.g., \u201cwashing\u201d instead of \u201cmaterial processing.\u201d<\/li>\n<li>Avoid the introduction of new classes and attributes whenever possible (e.g., avoid TBox statements) and re-use existing ontologies.<sup id=\"rdp-ebb-cite_ref-53\" class=\"reference\"><a href=\"#cite_note-53\">[52]<\/a><\/sup><\/li>\n<li>Use only information from the ELN protocol, and do not introduce further knowledge despite the references to other KGs.<\/li><\/ul>\n<p>Thus, the semantic model serves as demonstrator for the inherent potential of ELN protocols.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Structure-based_modelling_approach\">Structure-based modelling approach<\/span><\/h3>\n<p>Manual model engineering reveals the potential of ELN protocols for the semantic documentation of research data. However, in order to use this at large scale, a more automated approach is needed. To approach this target, the structure-based method presented here employs the textual structure in the ELN protocols, as well as basic text analysis, which is introduced in the following sections.\n<\/p><p>Considering the ELN protocol from the manual model, we observed that the main content is structured by:\n<\/p>\n<ul><li>headings and paragraphs,<\/li>\n<li>tables (table headings and body),<\/li>\n<li>enumerations and lists, and<\/li>\n<li>links to inventory items and research data.<\/li><\/ul>\n<p>Headings are used to structure the documentation, e.g., the general section about the experimental details, or a particular set of activities are preceded from a heading (upper and lower part in Fig. 2, respectively). In the latter case, different sets of activities in a protocol correspond to the templates we extracted, i.e., at each headline a new template was included.\n<\/p><p>Tables are used here for two different purposes. First, key-value mappings represent tables that encode general information about an experiment or inventory item, e.g., the objective of the investigation or the manufacturer of a resource. The description of inventory items mainly consists of a table of this kind (see Fig. 3). Second, lists of activities represent tables with two columns: \u201cStep\u201d and \u201cStarting time.\u201d Each row encodes an atomic activity of the experiment (see Fig. 2). Especially for the activity tables, cells include also enumerations, lists, and paragraphs which further describe the atomic activities and parameters, as well as the linking inventory items and the research data. As an example, see the last row in the activity table in Fig. 2. Note, that we assume each row defining an atomic activity that we do not split up at this stage.\n<\/p><p>Considering our ultimate goal of retrospective research data provenance documentation, we exploited the structure of the ELN protocol as follows:\n<\/p>\n<ol><li>General information such as the researcher conducting the experiment and the objective of the investigation are parsed from the key-value table at the beginning of the protocol. This information is added to the protocol activity using the relation <tt>qualifiedAssociation<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#qualifiedAssociation\" target=\"_blank\">prov:qualifiedAssociation<\/a>).<\/li>\n<li>Activities described within the ELN protocol are hierarchically structured to represent different levels of granularity. The top-level activity resembles the entire experiment, while the different main sections are represented by second-level activities. Note that each main section contains an activity table. Finally, the third level represents activities from table rows of those tables.<\/li>\n<li>All activities are augmented by inventory items mentioned in the respective description by the used (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#used\" target=\"_blank\">prov:used<\/a>) relation.<\/li>\n<li>For each research data file created during the investigation, a corresponding entity is created. Assuming that the mention of a file inside an activity marks the creation of this file, the activity is linked to the file using the relation <tt>wasGeneratedBy<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#wasGeneratedBy\" target=\"_blank\">prov:wasGeneratedBy<\/a>).<\/li><\/ol>\n<p>As previously described, we do not further split up the third-level activities, i.e., complex structures such as enumerations and lists, including their order inside a step description, are taken as atomic.\n<\/p><p>Aside from the use of structural elements in the ELN, which was the base for the manual model, we identified different repeating patterns that can be exploited. For example, from the textual description of activities such as \u201cincubate 5 min in [Device] SANYO CO2 Incubator at 37<sup>\u2218<\/sup>C\u201d or \u201cwash cells with [Washing solution] PBS without Ca\/Mg [..],\u201d we observed the use of verb phrases indicating the activity of the step: \u201cincubate\u201d and \u201cwash,\u201d respectively. Here, we use the head verb of those phrases to assign the corresponding ontological class from a prior mapping. Similarly, information about researchers and institutions, manufacturers, file mime-types, and experiment type are included. For large scale usage, these information might also be retrieved from an organizational or research information system.\n<\/p><p>Parameters that are used in the textual description are identified by their unit, e.g., \u201c1.5 ml,\u201d \u201c5 min,\u201d and \u201c37<sup>\u2218<\/sup>C\u201d by employing regular expressions. They are then represented as blank nodes connected to the step using the relation <tt>has value specification<\/tt> (OBI_0001938) with the <tt>value<\/tt> as the numerical value of the parameter and the unit connected by <tt>has measurement unit label<\/tt> (IAO_0000039). We observed that most of the units mentioned in the protocols at hand are defined in the units ontology (UO).<sup id=\"rdp-ebb-cite_ref-54\" class=\"reference\"><a href=\"#cite_note-54\">[53]<\/a><\/sup>\n<\/p><p>Another frequently used pattern observed in the textual description is the mixture of biological and chemical resources, e.g., \u201c89% [Culture Medium] DMEM + 10% [Serum] FCS + 1% [Antibiotic] Gentamicin\u201d. By employing the following regular expression, the contained information is extracted and transferred into a representation of activity of type <tt>creating a mixture of molecules in solution<\/tt> (OBI_0000685): \n<\/p>\n<dl><dd><tt>[\\. \\d] + \\s*% <item> ('+' [\\. \\d] + \\s*% <item>) +<\/tt><\/dd><\/dl>\n<p>Depending on the appearance of attribution notes in the corresponding contexts (e.g., \u201c(Attributed to Susanne Staehlke)\u201d), we create separate activities following the same specification. Figure 7 contains an example activity encoding the creation of the above mixture.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Preparing_ELN_protocol_template\">Preparing ELN protocol template<\/span><\/h3>\n<p>ELN protocols encode instructions (i.e., lists of activities) to (re-)produce the particular research findings. This does not restrict researchers but rather provides a guideline based on earlier experiments. Specifically, they include parameters, timestamps, and the research data. Taking the first experiment of our study, which was documented as an ELN protocol, we derived a protocol template by marking all variable information as placeholders. Together with the domain experts, this generalization has been validated to allow the usage as a basis for new experiments. The main advantage for the researchers conducting experiments in the wet lab is that all parameters that need to be documented during the experiment are highlighted while the overall description of the process is already done. Thus, errors introduced from missing parameters or instructions are reduced. If, however, the documentation needs to be modified during the experimental execution, researchers can adjust the activities and description.\n<\/p><p>This protocol template might already be used for the documentation of identical experiments (including identical ordering of parameter variations). However, as the researchers in our use case permute the different parts of the experiment (i.e., the stimulation parameters in each experiment), the templates were further split up in individual steps. For the use case at hand, we identified the following four parts: (i) Preparation, (ii) Fluo-3 Staining, (iii) Ca-imaging with Stimulation, and (iv) Ca-imaging without Stimulation. Figure 4 illustrates the template for the approach using electrical stimulation. Placeholders that will be replaced with specific parameter values during an experiment are marked with orange background color. These templates can be re-combined and used to encode new experiments. A protocol template, therefore, can be interpreted as a combination of templates which themselves are combinations of activities in a textually structured description. In consequence, an ELN protocol represents a completed protocol template with actual parameters.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"f8e58d55b52954c5219fffc300a71777\"><img alt=\"Fig4 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/78\/Fig4_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 4.<\/b> Template transferred from an ELN protocol section by highlighting parameters (marked with orange background color). The template contains the preparation and microscoping of a sample with stimulation. Note that this template aims at supporting researchers during their documentation, but the semantic translation approach is more general.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Bundling_research_data_and_re-use\">Bundling research data and re-use<\/span><\/h3>\n<p>The structure-based approach automatically translates the ELN protocol into a semantic representation of the activities and resources involved in the production of the research data. In order to combine this semantic representation (i.e., the documentation) with the research data, we employ the RO-Crate format. The RO-Crate bundle consists of the semantic model in a JSON-LD file <tt>ro-crate-metadata.json<\/tt>, the research data files, and a human-readable copy of the original ELN protocol and the inventory item description as HTML files.\n<\/p><p>By using the resulting RO-Crates for our use case, we answer the raised provenance questions. Therefore, we load all semantic representations from the RO-Crates into a linked data server with a SPARQL endpoint. In this study, we use Apache Jena Fuseki (v4.1.0)<sup id=\"rdp-ebb-cite_ref-Fuseki_55-0\" class=\"reference\"><a href=\"#cite_note-Fuseki-55\">[54]<\/a><\/sup> for this purpose.\n<\/p><p>An advantage of the semantic representation of the research data documentation is its machine interpretability. This enables the comparison of the experimental processes with respect to similarities and potential differences that may have influenced the final result. This includes the particular execution times, but also omitted or additional steps as well as different parameter combinations. Furthermore, influences of the order of the different parts can easily be investigated (W7).\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>First, we present the details of the manually engineered semantic representation of the Ca-imaging procedure which served as (i) a proof of concept for the effectiveness of retrospective provenance documentation from ELN protocols, (ii) a basis for analysis of the ELN protocol structure, and (iii) the development of the protocol template for research guidance. Second, details of the structure-based semantic translation for the seven Ca-imaging protocols with stimulation are given. Finally, we present the results of the evaluation of the RO-Crate bundles.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Manually_engineered_model\">Manually engineered model<\/span><\/h3>\n<p>The semantic representation of the Ca-imaging procedure is based on the upper-level ontology BFO. In addition, PROV-O<sup id=\"rdp-ebb-cite_ref-:12_26-1\" class=\"reference\"><a href=\"#cite_note-:12-26\">[25]<\/a><\/sup> is used for retrospective provenance documentation of the experimental results. Table 1 lists the most important ontologies used in the model. For the representation, an artifact-based modelling approach was selected, where artifacts are central to the model and are used to connect activities via their corresponding input and output relations. In total, the protocol as well as the inventory items are represented in about 80 resources of 46 types connected by almost 20 distinct predicates from 13 vocabularies.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Ontologies selected for the manually engineered model. Upper rows list general ontologies, while the lower rows list domain-specific ontologies for resources and activities.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Name\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Source\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Details\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">BFO\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Smith <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:14_29-2\" class=\"reference\"><a href=\"#cite_note-:14-29\">[28]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Basic Formal Ontology\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PROV-O\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Moreau <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:12_26-2\" class=\"reference\"><a href=\"#cite_note-:12-26\">[25]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PROV Ontology\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">BTO\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Gremse <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-56\" class=\"reference\"><a href=\"#cite_note-56\">[55]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">BRENDA Tissue Ontology\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CHEBI\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Degtyarenko <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-57\" class=\"reference\"><a href=\"#cite_note-57\">[56]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Chemical Entities of Biological Interest Ontology\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CLO\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sarntivijai <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-58\" class=\"reference\"><a href=\"#cite_note-58\">[57]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Cell Line Ontology\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">OBI\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Bandrowski <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-59\" class=\"reference\"><a href=\"#cite_note-59\">[58]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ontology for Biomedical Investigations\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">FOAF\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Brickley and Miller<sup id=\"rdp-ebb-cite_ref-BrickleyFOAF14_60-0\" class=\"reference\"><a href=\"#cite_note-BrickleyFOAF14-60\">[59]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">People and their web information\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>All inventory items that were mentioned as resources in the protocol were represented by instances of the corresponding ontology classes (ABox statements), which is exemplified in the following by use of the MG-63 cell line. The manually engineered representation, as well as the corresponding inventory database description, are illustrated in Figs. 5 and 3, respectively.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"bf65406ab7fd5ad289da7358a3c5f476\"><img alt=\"Fig5 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7a\/Fig5_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 5.<\/b> Graphical representation of the manually engineered semantic model of the MG-63 cell line used in the protocol. (See Schr\u00f6der <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:5_9-1\" class=\"reference\"><a href=\"#cite_note-:5-9\">[8]<\/a><\/sup>)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>In the ELN protocol, a passage with number <tt>25<\/tt> of the originally supplied <tt>MG-63<\/tt> cells with lot number <tt>57840088<\/tt> was used, i.e., \u201c[Cell line] MG-63 P25 LOT 57840088\u201d.<sup id=\"rdp-ebb-cite_ref-61\" class=\"reference\"><a href=\"#cite_note-61\">[b]<\/a><\/sup> This is modelled by using multiple instances of the corresponding class <i>MG-63 cell<\/i> (CLO_0007699), which are connected with the relation <tt>is_passage_of<\/tt>. The passage information are annotated using the attribute <tt>passage situation<\/tt> (CLO_0051628). Lot numbers are represented as an instance of <tt>lot number<\/tt> (IAO_0000132) and connected to the cell instances using the newly defined relation <tt>has_lot_number<\/tt>. The creation of a cell passage is attributed to a researcher using the relation <tt>wasAttributedTo<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#wasAttributedTo\" target=\"_blank\">prov:wasAttributedTo<\/a>). Finally, the supplier is an instance of class <tt>Organization<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#Organization\" target=\"_blank\">prov:Organization<\/a>) and related to the cells using <tt>has_supplier<\/tt> (OBI_0000647).\n<\/p><p>The modelling of the ELN protocol can be summarized as the creation of instances of activity classes that require their individual input entities and often produce an output entity which serves as an input for the subsequent activity (artifact-based modelling). Examples of atomic activities and their corresponding activity classes include <tt>washing<\/tt> (OBI_0302888), <tt>creating a mixture of molecules in solution<\/tt> (OBI_0000685), or <tt>cell line cell culturing<\/tt> (CLO_0000000 . The relations that are used to connect the entities to the activities are modelled in the corresponding ontology and depend on the actual activity class. Additionally, these processes are also of type <tt>Activity<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#Activity\" target=\"_blank\">prov:Activity<\/a>) in order to encode general provenance information.\n<\/p><p>This modelling approach was employed for the entire ELN protocol. However, the most interesting part when it comes to the provenance documentation of research data is the activity, which produces or uses the research data. The upper part in Fig. 6 illustrates the documentation from the ELN protocol relevant for the research data generation: the first two steps describe the creation of the data while the last step contains the details about the actual analysis.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"fa6519d32d55831bda851d4713fdbff6\"><img alt=\"Fig6 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/5\/54\/Fig6_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 6.<\/b> Graphical representation of the semantic model describing the data recording (see also Fig. 5). (See Schr\u00f6der <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:5_9-2\" class=\"reference\"><a href=\"#cite_note-:5-9\">[8]<\/a><\/sup>)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Structure-based_model\">Structure-based model<\/span><\/h3>\n<p>For the structure-based model, an activity-based modelling approach was used to resemble the textual structure of the ELN protocol. For this purpose, the model was build upon the general purpose ontologies RO-Crate, PROV-O, and BFO. In total, for the representation of the seven protocols and their corresponding inventory items, 1935 resources of 18 types connected by 36 distinct predicates from seven vocabularies were used.\n<\/p><p>The structural hierarchy of the activities was represented by <tt>bfo:hasPart<\/tt>, while the sequential order was represented by <tt>wasInformedBy<\/tt> (prov:wasInformedBy). Figure 7 illustrates this structure. For each activity, the general types <tt>Action<\/tt>, <tt>prov:Activity<\/tt>, and <tt>bfo:process<\/tt> were used. Further links to external ontologies were added by <tt>owl:sameAs<\/tt>, for instance \u201cwash\u201d was augmented by <tt>washing<\/tt> (OBI_0302888).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig7_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"e2eeda43ffc440d486e28148915f9db8\"><img alt=\"Fig7 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/17\/Fig7_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 7.<\/b> Graphical representation of an excerpt of the semantic model that was created semi-automatically.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The RO-Crate\u2019s root data entity that describes the research data is required to be an entity of type <tt>Dataset<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/schema.org\/Dataset\" target=\"_blank\">schema:Dataset<\/a>). Thus, research data files are added to this dataset by <tt>hasPart<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/schema.org\/hasPart\" target=\"_blank\">schema:hasPart<\/a>). The connection of these file entities and the hierarchical structure of the activities is represented by <tt>wasGeneratedBy<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#wasGeneratedBy\" target=\"_blank\">prov:wasGeneratedBy<\/a>) (see the right part of Fig. 7), when mentioned in the activities\u2019 textual description. This means that all files are included in this root data entity (via <tt>hasPart<\/tt>), but are not necessarily associated to the activities, if they are not mentioned.\n<\/p><p>Following the RO-Crate specification, ELN inventory database items are encoded as the domain-independent type <tt>IndividualProduct<\/tt> as they provide contextual information. However, the ontological knowledge about the type of the biological and chemical resource was added using the relation <tt>owl:sameAs<\/tt> by the external references from the description in the ELN. The resulting entity is connected to the activities using <tt>used<\/tt> (<a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/ns\/prov#used\" target=\"_blank\">prov:used<\/a>). Resources with a specific passage or lot number are added as individual entities connected to a general entity encoding the inventory database item using the relation <tt>is_instance_of<\/tt>. Furthermore, attributes <tt>has_passage_number<\/tt> and <tt>has_lot_number<\/tt> are added with their corresponding information.\n<\/p><p>Several mixtures are used in the ELN protocols. This information is modelled around the activity <tt>creating a mixture of molecules in solution<\/tt> (OBI_0000685). All resources that are used in this activity are linked by <tt>has_specified_input<\/tt> (OBI_0000293) and the resulting mixture entity by <tt>has_specified_output<\/tt> (OBI_0000299). To specify the recipe of this mixture, a <tt>material combination objective<\/tt> (OBI_0000686) is created and linked to the activity using <tt>achieves_planned_objective<\/tt> (OBI_0000417). If an attribution of this mixture is annotated in the ELN protocol, the corresponding agent is associated with the resulting mixture entity via <tt>wasAttributedTo<\/tt>. Note that recipes of a mixture are independent of the actual creation activity, i.e., if multiple researchers create a mixture using the same recipe, the same recipe entity is referenced, but individual activities and mixture entities are created.\n<\/p><p>With respect to parameters, we extracted values and units for the following types: (i) time and duration (min and ms), (ii) temperature (<sup>\u2218<\/sup>Celsius), (iii) frequency (Hz), and (iv) voltage (V) and represented by their corresponding classes. Specifically, the frequency and the voltage are of interest as they provide the parameters for the stimulation of the cells during the Ca-imaging approach.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"ELN_protocols_and_protocol_template\">ELN protocols and protocol template<\/span><\/h3>\n<p>By providing templates for the individual parts of the experiment (preparation, Fluo-3 staining, Ca-imaging with and without stimulation), the researchers were able to compile seven ELN protocols with different permutations of the experiment parameters. In comparison to the predefined protocol template, we observed that the researchers further modified the ELN protocol description to reflect the particular course of activities and observations conducted in the wet lab, e.g., the repetition of an experimental setting due to issues in the previous experiment or the documentation of issues during the experiment. That means the model represents such deviations from the original plan (prospective provenance) and allows for tracking the actually documented activity sequence by means of retrospective provenance.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Research_data_bundles\">Research data bundles<\/span><\/h3>\n<p>In summary, seven RO-Crates have been created, one for each ELN protocol of the Ca-imaging experiments with stimulation. The corresponding semantic representation was automatically created using the structure-based approach. All research data that was produced in a particular experiment, together with this semantic representation, was bundled in the RO-Crate. In order to foster readability, a copy of the ELN protocol and the inventory items' description was included in the form of HTML files. Thus, the RO-Crates contain between 110 and 135 files and are between 107 and 185 MB large. The particular ELN protocols are encoded in models of 2,174 to 2,553 triples with 15,823 triples in total. As some triples\u2014such as researchers, institutions, and resources\u2014are identical across all RO-Crates, the number of unique triples is only 13,490. The number of triples per protocol differ due to deviations in the documentation from the original plan and the number of research files.\n<\/p><p>The structure-based approach employs RO-Crate, PROV-O, and BFO as upper level ontologies. Especially RO-Crate and PROV-O are designed to encode provenance information about resources. Provenance information about experimenter, manufacturer, biological and chemical resources, activities, and research data are transferred by this approach into a semantic representation. To illustrate the capabilities of the resulting RO-Crate bundles, we evaluated SPARQL queries for the W7 questions in our use case. Considering the question \u201cHow was a particular file created?\u201d (W3), Fig. 8 presents the corresponding SPARQL query for a Ca-imaging approach in a particular experiment. Table 2 illustrates an excerpt of the result of this query, i.e., the sequence of activities from one experiment, providing the result to the question W3. That is, for every atomic activity within the Ca-imaging approach, the description as well as the created research data are listed in the order of the execution. Moreover, all resources and equipment (W2), as well as the parameters, are depicted as a result of the query.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig8_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"e25a5899a4633e838b9596c5846baf65\"><img alt=\"Fig8 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/3\/38\/Fig8_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 8.<\/b> This SPARQL query selects (1) the ontological activity classes, (2) the research data produced, (3) the resources and equipment that is used, and (4) the parameters for each atomic activity order by their execution in a Ca-imaging approach, with stimulation from one of the use case ELN protocols that have been translated using the structure-based modelling approach.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"7\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> An excerpt of the resulting output for the SPARQL query in Fig. 8.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Activity\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Text\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Act.-Class\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Resources\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Files\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Par.-Units\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Par.-Values\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">[...]\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/14\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">place [Device] IonOptix 12 well plate chamber electrodes on plate\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">obo:NCIT_C52253\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">IonOptix 12 well plate chamber\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/15\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">incubate for 10min with stimulation in LSM hood: [...]\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">obo:OMIT_0005807, obo:OBI_0001007, obo:OBI_0302893\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LSM780, ZEN 2011 (black edition)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Data\/02_Zeitserie-Stimulation_5V_7.9Hz.czi\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">obo:UO_0000031, obo:UO_0000028, obo:UO_0000218, obo:UO_0000106\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5, 10, 7.9\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">[...]\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Beside queries for individual experiments, the semantic models enable the comparison of the documentation of multiple experiments. As an example, we consider the question \u201cWhat was the order of the stimulation parameters in a particular experiment?\u201d (W7) that should be answered for seven experiments. Figure 9 illustrates the query for the comparison of multiple experiments based on the order of their stimulation parameters. The corresponding results are shown in Table 3.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig9_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"8ddbf677825c955101fbb9ba1ddb82e8\"><img alt=\"Fig9 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/22\/Fig9_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 9.<\/b> This SPARQL query selects all experiments following the Ca-imaging procedure and collects their stimulation parameters in the order that they have been investigated.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> The result for the SPARQL query in Fig. 9 illustrating a comparison of multiple experiments based on the order of their stimulation parameters.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Protocol\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Title\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Stimulation parameters\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1124\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation) 29.01.2021\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1042\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">20Hz, 1V | 7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1021\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">20Hz, 1V | 20Hz, 5V | 7.9Hz, 5V | 7.9Hz, 1V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1022\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.9Hz, 5V | 7.9Hz, 1V | 20Hz, 1V | 20Hz, 5V | 7.9Hz, 5V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1023\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation) Failed (durch ATP Zugabe hat sich der Bildausschnitt ver\u00e4ndert)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.9Hz, 1V | 7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln942\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.9Hz, 5V | 7.9Hz, 1V | 20Hz, 1V | 20Hz, 5V\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1071\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging (with stimulation) 22.01.2021\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.9Hz, 5V | 20Hz, 5V | 20Hz, 1V | 7.9Hz, 1V\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The remaining W7 questions could also be validated based on similar queries, as shown in the appendix of this paper. Thus, the proposed approach demonstrates the feasibility of research data documentation using ELN protocols.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>The results of the manual modelling show that it is feasible to translate the information of an ELN protocol into a semantic representation for documentation of retrospective provenance of research data. Moreover, it has been shown that the creation of ready-to-publish bundles containing the research data, the associated metadata and the retrospective provenance documentation by using of RO-Crate enables to answer questions about the experimental procedure raising the research data. The manually engineered model implements an artifact-based modelling approach that uses ontological terms in full extent. Thus, the resulting representation mainly consists of a sequential list of activities and entities connected via their specific input and output relations. The level of granularity of the model corresponds in most cases to the terms used in the documentation, although existing ontologies not always provide the same level of detail for all terms. As an example, the terms \u201crelocate,\u201d \u201ctransfer,\u201d and \u201ctake out\u201d can be subsumed under moving of materials, but still have some distinct differences. Furthermore, when \u201ctake out\u201d is used in the context of a fridge or freezer, an ontological modelling additionally requires encoding of the warming up of the material. Thus, providing ontological definitions for these different situations requires much work in future ontological engineering.\n<\/p><p>In contrast to the manual model, the structure-based approach implements an activity-based modelling mechanism and does not use the specific input and output relations of an activity, but the same activities. As a result, the structure-based approach does not specify the particular role of the used entities. Furthermore, in the manually engineered model, the semantic representation of an entity that results from the sequential execution of activities is difficult without introducing TBox statements. The reason is that this entity needs to reflect the result of the particular activity sequence. In the structure-based approach, these entities need not be defined as the main part of the model consists of a hierarchy of activities, including the used resources. This allows the model to represent only the information that is actually contained in the textual description of the ELN protocol, without artificially introducing entities with properties that are the direct result of the activities.\n<\/p><p>Beside the process documentation, the structure-based approach adds metadata about the mime type, the file size, and the checksum allowing to validate the integrity of the research data. This representation of the research data might be extended by additional metadata, which, however, would require the application of file-type-specific extraction methods (e.g., CZI files) or the researchers themselves to provide the information (e.g., in the form of data dictionaries for tabular data). Moreover, representing the research data itself in the same representation format as the metadata and the retrospective provenance documentation would enable further data integration and thus allow for automatic data analysis approaches.\n<\/p><p>Employing the structure-based approach at a large scale requires knowledge about the relation of terms from the textual description in the ELN to classes and attributes from ontologies. Here, we implemented this relation by a hard-coded mapping, for instance from verb phrases to ontology classes in the case of activities. This can also be achieved by use of a suggestion system for the researchers that proposes ontological classes selected from automated queries of ontological databases. Similarly, the external identifier might be augmented. The structure-based approach currently integrates the Open Researcher and Contributor ID (ORCID) and Research Organization Registry (ROR) for persons and organizations, respectively, and it also uses references to Wikidata entities. Several initiatives proposed the use of persistent identifiers for other aspects of wet lab experiments, e.g., RRIDs can be used to reference scientific resources similar to the inventory database of the ELN.<sup id=\"rdp-ebb-cite_ref-RRIDPortal_11-1\" class=\"reference\"><a href=\"#cite_note-RRIDPortal-11\">[10]<\/a><\/sup> While using persistent identifiers, we observed two aspects that are crucial:\n<\/p>\n<ol><li>The granularity of the entity referenced by the identifier needs to be on the same level as that needed for the application. As an example, the organization referenced by the Research Organization Registry (ROR)<sup id=\"rdp-ebb-cite_ref-RORHome_62-0\" class=\"reference\"><a href=\"#cite_note-RORHome-62\">[60]<\/a><\/sup> not reflect the particular department that the researchers are affiliated.<\/li>\n<li>The entity referenced by the identifier needs to reflect evolution, too. Although the identifier should reference a particular version of an entity, the entity behind might change and, thus, the registry needs to encode these versions and provide corresponding identifier for each version. To the best of our knowledge, this is currently not supported by, e.g., RRIDs.<\/li><\/ol>\n<p>A fine-grained solution for referencing researchers, organizations, and research projects on an institutional level might be implemented by organizational information systems.\n<\/p><p>Another important aspect is related to privacy protection, for instance, the names of all involved persons in an experiment. While for archival purposes the identity of all involved persons are of interest, it might not be wanted to publish all personal details with respect to privacy protection. The structured representation of the RO-Crate allows all involved persons (W1) to perform queries and thus would directly allow for easy implementation of pseudonymization via graph update operations.\n<\/p><p>With respect to the recent advances in information extraction, we employed basic methods. While this does not extract all information of interest, it sketches the potential benefits of automatic text analysis. By employing more sophisticated information extraction methods, for instance, training on labelled published protocols<sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[61]<\/a><\/sup>, this could further be improved. This is also true for the extraction of parameters and their assignment to activities, as can be seen by recently established NLP challenges such as MeasEval.<sup id=\"rdp-ebb-cite_ref-HarperWelcome21_64-0\" class=\"reference\"><a href=\"#cite_note-HarperWelcome21-64\">[62]<\/a><\/sup> Moreover, disambiguating detected terms with respect to their context and linking them to the corresponding ontology classes is one of the core challenges in modern NLP.\n<\/p><p>With respect to the completeness of the documentation of wet lab experiments, minimal information guidelines provide a reference that can potentially be exploited to create protocol templates. In combination with the proposed structure-based approach, this would allow deployment of minimum information checklists using the Minim model<sup id=\"rdp-ebb-cite_ref-Soiland-ReyesMinim17_65-0\" class=\"reference\"><a href=\"#cite_note-Soiland-ReyesMinim17-65\">[63]<\/a><\/sup> to enable the validation of the generated documentation.\n<\/p><p>During the use of ELNs for a longer period of time, inventory database items are regularly updated, because e.g., the supplier changes and the software or the firmware of a device is updated. Evolution provenance methods can be employed to represent such changes. In order to reflect these versions also for the research data in the RO-Crate, a data storage solution with versioning is needed. Intra-consortia sharing platforms<sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[64]<\/a><\/sup> can be employed for this purpose.\n<\/p><p>Overall, we have shown that our approach is able to help generate increasingly FAIR data. The ELN Protocols captured, together with the data entries in the RO-Crate format, increase the findability of data produced in wet lab experiments, creating a binding between experiment steps and data. Likewise, the approach increases accessibility by allowing rich SPARQL queries to be formulated that combine the experiment metadata with the data itself. In terms of interoperability and reusability, the use of common ontologies allows for different experiment runs to be easily compared and documentation to be more easily generated. However, as noted by Mons <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-67\" class=\"reference\"><a href=\"#cite_note-67\">[65]<\/a><\/sup>, making FAIR data is not an absolute but a spectrum where there are trade-offs in terms of ability to find and reuse and the effort in documentation. Our approach illustrates this by highlighting the differences between automated capture and manual capture. In particular, while automated capture reduces the burden in capturing FAIR data, it also means, for the time being, the decrease in the richness of the associated metadata needed for reusability. Having a target in terms of manual capture provides a valuable target for automated capture of metadata for the data produced in the wet lab.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>The presented study investigated the feasibility of creating semantic provenance documentation for research data using ELN protocols from wet-lab experiments. ELN protocols contain specific information about an experiment such as the produced research data but also timestamps, lot and passage number as well as parameters. This is in contrast to templates that serve as general guidelines without such information.\n<\/p><p>The manually engineered model was used as a proof of concept for the translation of ELN protocols using a Ca-imaging experiment. In order to support researchers in the wet lab, we derived four templates encoding parts of this initial protocol that can be used to create new experiment documentation. Based on these results, a structure-based approach was implemented to translate these protocols into a semantic representation. This approach uses the structure in the description, including headings, tables, and links, as well as some basic text analysis. Furthermore, the resulting semantic model is bundled together with the research data. Potential provenance questions from the viewpoint of other researchers using these bundles have been implemented as SPARQL queries in order to evaluate the proposed methodology. We have shown that the structure-based approach, in combination with RO-Crate bundling, can be used to successfully document research data based on the description in the form of ELN protocols. Thus, these RO-Crates enable the sharing, publication, and archiving of the research data in terms of the FAIR principles.<sup id=\"rdp-ebb-cite_ref-:0_1-2\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:1_2-2\" class=\"reference\"><a href=\"#cite_note-:1-2\">[2]<\/a><\/sup> Furthermore, in order to guide researchers during the conduction of Ca-imaging experiments, the four derived sub-templates can be combined to provide a documentation basis for new experiments.\n<\/p><p>Integrating the proposed approach, as well as the sketched extensions, into a comprehensive virtual research environment (VRE) would enable the tracking of the entire research process and the research data from the creation of a hypothesis to the publication of the data. In particular, the ELN can be used for the documentation of the wet lab investigation of a research project. The funding information of the research projects, including involved researchers and the consortia, can be stored in a research information system. Furthermore, the semantic representation of the protocol can be automatically synced with a linked data server, and the research data be stored in an institutional repository. The particular platforms can be connected with a semantic search interface for researchers that enables searching for similar experiments and data, as well as creating reports about experimental activities.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Appendix\">Appendix<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Queries_and_answers_for_the_W7_questions\">Queries and answers for the W7 questions<\/span><\/h3>\n<p>Note that for better readability, we shortened URIs in some of the following results, e.g., https:\/\/eln-provenance.elaine.uni-rostock.de\/942\/approach_1_with_stimulation\/1 has been shortened to <tt>ap_1_with_stimulation\/1<\/tt>, and http:\/\/localhost:3030\/Data\/02_Zeitserie-Stimulation_5V_7.9Hz.czi has been shortened to <tt>02_Zeitserie-Stimulation_5V_7.9Hz.czi<\/tt>.\n<\/p><p><br \/>\n<b>W1: Who participated in the study?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA1_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"a94024672f889c6703494223c37b6ef4\"><img alt=\"FigA1 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1d\/FigA1_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Experimentalist\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Involved persons\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Susanne Staehlke\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Person1 Anonymous, Person2 Anonymous\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Note that before publication, we pseudonymized some researchers with respect to privacy protection. Refer to the Discussion section for more details.\n<\/p><p><br \/>\n<b>W2: Which biological and chemical resources and which equipment was used in the study?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA2_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"b612c3facc00189711c2a981989880a5\"><img alt=\"FigA2 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a3\/FigA2_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Activity\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Used resources\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\"># of previous steps\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Tube: 10ml\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PBS without Ca\/Mg\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Eppendorf Centrifuge\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">50% HEPES I (isotonic) + 50% HEPES II (hypotonic)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Fluo-3\/AM\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Eppendorf Thermomixer C (incubation shaker)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LSM780, IonOptix 12 well plate chamber, IonOptix C-Pace EM\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Eppendorf Centrifuge\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/10\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/11\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">HEPES I (isotonic)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/12\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12 well plate, PBS without Ca\/Mg\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/13\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">HEPES I (isotonic)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/14\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">IonOptix 12 well plate chamber\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">13\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/15\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LSM780, ZEN 2011 (black edition)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">14\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">IonOptix 12 well plate chamber\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">15\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/17\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LSM780,ATP, ZEN 2011 (black edition)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<b>W3: How was a particular file created?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA3_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"c43094b60c9d934258fde2794e9a3a0f\"><img alt=\"FigA3 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/b\/be\/FigA3_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">File\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Activity\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Protocol\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Data\/02_Zeitserie-Stimulation_5V_7.9Hz.czi\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln942:ap_1_with_stimulation\/15\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln942:protocol\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<b>W4: When was an activity conducted?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA4_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"70925f1a8728bdaddb7e9f7cc9708cbd\"><img alt=\"FigA4 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cb\/FigA4_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" width=\"399\" height=\"304\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Activity\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Starting time\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\"># of previous steps\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/1\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:00:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:01:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:06:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:10:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:40:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/10\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:45:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/11\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/12\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/13\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/14\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">13\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/15\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">09:50:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">14\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10:00:00\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">15\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ap_1_with_stimulation\/17\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">immediately afterwards\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<b>W5: When was the experiment done?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA5_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"8384e67eda366a10815c761d4be67a73\"><img alt=\"FigA5 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/da\/FigA5_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" width=\"399\" height=\"277\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Template\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Protocol\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Objective\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1023\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1021\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln942\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1071\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1042\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1124\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ca-imaging\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">eln1022\/protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Intracellular calcium dynamic caused by electric fields\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<b>W6: Where was the experiment conducted?<\/b>\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA6_Schr%C3%B6der_JofBioSem22_13.png\" class=\"image wiki-link\" data-key=\"d851db78e7bc462764cb8891cd9b87d6\"><img alt=\"FigA6 Schr\u00f6der JofBioSem22 13.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/43\/FigA6_Schr%C3%B6der_JofBioSem22_13.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Organization\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">University Medical Center Rostock\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Note that the granularity of external identifiers is not always sufficient, e.g., the researchers and the equipment are affiliated in the \u201cDepartment of Cell Biology,\u201d which is part of the \u201cUniversity Medical Center Rostock.\u201d See the discussion on this issue in the Discussion section.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Abbreviations\">Abbreviations<\/span><\/h2>\n<p><b>BFO<\/b>: Basic Formal Ontology\n<\/p><p><b>DCAT<\/b>: Data Catalog Vocabulary\n<\/p><p><b>DDI<\/b>: Data Documentation Initiative\n<\/p><p><b>ELN<\/b>: Electronic Laboratory Notebook\n<\/p><p><b>EXACT2<\/b>: EXperimental ACTions\n<\/p><p><b>FAIR<\/b>: Findable, Accessible, Interoperable, and Reuseable\n<\/p><p><b>KG<\/b>: Knowledge Graph\n<\/p><p><b>KGC<\/b>: Knowledge Graph Cell\n<\/p><p><b>MIACA<\/b>: Minimum Information About a Cellular Assay\n<\/p><p><b>NLP<\/b>: Natural Language Processing\n<\/p><p><b>OBO<\/b>: Open Biological and Biomedical Ontology\n<\/p><p><b>OCFL<\/b>: Oxford Common File Layout\n<\/p><p><b>OPM<\/b>: Open Provenance Model\n<\/p><p><b>ORCID<\/b>: Open Researcher and Contributor ID\n<\/p><p><b>PAV<\/b>: Provenance, Authoring and Versioning\n<\/p><p><b>PROV-O<\/b>: PROV Ontology\n<\/p><p><b>REPRODUCE-ME<\/b>: Reproduce Microscopy Experiments\n<\/p><p><b>RO-Crate<\/b>: Research Object Crate\n<\/p><p><b>ROR<\/b>: Research Organization Registry\n<\/p><p><b>RRID<\/b>: Research Resource Identifiers\n<\/p><p><b>SMART Protocols<\/b>: SeMAntic RepresenTation for Experimental Protocols\n<\/p><p><b>SOP<\/b>: Standard Operating Procedure\n<\/p><p><b>UO<\/b>: Units Ontology\n<\/p><p><b>VRE<\/b>: Virtual Research Environment\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Footnotes\">Footnotes<\/span><\/h2>\n<div class=\"reflist\" style=\"list-style-type: lower-alpha;\">\n<div class=\"mw-references-wrap\"><ol class=\"references\">\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\">A lot number is an identifier for a particular set of materials produced by one manufacturer. Thus, lot numbers enable to track information about the provenance of these material productions.<\/span>\n<\/li>\n<li id=\"cite_note-61\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-61\">\u2191<\/a><\/span> <span class=\"reference-text\">Note that this is not part of the inventory item description, as this aims at the general cell specification. However, the particular information for a specific experiment are part of the ELN protocol.<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>We thank Tazin Hossain for her help with the prototypical implementation of parts of the structure-based approach.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Author contributions according to CRediT: MS: Conceptualization, Data curation, Methodology, Investigation, Software, Writing. SSt: Resources, Data curation. PG: Methodology, Writing. JBN: Resources, Funding acquisition. SSp: Funding acquisition, Supervision. FK: Conceptualization, Methodology, Writing, Funding acquisition, Supervision. All authors read and approved the final manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) \u2013 SFB 1270\/1 - 299150580. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results. Open Access funding enabled and organized by Projekt DEAL.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Availability_of_data_and_materials\">Availability of data and materials<\/span><\/h3>\n<p>The manually engineered model is published at <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/github.com\/SFB-ELAINE\/Semantic-Modelling-CA-Imaging\" target=\"_blank\">GitHub<\/a>. The results of the structure-based modelling approach and the research data are published as <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/github.com\/SFB-ELAINE\/Ca-imaging-RO-Crate\" target=\"_blank\">RO-Crates bundles<\/a>. The source that builds the model based on the ELN API is available <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/github.com\/m6121\/Structure-based-ELN2LOD\" target=\"_blank\">here<\/a>. This study is based on the previously published data by Staehlke and Nebe.<sup id=\"rdp-ebb-cite_ref-68\" class=\"reference\"><a href=\"#cite_note-68\">[66]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Competing_interests\">Competing interests<\/span><\/h3>\n<p>The authors declare that they have no competing interests.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-:0-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_1-0\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-1\">1.1<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-2\">1.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wilkinson, Mark D.; Dumontier, Michel; Aalbersberg, IJsbrand Jan; Appleton, Gabrielle; Axton, Myles; Baak, Arie; Blomberg, Niklas; Boiten, Jan-Willem <i>et al.<\/i> (1 December 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/sdata201618\" target=\"_blank\">\"The FAIR Guiding Principles for scientific data management and stewardship\"<\/a> (in en). <i>Scientific Data<\/i> <b>3<\/b> (1): 160018. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fsdata.2016.18\" target=\"_blank\">10.1038\/sdata.2016.18<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2052-4463\" target=\"_blank\">2052-4463<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4792175\/\" target=\"_blank\">PMC4792175<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26978244\" target=\"_blank\">26978244<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/sdata201618\" target=\"_blank\">http:\/\/www.nature.com\/articles\/sdata201618<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+FAIR+Guiding+Principles+for+scientific+data+management+and+stewardship&rft.jtitle=Scientific+Data&rft.aulast=Wilkinson&rft.aufirst=Mark+D.&rft.au=Wilkinson%2C%26%2332%3BMark+D.&rft.au=Dumontier%2C%26%2332%3BMichel&rft.au=Aalbersberg%2C%26%2332%3BIJsbrand+Jan&rft.au=Appleton%2C%26%2332%3BGabrielle&rft.au=Axton%2C%26%2332%3BMyles&rft.au=Baak%2C%26%2332%3BArie&rft.au=Blomberg%2C%26%2332%3BNiklas&rft.au=Boiten%2C%26%2332%3BJan-Willem&rft.au=da+Silva+Santos%2C%26%2332%3BLuiz+Bonino&rft.date=1+December+2016&rft.volume=3&rft.issue=1&rft.pages=160018&rft_id=info:doi\/10.1038%2Fsdata.2016.18&rft.issn=2052-4463&rft_id=info:pmc\/PMC4792175&rft_id=info:pmid\/26978244&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fsdata201618&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-2\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_2-0\">2.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_2-1\">2.1<\/a><\/sup> <sup><a href=\"#cite_ref-:1_2-2\">2.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jacobsen, Annika; de Miranda Azevedo, Ricardo; Juty, Nick; Batista, Dominique; Coles, Simon; Cornet, Ronald; Courtot, M\u00e9lanie; Crosas, Merc\u00e8 <i>et al.<\/i> (1 January 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/direct.mit.edu\/dint\/article\/2\/1-2\/10-29\/10017\" target=\"_blank\">\"FAIR Principles: Interpretations and Implementation Considerations\"<\/a> (in en). <i>Data Intelligence<\/i> <b>2<\/b> (1-2): 10\u201329. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1162%2Fdint_r_00024\" target=\"_blank\">10.1162\/dint_r_00024<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2641-435X\" target=\"_blank\">2641-435X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/direct.mit.edu\/dint\/article\/2\/1-2\/10-29\/10017\" target=\"_blank\">https:\/\/direct.mit.edu\/dint\/article\/2\/1-2\/10-29\/10017<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=FAIR+Principles%3A+Interpretations+and+Implementation+Considerations&rft.jtitle=Data+Intelligence&rft.aulast=Jacobsen&rft.aufirst=Annika&rft.au=Jacobsen%2C%26%2332%3BAnnika&rft.au=de+Miranda+Azevedo%2C%26%2332%3BRicardo&rft.au=Juty%2C%26%2332%3BNick&rft.au=Batista%2C%26%2332%3BDominique&rft.au=Coles%2C%26%2332%3BSimon&rft.au=Cornet%2C%26%2332%3BRonald&rft.au=Courtot%2C%26%2332%3BM%C3%A9lanie&rft.au=Crosas%2C%26%2332%3BMerc%C3%A8&rft.au=Dumontier%2C%26%2332%3BMichel&rft.date=1+January+2020&rft.volume=2&rft.issue=1-2&rft.pages=10%E2%80%9329&rft_id=info:doi\/10.1162%2Fdint_r_00024&rft.issn=2641-435X&rft_id=https%3A%2F%2Fdirect.mit.edu%2Fdint%2Farticle%2F2%2F1-2%2F10-29%2F10017&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-3\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_3-0\">3.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_3-1\">3.1<\/a><\/sup> <sup><a href=\"#cite_ref-:2_3-2\">3.2<\/a><\/sup> <sup><a href=\"#cite_ref-:2_3-3\">3.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFYuZhouLuGu2019\">Yu, Fangyu; Zhou, Beisi; Lu, Tun; Gu, Ning (2019), Sun, Yuqing; Lu, Tun; Xie, Xiaolan <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-13-3044-5_3\" target=\"_blank\">\"Research on Data Provenance Model for Multidisciplinary Collaboration\"<\/a>, <i>Computer Supported Cooperative Work and Social Computing<\/i> (Singapore: Springer Singapore) <b>917<\/b>: 32\u201349, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-981-13-3044-5_3\" target=\"_blank\">10.1007\/978-981-13-3044-5_3<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-981-13-3043-8<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-13-3044-5_3\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-981-13-3044-5_3<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-01<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+on+Data+Provenance+Model+for+Multidisciplinary+Collaboration&rft.jtitle=Computer+Supported+Cooperative+Work+and+Social+Computing&rft.aulast=Yu&rft.aufirst=Fangyu&rft.au=Yu%2C%26%2332%3BFangyu&rft.au=Zhou%2C%26%2332%3BBeisi&rft.au=Lu%2C%26%2332%3BTun&rft.au=Gu%2C%26%2332%3BNing&rft.date=2019&rft.volume=917&rft.pages=32%E2%80%9349&rft.place=Singapore&rft.pub=Springer+Singapore&rft_id=info:doi\/10.1007%2F978-981-13-3044-5_3&rft.isbn=978-981-13-3043-8&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-981-13-3044-5_3&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-4\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Moreau, Luc; Groth, Paul (15 September 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00528ED1V01Y201308WBE007\" target=\"_blank\">\"Provenance: An Introduction to PROV\"<\/a> (in en). <i>Synthesis Lectures on the Semantic Web: Theory and Technology<\/i> <b>3<\/b> (4): 1\u2013129. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2200%2FS00528ED1V01Y201308WBE007\" target=\"_blank\">10.2200\/S00528ED1V01Y201308WBE007<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2160-4711\" target=\"_blank\">2160-4711<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00528ED1V01Y201308WBE007\" target=\"_blank\">http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00528ED1V01Y201308WBE007<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Provenance%3A+An+Introduction+to+PROV&rft.jtitle=Synthesis+Lectures+on+the+Semantic+Web%3A+Theory+and+Technology&rft.aulast=Moreau&rft.aufirst=Luc&rft.au=Moreau%2C%26%2332%3BLuc&rft.au=Groth%2C%26%2332%3BPaul&rft.date=15+September+2013&rft.volume=3&rft.issue=4&rft.pages=1%E2%80%93129&rft_id=info:doi\/10.2200%2FS00528ED1V01Y201308WBE007&rft.issn=2160-4711&rft_id=http%3A%2F%2Fwww.morganclaypool.com%2Fdoi%2Fabs%2F10.2200%2FS00528ED1V01Y201308WBE007&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-5\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_5-0\">5.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_5-1\">5.1<\/a><\/sup> <sup><a href=\"#cite_ref-:3_5-2\">5.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Belhajjame, K.; B'Far, R.; Cheney, J. et al. (30 April 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/TR\/2013\/REC-prov-dm-20130430\/\" target=\"_blank\">\"PROV-DM: The PROV Data Model\"<\/a>. W3C<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.w3.org\/TR\/2013\/REC-prov-dm-20130430\/\" target=\"_blank\">https:\/\/www.w3.org\/TR\/2013\/REC-prov-dm-20130430\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=PROV-DM%3A+The+PROV+Data+Model&rft.atitle=&rft.aulast=Belhajjame%2C+K.%3B+B%27Far%2C+R.%3B+Cheney%2C+J.+et+al.&rft.au=Belhajjame%2C+K.%3B+B%27Far%2C+R.%3B+Cheney%2C+J.+et+al.&rft.date=30+April+2013&rft.pub=W3C&rft_id=https%3A%2F%2Fwww.w3.org%2FTR%2F2013%2FREC-prov-dm-20130430%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-6\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hogan, Aidan; Blomqvist, Eva; Cochez, Michael; D\u2019amato, Claudia; Melo, Gerard De; Gutierrez, Claudio; Kirrane, Sabrina; Gayo, Jos\u00e9 Emilio Labra <i>et al.<\/i> (31 May 2022). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3447772\" target=\"_blank\">\"Knowledge Graphs\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>54<\/b> (4): 1\u201337. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3447772\" target=\"_blank\">10.1145\/3447772<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3447772\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3447772<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Knowledge+Graphs&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Hogan&rft.aufirst=Aidan&rft.au=Hogan%2C%26%2332%3BAidan&rft.au=Blomqvist%2C%26%2332%3BEva&rft.au=Cochez%2C%26%2332%3BMichael&rft.au=D%E2%80%99amato%2C%26%2332%3BClaudia&rft.au=Melo%2C%26%2332%3BGerard+De&rft.au=Gutierrez%2C%26%2332%3BClaudio&rft.au=Kirrane%2C%26%2332%3BSabrina&rft.au=Gayo%2C%26%2332%3BJos%C3%A9+Emilio+Labra&rft.au=Navigli%2C%26%2332%3BRoberto&rft.date=31+May+2022&rft.volume=54&rft.issue=4&rft.pages=1%E2%80%9337&rft_id=info:doi\/10.1145%2F3447772&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3447772&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_7-0\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_7-1\">7.1<\/a><\/sup> <sup><a href=\"#cite_ref-:4_7-2\">7.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Staehlke, Susanne; Koertge, Andreas; Nebe, Barbara (1 April 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961214012666\" target=\"_blank\">\"Intracellular calcium dynamics dependent on defined microtopographical features of titanium\"<\/a> (in en). <i>Biomaterials<\/i> <b>46<\/b>: 48\u201357. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.biomaterials.2014.12.016\" target=\"_blank\">10.1016\/j.biomaterials.2014.12.016<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961214012666\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961214012666<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Intracellular+calcium+dynamics+dependent+on+defined+microtopographical+features+of+titanium&rft.jtitle=Biomaterials&rft.aulast=Staehlke&rft.aufirst=Susanne&rft.au=Staehlke%2C%26%2332%3BSusanne&rft.au=Koertge%2C%26%2332%3BAndreas&rft.au=Nebe%2C%26%2332%3BBarbara&rft.date=1+April+2015&rft.volume=46&rft.pages=48%E2%80%9357&rft_id=info:doi\/10.1016%2Fj.biomaterials.2014.12.016&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0142961214012666&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_9-0\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_9-1\">8.1<\/a><\/sup> <sup><a href=\"#cite_ref-:5_9-2\">8.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schr\u00f6der, Max; St\u00e4hlke, Susanne; Nebe, Barbara; Kr\u00fcger, Frank (2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/repository.publisso.de\/resource\/frl:6423288\" target=\"_blank\">\"Towards in-situ knowledge acquisition for research data provenance from electronic lab notebooks\"<\/a> (in en). <i>Proceedings of the 1st Workshop on Research Data Management for Linked Open Science (DaMaLOS) Co-located with 19th International Semantic Web Conference<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4126%2FFRL01-006423288\" target=\"_blank\">10.4126\/FRL01-006423288<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/repository.publisso.de\/resource\/frl:6423288\" target=\"_blank\">https:\/\/repository.publisso.de\/resource\/frl:6423288<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Towards+in-situ+knowledge+acquisition+for+research+data+provenance+from+electronic+lab+notebooks&rft.jtitle=Proceedings+of+the+1st+Workshop+on+Research+Data+Management+for+Linked+Open+Science+%28DaMaLOS%29+Co-located+with+19th+International+Semantic+Web+Conference&rft.aulast=Schr%C3%B6der&rft.aufirst=Max&rft.au=Schr%C3%B6der%2C%26%2332%3BMax&rft.au=St%C3%A4hlke%2C%26%2332%3BSusanne&rft.au=Nebe%2C%26%2332%3BBarbara&rft.au=Kr%C3%BCger%2C%26%2332%3BFrank&rft.date=2020&rft_id=info:doi\/10.4126%2FFRL01-006423288&rft_id=https%3A%2F%2Frepository.publisso.de%2Fresource%2Ffrl%3A6423288&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">CARPi, Nicolas; Minges, Alexander; Piel, Matthieu (14 April 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/joss.theoj.org\/papers\/10.21105\/joss.00146\" target=\"_blank\">\"eLabFTW: An open source laboratory notebook for research labs\"<\/a>. <i>The Journal of Open Source Software<\/i> <b>2<\/b> (12): 146. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.21105%2Fjoss.00146\" target=\"_blank\">10.21105\/joss.00146<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2475-9066\" target=\"_blank\">2475-9066<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/joss.theoj.org\/papers\/10.21105\/joss.00146\" target=\"_blank\">http:\/\/joss.theoj.org\/papers\/10.21105\/joss.00146<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=eLabFTW%3A+An+open+source+laboratory+notebook+for+research+labs&rft.jtitle=The+Journal+of+Open+Source+Software&rft.aulast=CARPi&rft.aufirst=Nicolas&rft.au=CARPi%2C%26%2332%3BNicolas&rft.au=Minges%2C%26%2332%3BAlexander&rft.au=Piel%2C%26%2332%3BMatthieu&rft.date=14+April+2017&rft.volume=2&rft.issue=12&rft.pages=146&rft_id=info:doi\/10.21105%2Fjoss.00146&rft.issn=2475-9066&rft_id=http%3A%2F%2Fjoss.theoj.org%2Fpapers%2F10.21105%2Fjoss.00146&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-RRIDPortal-11\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-RRIDPortal_11-0\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-RRIDPortal_11-1\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/scicrunch.org\/resources\" target=\"_blank\">\"RRID Portal\"<\/a>. SciCrunch. 2021<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/scicrunch.org\/resources\" target=\"_blank\">https:\/\/scicrunch.org\/resources<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=RRID+Portal&rft.atitle=&rft.date=2021&rft.pub=SciCrunch&rft_id=https%3A%2F%2Fscicrunch.org%2Fresources&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFRamLiu2007\">Ram, Sudha; Liu, Jun (2007), Chen, Peter P.; Wong, Leah Y., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-77503-4_3\" target=\"_blank\">\"Understanding the Semantics of Data Provenance to Support Active Conceptual Modeling\"<\/a>, <i>Active Conceptual Modeling of Learning<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>4512<\/b>: 17\u201329, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-540-77503-4_3\" target=\"_blank\">10.1007\/978-3-540-77503-4_3<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-540-77502-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-77503-4_3\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-540-77503-4_3<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-01<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Understanding+the+Semantics+of+Data+Provenance+to+Support+Active+Conceptual+Modeling&rft.jtitle=Active+Conceptual+Modeling+of+Learning&rft.aulast=Ram&rft.aufirst=Sudha&rft.au=Ram%2C%26%2332%3BSudha&rft.au=Liu%2C%26%2332%3BJun&rft.date=2007&rft.volume=4512&rft.pages=17%E2%80%9329&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-540-77503-4_3&rft.isbn=978-3-540-77502-7&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-540-77503-4_3&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-13\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_13-0\">12.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_13-1\">12.1<\/a><\/sup> <sup><a href=\"#cite_ref-:6_13-2\">12.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Herschel, Melanie; Diestelk\u00e4mper, Ralf; Ben Lahmar, Houssem (1 December 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00778-017-0486-1\" target=\"_blank\">\"A survey on provenance: What for? What form? What from?\"<\/a> (in en). <i>The VLDB Journal<\/i> <b>26<\/b> (6): 881\u2013906. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00778-017-0486-1\" target=\"_blank\">10.1007\/s00778-017-0486-1<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1066-8888\" target=\"_blank\">1066-8888<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00778-017-0486-1\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00778-017-0486-1<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+survey+on+provenance%3A+What+for%3F+What+form%3F+What+from%3F&rft.jtitle=The+VLDB+Journal&rft.aulast=Herschel&rft.aufirst=Melanie&rft.au=Herschel%2C%26%2332%3BMelanie&rft.au=Diestelk%C3%A4mper%2C%26%2332%3BRalf&rft.au=Ben+Lahmar%2C%26%2332%3BHoussem&rft.date=1+December+2017&rft.volume=26&rft.issue=6&rft.pages=881%E2%80%93906&rft_id=info:doi\/10.1007%2Fs00778-017-0486-1&rft.issn=1066-8888&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00778-017-0486-1&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-14\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_14-0\">13.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_14-1\">13.1<\/a><\/sup> <sup><a href=\"#cite_ref-:7_14-2\">13.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lim, Chunhyeok; Lu, Shiyong; Chebotko, Artem; Fotouhi, Farshad (1 July 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5557202\/\" target=\"_blank\">\"Prospective and Retrospective Provenance Collection in Scientific Workflow Environments\"<\/a>. <i>2010 IEEE International Conference on Services Computing<\/i> (Miami, FL, USA: IEEE): 449\u2013456. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FSCC.2010.18\" target=\"_blank\">10.1109\/SCC.2010.18<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4244-8147-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5557202\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/5557202\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Prospective+and+Retrospective+Provenance+Collection+in+Scientific+Workflow+Environments&rft.jtitle=2010+IEEE+International+Conference+on+Services+Computing&rft.aulast=Lim&rft.aufirst=Chunhyeok&rft.au=Lim%2C%26%2332%3BChunhyeok&rft.au=Lu%2C%26%2332%3BShiyong&rft.au=Chebotko%2C%26%2332%3BArtem&rft.au=Fotouhi%2C%26%2332%3BFarshad&rft.date=1+July+2010&rft.pages=449%E2%80%93456&rft.place=Miami%2C+FL%2C+USA&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FSCC.2010.18&rft.isbn=978-1-4244-8147-7&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F5557202%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Belhajjame, Khalid; Wolstencroft, Katy; Corcho, Oscar; Oinn, Tom; Tanoh, Franck; William, Alan; Goble, Carole (1 May 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/4534278\/\" target=\"_blank\">\"Metadata Management in the Taverna Workflow System\"<\/a>. <i>2008 Eighth IEEE International Symposium on Cluster Computing and the Grid (CCGRID)<\/i> (Lyon, France: IEEE): 651\u2013656. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FCCGRID.2008.17\" target=\"_blank\">10.1109\/CCGRID.2008.17<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/4534278\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/4534278\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Metadata+Management+in+the+Taverna+Workflow+System&rft.jtitle=2008+Eighth+IEEE+International+Symposium+on+Cluster+Computing+and+the+Grid+%28CCGRID%29&rft.aulast=Belhajjame&rft.aufirst=Khalid&rft.au=Belhajjame%2C%26%2332%3BKhalid&rft.au=Wolstencroft%2C%26%2332%3BKaty&rft.au=Corcho%2C%26%2332%3BOscar&rft.au=Oinn%2C%26%2332%3BTom&rft.au=Tanoh%2C%26%2332%3BFranck&rft.au=William%2C%26%2332%3BAlan&rft.au=Goble%2C%26%2332%3BCarole&rft.date=1+May+2008&rft.pages=651%E2%80%93656&rft.place=Lyon%2C+France&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FCCGRID.2008.17&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F4534278%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-16\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFAltintasBarneyJaeger-Frank2006\">Altintas, Ilkay; Barney, Oscar; Jaeger-Frank, Efrat (2006), Moreau, Luc; Foster, Ian, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/11890850_14\" target=\"_blank\">\"Provenance Collection Support in the Kepler Scientific Workflow System\"<\/a>, <i>Provenance and Annotation of Data<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>4145<\/b>: 118\u2013132, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F11890850_14\" target=\"_blank\">10.1007\/11890850_14<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-540-46302-3<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/11890850_14\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/11890850_14<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-01<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Provenance+Collection+Support+in+the+Kepler+Scientific+Workflow+System&rft.jtitle=Provenance+and+Annotation+of+Data&rft.aulast=Altintas&rft.aufirst=Ilkay&rft.au=Altintas%2C%26%2332%3BIlkay&rft.au=Barney%2C%26%2332%3BOscar&rft.au=Jaeger-Frank%2C%26%2332%3BEfrat&rft.date=2006&rft.volume=4145&rft.pages=118%E2%80%93132&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F11890850_14&rft.isbn=978-3-540-46302-3&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F11890850_14&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Goecks, Jeremy; Nekrutenko, Anton; Taylor, James; Galaxy Team, The (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/genomebiology.biomedcentral.com\/articles\/10.1186\/gb-2010-11-8-r86\" target=\"_blank\">\"Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences\"<\/a> (in en). <i>Genome Biology<\/i> <b>11<\/b> (8): R86. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fgb-2010-11-8-r86\" target=\"_blank\">10.1186\/gb-2010-11-8-r86<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1465-6906\" target=\"_blank\">1465-6906<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2945788\/\" target=\"_blank\">PMC2945788<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20738864\" target=\"_blank\">20738864<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/genomebiology.biomedcentral.com\/articles\/10.1186\/gb-2010-11-8-r86\" target=\"_blank\">http:\/\/genomebiology.biomedcentral.com\/articles\/10.1186\/gb-2010-11-8-r86<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Galaxy%3A+a+comprehensive+approach+for+supporting+accessible%2C+reproducible%2C+and+transparent+computational+research+in+the+life+sciences&rft.jtitle=Genome+Biology&rft.aulast=Goecks&rft.aufirst=Jeremy&rft.au=Goecks%2C%26%2332%3BJeremy&rft.au=Nekrutenko%2C%26%2332%3BAnton&rft.au=Taylor%2C%26%2332%3BJames&rft.au=Galaxy+Team%2C%26%2332%3BThe&rft.date=2010&rft.volume=11&rft.issue=8&rft.pages=R86&rft_id=info:doi\/10.1186%2Fgb-2010-11-8-r86&rft.issn=1465-6906&rft_id=info:pmc\/PMC2945788&rft_id=info:pmid\/20738864&rft_id=http%3A%2F%2Fgenomebiology.biomedcentral.com%2Farticles%2F10.1186%2Fgb-2010-11-8-r86&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-18\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_18-0\">17.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_18-1\">17.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Samuel, S.; K\u00f6nig-Ries, B. (2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ceur-ws.org\/Vol-2180\/paper-57.pdf\" target=\"_blank\">\"ProvBook: Provenance-based Semantic Enrichment of Interactive Notebooks for Reproducibility\"<\/a> (Pdf). <i>Proceedings of the ISWC 2018 Posters & Demonstrations, Industry and Blue Sky Ideas Tracks co-located with 17th International Semantic Web Conference<\/i> <b>2180<\/b><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ceur-ws.org\/Vol-2180\/paper-57.pdf\" target=\"_blank\">http:\/\/ceur-ws.org\/Vol-2180\/paper-57.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ProvBook%3A+Provenance-based+Semantic+Enrichment+of+Interactive+Notebooks+for+Reproducibility&rft.jtitle=Proceedings+of+the+ISWC+2018+Posters+%26+Demonstrations%2C+Industry+and+Blue+Sky+Ideas+Tracks+co-located+with+17th+International+Semantic+Web+Conference&rft.aulast=Samuel%2C+S.%3B+K%C3%B6nig-Ries%2C+B.&rft.au=Samuel%2C+S.%3B+K%C3%B6nig-Ries%2C+B.&rft.date=2018&rft.volume=2180&rft_id=http%3A%2F%2Fceur-ws.org%2FVol-2180%2Fpaper-57.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-19\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_19-0\">18.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_19-1\">18.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Soldatova, Larisa N; Nadis, Daniel; King, Ross D; Basu, Piyali S; Haddi, Emma; Bauml\u00e9, V\u00e9ronique; Saunders, Nigel J; Marwan, Wolfgang <i>et al.<\/i> (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-15-S14-S5\" target=\"_blank\">\"EXACT2: the semantics of biomedical protocols\"<\/a> (in en). <i>BMC Bioinformatics<\/i> <b>15<\/b> (S14): S5. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1471-2105-15-S14-S5\" target=\"_blank\">10.1186\/1471-2105-15-S14-S5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-2105\" target=\"_blank\">1471-2105<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4255744\/\" target=\"_blank\">PMC4255744<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25472549\" target=\"_blank\">25472549<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-15-S14-S5\" target=\"_blank\">https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-15-S14-S5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=EXACT2%3A+the+semantics+of+biomedical+protocols&rft.jtitle=BMC+Bioinformatics&rft.aulast=Soldatova&rft.aufirst=Larisa+N&rft.au=Soldatova%2C%26%2332%3BLarisa+N&rft.au=Nadis%2C%26%2332%3BDaniel&rft.au=King%2C%26%2332%3BRoss+D&rft.au=Basu%2C%26%2332%3BPiyali+S&rft.au=Haddi%2C%26%2332%3BEmma&rft.au=Bauml%C3%A9%2C%26%2332%3BV%C3%A9ronique&rft.au=Saunders%2C%26%2332%3BNigel+J&rft.au=Marwan%2C%26%2332%3BWolfgang&rft.au=Rudkin%2C%26%2332%3BBrian+B&rft.date=1+December+2014&rft.volume=15&rft.issue=S14&rft.pages=S5&rft_id=info:doi\/10.1186%2F1471-2105-15-S14-S5&rft.issn=1471-2105&rft_id=info:pmc\/PMC4255744&rft_id=info:pmid\/25472549&rft_id=https%3A%2F%2Fbmcbioinformatics.biomedcentral.com%2Farticles%2F10.1186%2F1471-2105-15-S14-S5&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-20\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_20-0\">19.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_20-1\">19.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Giraldo Pasm\u00edn, O.X., Corcho, O.; Castro, A.G., (2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/oa.upm.es\/36778\/\" target=\"_blank\">\"SMART Protocols: seMAntic represenTation for experimental protocols\"<\/a>. <i>Linked Science 2014: Proceedings of the 4th Workshop on Linked Science 2014 - Making Sense Out of Data<\/i>. <b>1282<\/b>. pp. 36\u201347. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 1613-0073<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/oa.upm.es\/36778\/\" target=\"_blank\">https:\/\/oa.upm.es\/36778\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=SMART+Protocols%3A+seMAntic+represenTation+for+experimental+protocols&rft.atitle=Linked+Science+2014%3A+Proceedings+of+the+4th+Workshop+on+Linked+Science+2014+-+Making+Sense+Out+of+Data&rft.aulast=Giraldo+Pasm%C3%ADn%2C+O.X.%2C+Corcho%2C+O.%3B+Castro%2C+A.G.%2C&rft.au=Giraldo+Pasm%C3%ADn%2C+O.X.%2C+Corcho%2C+O.%3B+Castro%2C+A.G.%2C&rft.date=2014&rft.volume=1282&rft.pages=pp.%26nbsp%3B36%E2%80%9347&rft.isbn=1613-0073&rft_id=https%3A%2F%2Foa.upm.es%2F36778%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hughes, Gareth; Mills, Hugo; De Roure, David; Frey, Jeremy G.; Moreau, Luc; schraefel, m. c.; Smith, Graham; Zaluska, Ed (2004). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/xlink.rsc.org\/?DOI=b410075a\" target=\"_blank\">\"The semantic smart laboratory: a system for supporting the chemical eScientist\"<\/a> (in en). <i>Organic & Biomolecular Chemistry<\/i> <b>2<\/b> (22): 3284. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1039%2Fb410075a\" target=\"_blank\">10.1039\/b410075a<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1477-0520\" target=\"_blank\">1477-0520<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/xlink.rsc.org\/?DOI=b410075a\" target=\"_blank\">http:\/\/xlink.rsc.org\/?DOI=b410075a<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+semantic+smart+laboratory%3A+a+system+for+supporting+the+chemical+eScientist&rft.jtitle=Organic+%26++Biomolecular+Chemistry&rft.aulast=Hughes&rft.aufirst=Gareth&rft.au=Hughes%2C%26%2332%3BGareth&rft.au=Mills%2C%26%2332%3BHugo&rft.au=De+Roure%2C%26%2332%3BDavid&rft.au=Frey%2C%26%2332%3BJeremy+G.&rft.au=Moreau%2C%26%2332%3BLuc&rft.au=schraefel%2C%26%2332%3Bm.+c.&rft.au=Smith%2C%26%2332%3BGraham&rft.au=Zaluska%2C%26%2332%3BEd&rft.date=2004&rft.volume=2&rft.issue=22&rft.pages=3284&rft_id=info:doi\/10.1039%2Fb410075a&rft.issn=1477-0520&rft_id=http%3A%2F%2Fxlink.rsc.org%2F%3FDOI%3Db410075a&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-22\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_22-0\">21.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_22-1\">21.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Moreau, Luc; Batlajery, Belfrit Victor; Huynh, Trung Dong; Michaelides, Danius; Packer, Heather (1 February 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7909036\/\" target=\"_blank\">\"A Templating System to Generate Provenance\"<\/a>. <i>IEEE Transactions on Software Engineering<\/i> <b>44<\/b> (2): 103\u2013121. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTSE.2017.2659745\" target=\"_blank\">10.1109\/TSE.2017.2659745<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0098-5589\" target=\"_blank\">0098-5589<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7909036\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/7909036\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Templating+System+to+Generate+Provenance&rft.jtitle=IEEE+Transactions+on+Software+Engineering&rft.aulast=Moreau&rft.aufirst=Luc&rft.au=Moreau%2C%26%2332%3BLuc&rft.au=Batlajery%2C%26%2332%3BBelfrit+Victor&rft.au=Huynh%2C%26%2332%3BTrung+Dong&rft.au=Michaelides%2C%26%2332%3BDanius&rft.au=Packer%2C%26%2332%3BHeather&rft.date=1+February+2018&rft.volume=44&rft.issue=2&rft.pages=103%E2%80%93121&rft_id=info:doi\/10.1109%2FTSE.2017.2659745&rft.issn=0098-5589&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7909036%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Curcin, Vasa; Fairweather, Elliot; Danger, Roxana; Corrigan, Derek (1 January 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046416301599\" target=\"_blank\">\"Templates as a method for implementing data provenance in decision support systems\"<\/a> (in en). <i>Journal of Biomedical Informatics<\/i> <b>65<\/b>: 1\u201321. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbi.2016.10.022\" target=\"_blank\">10.1016\/j.jbi.2016.10.022<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046416301599\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046416301599<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Templates+as+a+method+for+implementing+data+provenance+in+decision+support+systems&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Curcin&rft.aufirst=Vasa&rft.au=Curcin%2C%26%2332%3BVasa&rft.au=Fairweather%2C%26%2332%3BElliot&rft.au=Danger%2C%26%2332%3BRoxana&rft.au=Corrigan%2C%26%2332%3BDerek&rft.date=1+January+2017&rft.volume=65&rft.pages=1%E2%80%9321&rft_id=info:doi\/10.1016%2Fj.jbi.2016.10.022&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046416301599&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vogt, Lars; D'Souza, Jennifer; Stocker, Markus; Auer, S\u00f6ren (1 August 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3383583.3398530\" target=\"_blank\">\"Toward Representing Research Contributions in Scholarly Knowledge Graphs Using Knowledge Graph Cells\"<\/a> (in en). <i>Proceedings of the ACM\/IEEE Joint Conference on Digital Libraries in 2020<\/i> (Virtual Event China: ACM): 107\u2013116. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F3383583.3398530\" target=\"_blank\">10.1145\/3383583.3398530<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-7585-6<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/3383583.3398530\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/3383583.3398530<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Toward+Representing+Research+Contributions+in+Scholarly+Knowledge+Graphs+Using+Knowledge+Graph+Cells&rft.jtitle=Proceedings+of+the+ACM%2FIEEE+Joint+Conference+on+Digital+Libraries+in+2020&rft.aulast=Vogt&rft.aufirst=Lars&rft.au=Vogt%2C%26%2332%3BLars&rft.au=D%27Souza%2C%26%2332%3BJennifer&rft.au=Stocker%2C%26%2332%3BMarkus&rft.au=Auer%2C%26%2332%3BS%C3%B6ren&rft.date=1+August+2020&rft.pages=107%E2%80%93116&rft.place=Virtual+Event+China&rft.pub=ACM&rft_id=info:doi\/10.1145%2F3383583.3398530&rft.isbn=978-1-4503-7585-6&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F3383583.3398530&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFSamuelK.C3.B6nig-Ries2017\">Samuel, Sheeba; K\u00f6nig-Ries, Birgitta (2017), Blomqvist, Eva; Hose, Katja; Paulheim, Heiko <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-70407-4_4\" target=\"_blank\">\"REPRODUCE-ME: Ontology-Based Data Access for Reproducibility of Microscopy Experiments\"<\/a>, <i>The Semantic Web: ESWC 2017 Satellite Events<\/i> (Cham: Springer International Publishing) <b>10577<\/b>: 17\u201320, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-70407-4_4\" target=\"_blank\">10.1007\/978-3-319-70407-4_4<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-70406-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-70407-4_4\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-70407-4_4<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-01<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=REPRODUCE-ME%3A+Ontology-Based+Data+Access+for+Reproducibility+of+Microscopy+Experiments&rft.jtitle=The+Semantic+Web%3A+ESWC+2017+Satellite+Events&rft.aulast=Samuel&rft.aufirst=Sheeba&rft.au=Samuel%2C%26%2332%3BSheeba&rft.au=K%C3%B6nig-Ries%2C%26%2332%3BBirgitta&rft.date=2017&rft.volume=10577&rft.pages=17%E2%80%9320&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-70407-4_4&rft.isbn=978-3-319-70406-7&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-70407-4_4&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-26\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_26-0\">25.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_26-1\">25.1<\/a><\/sup> <sup><a href=\"#cite_ref-:12_26-2\">25.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Moreau, Luc; Groth, Paul; Cheney, James; Lebo, Timothy; Miles, Simon (1 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1570826815000177\" target=\"_blank\">\"The rationale of PROV\"<\/a> (in en). <i>Journal of Web Semantics<\/i> <b>35<\/b>: 235\u2013257. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.websem.2015.04.001\" target=\"_blank\">10.1016\/j.websem.2015.04.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1570826815000177\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1570826815000177<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+rationale+of+PROV&rft.jtitle=Journal+of+Web+Semantics&rft.aulast=Moreau&rft.aufirst=Luc&rft.au=Moreau%2C%26%2332%3BLuc&rft.au=Groth%2C%26%2332%3BPaul&rft.au=Cheney%2C%26%2332%3BJames&rft.au=Lebo%2C%26%2332%3BTimothy&rft.au=Miles%2C%26%2332%3BSimon&rft.date=1+December+2015&rft.volume=35&rft.pages=235%E2%80%93257&rft_id=info:doi\/10.1016%2Fj.websem.2015.04.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1570826815000177&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ciccarese, Paolo; Soiland-Reyes, Stian; Belhajjame, Khalid; Gray, Alasdair JG; Goble, Carole; Clark, Tim (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-4-37\" target=\"_blank\">\"PAV ontology: provenance, authoring and versioning\"<\/a> (in en). <i>Journal of Biomedical Semantics<\/i> <b>4<\/b> (1): 37. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F2041-1480-4-37\" target=\"_blank\">10.1186\/2041-1480-4-37<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2041-1480\" target=\"_blank\">2041-1480<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4177195\/\" target=\"_blank\">PMC4177195<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24267948\" target=\"_blank\">24267948<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-4-37\" target=\"_blank\">http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-4-37<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=PAV+ontology%3A+provenance%2C+authoring+and+versioning&rft.jtitle=Journal+of+Biomedical+Semantics&rft.aulast=Ciccarese&rft.aufirst=Paolo&rft.au=Ciccarese%2C%26%2332%3BPaolo&rft.au=Soiland-Reyes%2C%26%2332%3BStian&rft.au=Belhajjame%2C%26%2332%3BKhalid&rft.au=Gray%2C%26%2332%3BAlasdair+JG&rft.au=Goble%2C%26%2332%3BCarole&rft.au=Clark%2C%26%2332%3BTim&rft.date=2013&rft.volume=4&rft.issue=1&rft.pages=37&rft_id=info:doi\/10.1186%2F2041-1480-4-37&rft.issn=2041-1480&rft_id=info:pmc\/PMC4177195&rft_id=info:pmid\/24267948&rft_id=http%3A%2F%2Fjbiomedsem.biomedcentral.com%2Farticles%2F10.1186%2F2041-1480-4-37&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:13-28\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:13_28-0\">27.0<\/a><\/sup> <sup><a href=\"#cite_ref-:13_28-1\">27.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">The OBI Consortium; Smith, Barry; Ashburner, Michael; Rosse, Cornelius; Bard, Jonathan; Bug, William; Ceusters, Werner; Goldberg, Louis J <i>et al.<\/i> (1 November 2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/nbt1346\" target=\"_blank\">\"The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration\"<\/a> (in en). <i>Nature Biotechnology<\/i> <b>25<\/b> (11): 1251\u20131255. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fnbt1346\" target=\"_blank\">10.1038\/nbt1346<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1087-0156\" target=\"_blank\">1087-0156<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2814061\/\" target=\"_blank\">PMC2814061<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17989687\" target=\"_blank\">17989687<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/nbt1346\" target=\"_blank\">http:\/\/www.nature.com\/articles\/nbt1346<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+OBO+Foundry%3A+coordinated+evolution+of+ontologies+to+support+biomedical+data+integration&rft.jtitle=Nature+Biotechnology&rft.aulast=The+OBI+Consortium&rft.au=The+OBI+Consortium&rft.au=Smith%2C%26%2332%3BBarry&rft.au=Ashburner%2C%26%2332%3BMichael&rft.au=Rosse%2C%26%2332%3BCornelius&rft.au=Bard%2C%26%2332%3BJonathan&rft.au=Bug%2C%26%2332%3BWilliam&rft.au=Ceusters%2C%26%2332%3BWerner&rft.au=Goldberg%2C%26%2332%3BLouis+J&rft.au=Eilbeck%2C%26%2332%3BKaren&rft.date=1+November+2007&rft.volume=25&rft.issue=11&rft.pages=1251%E2%80%931255&rft_id=info:doi\/10.1038%2Fnbt1346&rft.issn=1087-0156&rft_id=info:pmc\/PMC2814061&rft_id=info:pmid\/17989687&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fnbt1346&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:14-29\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:14_29-0\">28.0<\/a><\/sup> <sup><a href=\"#cite_ref-:14_29-1\">28.1<\/a><\/sup> <sup><a href=\"#cite_ref-:14_29-2\">28.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Smith, B.; 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(2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ontology.buffalo.edu\/smith\/articles\/BFO_for_bioinformatics.pdf\" target=\"_blank\">\"Basic Formal Ontology for Bioinformatics\"<\/a> (PDF). <i>IFOMIS Reports<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ontology.buffalo.edu\/smith\/articles\/BFO_for_bioinformatics.pdf\" target=\"_blank\">http:\/\/ontology.buffalo.edu\/smith\/articles\/BFO_for_bioinformatics.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Basic+Formal+Ontology+for+Bioinformatics&rft.atitle=IFOMIS+Reports&rft.aulast=Smith%2C+B.%3B+Kumar%2C+A.%3B+Bittner%2C+T.&rft.au=Smith%2C+B.%3B+Kumar%2C+A.%3B+Bittner%2C+T.&rft.date=2005&rft_id=http%3A%2F%2Fontology.buffalo.edu%2Fsmith%2Farticles%2FBFO_for_bioinformatics.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bartusch, F.; Hanussek, M.; Kr\u00fcger, J. 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Atkinson, M.; Gesing, S.. ed. <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ceur-ws.org\/Vol-2357\/paper8.pdf\" target=\"_blank\">\"Automatic generation of provenance metadata during execution of scientific workflows\"<\/a> (PDF). <i>Proceedings of the 10th International Workshop on Science Gateways<\/i> <b>2357<\/b>: 1\u20136<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ceur-ws.org\/Vol-2357\/paper8.pdf\" target=\"_blank\">http:\/\/ceur-ws.org\/Vol-2357\/paper8.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Automatic+generation+of+provenance+metadata+during+execution+of+scientific+workflows&rft.jtitle=Proceedings+of+the+10th+International+Workshop+on+Science+Gateways&rft.aulast=Bartusch%2C+F.%3B+Hanussek%2C+M.%3B+Kr%C3%BCger%2C+J.&rft.au=Bartusch%2C+F.%3B+Hanussek%2C+M.%3B+Kr%C3%BCger%2C+J.&rft.date=2018&rft.volume=2357&rft.pages=1%E2%80%936&rft_id=http%3A%2F%2Fceur-ws.org%2FVol-2357%2Fpaper8.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFMurtaBraganholoChirigatiKoop2015\">Murta, Leonardo; Braganholo, Vanessa; Chirigati, Fernando; Koop, David; Freire, Juliana (2015), Lud\u00e4scher, Bertram; Plale, Beth, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-16462-5_6\" target=\"_blank\">\"noWorkflow: Capturing and Analyzing Provenance of Scripts\"<\/a> (in en), <i>Provenance and Annotation of Data and Processes<\/i> (Cham: Springer International Publishing) <b>8628<\/b>: 71\u201383, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-16462-5_6\" target=\"_blank\">10.1007\/978-3-319-16462-5_6<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-16461-8<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-16462-5_6\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-16462-5_6<\/a><\/span><span class=\"reference-accessdate\">. 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Frew, James (1 March 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/1057977.1057978\" target=\"_blank\">\"Lineage retrieval for scientific data processing: a survey\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>37<\/b> (1): 1\u201328. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1057977.1057978\" target=\"_blank\">10.1145\/1057977.1057978<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/1057977.1057978\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/1057977.1057978<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Lineage+retrieval+for+scientific+data+processing%3A+a+survey&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Bose&rft.aufirst=Rajendra&rft.au=Bose%2C%26%2332%3BRajendra&rft.au=Frew%2C%26%2332%3BJames&rft.date=1+March+2005&rft.volume=37&rft.issue=1&rft.pages=1%E2%80%9328&rft_id=info:doi\/10.1145%2F1057977.1057978&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F1057977.1057978&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-33\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Davidson, Susan B.; Freire, Juliana (2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1376616.1376772\" target=\"_blank\">\"Provenance and scientific workflows: challenges and opportunities\"<\/a> (in en). <i>Proceedings of the 2008 ACM SIGMOD international conference on Management of data - SIGMOD '08<\/i> (Vancouver, Canada: ACM Press): 1345. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1376616.1376772\" target=\"_blank\">10.1145\/1376616.1376772<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-60558-102-6<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1376616.1376772\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=1376616.1376772<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Provenance+and+scientific+workflows%3A+challenges+and+opportunities&rft.jtitle=Proceedings+of+the+2008+ACM+SIGMOD+international+conference+on+Management+of+data++-+SIGMOD+%2708&rft.aulast=Davidson&rft.aufirst=Susan+B.&rft.au=Davidson%2C%26%2332%3BSusan+B.&rft.au=Freire%2C%26%2332%3BJuliana&rft.date=2008&rft.pages=1345&rft.place=Vancouver%2C+Canada&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F1376616.1376772&rft.isbn=978-1-60558-102-6&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D1376616.1376772&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-34\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Deelman, Ewa; Gannon, Dennis; Shields, Matthew; Taylor, Ian (1 May 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167739X08000861\" target=\"_blank\">\"Workflows and e-Science: An overview of workflow system features and capabilities\"<\/a> (in en). <i>Future Generation Computer Systems<\/i> <b>25<\/b> (5): 528\u2013540. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.future.2008.06.012\" target=\"_blank\">10.1016\/j.future.2008.06.012<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167739X08000861\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167739X08000861<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Workflows+and+e-Science%3A+An+overview+of+workflow+system+features+and+capabilities&rft.jtitle=Future+Generation+Computer+Systems&rft.aulast=Deelman&rft.aufirst=Ewa&rft.au=Deelman%2C%26%2332%3BEwa&rft.au=Gannon%2C%26%2332%3BDennis&rft.au=Shields%2C%26%2332%3BMatthew&rft.au=Taylor%2C%26%2332%3BIan&rft.date=1+May+2009&rft.volume=25&rft.issue=5&rft.pages=528%E2%80%93540&rft_id=info:doi\/10.1016%2Fj.future.2008.06.012&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0167739X08000861&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Budde, Kai; Zimmermann, Julius; Neuhaus, Elisa; Schroder, Max; Uhrmacher, Adelinde M.; van Rienen, Ursula (1 July 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8856863\/\" target=\"_blank\">\"Requirements for Documenting Electrical Cell Stimulation Experiments for Replicability and Numerical Modeling \u2217\"<\/a>. <i>2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)<\/i> (Berlin, Germany: IEEE): 1082\u20131088. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FEMBC.2019.8856863\" target=\"_blank\">10.1109\/EMBC.2019.8856863<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-5386-1311-5<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8856863\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8856863\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Requirements+for+Documenting+Electrical+Cell+Stimulation+Experiments+for+Replicability+and+Numerical+Modeling+%E2%88%97&rft.jtitle=2019+41st+Annual+International+Conference+of+the+IEEE+Engineering+in+Medicine+and+Biology+Society+%28EMBC%29&rft.aulast=Budde&rft.aufirst=Kai&rft.au=Budde%2C%26%2332%3BKai&rft.au=Zimmermann%2C%26%2332%3BJulius&rft.au=Neuhaus%2C%26%2332%3BElisa&rft.au=Schroder%2C%26%2332%3BMax&rft.au=Uhrmacher%2C%26%2332%3BAdelinde+M.&rft.au=van+Rienen%2C%26%2332%3BUrsula&rft.date=1+July+2019&rft.pages=1082%E2%80%931088&rft.place=Berlin%2C+Germany&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FEMBC.2019.8856863&rft.isbn=978-1-5386-1311-5&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8856863%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-MIACA-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-MIACA_36-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">MIACA Standards Initiative (2006). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/miaca.sourceforge.net\/\" target=\"_blank\">\"MIACA - Minimum Information About a Cellular Assay\"<\/a>. <i>SourceForge<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/miaca.sourceforge.net\/\" target=\"_blank\">http:\/\/miaca.sourceforge.net\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=MIACA+-+Minimum+Information+About+a+Cellular+Assay&rft.atitle=SourceForge&rft.aulast=MIACA+Standards+Initiative&rft.au=MIACA+Standards+Initiative&rft.date=2006&rft_id=http%3A%2F%2Fmiaca.sourceforge.net%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rasmussen, Karsten Boye; Blank, Grant (1 March 2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10502-006-9036-0\" target=\"_blank\">\"The data documentation initiative: a preservation standard for research\"<\/a> (in en). <i>Archival Science<\/i> <b>7<\/b> (1): 55\u201371. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10502-006-9036-0\" target=\"_blank\">10.1007\/s10502-006-9036-0<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1389-0166\" target=\"_blank\">1389-0166<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10502-006-9036-0\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10502-006-9036-0<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+data+documentation+initiative%3A+a+preservation+standard+for+research&rft.jtitle=Archival+Science&rft.aulast=Rasmussen&rft.aufirst=Karsten+Boye&rft.au=Rasmussen%2C%26%2332%3BKarsten+Boye&rft.au=Blank%2C%26%2332%3BGrant&rft.date=1+March+2007&rft.volume=7&rft.issue=1&rft.pages=55%E2%80%9371&rft_id=info:doi\/10.1007%2Fs10502-006-9036-0&rft.issn=1389-0166&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10502-006-9036-0&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Weibel, S.; Kunze, J.; Lagoze, C.; Wolf, M. (1 September 1998) (in en). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc2413\" target=\"_blank\"><i>Dublin Core Metadata for Resource Discovery<\/i><\/a>. pp. RFC2413. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17487%2Frfc2413\" target=\"_blank\">10.17487\/rfc2413<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc2413\" target=\"_blank\">https:\/\/www.rfc-editor.org\/info\/rfc2413<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Dublin+Core+Metadata+for+Resource+Discovery&rft.aulast=Weibel&rft.aufirst=S.&rft.au=Weibel%2C%26%2332%3BS.&rft.au=Kunze%2C%26%2332%3BJ.&rft.au=Lagoze%2C%26%2332%3BC.&rft.au=Wolf%2C%26%2332%3BM.&rft.date=1+September+1998&rft.pages=pp.+RFC2413&rft_id=info:doi\/10.17487%2Frfc2413&rft_id=https%3A%2F%2Fwww.rfc-editor.org%2Finfo%2Frfc2413&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kunze, J.; Baker, T. (1 August 2007) (in en). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc5013\" target=\"_blank\"><i>The Dublin Core Metadata Element Set<\/i><\/a>. pp. RFC5013. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17487%2Frfc5013\" target=\"_blank\">10.17487\/rfc5013<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc5013\" target=\"_blank\">https:\/\/www.rfc-editor.org\/info\/rfc5013<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+Dublin+Core+Metadata+Element+Set&rft.aulast=Kunze&rft.aufirst=J.&rft.au=Kunze%2C%26%2332%3BJ.&rft.au=Baker%2C%26%2332%3BT.&rft.date=1+August+2007&rft.pages=pp.+RFC5013&rft_id=info:doi\/10.17487%2Frfc5013&rft_id=https%3A%2F%2Fwww.rfc-editor.org%2Finfo%2Frfc5013&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Albertoni, R.; Browning, D.; Cox, S. et al. (4 February 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/TR\/2020\/REC-vocab-dcat-2-20200204\/\" target=\"_blank\">\"Data Catalog Vocabulary (DCAT) - Version 2\"<\/a>. W3C<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.w3.org\/TR\/2020\/REC-vocab-dcat-2-20200204\/\" target=\"_blank\">https:\/\/www.w3.org\/TR\/2020\/REC-vocab-dcat-2-20200204\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Data+Catalog+Vocabulary+%28DCAT%29+-+Version+2&rft.atitle=&rft.aulast=Albertoni%2C+R.%3B+Browning%2C+D.%3B+Cox%2C+S.+et+al.&rft.au=Albertoni%2C+R.%3B+Browning%2C+D.%3B+Cox%2C+S.+et+al.&rft.date=4+February+2020&rft.pub=W3C&rft_id=https%3A%2F%2Fwww.w3.org%2FTR%2F2020%2FREC-vocab-dcat-2-20200204%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kunis, S. (22 October 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/zenodo.org\/record\/5591958\" target=\"_blank\">\"Workgroup RDM4mic - Research data management for microscopy\"<\/a>. <i>Zenodo<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5281%2Fzenodo.5591958\" target=\"_blank\">10.5281\/zenodo.5591958<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/zenodo.org\/record\/5591958\" target=\"_blank\">https:\/\/zenodo.org\/record\/5591958<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Workgroup+RDM4mic+-+Research+data+management+for+microscopy&rft.jtitle=Zenodo&rft.aulast=Kunis%2C+S.&rft.au=Kunis%2C+S.&rft.date=22+October+2021&rft_id=info:doi\/10.5281%2Fzenodo.5591958&rft_id=https%3A%2F%2Fzenodo.org%2Frecord%2F5591958&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Buchanan, Erin M.; Crain, Sarah E.; Cunningham, Ari L.; Johnson, Hannah R.; Stash, Hannah; Papadatou-Pastou, Marietta; Isager, Peder M.; Carlsson, Rickard <i>et al.<\/i> (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/2515245920928007\" target=\"_blank\">\"Getting Started Creating Data Dictionaries: How to Create a Shareable Data Set\"<\/a> (in en). <i>Advances in Methods and Practices in Psychological Science<\/i> <b>4<\/b> (1): 251524592092800. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F2515245920928007\" target=\"_blank\">10.1177\/2515245920928007<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2515-2459\" target=\"_blank\">2515-2459<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/2515245920928007\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/2515245920928007<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Getting+Started+Creating+Data+Dictionaries%3A+How+to+Create+a+Shareable+Data+Set&rft.jtitle=Advances+in+Methods+and+Practices+in+Psychological+Science&rft.aulast=Buchanan&rft.aufirst=Erin+M.&rft.au=Buchanan%2C%26%2332%3BErin+M.&rft.au=Crain%2C%26%2332%3BSarah+E.&rft.au=Cunningham%2C%26%2332%3BAri+L.&rft.au=Johnson%2C%26%2332%3BHannah+R.&rft.au=Stash%2C%26%2332%3BHannah&rft.au=Papadatou-Pastou%2C%26%2332%3BMarietta&rft.au=Isager%2C%26%2332%3BPeder+M.&rft.au=Carlsson%2C%26%2332%3BRickard&rft.au=Aczel%2C%26%2332%3BBalazs&rft.date=1+January+2021&rft.volume=4&rft.issue=1&rft.pages=251524592092800&rft_id=info:doi\/10.1177%2F2515245920928007&rft.issn=2515-2459&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F2515245920928007&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rashid, Sabbir M.; McCusker, James P.; Pinheiro, Paulo; Bax, Marcello P.; Santos, Henrique O.; Stingone, Jeanette A.; Das, Amar K.; McGuinness, Deborah L. (1 October 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/direct.mit.edu\/dint\/article\/2\/4\/443-486\/94892\" target=\"_blank\">\"The Semantic Data Dictionary \u2013 An Approach for Describing and Annotating Data\"<\/a> (in en). <i>Data Intelligence<\/i> <b>2<\/b> (4): 443\u2013486. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1162%2Fdint_a_00058\" target=\"_blank\">10.1162\/dint_a_00058<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2641-435X\" target=\"_blank\">2641-435X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7583433\/\" target=\"_blank\">PMC7583433<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33103120\" target=\"_blank\">33103120<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/direct.mit.edu\/dint\/article\/2\/4\/443-486\/94892\" target=\"_blank\">https:\/\/direct.mit.edu\/dint\/article\/2\/4\/443-486\/94892<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Semantic+Data+Dictionary+%E2%80%93+An+Approach+for+Describing+and+Annotating+Data&rft.jtitle=Data+Intelligence&rft.aulast=Rashid&rft.aufirst=Sabbir+M.&rft.au=Rashid%2C%26%2332%3BSabbir+M.&rft.au=McCusker%2C%26%2332%3BJames+P.&rft.au=Pinheiro%2C%26%2332%3BPaulo&rft.au=Bax%2C%26%2332%3BMarcello+P.&rft.au=Santos%2C%26%2332%3BHenrique+O.&rft.au=Stingone%2C%26%2332%3BJeanette+A.&rft.au=Das%2C%26%2332%3BAmar+K.&rft.au=McGuinness%2C%26%2332%3BDeborah+L.&rft.date=1+October+2020&rft.volume=2&rft.issue=4&rft.pages=443%E2%80%93486&rft_id=info:doi\/10.1162%2Fdint_a_00058&rft.issn=2641-435X&rft_id=info:pmc\/PMC7583433&rft_id=info:pmid\/33103120&rft_id=https%3A%2F%2Fdirect.mit.edu%2Fdint%2Farticle%2F2%2F4%2F443-486%2F94892&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kunze, J.; Littman, J.; Madden, E.; Scancella, J.; Adams, C. (1 October 2018) (in en). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc8493\" target=\"_blank\"><i>The BagIt File Packaging Format (V1.0)<\/i><\/a>. pp. RFC8493. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17487%2Frfc8493\" target=\"_blank\">10.17487\/rfc8493<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.rfc-editor.org\/info\/rfc8493\" target=\"_blank\">https:\/\/www.rfc-editor.org\/info\/rfc8493<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+BagIt+File+Packaging+Format+%28V1.0%29&rft.aulast=Kunze&rft.aufirst=J.&rft.au=Kunze%2C%26%2332%3BJ.&rft.au=Littman%2C%26%2332%3BJ.&rft.au=Madden%2C%26%2332%3BE.&rft.au=Scancella%2C%26%2332%3BJ.&rft.au=Adams%2C%26%2332%3BC.&rft.date=1+October+2018&rft.pages=pp.+RFC8493&rft_id=info:doi\/10.17487%2Frfc8493&rft_id=https%3A%2F%2Fwww.rfc-editor.org%2Finfo%2Frfc8493&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hankinson, Andrew; Brower, Donald; Jefferies, Neil; Metz, Rosalyn; Morley, Julian; Warner, Simeon; Woods, Andrew (4 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2304-6775\/7\/2\/39\" target=\"_blank\">\"The Oxford Common File Layout: A Common Approach to Digital Preservation\"<\/a> (in en). <i>Publications<\/i> <b>7<\/b> (2): 39. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fpublications7020039\" target=\"_blank\">10.3390\/publications7020039<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2304-6775\" target=\"_blank\">2304-6775<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2304-6775\/7\/2\/39\" target=\"_blank\">https:\/\/www.mdpi.com\/2304-6775\/7\/2\/39<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Oxford+Common+File+Layout%3A+A+Common+Approach+to+Digital+Preservation&rft.jtitle=Publications&rft.aulast=Hankinson&rft.aufirst=Andrew&rft.au=Hankinson%2C%26%2332%3BAndrew&rft.au=Brower%2C%26%2332%3BDonald&rft.au=Jefferies%2C%26%2332%3BNeil&rft.au=Metz%2C%26%2332%3BRosalyn&rft.au=Morley%2C%26%2332%3BJulian&rft.au=Warner%2C%26%2332%3BSimeon&rft.au=Woods%2C%26%2332%3BAndrew&rft.date=4+June+2019&rft.volume=7&rft.issue=2&rft.pages=39&rft_id=info:doi\/10.3390%2Fpublications7020039&rft.issn=2304-6775&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2304-6775%2F7%2F2%2F39&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:15-46\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:15_46-0\">45.0<\/a><\/sup> <sup><a href=\"#cite_ref-:15_46-1\">45.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Carrag\u00e1in, Eoghan \u00d3; Goble, Carole; Sefton, Peter; Soiland-Reyes, Stian (20 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/zenodo.org\/record\/3250687\" target=\"_blank\"><i>A lightweight approach to research object data packaging<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5281%2FZENODO.3250687\" target=\"_blank\">10.5281\/ZENODO.3250687<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/zenodo.org\/record\/3250687\" target=\"_blank\">https:\/\/zenodo.org\/record\/3250687<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=A+lightweight+approach+to+research+object+data+packaging&rft.aulast=Carrag%C3%A1in&rft.aufirst=Eoghan+%C3%93&rft.au=Carrag%C3%A1in%2C%26%2332%3BEoghan+%C3%93&rft.au=Goble%2C%26%2332%3BCarole&rft.au=Sefton%2C%26%2332%3BPeter&rft.au=Soiland-Reyes%2C%26%2332%3BStian&rft.date=20+June+2019&rft_id=info:doi\/10.5281%2FZENODO.3250687&rft_id=https%3A%2F%2Fzenodo.org%2Frecord%2F3250687&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-47\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-47\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chard, Kyle; Gaffney, Niall; Jones, Matthew B.; Kowalik, Kacper; Ludascher, Bertram; McPhillips, Timothy; Nabrzyski, Jarek; Stodden, Victoria <i>et al.<\/i> (1 September 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/9041738\/\" target=\"_blank\">\"Application of BagIt-Serialized Research Object Bundles for Packaging and Re-Execution of Computational Analyses\"<\/a>. <i>2019 15th International Conference on eScience (eScience)<\/i> (San Diego, CA, USA: IEEE): 514\u2013521. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FeScience.2019.00068\" target=\"_blank\">10.1109\/eScience.2019.00068<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-7281-2451-3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/9041738\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/9041738\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Application+of+BagIt-Serialized+Research+Object+Bundles+for+Packaging+and+Re-Execution+of+Computational+Analyses&rft.jtitle=2019+15th+International+Conference+on+eScience+%28eScience%29&rft.aulast=Chard&rft.aufirst=Kyle&rft.au=Chard%2C%26%2332%3BKyle&rft.au=Gaffney%2C%26%2332%3BNiall&rft.au=Jones%2C%26%2332%3BMatthew+B.&rft.au=Kowalik%2C%26%2332%3BKacper&rft.au=Ludascher%2C%26%2332%3BBertram&rft.au=McPhillips%2C%26%2332%3BTimothy&rft.au=Nabrzyski%2C%26%2332%3BJarek&rft.au=Stodden%2C%26%2332%3BVictoria&rft.au=Taylor%2C%26%2332%3BIan&rft.date=1+September+2019&rft.pages=514%E2%80%93521&rft.place=San+Diego%2C+CA%2C+USA&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FeScience.2019.00068&rft.isbn=978-1-7281-2451-3&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F9041738%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Musen, Mark A. (16 June 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2757001.2757003\" target=\"_blank\">\"The prot\u00e9g\u00e9 project: a look back and a look forward\"<\/a> (in en). <i>AI Matters<\/i> <b>1<\/b> (4): 4\u201312. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2757001.2757003\" target=\"_blank\">10.1145\/2757001.2757003<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2372-3483\" target=\"_blank\">2372-3483<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4883684\/\" target=\"_blank\">PMC4883684<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27239556\" target=\"_blank\">27239556<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2757001.2757003\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/2757001.2757003<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+prot%C3%A9g%C3%A9+project%3A+a+look+back+and+a+look+forward&rft.jtitle=AI+Matters&rft.aulast=Musen&rft.aufirst=Mark+A.&rft.au=Musen%2C%26%2332%3BMark+A.&rft.date=16+June+2015&rft.volume=1&rft.issue=4&rft.pages=4%E2%80%9312&rft_id=info:doi\/10.1145%2F2757001.2757003&rft.issn=2372-3483&rft_id=info:pmc\/PMC4883684&rft_id=info:pmid\/27239556&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F2757001.2757003&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-BioPortal-49\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-BioPortal_49-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">National Center for Biomedical Ontology (2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/bioportal.bioontology.org\/\" target=\"_blank\">\"BioPortal\"<\/a>. Board of Trustees of Leland Stanford Junior University<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/bioportal.bioontology.org\/\" target=\"_blank\">https:\/\/bioportal.bioontology.org\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=BioPortal&rft.atitle=&rft.aulast=National+Center+for+Biomedical+Ontology&rft.au=National+Center+for+Biomedical+Ontology&rft.date=2021&rft.pub=Board+of+Trustees+of+Leland+Stanford+Junior+University&rft_id=https%3A%2F%2Fbioportal.bioontology.org%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-50\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-50\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ong, Edison; Xiang, Zuoshuang; Zhao, Bin; Liu, Yue; Lin, Yu; Zheng, Jie; Mungall, Chris; Courtot, M\u00e9lanie <i>et al.<\/i> (4 January 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/27733503\" target=\"_blank\">\"Ontobee: A linked ontology data server to support ontology term dereferencing, linkage, query and integration\"<\/a>. <i>Nucleic Acids Research<\/i> <b>45<\/b> (D1): D347\u2013D352. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fnar%2Fgkw918\" target=\"_blank\">10.1093\/nar\/gkw918<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1362-4962\" target=\"_blank\">1362-4962<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/5210626\/\" target=\"_blank\">5210626<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27733503\" target=\"_blank\">27733503<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/27733503\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/27733503<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ontobee%3A+A+linked+ontology+data+server+to+support+ontology+term+dereferencing%2C+linkage%2C+query+and+integration&rft.jtitle=Nucleic+Acids+Research&rft.aulast=Ong&rft.aufirst=Edison&rft.au=Ong%2C%26%2332%3BEdison&rft.au=Xiang%2C%26%2332%3BZuoshuang&rft.au=Zhao%2C%26%2332%3BBin&rft.au=Liu%2C%26%2332%3BYue&rft.au=Lin%2C%26%2332%3BYu&rft.au=Zheng%2C%26%2332%3BJie&rft.au=Mungall%2C%26%2332%3BChris&rft.au=Courtot%2C%26%2332%3BM%C3%A9lanie&rft.au=Ruttenberg%2C%26%2332%3BAlan&rft.date=4+January+2017&rft.volume=45&rft.issue=D1&rft.pages=D347%E2%80%93D352&rft_id=info:doi\/10.1093%2Fnar%2Fgkw918&rft.issn=1362-4962&rft_id=info:pmc\/5210626&rft_id=info:pmid\/27733503&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F27733503&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-51\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-51\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vrande\u010di\u0107, Denny; Kr\u00f6tzsch, Markus (23 September 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2629489\" target=\"_blank\">\"Wikidata: a free collaborative knowledgebase\"<\/a> (in en). <i>Communications of the ACM<\/i> <b>57<\/b> (10): 78\u201385. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2629489\" target=\"_blank\">10.1145\/2629489<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0001-0782\" target=\"_blank\">0001-0782<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2629489\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/2629489<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Wikidata%3A+a+free+collaborative+knowledgebase&rft.jtitle=Communications+of+the+ACM&rft.aulast=Vrande%C4%8Di%C4%87&rft.aufirst=Denny&rft.au=Vrande%C4%8Di%C4%87%2C%26%2332%3BDenny&rft.au=Kr%C3%B6tzsch%2C%26%2332%3BMarkus&rft.date=23+September+2014&rft.volume=57&rft.issue=10&rft.pages=78%E2%80%9385&rft_id=info:doi\/10.1145%2F2629489&rft.issn=0001-0782&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F2629489&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-HylandLinked13-52\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-HylandLinked13_52-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Hyland, B.; Atemezing, G.; Pendleton, M. et al., ed. (27 June 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dvcs.w3.org\/hg\/gld\/raw-file\/default\/glossary\/index.html\" target=\"_blank\">\"Linked Data Glossary\"<\/a>. W3C<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dvcs.w3.org\/hg\/gld\/raw-file\/default\/glossary\/index.html\" target=\"_blank\">https:\/\/dvcs.w3.org\/hg\/gld\/raw-file\/default\/glossary\/index.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Linked+Data+Glossary&rft.atitle=&rft.date=27+June+2013&rft.pub=W3C&rft_id=https%3A%2F%2Fdvcs.w3.org%2Fhg%2Fgld%2Fraw-file%2Fdefault%2Fglossary%2Findex.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-53\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-53\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Heath, Tom; Bizer, Christian (9 February 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00334ED1V01Y201102WBE001\" target=\"_blank\">\"Linked Data: Evolving the Web into a Global Data Space\"<\/a> (in en). <i>Synthesis Lectures on the Semantic Web: Theory and Technology<\/i> <b>1<\/b> (1): 1\u2013136. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2200%2FS00334ED1V01Y201102WBE001\" target=\"_blank\">10.2200\/S00334ED1V01Y201102WBE001<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2160-4711\" target=\"_blank\">2160-4711<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00334ED1V01Y201102WBE001\" target=\"_blank\">http:\/\/www.morganclaypool.com\/doi\/abs\/10.2200\/S00334ED1V01Y201102WBE001<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Linked+Data%3A+Evolving+the+Web+into+a+Global+Data+Space&rft.jtitle=Synthesis+Lectures+on+the+Semantic+Web%3A+Theory+and+Technology&rft.aulast=Heath&rft.aufirst=Tom&rft.au=Heath%2C%26%2332%3BTom&rft.au=Bizer%2C%26%2332%3BChristian&rft.date=9+February+2011&rft.volume=1&rft.issue=1&rft.pages=1%E2%80%93136&rft_id=info:doi\/10.2200%2FS00334ED1V01Y201102WBE001&rft.issn=2160-4711&rft_id=http%3A%2F%2Fwww.morganclaypool.com%2Fdoi%2Fabs%2F10.2200%2FS00334ED1V01Y201102WBE001&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-54\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-54\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gkoutos, G. V.; Schofield, P. N.; Hoehndorf, R. (10 October 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/database\/article-lookup\/doi\/10.1093\/database\/bas033\" target=\"_blank\">\"The Units Ontology: a tool for integrating units of measurement in science\"<\/a> (in en). <i>Database<\/i> <b>2012<\/b> (0): bas033\u2013bas033. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fdatabase%2Fbas033\" target=\"_blank\">10.1093\/database\/bas033<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1758-0463\" target=\"_blank\">1758-0463<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3468815\/\" target=\"_blank\">PMC3468815<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23060432\" target=\"_blank\">23060432<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/database\/article-lookup\/doi\/10.1093\/database\/bas033\" target=\"_blank\">https:\/\/academic.oup.com\/database\/article-lookup\/doi\/10.1093\/database\/bas033<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Units+Ontology%3A+a+tool+for+integrating+units+of+measurement+in+science&rft.jtitle=Database&rft.aulast=Gkoutos&rft.aufirst=G.+V.&rft.au=Gkoutos%2C%26%2332%3BG.+V.&rft.au=Schofield%2C%26%2332%3BP.+N.&rft.au=Hoehndorf%2C%26%2332%3BR.&rft.date=10+October+2012&rft.volume=2012&rft.issue=0&rft.pages=bas033%E2%80%93bas033&rft_id=info:doi\/10.1093%2Fdatabase%2Fbas033&rft.issn=1758-0463&rft_id=info:pmc\/PMC3468815&rft_id=info:pmid\/23060432&rft_id=https%3A%2F%2Facademic.oup.com%2Fdatabase%2Farticle-lookup%2Fdoi%2F10.1093%2Fdatabase%2Fbas033&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-Fuseki-55\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-Fuseki_55-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">The Apache Software Foundation (2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/jena.apache.org\/documentation\/fuseki2\/index.html\" target=\"_blank\">\"Apache Jena Fuseki\"<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/jena.apache.org\/documentation\/fuseki2\/index.html\" target=\"_blank\">https:\/\/jena.apache.org\/documentation\/fuseki2\/index.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Apache+Jena+Fuseki&rft.atitle=&rft.aulast=The+Apache+Software+Foundation&rft.au=The+Apache+Software+Foundation&rft.date=2021&rft_id=https%3A%2F%2Fjena.apache.org%2Fdocumentation%2Ffuseki2%2Findex.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-56\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-56\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gremse, M.; Chang, A.; Schomburg, I.; Grote, A.; Scheer, M.; Ebeling, C.; Schomburg, D. (1 January 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkq968\" target=\"_blank\">\"The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources\"<\/a> (in en). <i>Nucleic Acids Research<\/i> <b>39<\/b> (Database): D507\u2013D513. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fnar%2Fgkq968\" target=\"_blank\">10.1093\/nar\/gkq968<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0305-1048\" target=\"_blank\">0305-1048<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3013802\/\" target=\"_blank\">PMC3013802<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21030441\" target=\"_blank\">21030441<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkq968\" target=\"_blank\">https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkq968<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+BRENDA+Tissue+Ontology+%28BTO%29%3A+the+first+all-integrating+ontology+of+all+organisms+for+enzyme+sources&rft.jtitle=Nucleic+Acids+Research&rft.aulast=Gremse&rft.aufirst=M.&rft.au=Gremse%2C%26%2332%3BM.&rft.au=Chang%2C%26%2332%3BA.&rft.au=Schomburg%2C%26%2332%3BI.&rft.au=Grote%2C%26%2332%3BA.&rft.au=Scheer%2C%26%2332%3BM.&rft.au=Ebeling%2C%26%2332%3BC.&rft.au=Schomburg%2C%26%2332%3BD.&rft.date=1+January+2011&rft.volume=39&rft.issue=Database&rft.pages=D507%E2%80%93D513&rft_id=info:doi\/10.1093%2Fnar%2Fgkq968&rft.issn=0305-1048&rft_id=info:pmc\/PMC3013802&rft_id=info:pmid\/21030441&rft_id=https%3A%2F%2Facademic.oup.com%2Fnar%2Farticle-lookup%2Fdoi%2F10.1093%2Fnar%2Fgkq968&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-57\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-57\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Degtyarenko, K.; de Matos, P.; Ennis, M.; Hastings, J.; Zbinden, M.; McNaught, A.; Alcantara, R.; Darsow, M. <i>et al.<\/i> (23 December 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkm791\" target=\"_blank\">\"ChEBI: a database and ontology for chemical entities of biological interest\"<\/a> (in en). <i>Nucleic Acids Research<\/i> <b>36<\/b> (Database): D344\u2013D350. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fnar%2Fgkm791\" target=\"_blank\">10.1093\/nar\/gkm791<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0305-1048\" target=\"_blank\">0305-1048<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2238832\/\" target=\"_blank\">PMC2238832<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17932057\" target=\"_blank\">17932057<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkm791\" target=\"_blank\">https:\/\/academic.oup.com\/nar\/article-lookup\/doi\/10.1093\/nar\/gkm791<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ChEBI%3A+a+database+and+ontology+for+chemical+entities+of+biological+interest&rft.jtitle=Nucleic+Acids+Research&rft.aulast=Degtyarenko&rft.aufirst=K.&rft.au=Degtyarenko%2C%26%2332%3BK.&rft.au=de+Matos%2C%26%2332%3BP.&rft.au=Ennis%2C%26%2332%3BM.&rft.au=Hastings%2C%26%2332%3BJ.&rft.au=Zbinden%2C%26%2332%3BM.&rft.au=McNaught%2C%26%2332%3BA.&rft.au=Alcantara%2C%26%2332%3BR.&rft.au=Darsow%2C%26%2332%3BM.&rft.au=Guedj%2C%26%2332%3BM.&rft.date=23+December+2007&rft.volume=36&rft.issue=Database&rft.pages=D344%E2%80%93D350&rft_id=info:doi\/10.1093%2Fnar%2Fgkm791&rft.issn=0305-1048&rft_id=info:pmc\/PMC2238832&rft_id=info:pmid\/17932057&rft_id=https%3A%2F%2Facademic.oup.com%2Fnar%2Farticle-lookup%2Fdoi%2F10.1093%2Fnar%2Fgkm791&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-58\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-58\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Meehan, Terrence F; Diehl, Alexander D; Vempati, Uma D; Sch\u00fcrer, Stephan C; Pang, Chao <i>et al.<\/i> (2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-5-37\" target=\"_blank\">\"CLO: The cell line ontology\"<\/a> (in en). <i>Journal of Biomedical Semantics<\/i> <b>5<\/b> (1): 37. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F2041-1480-5-37\" target=\"_blank\">10.1186\/2041-1480-5-37<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2041-1480\" target=\"_blank\">2041-1480<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4387853\/\" target=\"_blank\">PMC4387853<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25852852\" target=\"_blank\">25852852<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-5-37\" target=\"_blank\">http:\/\/jbiomedsem.biomedcentral.com\/articles\/10.1186\/2041-1480-5-37<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=CLO%3A+The+cell+line+ontology&rft.jtitle=Journal+of+Biomedical+Semantics&rft.aulast=Sarntivijai&rft.aufirst=Sirarat&rft.au=Sarntivijai%2C%26%2332%3BSirarat&rft.au=Lin%2C%26%2332%3BYu&rft.au=Xiang%2C%26%2332%3BZuoshuang&rft.au=Meehan%2C%26%2332%3BTerrence+F&rft.au=Diehl%2C%26%2332%3BAlexander+D&rft.au=Vempati%2C%26%2332%3BUma+D&rft.au=Sch%C3%BCrer%2C%26%2332%3BStephan+C&rft.au=Pang%2C%26%2332%3BChao&rft.au=Malone%2C%26%2332%3BJames&rft.date=2014&rft.volume=5&rft.issue=1&rft.pages=37&rft_id=info:doi\/10.1186%2F2041-1480-5-37&rft.issn=2041-1480&rft_id=info:pmc\/PMC4387853&rft_id=info:pmid\/25852852&rft_id=http%3A%2F%2Fjbiomedsem.biomedcentral.com%2Farticles%2F10.1186%2F2041-1480-5-37&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-59\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-59\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bandrowski, Anita; Brinkman, Ryan; Brochhausen, Mathias; Brush, Matthew H.; Bug, Bill; Chibucos, Marcus C.; Clancy, Kevin; Courtot, M\u00e9lanie <i>et al.<\/i> (29 April 2016). 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(17 October 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/github.com\/wf4ever\/ro-manager\/blob\/master\/Minim\/Minim-description.md\" target=\"_blank\">\"Minim model for defining checklists\"<\/a>. <i>RO-manager on GitHub<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/github.com\/wf4ever\/ro-manager\/blob\/master\/Minim\/Minim-description.md\" target=\"_blank\">https:\/\/github.com\/wf4ever\/ro-manager\/blob\/master\/Minim\/Minim-description.md<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Minim+model+for+defining+checklists&rft.atitle=RO-manager+on+GitHub&rft.aulast=Soiland-Reyes%2C+S.%3B+Klyne%2C+G.&rft.au=Soiland-Reyes%2C+S.%3B+Klyne%2C+G.&rft.date=17+October+2017&rft_id=https%3A%2F%2Fgithub.com%2Fwf4ever%2Fro-manager%2Fblob%2Fmaster%2FMinim%2FMinim-description.md&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schr\u00f6der, Max; LeBlanc, Hayley; Spors, Sascha; Kr\u00fcger, Frank (25 February 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/itit-2019-0039\/html\" target=\"_blank\">\"Intra-consortia data sharing platforms for interdisciplinary collaborative research projects\"<\/a> (in en). <i>it - Information Technology<\/i> <b>62<\/b> (1): 19\u201328. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1515%2Fitit-2019-0039\" target=\"_blank\">10.1515\/itit-2019-0039<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2196-7032\" target=\"_blank\">2196-7032<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/itit-2019-0039\/html\" target=\"_blank\">https:\/\/www.degruyter.com\/document\/doi\/10.1515\/itit-2019-0039\/html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Intra-consortia+data+sharing+platforms+for+interdisciplinary+collaborative+research+projects&rft.jtitle=it+-+Information+Technology&rft.aulast=Schr%C3%B6der&rft.aufirst=Max&rft.au=Schr%C3%B6der%2C%26%2332%3BMax&rft.au=LeBlanc%2C%26%2332%3BHayley&rft.au=Spors%2C%26%2332%3BSascha&rft.au=Kr%C3%BCger%2C%26%2332%3BFrank&rft.date=25+February+2020&rft.volume=62&rft.issue=1&rft.pages=19%E2%80%9328&rft_id=info:doi\/10.1515%2Fitit-2019-0039&rft.issn=2196-7032&rft_id=https%3A%2F%2Fwww.degruyter.com%2Fdocument%2Fdoi%2F10.1515%2Fitit-2019-0039%2Fhtml&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-67\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-67\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mons, Barend; Neylon, Cameron; Velterop, Jan; Dumontier, Michel; da Silva Santos, Luiz Olavo Bonino; Wilkinson, Mark D. (7 March 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/ISU-170824\" target=\"_blank\">\"Cloudy, increasingly FAIR; revisiting the FAIR Data guiding principles for the European Open Science Cloud\"<\/a>. <i>Information Services & Use<\/i> <b>37<\/b> (1): 49\u201356. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3233%2FISU-170824\" target=\"_blank\">10.3233\/ISU-170824<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/ISU-170824\" target=\"_blank\">https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/ISU-170824<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cloudy%2C+increasingly+FAIR%3B+revisiting+the+FAIR+Data+guiding+principles+for+the+European+Open+Science+Cloud&rft.jtitle=Information+Services+%26+Use&rft.aulast=Mons&rft.aufirst=Barend&rft.au=Mons%2C%26%2332%3BBarend&rft.au=Neylon%2C%26%2332%3BCameron&rft.au=Velterop%2C%26%2332%3BJan&rft.au=Dumontier%2C%26%2332%3BMichel&rft.au=da+Silva+Santos%2C%26%2332%3BLuiz+Olavo+Bonino&rft.au=Wilkinson%2C%26%2332%3BMark+D.&rft.date=7+March+2017&rft.volume=37&rft.issue=1&rft.pages=49%E2%80%9356&rft_id=info:doi\/10.3233%2FISU-170824&rft_id=https%3A%2F%2Fwww.medra.org%2Fservlet%2FaliasResolver%3Falias%3Diospress%26doi%3D10.3233%2FISU-170824&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-68\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-68\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFStaehlke.2C_SusanneNebe.2C_J._Barbara2021\">Staehlke, Susanne; Nebe, J. Barbara (10 June 2021), <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/zenodo.org\/record\/4923173\" target=\"_blank\">\"Research data of Calcium Imaging after electrical stimulation\"<\/a> (in en), <i>Zenodo<\/i> (Zenodo), <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5281%2Fzenodo.4923173\" target=\"_blank\">10.5281\/zenodo.4923173<\/a><span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/zenodo.org\/record\/4923173\" target=\"_blank\">https:\/\/zenodo.org\/record\/4923173<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-01<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+data+of+Calcium+Imaging+after+electrical+stimulation&rft.jtitle=Zenodo&rft.aulast=Staehlke%2C+Susanne&rft.au=Staehlke%2C+Susanne&rft.au=Nebe%2C+J.+Barbara&rft.date=10+June+2021&rft.pub=Zenodo&rft_id=info:doi\/10.5281%2Fzenodo.4923173&rft_id=https%3A%2F%2Fzenodo.org%2Frecord%2F4923173&rfr_id=info:sid\/en.wikipedia.org:Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. To more easily differentiate footnotes from references, the original footnotes (which were numbered) were updated to use lowercase letters. Most footnotes referencing web pages were turned into proper citations.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628171500\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.795 seconds\nReal time usage: 1.554 seconds\nPreprocessor visited node count: 66147\/1000000\nPost\u2010expand include size: 561967\/2097152 bytes\nTemplate argument size: 165031\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 158614\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 677.215 1 -total\n 89.33% 604.977 2 Template:Reflist\n 70.04% 474.338 66 Template:Citation\/core\n 55.85% 378.246 47 Template:Cite_journal\n 11.30% 76.548 63 Template:Date\n 10.97% 74.315 12 Template:Cite_web\n 7.25% 49.088 6 Template:Citation\n 7.24% 49.023 115 Template:Citation\/identifier\n 4.18% 28.285 1 Template:Infobox_journal_article\n 3.53% 23.917 1 Template:Infobox\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13125-0!canonical and timestamp 20220628171458 and revision id 47174. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation\">https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","d40238949d238978e30434ffe18aa050_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/20\/Fig1_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/c8\/Fig2_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/3\/38\/Fig3_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/78\/Fig4_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7a\/Fig5_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/5\/54\/Fig6_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/17\/Fig7_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/3\/38\/Fig8_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/22\/Fig9_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1d\/FigA1_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a3\/FigA2_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/b\/be\/FigA3_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/c\/cb\/FigA4_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/da\/FigA5_Schr%C3%B6der_JofBioSem22_13.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/4\/43\/FigA6_Schr%C3%B6der_JofBioSem22_13.png"],"d40238949d238978e30434ffe18aa050_timestamp":1656439827,"5c4c23816cc524a349b691a9b6846809_type":"article","5c4c23816cc524a349b691a9b6846809_title":"Using knowledge graph structures for semantic interoperability in electronic health records data exchanges (Sachdeva and Bhalla 2022)","5c4c23816cc524a349b691a9b6846809_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges","5c4c23816cc524a349b691a9b6846809_plaintext":"\n\nJournal:Using knowledge graph structures for semantic interoperability in electronic health records data exchangesFrom LIMSWikiJump to navigationJump to searchFull article title\n \nUsing knowledge graph structures for semantic interoperability in electronic health records data exchangesJournal\n \nInformationAuthor(s)\n \nSachdeva, Shelly; Bhalla, SubhashAuthor affiliation(s)\n \nNational Institute of Technology Delhi, University of AizuPrimary contact\n \nEmail: shellysachdeva at nitdelhi dot ac dot inYear published\n \n2022Volume and issue\n \n13(2)Article #\n \n52DOI\n \n10.3390\/info13020052ISSN\n \n2078-2489Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2078-2489\/13\/2\/52\/htmDownload\n \nhttps:\/\/www.mdpi.com\/2078-2489\/13\/2\/52\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n\n2.1 Overview of EHRs \n2.2 Archetypes and semantic interoperability \n2.3 Representing internal data in archetypes \n2.4 EHRs and data modeling \n\n\n3 Formalisms in transformation of archetypes among different standards: Background \n4 Knowledge representation \n\n4.1 ADL and XML \n4.2 ADL and OWL \n4.3 ADL and other formalisms \n\n\n5 Evaluation in practice \n\n5.1 KnowledgeRep: Simulation \n5.2 Methodology \n\n5.2.1 Representation in ADL \n5.2.2 Representation in XML \n5.2.3 Representation in OWL \n\n\n5.3 Findings \n\n\n6 Discussion \n7 Conclusions \n8 Abbreviations, acronyms, and initialisms \n9 Appendices \n\n9.1 Appendix A. Parameter Heart_rate as an archetype \n9.2 Appendix B. Comparison of ADL and XML \n9.3 Appendix C. List of archetypes \n9.4 Appendix D. XML and ADL representation of Heart_rate \n\n\n10 Acknowledgements \n\n10.1 Author contributions \n10.2 Funding \n10.3 Conflict of interest \n\n\n11 References \n12 Notes \n\n\n\nAbstract \nInformation sharing across medical institutions is restricted to information exchange between specific partners. The lifelong electronic health record (EHR) structure and content require standardization efforts. Existing standards such as openEHR, Health Level 7 (HL7), and ISO\/EN 13606 aim to achieve data independence along with semantic interoperability. This study aims to discover knowledge representation to achieve semantic health data exchange. openEHR and ISO\/EN 13606 use archetype-based technology for semantic interoperability. The HL7 Clinical Document Architecture is on its way to adopting this through HL7 templates. Archetypes are the basis for knowledge-based systems, as these are means to define clinical knowledge. \nThe paper examines a set of formalisms for the suitability of describing, representing, and reasoning about archetypes. Each of the information exchange technologies\u2014such as XML, Web Ontology Language (OWL), Object Constraint Language (OCL), and Knowledge Interchange Format (KIF)\u2014is evaluated as a part of the knowledge representation experiment. These examine the representation of archetypes as described by Archetype Definition Language (ADL). The evaluation maintains a clear focus on the syntactic and semantic transformations among different EHR standards.\nKeywords: archetypes, electronic health records, dual-model approach, knowledge representation, EHR, XML, ADL, OWL, KIF\n\nIntroduction \nHealthcare is a continuously evolving domain. New findings of diseases and clinical treatments are continuously being made. It has raised the need for increased information exchange among various medical institutions. Electronic health records (EHRs) contain the medical history and treatments of the patients at those medical institutions. In the classical approach, information and knowledge are stored together. However, storage of each clinical concept in a single relation led to a huge data model that was difficult to manage and expensive to maintain. Among the existing interoperability approaches for EHRs, the dual-model approach[1] seems to be most promising. It consists of an information layer and a knowledge layer. The key benefit of this approach is the segregation of knowledge (represented as archetypes[2]). A conceptual idea is virtually transferred through the medium of an intermediate structure of a knowledge graph. This study analyzes that knowledge graph's components.\nKnowledge graphs are used to capture knowledge in application-based situations that require large-scale integration, management, and extraction of value from a variety of data sources. Recent studies examine all currently available knowledge graphs (KGs), including their characteristics, approaches, applications, issues, and challenges.[3][4]\nThis paper focuses on using knowledge representation and information interchange technologies for archetype representation.\n\nOverview of EHRs \nThe domain of the modern EHR is complex. It consists of different types of data (from textual to multimedia), with new data requirements emerging over time. For example, there are about 300,000 medical terms at present (as defined by SNOMED CT), and medical tests and procedures are constantly created and modified. EHRs have a complex structure based on archetypes. These may include data based on hundreds of parameters, such as temperature, blood pressure, and body mass index (BMI). Each of the individual parameters (or concepts) has its own specific content and is represented as an archetype. For example, one archetype could contain an item such as \"data,\" which can, for example, be represented as a documented heart rate observation. This archetype ideally offers complete knowledge about a clinical context (i.e., attributes of data), the data's \"state\" (i.e., context for interpretation of data), and its \"protocol\" (i.e., information regarding the gathering of data) (see Appendix A). Various standards development organizations are working to improve the interoperability of semantic EHRs through these archetypes and more.\nIt is desirable to have EHR systems that are functionally and semantically interoperable systems. Interoperability can be defined as an ability to communicate data such that the data are sufficient to perform the tasks at the receiving system. The associated data items have the same meaning for the creator of the sending party and the users of the receiving party, and the tasks performed using the data must be to the satisfaction of the receiving party. To tackle the EHR interoperability problem, many authorized organizations have defined several standards. Examples include Health Level 7 (HL7) and its Clinical Document Architecture (CDA), ASTM International's Continuity of Care Record (CCR), European Committee for Standardization (CEN) Technical Committee 251 and International Organization for Standardization (ISO)'s ISO\/EN 13606, and the openEHR Foundation's openEHR. The main objective of all these EHR standards is to structure the data and mark up the content of the medical information to be more readily exchanged.\nFor this work, three levels of interoperability stand out, namely syntactic (data) interoperability, structural interoperability\/semantic interpretability, and semantic interoperability.[5] The main mechanisms for interoperability are reference models, archetypes, and domain knowledge governance.\n\nArchetypes and semantic interoperability \nThe standards for semantic interoperability (such as CDA, openEHR, and ISO\/EN 13606) endorse the two-level modeling approach for storing EHR content.[6] It consists of two layers that propose to segregate information modeling from content (knowledge) modeling. The reference (information) model layer represents the generic structures of components of the healthcare data. The content model on the other hand is used to represent more domain-specific data, which in general have instability due to variability and high rate of change in their usage (e.g., a formal description of a physical examination or prescription).\nIn openEHR and ISO\/EN 13606, the first level is known as the reference model (RM) and the second level consists of archetypes. The RM defines the basic fundamental structure and represents the generic structures of components of the healthcare data at the storage level (i.e., information modeling). At the second layer, the archetype model (AM) constrains the generic structure to encompass logical semantics and, thus, provide a standard definition that aids in semantic interoperability. AM provides deliverables in the form of archetypes and templates. An archetype provides the meta-description of structured clinical records as a computable formalism. In HL7's CDA, the two levels are the Reference Information Model (RIM) and the HL7 templates, which function essentially the same as the archetype concept.\nThese standards support compatibility among each other. In the case of openEHR and ISO\/EN 13606, the only means of achieving interoperability with a generic information model is through their archetypes. In fact, ADL archetypes can be defined against any Unified Modeling Language (UML) model, and it is also possible to write the archetypes against the HL7 Version 3 RIM and the CDA in general. Kilic and Dogac[7] note this in their work, describing how the clinical statements of two different EHR standards derived from the same RIM can be mapped to each other by using archetypes, Refined Message Information Model derivations, and semantic tools.\nAs mentioned prior, an archetype is an agreed upon formal and interoperable specification of a re-usable clinical data set that underpins an EHR. It captures the maximum possible information about a particular and discrete clinical concept.[2] A conceptual definition of data as archetypes can be developed in terms of constraints on structure, types, values, and behaviors of RM classes based on the dual-model approach. It consists of the knowledge layer as archetypes and an RM. An example of a simple archetype is \"Weight,\" which can be used in multiple places as required within an EHR. \nSemantics in archetypes have a dual nature. They consist of both structural and terminological components. The structure of an archetype provides support for semantics, while EHR component links form a set of interrelated conceptual, clinical entities. Each entity has a set of terminological bindings associated with it (specified by links to terms of specific medical terminologies).\nIf data elements are created and modified using archetypes, the archetypes constrain the configuration of data instances to be valid according to the archetype. These are a paradigm for building semantically enabled software systems, providing data validation, clinical modeling (by domain experts), a basis for querying, and form design. An archetype might define or constrain relationships between data values within a data structure. These are expressed as algorithms, formula, or rules. An archetype's metadata defines its core concept, purpose, use, evidence, authorship, and versioning. An archetype also ensures a maximal dataset. It contains all the relevant information regarding a clinical concept. Once the format of an archetype is agreed upon and published, it is held in a \"library\u2019\" and made available for use in any part of a given application by multiple vendor systems, multiple institutions, and multiple geographical regions. Each group or entity using the same archetype will understand and compute data captured by the same archetype in another clinical environment. Thus, an archetype serves the following key purposes[8][9]:\n\nIt allows domain experts (clinicians) to capture data for their information systems.\nIt provides runtime validation of data input, thus improving data entry quality.\nIt provides a basis for intelligent querying of data.\nRepresenting internal data in archetypes \nMatching clinical data to codes in controlled terminologies is the first step towards achieving data standardization for safe and accurate data interoperability. Archetypes have the advantage of being able to separate the internal model data from formal terminologies. Existing terminologies, taxonomies, and ontologies have been written in many languages. For example, Medical Subject Headings (MESH)[10] and the National Cancer Institute (NCI)[11] have their own proprietary formalisms (now commonly expressed also in XML). The \"term binding\" section of the archetype is used to describe the equivalences between archetype local terms and terms found in external terminologies, such as SNOMED CT or Unified Medical Language System (UMLS). The internal data are assigned local names and later bound or mapped to external terminology codes. This feature eliminates the need to make changes to the model whenever the terminology changes. For formal descriptions, the Archetype Definition Language (ADL) uses three other syntaxes\u2014cADL (constraint form of ADL), dADL (data definition form of ADL), and a version of first-order predicate logic (FOPL)\u2014to describe constraints on data, which are instances of some information model (e.g., expressed in UML).[12] Thus, ADL can be used to write archetypes for any domain where formal object model(s) exist, which describe data instances.\n\nEHRs and data modeling \nThe openEHR architecture[1] includes a design principle called \"ontological separation,\" which regulates the EHR modeling (Figure 1). The model consists of two main categories: \"ontologies of information\" and \"ontologies of reality.\" The ontologies of information contain the information models of the EHR content, whereas the ontologies of reality describe real phenomena with descriptions and classifications.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 Illustration of openEHR\u2019s ontological structure\n\n\n\nThe ontologies of information are divided into several models:\n\nDomain content models (knowledge models) containing formal definitions of the clinical content. These are developed using archetypes, which are designed such that these can change when new clinical needs arise.\nInformation representation models are implemented in the electronic healthcare system's software. These are used as a foundation for the domain content models and are designed to be stable regarding model changes. In openEHR, this component is the RM.\nIn simpler terms, if RM is equivalent to the set of letters\/digits, then each and every archetype would be a set of grammar constraining which strings could be expressed for that archetype. In formal terms:\n\nRM = {Set of classes C1, C2, C3 ...C<i>n<\/i>}\nArchetype = {Set of rules for valid combination of classes of RM}\nThe ontologies of reality can be broken down as:\n\nClassifications: ICDx (International Classification of Diseases) and ICPC (International Classification of Primary Care)\nProcess descriptions: Clinical guidelines\nDescriptive terminologies: SNOMED CT or LOINC\nIn Figure 1, the EHR extracts are based on commonly shared archetypes. These are proposed as a means to exchange information between different health care providers.[1] The semantics of the domain content models (e.g., archetypes) are provided by terminology binding. The meaning of nodes in archetypes is given by textual descriptions and references to external terminology systems. These are in the form of term definition and term binding. Representation of archetypes in various possibilities such as ADL, XML (Extensible Markup Language), and OWL (Web Ontology Language) has been described in the paper. Subsequently, a comparison is drawn amongst these information exchange technologies, and the advantages and disadvantages of each have been analyzed. The main aim of this study is to find the best representation of an archetype. The paper examines a set of formalisms for the suitability of describing, representing, and reasoning about archetypes.\n\nFormalisms in transformation of archetypes among different standards: Background \nPrevalent standards such as CDA, openEHR, and ISO\/EN 13606 use archetype-based technology for semantically interoperable exchange. ADL archetypes can be written against any UML model, and it would be possible to write archetypes directly against the RIM[13], and also the CDA specification[14] (using a UML expression derived from its XML schema). These standards define the structure and the markup of the clinical content to make EHR exchange interoperable. They all rely on dual-model technology for semantic interoperability. They have different classes in the RM, having abstract semantics. Although the names of the classes are not shared between these standards, their semantics are similar. The RM for all the standards is stable. If alignments are performed between archetypes of different standards, aligning algorithms based on similarity measures will fail, as class names (of RM) are disparate. Dictionary-based approaches will not be of much help, as all names are quite abstract.[15] The various ongoing exchange efforts based on archetypes use different formalisms to represent archetypes. The mapping among different standards makes use of model management and uses OWL transformations and XML representation of archetypes.\nFor interoperability among EHR standards based on ontologies, the possible approaches are (i) building common ontology and (ii) reusing existing ontologies and combining them. The first approach requires the transformation of ADL archetypes into OWL.[16][17] The ontological information and AMs have been compared to find similarities and differences among the CEN and openEHR representations. The software tool available based on this approach is Poseacle Convertor.[18] This approach involves the use of XML and OWL representations, with the latter being obtained by reusing existing ontologies and combining them through ontology mapping. The ARTEMIS project was implemented based on this, using the various formalisms such as XML, ADL, and OWL.[19]\nBroadly speaking, archetypes must be agreed upon before communication. However, it does not seem feasible to expect all professionals of various disciplines to agree on exactly all details of the archetypes associated with the data they would like to exchange. If this approach becomes widely accepted, it is certain that the number of available archetypes will become very large. Although archetypes are annotated with terms from standardized ontologies (terminologies, taxonomies, etc.), there will still be differences at the archetype level and at the terminology level. Due to competing standards, local variations at the archetype level will stem from the specialization of archetypes for specific purposes and research projects. Further, several widely used terminologies could be used to annotate archetypes (e.g., SNOMED CT, MeSH, NCI). Local ontologies are also used to annotate archetypes; therefore, a sound and general process for matching archetypes are essential. \nIn 2019, Adel et al.[20] proposed a unified framework based on a fuzzy ontology to show how to exploit semantic web technologies to support EHR semantic interoperability. Prior to that, Martinez-Costa et al.[21] introduced ontologies and rules as a means of establishing interoperability amongst heterogeneous health systems (openEHR and HL7). Recently, Roehrs et al.[22] proposed an application model called OmniPHR, a model for assessing the structure of semantic interoperability and database integration from various health standards. OmniPHR uses artificial intelligence, natural language processing, and a standard ontology to achieve interoperability. Knowledge graphs are represented using a variety of methodologies, but machine learning methods are frequently employed to create a low-dimensional representation that can support a wide range of applications.[23]\nGiven this, there is a requirement to identify the role of the suitability of various formalisms for achieving full semantic interoperability through archetypes, which addressed in the current research.\n\nKnowledge representation \nIn a 2019 review of more than 100 papers on knowledge representation in health care, Ria\u00f1o et al.[24] found that ontologies (31%), semantic web-related formalisms (26%), decision tables and rules (19%), logic (14%), and probabilistic models (10%) represented the most common knowledge representation approaches. They also found that medical informatics knowledge was primarily represented as computer interpretable clinical recommendations (43%), medical domain ontologies (26%), and EHRs (22%).[24] In most of these cases, embedding codes can convey the meaning of the concepts that are represented by an archetype from a commonly recognized terminology at appropriate points in the archetype. Archetypes are the unit of communication between interoperating applications, as they define the minimum context that must be considered for safe communication.[15] Expressivity is a key parameter in choosing or creating a knowledge representation. It is easier and more compact to express a fact or element of knowledge within the semantics and grammar of a more expressive knowledge representation. However, more expressive languages will likely require more complex logic and algorithms to construct equivalent inferences. A highly expressive knowledge representation is also less likely to be complete and consistent. Less expressive KRs may be both complete and consistent.[25] This section describes the knowledge technologies for the representation of archetypes.\n\nADL and XML \nThe ADL approach uses existing UML semantics and existing terminologies and adds convenient syntax for expressing the required constraints. Expressing the semantics of archetypes using XML-based exchange formats leads to the conflation of abstract and concrete representational semantics.[12] ADL syntax is straightforward and powerful. It has allowed mappings to other formalisms to be more correctly defined and understood. Previously, archetypes have been expressed as XML instance documents conforming to W3C XML schemas[26], for example, in the Good Electronic Health Record (GEHR)[27] and openEHR projects. Subsequently, expressing archetype constraints using numerous schema languages for XML (such as XML schema, RELAX NG, and Schematron) has been examined. Because of the issues reported, these languages were abandoned for archetype validation.[28][29] For example, in XML schema, classes in RM were mapped to complex types, and archetypes were mapped to class restrictions. The strict rules (unique particle attribution, complex enumerations, placing regular expression constraint) in using the restriction feature in XML schema did not permit the implementation of archetype constraints.\nWith ADL parsing tools, it is possible to convert ADL to any number of forms, including various XML formats. XML instances can be generated from the object form of an archetype in memory. XML archetypes are equivalent to serialized instances of the parse tree, i.e., particular ADL archetypes serialized from objects into XML instances. Archetypes connect information structures to formal terminologies. Similar to XML data, they are path-addressable using path expressions directly convertible to Xpath expressions. An XML schema corresponding to the ADL object model has been published at openEHR.org.[30] The XML schema corresponding to RM is published in the work of Martinez-Costa et al.[21]\nThe XML has a role in the exchange requirement. The EHR_Extract, used for exchange, is expressed using XML.[1] A recent study examines whether the W3C XML schema provides a practicable solution for the semantic validation of standard-based EHR documents.[28] The EHR_Extract needs to be validated against the RM and the associated archetypes.\nAn example of XML\/ADL use can be found in openEHR. To accept a report from the pathology laboratory for inclusion in the EHR repository of a patient (in the ADL form), an XML form is generated using the archetype. This form is shared with the laboratory for on-site validation of data input. Thus, XML is used as an input and transport medium.\nA comparison between ADL and XML is stated below, and in Appendix B:\n\nBoth are machine processable.\nADL is human readable, whereas XML is sometimes unreadable (e.g., XML schema instances, OWL-RDF ontologies).\nADL adheres to object-oriented semantics, particularly for container types, whereas XML schema languages do not follow object-oriented semantics.\nFor ontological reference, ADL has domain entities\/archetypes, and XML has global terms\/concepts.\nADL uses attributes, and XML uses attributes and sub-elements to represent object properties.\nADL uses nearly half of its required space (storage) for tags, and XML may have data redundancy in contents.\nIn terms of efficiency, ADL is a domain-specific language (sufficiently rich to capture and model the medical domain) in comparison to XML, which is good for web document modeling, though with limited ability to represent database contents.\nADL and OWL \nOWL[31] is a language for the semantic web, which:\n\noffers expressiveness and the possibility of reasoning over the information it describes;\nallows making annotations on classes or properties and makes semantic similarity functions available;\nis related to terminologies (e.g., SNOMED CT is currently in the process of adapting its representation to semantic web environments[32], recognizing that having a representation of both the clinical and terminological information in the same formalism would facilitate better clinical knowledge management and would enrich archetypes by adding more information to them);\nbrings all information concerning a particular term together through modeling (e.g., code, definition, bindings, and translations); and\nis supported by several tools which can process it.\nOWL has an abstract syntax, an extension of XML-based syntax known as the Resource Description Framework (RDF). OWL is general-purpose description logic (DL) and is primarily used to describe \u201cclasses\u201d of things in such a way as to support subsumptive inferencing within the ontology, and by extension, on data that are instances of ontology classes. OWL includes intersection, union, complement of existential quantification, universal quantification, min cardinality, max cardinality, equivalence, and specialization. Thus, it demonstrates decidability and computability, offering expressiveness and the possibility of reasoning over the information it describes. OWL version 2 has a property of qualified cardinality restrictions (which makes it possible to capture the occurrences restrictions from ADL), property chain inclusions, and OWL\/XML syntax.\nADL provides a rich set of constraints on primitive types, including dates and times; however, ADL has significant drawbacks for achieving the goal of semantic interoperability, such as its syntactic orientation. Consequently, the formalization of the exchange and transformation processes is more than using semantic-oriented models such as ontological ones. In addition to this, syntactic approaches also make important archetype-related tasks, such as comparing and classifying archetypes, difficult. \nArchetypes in ADL can be represented in OWL. However, it requires[12]:\n\nthe expression of the relevant RMs in OWL;\nthe expression of the relevant terminologies in OWL;\nthe representation of concepts (i.e., constraints) independently of natural language; and\nthe conversion of the cADL part of an archetype to OWL.\nUsing OWL-expressed archetypes to validate data (which would require massive amounts of data to be converted to OWL statements) is unlikely to be anywhere near as efficient as doing it with archetypes expressed in ADL or one of its concrete expressions.[12] The UML-like representation is not suitable for performing formal reasoning at the conceptual level; however, OWL offers a great deal of inferencing power of the far wider scope in comparison to specific reasoning.\nThe object-oriented semantics apply in the UML specification of RM and the corresponding XML schema mapped from it. This needs to be mapped for conversion to OWL. Practically, this is possible, as illustrated in a recent study.[16] The XML-schema class is mapped to an OWL class with the same name. The restricted data type definitions in XML schema are mapped to an OWL data type. The attributes in XML-schema are mapped to an OWL property. The instances\/objects in XML are equivalent to individuals in OWL.\nKilic et al.[33] provide mapping archetypes to OWL. For automatically transforming archetype definitions from ADL to OWL, the archetype ontologies use the ehr2ont framework.[34] LinkEHR[35] is a more recent project for obtaining the OWL representation of archetypes.\n\nADL and other formalisms \nA comparative analysis of ADL with other formalisms such as the Object Constraint Language (OCL) and Knowledge Interchange Format (KIF) is shown later in the next section. The OCL allows constraining all class instances to conform to the specific configuration of instances. In contrast, ADL provides the ability to create numerous archetypes, each describing in detail a concrete configuration of instances of a class. ADL archetypes include invariants (which are expressed in a syntax similar to OCL).\nRDF is a data model for objects (\u201cresources\u201d), and relations between them provide simple semantics for this data model.[36] OWL takes the essential fact-stating ability of RDF and the class- and property-structuring capabilities of RDF schema and extends them in essential ways. OWL classes can be specified as logical combinations (intersections, unions, or complements) of other classes, or as enumerations of specified objects, going beyond the capabilities of the RDF schema. OWL can declare classes and organize these classes in a subsumption (\u201csubclass\u201d) hierarchy, as an RDF schema. The significant extension over RDF schema is the ability in OWL to provide restrictions on how properties behave (that are local to a class). A recent study concentrates on the semantic interoperability of diverse EHRs and their standards, proposing the transformation of heterogeneous EHR datasets into XML syntactic models and their translation into a common ontological representation for semantic knowledge acquisition.[37]\n\nEvaluation in practice \nWe ran into many problems concerning alternative representations of the archetype and the inability to express some of the constraints in different knowledge representation languages. We detail these problems as a cautionary tale to others planning to use pre-existing archetypes for semantic interoperability, as a list of issues to consider when describing concepts formally in any language, and as a collection of criteria for evaluating alternative representations.\nThe three best-suited knowledge formalisms\u2014ADL, XML, and OWL\u2014for archetype representation have been evaluated for the features mentioned in the paper through the experimental setup KnowledgeRep. The ADL formalism has been compared with XML and OWL to find the suitable role of these formalisms in a working semantic interoperable system.\n\nKnowledgeRep: Simulation \nVarious knowledge formalisms used in different EHR standards for obtaining semantic interoperability have been examined in current research with the openEHR standard. The underlying Java Reference Implementation[19] of openEHR has been used, referred to as KnowledgeRep. It is an evaluation setup for examining various archetype representations for EHR concepts. Figure 2, shows an application GUI (graphical user interface), the knowledge representations, and the communication classes. The application GUI represents various system interactions between the users and the EHR system. It is responsible for multiple calls to the utility and server-side classes to perform the formatting and transformations of the data and extract relevant data. It comprises the following modules: the form presented to the user, the template mechanism required to create the template corresponding to the EHR system, the data binding module, and the result viewer, which represents the report desired by the user. GWT (Google Web Toolkit) facilitates all these modules. It introduces the necessary flexibility into the model-driven approach of standard-based EHR system development.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 KnowledgeRep: Evaluation setup for various archetype representations for EHR concepts\n\n\n\nThe knowledge representation (archetypes) in ADL, XML, and OWL formalisms and the communication classes are shown in the second part of the diagram. It contains components that are responsible for communication. It also contains logic that connects the GUI with the underlying Java Reference Implementation of openEHR. The entire set of knowledge is parsed from ADL\/XML\/OWL files using the classes of RM and mapped to the GUI (form). The knowledge representation and communication part of the setup comprises the <ArchetypeWrapper and DatabaseWrapper classes, which act as the communication nodes. ArchetypeDAO maps the database and the basic RM data types. The clinical software database is shown (the details are beyond the scope of the current research).\n\nMethodology \nHere we describe the analysis procedure applied for each formalism, ADL, XML, and OWL. The archetypes used for the analysis have been downloaded from Clinical Knowledge Manager (CKM)[38], Appendix C. Each knowledge representation has been analyzed from the perspective of how strong it is to support the client side and the server side of the EHR system. In other words, we have tried to explore knowledge representation from a user\u2019s perspective and the machine\u2019s perspective.\n\nRepresentation in ADL \nThe analysis of ADL was performed as given. A user selects a form to make a data entry, the corresponding .adl file is picked up from the archetype repository, it is parsed to extract all the node paths of the mandatory fields, and then a form is generated. When the user enters the value of any of the fields in the archetype, they are bonded with the exact path in the .adl file. We see that the ADL formalism is a powerful knowledge representation that can act as a GUI generator. At the same time, when the data are to be persisted, a user inputs to the corresponding archetype are mapped to the RM data types by intermediate classes and stored in the database. Along with the data type and the data value, the path of the node in the .adl file and the name of the .adl file are also persisted\u2014this aids in the retrieval of the data from the database. Whenever the data are to be represented as a report, the data value is picked, mapped to the node whose path corresponds to it in the database, and then represented in the form corresponding to the archetype. Thus, ADL formalism plays a major role in data persistence in this case. From the above analysis, we can conclude that ADL, on the one hand, provides the object-oriented semantics and, on the other hand, is machine-processable; thus, it plays a significant role in both the client side and backend of an EHR system, making it a powerful knowledge formalism.\nHowever, parsing of the ADL archetype returns objects according to the archetype object model (AOM). AOM is the definitive formal representation of archetype semantics. It is independent of syntax. The primary goal of the AOM specification is to tell developers how to build archetype tools and EHR components that utilize archetypes. It can be used to generate the output side of parsers that process archetypes in a linguistic format, such as the openEHR ADL. The semantics defined in the AOM is used to express the object structures of archetypes. These objects are equivalent to a syntax tree. The AOM can be thought of as a model of an in-memory archetype or template, or as a standard syntax tree for any serialized format\u2014not only ADL. An archetype\u2019s canonical abstract syntactic form is ADL, although it may also be parsed from and serialized to XML, JSON, or any other format. Calls to an appropriate AOM construction API from an archetype or template editing tool can also produce the in-memory archetype representation. This model is common to all dual-model-based standards; it will have no information about the particular RM for which the archetype was built. Thus, the obtained objects cannot be used to perform any semantic activity such as comparison, selection, or classification.\n\nRepresentation in XML \nFor experimental analysis, an XML representation automatically generated by the archetype editor is being used. This XML format conforms to the archetype constraint classes defined in the openEHR RM, and it can be directly imported into the oenEHR RM to initialize the relevant archetypes. Thus, the XML format is again generated via the archetype editor from a corresponding ADL counterpart. Each piece of data can subsequently be referenced using its XML path. For example, the patient\u2019s first name (Paul) could be referenced as \u201c\/record\/name\/firstname.\u201d The drawback of this formalism can be tracked in its inefficiency to represent the archetype constraints completely. It is, however, a suitable formalism for transforming and exchanging data from one form to another.\n\nRepresentation in OWL \nThe semantic web enables greater access not only to content but also to services on the web.[39] Users and software agents should discover, invoke, compose, and monitor web resources offering particular services and having specific properties. They should be able to do so with a high degree of automation if desired. Powerful tools should be enabled by service descriptions across the web service lifecycle. OWL-S (formerly DAML-S)[39] is an ontology of services that makes these functionalities possible.\nSince the experiment used the openEHR Java Reference Implementation of RM, it has been found that in order to use OWL formalism, the RM (i.e., information model) should be transformed into OWL statements (OWL is found to be at a more abstract level as compared to ADL, XML, and XML schema). As such, there exists a method for binding terminology to the EHR system with OWL as a bridging technology, given that the terminology is expressible in OWL.\nRecent research[40] describes the ADL-to-OWL translation approach, describes the techniques to map archetypes to formal ontologies, and demonstrates how rules can be applied to the resulting representation. It translates definitions expressed in the openEHR ADL to a formal representation expressed using OWL. The formal representations are then integrated with rules expressed with Semantic Web Rule Language (SWRL)[41] expressions, providing an approach to apply the SWRL rules to concrete instances of clinical data. Sharing the knowledge expressed in rules is consistent with the philosophy of open sharing, encouraged by archetypes. The approach also allows the reuse of formal knowledge, expressed through ontologies, and extends reuse to propositions of declarative knowledge, such as those encoded in clinical guidelines.\n\nFindings \nTo the best of the authors' knowledge, KnowledgeRep has investigated the suitability of various formalisms in the context of archetypes, using the specific semantics of their underlying RMs and hierarchical structure (tree) of archetype definitions. It examines whether currently available archetype languages provide direct support for mapping to formal ontologies and then exploiting reasoning on clinical knowledge, which are critical ingredients of full semantic interoperability.\nThrough KnowledgeRep, various comparisons, presented in Table 1, have been obtained. The conclusions of various results are also shown in Table 2 and Table 3.\n\n\n\n\n\n\n\nTable 1. Comparative analysis of various knowledge representations (in context to archetype)\n\n\nFeatures\n\nADL\n\nXML\n\nOWL\n\nOCL\n\nKIF\n\n\nDomain Modeling\n\nArchetype Description Language (ADL)\n\nWeb document model\n\nWeb-enabled ontologies for building the semantic web\n\nConstraints on object models (not on data) can describe archetypes\n\nFormal semantics (sharable among software entities)\n\n\nReference Model (RM) with object-oriented semantics\n\nADL syntax adheres to object-oriented RMs (expressed in UML for constraints)\n\nXML and XML schema languages do not follow object-oriented semantics\n\nRequires explicit expression of an RM in OWL to represent archetype constraints\n\nAll statements are FOPL statements; it is impossible to express an archetype in a structural way\n\nExisting information model and terminologies have to be converted to KIF statements to describe archetypes\n\n\nConstraint Representation\n\nADL enables constraints to be expressed in a structural and nested way for archetypes\n\nStrict rules in XML schema cannot express archetype constraints\n\nInconvenient in OWL\n\nOCL constraint types include function pre- and post-conditions, and class variants\n\n\n\n\nPath Traceability\n\nADL has a path syntax based on XPath (openEHR path) to deal with heavily nested structures\n\nInbuilt Xpath mechanism\n\nNo inbuilt path mechanism\n\nThe OCL syntax for paths (that traverse associations) is similar to XPath\n\nNo inbuilt path mechanism\n\n\nInbuilt Ontology Section\n\nADL provides independence from natural language and terminology issues by having a separate ontology per archetype, containing \"bindings\" and language-specific translations\n\nNo built-in syntax\n\nNo built-in syntax and requires the semantics to be represented from first principles\n\nNo built-in syntax\n\nNo built-in syntax\n\n\n\n\n\n\n\n\n\nTable 2. Suitability of ADL, XML, and OWL\n\n\nVarious formalisms\n\nSuitability\n\n\nADL\n\nRepresentation of archetypes\n\n\nXML\n\nInformation interchange\n\n\nOWL\n\nSemantic activities and transformation among archetypes\n\n\n\n\n\n\n\n\nTable 3. Summary of transformation of ADL with other formalisms\n\n\nTask\n\nXML\n\nOCL\n\nOWL\n\nKIF\n\n\nTransformation of ADL archetypes\n\nYes (GEHR Project)[27]\n\nNo\n\nYes (Poseacle Convertor, ARTEMIS project, Archetype Ontologiser, LinkEHR project)[35]\n\nYes [42]\n\n\n\nFrom Table 1 we infer that ADL best represents archetypes definitions. The XML schema languages were not able to specify the archetype constraints; therefore, the XML-encoded EHR data and archetype definitions will be read into the EHR system, which will validate the EHR data against the archetype constraints programmatically. XML has a role in the exchange requirement over the web. OWL would not be a suitable representation for storing the EHR data itself. It is designed on a mathematical base specifically for reasoning. Thus, it is suitable for semantic activities such as classification, comparing, reasoning, and transformation.\nTable 3 presents a consolidated view of the possibility of transformation of ADL archetypes. Thus, the XML archetypes are serialized instances of the parse tree obtained from ADL parser. Expressing archetypes using OWL\/KIF requires the existing information model and relevant terminologies to be converted to OWL\/KIF statements. Valuing data using OWL expressed archetypes requires massive amounts of data to be converted to OWL statements; however, OWL plays a significant role in ontology mapping, which permits the exchange of information among healthcare information systems conforming to different standards. The transformation to OCL is impossible, but the ADL syntax includes assertion language based on OCL.\nHowever, OWL is not suitable for representing conditional expressions used in representing constraints and rules. Some researchers have proposed ways to represent such richer expressions, for example, by adopting rule languages (e.g., RuleML) into RDF and OWL representations.[39] RuleML is a family of languages whose modular system of XML schemas permits high-precision web rule interchange.[43] Recent work[40][44] makes a case for the potential of combining the translated openEHR Archetype Definitions with a rule-based approach using SWRL[41] rules. El Hajjamy et al.[45] developed a semi-automatic integration approach for integrating data from traditional information systems to a better ontologies-based system. Different data sources via UML, RDB, and XML are converted into local ontologies (OWL2) in the mentioned approach. Based on semantic, structural, and syntactic similarity measurement, all the local ontologies output then merge into a global ontology.[45]\n\nDiscussion \nADL has various advantages and a few disadvantages compared to the other languages, as shown in Table 1. A recent study[16] states the difference between openEHR RM\/ADL and XML\/XML schema as:\n\nThe openEHR RM has a \u201cdomain bias\u201d and is, therefore, more extensive and expressive than XML, a minimal generic model to describe hierarchical textual structures. This means that more has to be expressed in an XML schema in order to obtain a document class that is semantically equivalent to an archetype.\nThe openEHR RM and AOMs are modeled in UML. There is a direct correspondence between an ADL instance and the AOM. These models have an object-oriented bias, which is beneficial when seen as representations for software systems. They may be further equipped with logical artifacts, such as pre-and post-conditions, loop, and class invariants, and finally, operational implementation artifacts.\nAs such, the XML\/XML schema models can be considered more abstract than the openEHR RM\/AOM\/ADL models, in the sense that the latter is more \u201cimplementation-oriented.\u201d\nTo standardize knowledge representation in the clinical domain, a significant contribution comes from languages such as the RDF schema or OWL.[46] OWL is even more abstract (omitting as much as possible about internal structures and reducing the description to a set of statements about what is true in the description). This minimalism enables formal reasoner engines to operate on the models, assisting us in discovering irregularities and inconsistencies.[16]\nTo publish pre-existing ontologies (e.g., UMLS) on the semantic web, there exist several problems concerning alternative interpretations of the semantic network notation and the inability to express some of the interpretations in OWL. Kashyap and Bordiga[47] run into several difficulties in this undertaking. Some obstacles were due to ambiguities in the SN notation\u2019s semantics or the notation\u2019s under-specification (e.g., what can be inferred from the absence of edges?). Other problems were the inability to express the SN as OWL axioms that would provide the desired inferences, and the difficulty of making choices among multiple possible representations. The authors encountered obstacles representing the semantics of \u201clinks\u201d in the SN, especially in the context of requirements such as \u03b4\/\u03c1 inheritance, inheritance blocking, and polymorphism. Thus, OWL language cannot be used to represent some notions in UMLS. \u03b4\/\u03c1 inheritance is domain and range inheritance. The \u201cis-a\u201d link in SN gives rise to inheritance. Whenever there is a conflict between the placement of types in the SN and the links to be inherited, the SN provides a mechanism to explicitly \u201cblock\u201d inheritance. The relationships whose arguments (i.e., domain and range values) can be instances of multiple classes are called polymorphic relationships. These requirements led Kashyap and Bordiga[47] to investigate the possible interpretations and encodings of a \u201clink\u201d in the SN.\nCodes representing the meanings of nodes and constraints on text or terms, bindings to terminologies such as SNOMED or LOINC, are stated in the ontology section of an archetype. The report[15] describes a novel approach to address semantic interoperability in the healthcare domain, taking into account ontology mapping. Archetypes are used to scope the context of the matching process that will allow two independent healthcare providers to interoperate. It structures the matching algorithms at two different levels\u2014terminology and archetype\u2014leveraging the most mature research on ontology matching. The approach identifies relationships between ontological terms that have been embedded in pairs of archetypes as a means of matching these terms. The matched terms can then, in turn, be used to identify similarities between archetypes. The context of the archetype will limit the matching space to allow for more accurate mapping results and, due to the nature of archetypes, ultimately to a very high level of automation. The Simple Knowledge Organization System (SKOS)[48] is a standard data model for sharing and linking knowledge organization systems via the semantic web. The possibility of exploring SKOS shortly to bridge the gaps among records that have been created by different representation languages or represented on different semantics of terms may be done. da Costa et al.[49] introduced a method of achieving interoperability heterogeneous health systems through ontologies and rules; that approach used OWL features to map out the balance between openEHR records mixed with HL7. Recent research proposes a semantic ontological framework that might unify several EHR data formats. It takes different data formats as input (ADL, SQL, XML, and CDA) and converts them into an OWL ontology.[49]\n\nConclusions \nSemantic interoperability is essential to facilitate the computerized support for alerts, workflow management, and evidence-based healthcare across heterogeneous EHR systems. The archetypes have been presented as a key to knowledge representation and information exchange; however, currently available archetype languages do not provide direct support for mapping to formal ontologies and then exploiting reasoning on clinical knowledge, which are critical ingredients of full semantic interoperability. This study presented various technologies for representing archetypes such as XML, ADL, and OWL through the simulation tool KnowledgeRep. The comparative analysis among formalisms such as OWL, OCL, and KIF were presented (Table 1). The semantic interoperable exchange among different standards requires these formalisms, as is illustrated by recent research projects (Table 3) in the study.\nThe KnowledgeRep study has explored the following objectives:\n\n1. Given an EHR system expressed in OWL (ESOWL) and a terminology system expressed in OWL (TSOWL), there exists a method for binding terminology to EHR expressed in OWL (TOWL). The EHR system here includes the RM and archetype. This enables both the RM and archetypes to be expressed in OWL representation. That is, \u2203 TOWL (ESOWL, TSOWL).\n2. It has been found that given an EHR system expressed in UML+ADL (ESUML+ADL) and a terminology system (TSF) expressed in formalism F, there exists a method for binding terminology to EHR through the \"term binding\" (TB) section of archetype (TTB). The EHR system here includes the RM (expressed in UML) and archetypes (expressed in ADL representation). The archetypes contain a \"term binding\" section. That is, \u2203 TTB (ESUML+ADL, TSF).\n3. It has also been found that given an EHR system expressed in XML (ESXML) and a terminology system expressed in XML (TSXML), there exists a method for binding terminology to EHR. The EHR system here includes the RM (expressed in XML schema) and Archetypes (represented in XML). That is, \u2203 TXML (ESXML, TSXML).\nHowever, for coping with the semantics, two things are required. First, terminology binding must established through archetypes. Second, mappings between different standardized EHR systems must be established. In other words, data elements of one EHR system need to be transformed to the data elements of another EHR system and vice versa (through various knowledge formalisms, see Table 1).\nThus, the paper concludes that ADL is suitable for domain modeling and constraint representation. XML schema do not provide the support for defining archetypes constraints[29]; however, XML is the global standard for exchange requirements and is also used for bringing the data from a non-archetype-based EHR system into an archetype-based EHR repository (through XSLT transformations). OWL representation is the best fit for semantic activities, without which the semantic exchange among the three prevalent standards is impossible. The structural components of a knowledge graph have been considered for forming virtual intermediate support for the information exchanges. Current research can contribute to helping EHR system vendors and developers to choose the appropriate technology for the required purpose, keeping in mind semantic interoperability.\nNote that this study is limited to establishing a comparison between distinct approaches (XML, OWL, OCL, and KIF) to interoperate within domain-specific applications such as healthcare. Tt does not discuss intelligent, semi-auto-constructed knowledge graph framework in the e-health context, a subject requiring further examination. Moreover, the research shows potential for being extended for various knowledge graph problems[3] such as data insufficiency, explainability, incomplete and incorrect knowledge, inconsistencies, and integration of knowledge.\n\n Abbreviations, acronyms, and initialisms \nADL: Archetype Definition Language\nAM: archetype model\nAOM: archetype object model\nCCR: Continuity of Care Record\nCDA: Clinical Document Architecture\nCEN: European Committee for Standardization\nCKM: Clinical Knowledge Manager\nDL: description logic\nEHR: electronic health record\nGEHR: Good Electronic Health Record\nGWT: Google Web Toolkit\nHL7: Health Level 7\nISO: International Organization for Standardization \nKG: knowledge graph\nKIF: Knowledge Interchange Format\nMeSH: Medical Subject Heading\nNCI: National Cancer Institute\nOCL: Object Constraint Language\nOWL: Web Ontology Language\nRDF: Resource Description Framework\nRIM: Reference Information Model\nRM: reference model\nSKOS: Simple Knowledge Organization System\nSWRL: Semantic Web Rule Language\nUML: Unified Modeling Language\nUMLS: Unified Medical Language System\nXML: Extensible Markup Language\n\nAppendices \nAppendix A. Parameter Heart_rate as an archetype \nThe structure of an archetype is given in Figure A1.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. A1 Parameter Heart_rate as an archetype.\n\n\n\nAppendix B. Comparison of ADL and XML \nThe comparison of ADL and XML is given in Table A1.\n\n\n\n\n\n\n\nTable A1. Comparison of ADL and XML\n\n\nProperties\n\nADL\n\nXML\n\n\nMachine-processable\n\nYes\n\nYes\n\n\nHuman-readable\n\nYes\n\nSometimes unreadable (e.g., XML schema instance, OWL-RDF ontologies)\n\n\nLeaf data types\n\nMore comprehensive set, including interval of numerics and date\/time types\n\nString data; with XML String data; schema option- more comprehensive set\n\n\nStructure\n\nUniversal schema for temporal database (EHRs) (history database)\n\nSemi-structured data (rooted acyclic graph with unique path from root to leaf)\n\n\nAdhering to object-oriented semantics\n\nYes, particularly for container types\n\nXML schema languages do not follow object-oriented semantics\n\n\nOntological reference\n\nDomain entities\/archetypes\n\nGlobal terms\/concepts\n\n\nRepresentation of object properties\n\nUses attributes\n\nUses attributes and sub-elements\n\n\nSpace (for storage)\n\nUses nearly half of space for tags\n\nMay have data redundancy in contents\n\n\nEfficiency\n\nIs a domain specific language (sufficiently rich to capture and model medical domain)\n\nGood for web document modeling with limited ability to represent database contents\n\n\nExample (Archetype)\n\nADL representation of Heart_rate (Appendix D)\n\nXML representation of Heart_rate (Appendix D)\n\n\n\nAppendix C. List of archetypes \nopenEHR-EHR-ITEM_TREE.medication.v1\nopenEHR-EHR-OBSERVATION.heart_rate.v1\nopenEHR-EHR-OBSERVATION.blood_pressure.v1\nopenEHR-EHR-COMPOSITION.report.v1\nopenEHR-EHR-OBSERVATION.body_weight.v1\nAppendix D. XML and ADL representation of Heart_rate \nThe XML and ADL representation of the Heart_rate archetype is given in Table A2.\n\n\n\n\n\n\n\nTable A2. XML and ADL representation of Heart_rate\n\n\nXML representation\n\nADL representation\n\n\n<?xml version=\"1.0\" encoding=\"UTF-8\"?>\n<archetype xmlns=\"http:\/\/schemas.openehr.org\/v1\" xmlns:xsi=\"http:\/\/www.w3.org\/2001\/XMLSchema-instance\" xmlns:xsd=\"http:\/\/www.w3.org\/2001\/XMLSchema\">\n.\r\n\n.\r\n\n.\r\n\n<ontology>\r\n\n<term_definitions language=\"ar-sy\">\r\n\n<items code=\"at0000\">\n\n<items id=\"text\">*Pulse\/Heart beat(en)<\/items>\n<items id=\"description\">*The rate and associated attributes for a pulse or heart beat. (en)<\/items>\n<\/items>\n<items code=\"at1037\">\n\n<items id=\"text\">*Body site(en)<\/items>\n<items id=\"description\">*Body site where the pulse or heart beat were observed.(en)<\/items>\n<\/items>\n<items code=\"at1005\">\n\n<items id=\"text\">*Presence(en)<\/items>\n<items id=\"description\">*Presence of a pulse or heart beat.(en)<\/items>\n<items id=\"comment\">*It can be implied that the pulse or heart beat is present if Rate >0 \/min. (en)<\/items>\n<\/items>\n<items code=\"at1013\">\n\n<items id=\"text\">*Device(en)<\/items>\n<items id=\"description\">*Details about the device used to measure the pulse rate or heart rate.(en)<\/items>\n<\/items>\n<items code=\"at0013\">\n\n<items id=\"text\">*Position(en)<\/items>\n<items id=\"description\">*The body position of the subject during the observation.(en)<\/items>\n<\/items>\n.\r\n\n.\r\n\n.\r\n\n<\/ontology>\r\n\n<\/archetype>\n\n\n\narchetype (adl_version=1.4; uid=566c355d-9e8f-473d-a80d-90fcd8d61414)\nopenEHR-EHR-OBSERVATION.pulse.v2\n.\r\n\n.\r\n\n.\r\n\nontology\n\nterm_definitions = <\n[\"ar-sy\"] = <\nitems = <[\"at0000\"] = <\ntext = <\"*Pulse\/Heart beat(en)\">\ndescription = <\"*The rate and associated attributes for a pulse or heart beat. (en)\"><\/dd>\n[\"at1037\"] = <\ntext = <\"*Body site(en)\">\ndescription = <\"*Body site where the pulse or heart beat were observed.(en)\"><\/dd><\/dd>\n[\"at1005\"] = <\ntext = <\"*Presence(en)\">\ndescription = <\"*Presence of a pulse or heart beat.(en)\">\ncomment = <\"*It can be implied that the pulse or heart beat is present if Rate >0 \/min. (en)\"><\/dd><\/dd>\n[\"at1013\"] = <\ntext = <\"*Device(en)\">\ndescription = <\"*Details about the device used to measure the pulse rate or heart rate.(en)\"><\/dd><\/dd>\n[\"at0013\"] = <\ntext = <\"*Position(en)\">\ndescription = <\"*The body position of the subject during the observation.(en)\"><\/dd><\/dd>\n>      >\r\n\n.\r\n\n.\r\n\n.\r\n\n\n>\n>\n\n\n\n\nAcknowledgements \nAuthor contributions \nS.S. and S.B. conceived, formulated, and verified the formalisms for archetypes. S.S. and S.B. analyzed the results, proofread the manuscript, and corrected the manuscript. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis research received no external funding.\n\nConflict of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 1.0 1.1 1.2 1.3 openEHR Foundation (15 December 2015). \"openEHR Architecture Overview\". BASE Release-1.0.3. openEHR Foundation. https:\/\/specifications.openehr.org\/releases\/BASE\/Release-1.0.3\/architecture_overview.html . Retrieved 19 January 2022 .   \n \n\n\u2191 2.0 2.1 Beale, T. (2002). \"Archetypes: Constraint-based Domain Models for Future-proof Information Systems\". OOPSLA 2002: Eleventh OOPSLA Workshop on Behavioral Semantics: 16\u201332. https:\/\/www.researchgate.net\/publication\/237033734_Archetypes_Constraint-based_Domain_Models_for_Future-proof_Information_Systems .   \n \n\n\u2191 3.0 3.1 Tiwari, Sanju; Al-Aswadi, Fatima N.; Gaurav, Devottam (1 July 2021). \"Recent trends in knowledge graphs: theory and practice\" (in en). 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ISBN 978-989-758-170-0. http:\/\/www.scitepress.org\/DigitalLibrary\/Link.aspx?doi=10.5220\/0005648801590165 .   \n \n\n\u2191 47.0 47.1 Kashyap, Vipul; Borgida, Alex (2003), Fensel, Dieter; Sycara, Katia; Mylopoulos, John, eds., \"Representing the UMLS\u00ae Semantic Network Using OWL\", The Semantic Web - ISWC 2003 (Berlin, Heidelberg: Springer Berlin Heidelberg) 2870: 1\u201316, doi:10.1007\/978-3-540-39718-2_1, ISBN 978-3-540-20362-9, http:\/\/link.springer.com\/10.1007\/978-3-540-39718-2_1   \n \n\n\u2191 Miles, A.; Bechhofer, S. (20 August 2008). \"SKOS Simple Knowledge Organization System RDF Schema\". WC3. https:\/\/www.w3.org\/TR\/2008\/WD-skos-reference-20080829\/skos.html . Retrieved 06 November 2021 .   \n \n\n\u2191 49.0 49.1 da Costa, C.A.; Wichman, M.H.; Righi, R.R. et al. (2019). \"Ontology-based Model for Interoperability between openEHR and HL7 Health Applications\". In Arabnia, H.R.; Deligiannidis, L.; Tinetti, F.G. et al. (in English). HIMS'19 proceedings of the 2019 International Conference on Health Informatics and Medical Systems. ISBN 978-1-68392-570-5. OCLC 1151199195. http:\/\/public.eblib.com\/choice\/PublicFullRecord.aspx?p=6143762 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. The original references are in alphabetical order; this version places them in or order of appearance, by design. The original gives the same citation for both 35 and 50; for this version, only one instance is used. \n|}\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\">https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges<\/a>\nNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 14 June 2022, at 21:06.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 163 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","5c4c23816cc524a349b691a9b6846809_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges rootpage-Journal_Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Using knowledge graph structures for semantic interoperability in electronic health records data exchanges<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/Data_sharing\" title=\"Data sharing\" class=\"wiki-link\" data-key=\"a99d5fda27f755c693c65864d9286130\">Information sharing<\/a> across medical institutions is restricted to <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> exchange between specific partners. The lifelong <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">electronic health record<\/a> (EHR) structure and content require standardization efforts. Existing standards such as <a href=\"https:\/\/www.limswiki.org\/index.php\/OpenEHR\" title=\"OpenEHR\" class=\"wiki-link\" data-key=\"4c3f67f4e3102639ce8c6bff842b8982\">openEHR<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_7\" title=\"Health Level 7\" class=\"wiki-link\" data-key=\"e0bf845fb58d2bae05a846b47629e86f\">Health Level 7<\/a> (HL7), and ISO\/EN 13606 aim to achieve data independence along with semantic interoperability. This study aims to discover knowledge representation to achieve semantic health data exchange. openEHR and ISO\/EN 13606 use archetype-based technology for semantic interoperability. The HL7 Clinical Document Architecture is on its way to adopting this through HL7 templates. Archetypes are the basis for knowledge-based systems, as these are means to define clinical knowledge. \n<\/p><p>The paper examines a set of formalisms for the suitability of describing, representing, and reasoning about archetypes. Each of the information exchange technologies\u2014such as XML, Web Ontology Language (OWL), Object Constraint Language (OCL), and Knowledge Interchange Format (KIF)\u2014is evaluated as a part of the knowledge representation experiment. These examine the representation of archetypes as described by Archetype Definition Language (ADL). The evaluation maintains a clear focus on the syntactic and semantic transformations among different EHR standards.\n<\/p><p><b>Keywords<\/b>: archetypes, electronic health records, dual-model approach, knowledge representation, EHR, XML, ADL, OWL, KIF\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>Healthcare is a continuously evolving domain. New findings of diseases and clinical treatments are continuously being made. It has raised the need for increased <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_sharing\" title=\"Data sharing\" class=\"wiki-link\" data-key=\"a99d5fda27f755c693c65864d9286130\">information exchange<\/a> among various medical institutions. <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">Electronic health records<\/a> (EHRs) contain the medical history and treatments of the patients at those medical institutions. In the classical approach, information and knowledge are stored together. However, storage of each clinical concept in a single relation led to a huge data model that was difficult to manage and expensive to maintain. Among the existing interoperability approaches for EHRs, the dual-model approach<sup id=\"rdp-ebb-cite_ref-:0_1-0\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> seems to be most promising. It consists of an information layer and a knowledge layer. The key benefit of this approach is the segregation of knowledge (represented as archetypes<sup id=\"rdp-ebb-cite_ref-:1_2-0\" class=\"reference\"><a href=\"#cite_note-:1-2\">[2]<\/a><\/sup>). A conceptual idea is virtually transferred through the medium of an intermediate structure of a knowledge graph. This study analyzes that knowledge graph's components.\n<\/p><p>Knowledge graphs are used to capture knowledge in application-based situations that require large-scale integration, management, and extraction of value from a variety of data sources. Recent studies examine all currently available knowledge graphs (KGs), including their characteristics, approaches, applications, issues, and challenges.<sup id=\"rdp-ebb-cite_ref-:11_3-0\" class=\"reference\"><a href=\"#cite_note-:11-3\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup>\n<\/p><p>This paper focuses on using knowledge representation and information interchange technologies for archetype representation.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Overview_of_EHRs\">Overview of EHRs<\/span><\/h3>\n<p>The domain of the modern EHR is complex. It consists of different types of data (from textual to multimedia), with new data requirements emerging over time. For example, there are about 300,000 medical terms at present (as defined by <a href=\"https:\/\/www.limswiki.org\/index.php\/SNOMED_CT\" title=\"SNOMED CT\" class=\"wiki-link\" data-key=\"a04000c818ae954bf52cfea5efdf020d\">SNOMED CT<\/a>), and medical tests and procedures are constantly created and modified. EHRs have a complex structure based on archetypes. These may include data based on hundreds of parameters, such as temperature, blood pressure, and body mass index (BMI). Each of the individual parameters (or concepts) has its own specific content and is represented as an archetype. For example, one archetype could contain an item such as \"data,\" which can, for example, be represented as a documented heart rate observation. This archetype ideally offers complete knowledge about a clinical context (i.e., attributes of data), the data's \"state\" (i.e., context for interpretation of data), and its \"protocol\" (i.e., information regarding the gathering of data) (see Appendix A). Various standards development organizations are working to improve the interoperability of semantic EHRs through these archetypes and more.\n<\/p><p>It is desirable to have EHR systems that are functionally and semantically interoperable systems. Interoperability can be defined as an ability to communicate data such that the data are sufficient to perform the tasks at the receiving system. The associated data items have the same meaning for the creator of the sending party and the users of the receiving party, and the tasks performed using the data must be to the satisfaction of the receiving party. To tackle the EHR interoperability problem, many authorized organizations have defined several standards. Examples include <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_7\" title=\"Health Level 7\" class=\"wiki-link\" data-key=\"e0bf845fb58d2bae05a846b47629e86f\">Health Level 7<\/a> (HL7) and its Clinical Document Architecture (CDA), ASTM International's Continuity of Care Record (CCR), European Committee for Standardization (CEN) Technical Committee 251 and International Organization for Standardization (ISO)'s ISO\/EN 13606, and the openEHR Foundation's <a href=\"https:\/\/www.limswiki.org\/index.php\/OpenEHR\" title=\"OpenEHR\" class=\"wiki-link\" data-key=\"4c3f67f4e3102639ce8c6bff842b8982\">openEHR<\/a>. The main objective of all these EHR standards is to structure the data and mark up the content of the medical information to be more readily exchanged.\n<\/p><p>For this work, three levels of interoperability stand out, namely syntactic (data) interoperability, structural interoperability\/semantic interpretability, and semantic interoperability.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> The main mechanisms for interoperability are reference models, archetypes, and domain knowledge governance.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Archetypes_and_semantic_interoperability\">Archetypes and semantic interoperability<\/span><\/h3>\n<p>The standards for semantic interoperability (such as CDA, openEHR, and ISO\/EN 13606) endorse the two-level modeling approach for storing EHR content.<sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup> It consists of two layers that propose to segregate information modeling from content (knowledge) modeling. The reference (information) model layer represents the generic structures of components of the healthcare data. The content model on the other hand is used to represent more domain-specific data, which in general have instability due to variability and high rate of change in their usage (e.g., a formal description of a physical examination or prescription).\n<\/p><p>In openEHR and ISO\/EN 13606, the first level is known as the reference model (RM) and the second level consists of archetypes. The RM defines the basic fundamental structure and represents the generic structures of components of the healthcare data at the storage level (i.e., information modeling). At the second layer, the archetype model (AM) constrains the generic structure to encompass logical semantics and, thus, provide a standard definition that aids in semantic interoperability. AM provides deliverables in the form of archetypes and templates. An archetype provides the meta-description of structured clinical records as a computable formalism. In HL7's CDA, the two levels are the Reference Information Model (RIM) and the HL7 templates, which function essentially the same as the archetype concept.\n<\/p><p>These standards support compatibility among each other. In the case of openEHR and ISO\/EN 13606, the only means of achieving interoperability with a generic information model is through their archetypes. In fact, ADL archetypes can be defined against any Unified Modeling Language (UML) model, and it is also possible to write the archetypes against the HL7 Version 3 RIM and the CDA in general. Kilic and Dogac<sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup> note this in their work, describing how the clinical statements of two different EHR standards derived from the same RIM can be mapped to each other by using archetypes, Refined Message Information Model derivations, and semantic tools.\n<\/p><p>As mentioned prior, an archetype is an agreed upon formal and interoperable specification of a re-usable clinical data set that underpins an EHR. It captures the maximum possible information about a particular and discrete clinical concept.<sup id=\"rdp-ebb-cite_ref-:1_2-1\" class=\"reference\"><a href=\"#cite_note-:1-2\">[2]<\/a><\/sup> A conceptual definition of data as archetypes can be developed in terms of constraints on structure, types, values, and behaviors of RM classes based on the dual-model approach. It consists of the knowledge layer as archetypes and an RM. An example of a simple archetype is \"Weight,\" which can be used in multiple places as required within an EHR. \n<\/p><p>Semantics in archetypes have a dual nature. They consist of both structural and terminological components. The structure of an archetype provides support for semantics, while EHR component links form a set of interrelated conceptual, clinical entities. Each entity has a set of terminological bindings associated with it (specified by links to terms of specific medical terminologies).\n<\/p><p>If data elements are created and modified using archetypes, the archetypes constrain the configuration of data instances to be valid according to the archetype. These are a paradigm for building semantically enabled software systems, providing data validation, clinical modeling (by domain experts), a basis for querying, and form design. An archetype might define or constrain relationships between data values within a data structure. These are expressed as algorithms, formula, or rules. An archetype's <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" title=\"Metadata\" class=\"wiki-link\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">metadata<\/a> defines its core concept, purpose, use, evidence, authorship, and versioning. An archetype also ensures a maximal dataset. It contains all the relevant information regarding a clinical concept. Once the format of an archetype is agreed upon and published, it is held in a \"library\u2019\" and made available for use in any part of a given application by multiple vendor systems, multiple institutions, and multiple geographical regions. Each group or entity using the same archetype will understand and compute data captured by the same archetype in another clinical environment. Thus, an archetype serves the following key purposes<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup>:\n<\/p>\n<ol><li>It allows domain experts (clinicians) to capture data for their information systems.<\/li>\n<li>It provides runtime validation of data input, thus improving data entry quality.<\/li>\n<li>It provides a basis for intelligent querying of data.<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"Representing_internal_data_in_archetypes\">Representing internal data in archetypes<\/span><\/h3>\n<p>Matching clinical data to codes in controlled terminologies is the first step towards achieving data standardization for safe and accurate data interoperability. Archetypes have the advantage of being able to separate the internal model data from formal terminologies. Existing terminologies, taxonomies, and <a href=\"https:\/\/www.limswiki.org\/index.php\/Ontology_(information_science)\" title=\"Ontology (information science)\" class=\"wiki-link\" data-key=\"52d0664bde4b458e81fbc128b911a4a6\">ontologies<\/a> have been written in many languages. For example, <a href=\"https:\/\/www.limswiki.org\/index.php\/Medical_Subject_Headings_(MeSH)\" title=\"Medical Subject Headings (MeSH)\" class=\"wiki-link\" data-key=\"5a78d7a7cdb189a093388e284b249efc\">Medical Subject Headings<\/a> (MESH)<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup> and the <a href=\"https:\/\/www.limswiki.org\/index.php\/National_Cancer_Institute\" title=\"National Cancer Institute\" class=\"wiki-link\" data-key=\"281916a9fbd28f1e14ba3a07ff64abc8\">National Cancer Institute<\/a> (NCI)<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup> have their own proprietary formalisms (now commonly expressed also in XML). The \"term binding\" section of the archetype is used to describe the equivalences between archetype local terms and terms found in external terminologies, such as SNOMED CT or <a href=\"https:\/\/www.limswiki.org\/index.php\/Unified_Medical_Language_System\" title=\"Unified Medical Language System\" class=\"wiki-link\" data-key=\"cdee33b213990e5416c0b7fba322ce7c\">Unified Medical Language System<\/a> (UMLS). The internal data are assigned local names and later bound or mapped to external terminology codes. This feature eliminates the need to make changes to the model whenever the terminology changes. For formal descriptions, the Archetype Definition Language (ADL) uses three other syntaxes\u2014cADL (constraint form of ADL), dADL (data definition form of ADL), and a version of first-order predicate logic (FOPL)\u2014to describe constraints on data, which are instances of some information model (e.g., expressed in UML).<sup id=\"rdp-ebb-cite_ref-:2_12-0\" class=\"reference\"><a href=\"#cite_note-:2-12\">[12]<\/a><\/sup> Thus, ADL can be used to write archetypes for any domain where formal object model(s) exist, which describe data instances.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"EHRs_and_data_modeling\">EHRs and data modeling<\/span><\/h3>\n<p>The openEHR architecture<sup id=\"rdp-ebb-cite_ref-:0_1-1\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> includes a design principle called \"ontological separation,\" which regulates the EHR modeling (Figure 1). The model consists of two main categories: \"ontologies of information\" and \"ontologies of reality.\" The ontologies of information contain the information models of the EHR content, whereas the ontologies of reality describe real phenomena with descriptions and classifications.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Sachdeva_Information22_13-2.png\" class=\"image wiki-link\" data-key=\"121d2893baf27ac84ea03d8f2a549853\"><img alt=\"Fig1 Sachdeva Information22 13-2.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6e\/Fig1_Sachdeva_Information22_13-2.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> Illustration of openEHR\u2019s ontological structure<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The ontologies of information are divided into several models:\n<\/p>\n<ol><li>Domain content models (knowledge models) containing formal definitions of the clinical content. These are developed using archetypes, which are designed such that these can change when new clinical needs arise.<\/li>\n<li>Information representation models are implemented in the electronic healthcare system's software. These are used as a foundation for the domain content models and are designed to be stable regarding model changes. In openEHR, this component is the RM.<\/li><\/ol>\n<p>In simpler terms, if RM is equivalent to the set of letters\/digits, then each and every archetype would be a set of grammar constraining which strings could be expressed for that archetype. In formal terms:\n<\/p>\n<dl><dd>RM = {Set of classes C1, C2, C3 ...C<i>n<\/i>}<\/dd>\n<dd>Archetype = {Set of rules for valid combination of classes of RM}<\/dd><\/dl>\n<p>The ontologies of reality can be broken down as:\n<\/p>\n<ol><li>Classifications: ICDx (<a href=\"https:\/\/www.limswiki.org\/index.php\/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems\" title=\"International Statistical Classification of Diseases and Related Health Problems\" class=\"wiki-link\" data-key=\"1de9af67005dfe2895e5d8cf6de57d4a\">International Classification of Diseases<\/a>) and ICPC (<a href=\"https:\/\/www.limswiki.org\/index.php\/International_Classification_of_Primary_Care\" title=\"International Classification of Primary Care\" class=\"wiki-link\" data-key=\"1d78efeef60297733e4934ae83d6067f\">International Classification of Primary Care<\/a>)<\/li>\n<li>Process descriptions: Clinical guidelines<\/li>\n<li>Descriptive terminologies: SNOMED CT or <a href=\"https:\/\/www.limswiki.org\/index.php\/LOINC\" title=\"LOINC\" class=\"wiki-link\" data-key=\"b20c83dbfab36194bab6c223e31ebfdc\">LOINC<\/a><\/li><\/ol>\n<p>In Figure 1, the EHR extracts are based on commonly shared archetypes. These are proposed as a means to exchange information between different health care providers.<sup id=\"rdp-ebb-cite_ref-:0_1-2\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> The semantics of the domain content models (e.g., archetypes) are provided by terminology binding. The meaning of nodes in archetypes is given by textual descriptions and references to external terminology systems. These are in the form of term definition and term binding. Representation of archetypes in various possibilities such as ADL, XML (Extensible Markup Language), and OWL (Web Ontology Language) has been described in the paper. Subsequently, a comparison is drawn amongst these information exchange technologies, and the advantages and disadvantages of each have been analyzed. The main aim of this study is to find the best representation of an archetype. The paper examines a set of formalisms for the suitability of describing, representing, and reasoning about archetypes.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Formalisms_in_transformation_of_archetypes_among_different_standards:_Background\">Formalisms in transformation of archetypes among different standards: Background<\/span><\/h2>\n<p>Prevalent standards such as CDA, openEHR, and ISO\/EN 13606 use archetype-based technology for semantically interoperable exchange. ADL archetypes can be written against any UML model, and it would be possible to write archetypes directly against the RIM<sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup>, and also the CDA specification<sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup> (using a UML expression derived from its XML schema). These standards define the structure and the markup of the clinical content to make EHR exchange interoperable. They all rely on dual-model technology for semantic interoperability. They have different classes in the RM, having abstract semantics. Although the names of the classes are not shared between these standards, their semantics are similar. The RM for all the standards is stable. If alignments are performed between archetypes of different standards, aligning algorithms based on similarity measures will fail, as class names (of RM) are disparate. Dictionary-based approaches will not be of much help, as all names are quite abstract.<sup id=\"rdp-ebb-cite_ref-:3_15-0\" class=\"reference\"><a href=\"#cite_note-:3-15\">[15]<\/a><\/sup> The various ongoing exchange efforts based on archetypes use different formalisms to represent archetypes. The mapping among different standards makes use of model management and uses OWL transformations and XML representation of archetypes.\n<\/p><p>For interoperability among EHR standards based on ontologies, the possible approaches are (i) building common ontology and (ii) reusing existing ontologies and combining them. The first approach requires the transformation of ADL archetypes into OWL.<sup id=\"rdp-ebb-cite_ref-:4_16-0\" class=\"reference\"><a href=\"#cite_note-:4-16\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup> The ontological information and AMs have been compared to find similarities and differences among the CEN and openEHR representations. The software tool available based on this approach is Poseacle Convertor.<sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup> This approach involves the use of XML and OWL representations, with the latter being obtained by reusing existing ontologies and combining them through ontology mapping. The ARTEMIS project was implemented based on this, using the various formalisms such as XML, ADL, and OWL.<sup id=\"rdp-ebb-cite_ref-:5_19-0\" class=\"reference\"><a href=\"#cite_note-:5-19\">[19]<\/a><\/sup>\n<\/p><p>Broadly speaking, archetypes must be agreed upon before communication. However, it does not seem feasible to expect all professionals of various disciplines to agree on exactly all details of the archetypes associated with the data they would like to exchange. If this approach becomes widely accepted, it is certain that the number of available archetypes will become very large. Although archetypes are annotated with terms from standardized ontologies (terminologies, taxonomies, etc.), there will still be differences at the archetype level and at the terminology level. Due to competing standards, local variations at the archetype level will stem from the specialization of archetypes for specific purposes and research projects. Further, several widely used terminologies could be used to annotate archetypes (e.g., SNOMED CT, MeSH, NCI). Local ontologies are also used to annotate archetypes; therefore, a sound and general process for matching archetypes are essential. \n<\/p><p>In 2019, Adel <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-20\" class=\"reference\"><a href=\"#cite_note-20\">[20]<\/a><\/sup> proposed a unified framework based on a fuzzy ontology to show how to exploit semantic web technologies to support EHR semantic interoperability. Prior to that, Martinez-Costa <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:6_21-0\" class=\"reference\"><a href=\"#cite_note-:6-21\">[21]<\/a><\/sup> introduced ontologies and rules as a means of establishing interoperability amongst heterogeneous health systems (openEHR and HL7). Recently, Roehrs <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup> proposed an application model called OmniPHR, a model for assessing the structure of semantic interoperability and database integration from various health standards. OmniPHR uses <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a>, <a href=\"https:\/\/www.limswiki.org\/index.php\/Natural_language_processing\" title=\"Natural language processing\" class=\"wiki-link\" data-key=\"e6954531e0725edfd19e425540be5c3a\">natural language processing<\/a>, and a standard ontology to achieve interoperability. Knowledge graphs are represented using a variety of methodologies, but <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> methods are frequently employed to create a low-dimensional representation that can support a wide range of applications.<sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup>\n<\/p><p>Given this, there is a requirement to identify the role of the suitability of various formalisms for achieving full semantic interoperability through archetypes, which addressed in the current research.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Knowledge_representation\">Knowledge representation<\/span><\/h2>\n<p>In a 2019 review of more than 100 papers on knowledge representation in health care, Ria\u00f1o <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:7_24-0\" class=\"reference\"><a href=\"#cite_note-:7-24\">[24]<\/a><\/sup> found that ontologies (31%), semantic web-related formalisms (26%), decision tables and rules (19%), logic (14%), and probabilistic models (10%) represented the most common knowledge representation approaches. They also found that <a href=\"https:\/\/www.limswiki.org\/index.php\/Medical_informatics\" class=\"mw-redirect wiki-link\" title=\"Medical informatics\" data-key=\"f89ecb3b26617b8c6e09bc5e050cfd5d\">medical informatics<\/a> knowledge was primarily represented as computer interpretable clinical recommendations (43%), medical domain ontologies (26%), and EHRs (22%).<sup id=\"rdp-ebb-cite_ref-:7_24-1\" class=\"reference\"><a href=\"#cite_note-:7-24\">[24]<\/a><\/sup> In most of these cases, embedding codes can convey the meaning of the concepts that are represented by an archetype from a commonly recognized terminology at appropriate points in the archetype. Archetypes are the unit of communication between interoperating applications, as they define the minimum context that must be considered for safe communication.<sup id=\"rdp-ebb-cite_ref-:3_15-1\" class=\"reference\"><a href=\"#cite_note-:3-15\">[15]<\/a><\/sup> Expressivity is a key parameter in choosing or creating a knowledge representation. It is easier and more compact to express a fact or element of knowledge within the semantics and grammar of a more expressive knowledge representation. However, more expressive languages will likely require more complex logic and algorithms to construct equivalent inferences. A highly expressive knowledge representation is also less likely to be complete and consistent. Less expressive KRs may be both complete and consistent.<sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[25]<\/a><\/sup> This section describes the knowledge technologies for the representation of archetypes.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"ADL_and_XML\">ADL and XML<\/span><\/h3>\n<p>The ADL approach uses existing UML semantics and existing terminologies and adds convenient syntax for expressing the required constraints. Expressing the semantics of archetypes using XML-based exchange formats leads to the conflation of abstract and concrete representational semantics.<sup id=\"rdp-ebb-cite_ref-:2_12-1\" class=\"reference\"><a href=\"#cite_note-:2-12\">[12]<\/a><\/sup> ADL syntax is straightforward and powerful. It has allowed mappings to other formalisms to be more correctly defined and understood. Previously, archetypes have been expressed as XML instance documents conforming to W3C XML schemas<sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup>, for example, in the Good Electronic Health Record (GEHR)<sup id=\"rdp-ebb-cite_ref-:8_27-0\" class=\"reference\"><a href=\"#cite_note-:8-27\">[27]<\/a><\/sup> and openEHR projects. Subsequently, expressing archetype constraints using numerous schema languages for XML (such as XML schema, RELAX NG, and Schematron) has been examined. Because of the issues reported, these languages were abandoned for archetype validation.<sup id=\"rdp-ebb-cite_ref-:9_28-0\" class=\"reference\"><a href=\"#cite_note-:9-28\">[28]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:12_29-0\" class=\"reference\"><a href=\"#cite_note-:12-29\">[29]<\/a><\/sup> For example, in XML schema, classes in RM were mapped to complex types, and archetypes were mapped to class restrictions. The strict rules (unique particle attribution, complex enumerations, placing regular expression constraint) in using the restriction feature in XML schema did not permit the implementation of archetype constraints.\n<\/p><p>With ADL parsing tools, it is possible to convert ADL to any number of forms, including various XML formats. XML instances can be generated from the object form of an archetype in memory. XML archetypes are equivalent to serialized instances of the parse tree, i.e., particular ADL archetypes serialized from objects into XML instances. Archetypes connect information structures to formal terminologies. Similar to XML data, they are path-addressable using path expressions directly convertible to Xpath expressions. An XML schema corresponding to the ADL object model has been published at openEHR.org.<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup> The XML schema corresponding to RM is published in the work of Martinez-Costa <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:6_21-1\" class=\"reference\"><a href=\"#cite_note-:6-21\">[21]<\/a><\/sup>\n<\/p><p>The XML has a role in the exchange requirement. The EHR_Extract, used for exchange, is expressed using XML.<sup id=\"rdp-ebb-cite_ref-:0_1-3\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup> A recent study examines whether the W3C XML schema provides a practicable solution for the semantic validation of standard-based EHR documents.<sup id=\"rdp-ebb-cite_ref-:9_28-1\" class=\"reference\"><a href=\"#cite_note-:9-28\">[28]<\/a><\/sup> The EHR_Extract needs to be validated against the RM and the associated archetypes.\n<\/p><p>An example of XML\/ADL use can be found in openEHR. To accept a report from the <a href=\"https:\/\/www.limswiki.org\/index.php\/Pathology\" title=\"Pathology\" class=\"wiki-link\" data-key=\"5d8e2230b55d8760dcb729fc7dcd3dc1\">pathology<\/a> <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> for inclusion in the EHR repository of a patient (in the ADL form), an XML form is generated using the archetype. This form is shared with the laboratory for on-site validation of data input. Thus, XML is used as an input and transport medium.\n<\/p><p>A comparison between ADL and XML is stated below, and in Appendix B:\n<\/p>\n<ol><li>Both are machine processable.<\/li>\n<li>ADL is human readable, whereas XML is sometimes unreadable (e.g., XML schema instances, OWL-RDF ontologies).<\/li>\n<li>ADL adheres to object-oriented semantics, particularly for container types, whereas XML schema languages do not follow object-oriented semantics.<\/li>\n<li>For ontological reference, ADL has domain entities\/archetypes, and XML has global terms\/concepts.<\/li>\n<li>ADL uses attributes, and XML uses attributes and sub-elements to represent object properties.<\/li>\n<li>ADL uses nearly half of its required space (storage) for tags, and XML may have data redundancy in contents.<\/li>\n<li>In terms of efficiency, ADL is a domain-specific language (sufficiently rich to capture and model the medical domain) in comparison to XML, which is good for web document modeling, though with limited ability to represent database contents.<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"ADL_and_OWL\">ADL and OWL<\/span><\/h3>\n<p>OWL<sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup> is a language for the semantic web, which:\n<\/p>\n<ul><li>offers expressiveness and the possibility of reasoning over the information it describes;<\/li>\n<li>allows making annotations on classes or properties and makes semantic similarity functions available;<\/li>\n<li>is related to terminologies (e.g., SNOMED CT is currently in the process of adapting its representation to semantic web environments<sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup>, recognizing that having a representation of both the clinical and terminological information in the same formalism would facilitate better clinical knowledge management and would enrich archetypes by adding more information to them);<\/li>\n<li>brings all information concerning a particular term together through modeling (e.g., code, definition, bindings, and translations); and<\/li>\n<li>is supported by several tools which can process it.<\/li><\/ul>\n<p>OWL has an abstract syntax, an extension of XML-based syntax known as the Resource Description Framework (RDF). OWL is general-purpose description logic (DL) and is primarily used to describe \u201cclasses\u201d of things in such a way as to support subsumptive inferencing within the ontology, and by extension, on data that are instances of ontology classes. OWL includes intersection, union, complement of existential quantification, universal quantification, min cardinality, max cardinality, equivalence, and specialization. Thus, it demonstrates decidability and computability, offering expressiveness and the possibility of reasoning over the information it describes. OWL version 2 has a property of qualified cardinality restrictions (which makes it possible to capture the occurrences restrictions from ADL), property chain inclusions, and OWL\/XML syntax.\n<\/p><p>ADL provides a rich set of constraints on primitive types, including dates and times; however, ADL has significant drawbacks for achieving the goal of semantic interoperability, such as its syntactic orientation. Consequently, the formalization of the exchange and transformation processes is more than using semantic-oriented models such as ontological ones. In addition to this, syntactic approaches also make important archetype-related tasks, such as comparing and classifying archetypes, difficult. \n<\/p><p>Archetypes in ADL can be represented in OWL. However, it requires<sup id=\"rdp-ebb-cite_ref-:2_12-2\" class=\"reference\"><a href=\"#cite_note-:2-12\">[12]<\/a><\/sup>:\n<\/p>\n<ul><li>the expression of the relevant RMs in OWL;<\/li>\n<li>the expression of the relevant terminologies in OWL;<\/li>\n<li>the representation of concepts (i.e., constraints) independently of natural language; and<\/li>\n<li>the conversion of the cADL part of an archetype to OWL.<\/li><\/ul>\n<p>Using OWL-expressed archetypes to validate data (which would require massive amounts of data to be converted to OWL statements) is unlikely to be anywhere near as efficient as doing it with archetypes expressed in ADL or one of its concrete expressions.<sup id=\"rdp-ebb-cite_ref-:2_12-3\" class=\"reference\"><a href=\"#cite_note-:2-12\">[12]<\/a><\/sup> The UML-like representation is not suitable for performing formal reasoning at the conceptual level; however, OWL offers a great deal of inferencing power of the far wider scope in comparison to specific reasoning.\n<\/p><p>The object-oriented semantics apply in the UML specification of RM and the corresponding XML schema mapped from it. This needs to be mapped for conversion to OWL. Practically, this is possible, as illustrated in a recent study.<sup id=\"rdp-ebb-cite_ref-:4_16-1\" class=\"reference\"><a href=\"#cite_note-:4-16\">[16]<\/a><\/sup> The XML-schema class is mapped to an OWL class with the same name. The restricted data type definitions in XML schema are mapped to an OWL data type. The attributes in XML-schema are mapped to an OWL property. The instances\/objects in XML are equivalent to individuals in OWL.\n<\/p><p>Kilic <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup> provide mapping archetypes to OWL. For automatically transforming archetype definitions from ADL to OWL, the archetype ontologies use the ehr2ont framework.<sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[34]<\/a><\/sup> LinkEHR<sup id=\"rdp-ebb-cite_ref-:13_35-0\" class=\"reference\"><a href=\"#cite_note-:13-35\">[35]<\/a><\/sup> is a more recent project for obtaining the OWL representation of archetypes.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"ADL_and_other_formalisms\">ADL and other formalisms<\/span><\/h3>\n<p>A comparative analysis of ADL with other formalisms such as the Object Constraint Language (OCL) and Knowledge Interchange Format (KIF) is shown later in the next section. The OCL allows constraining all class instances to conform to the specific configuration of instances. In contrast, ADL provides the ability to create numerous archetypes, each describing in detail a concrete configuration of instances of a class. ADL archetypes include invariants (which are expressed in a syntax similar to OCL).\n<\/p><p>RDF is a data model for objects (\u201cresources\u201d), and relations between them provide simple semantics for this data model.<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup> OWL takes the essential fact-stating ability of RDF and the class- and property-structuring capabilities of RDF schema and extends them in essential ways. OWL classes can be specified as logical combinations (intersections, unions, or complements) of other classes, or as enumerations of specified objects, going beyond the capabilities of the RDF schema. OWL can declare classes and organize these classes in a subsumption (\u201csubclass\u201d) hierarchy, as an RDF schema. The significant extension over RDF schema is the ability in OWL to provide restrictions on how properties behave (that are local to a class). A recent study concentrates on the semantic interoperability of diverse EHRs and their standards, proposing the transformation of heterogeneous EHR datasets into XML syntactic models and their translation into a common ontological representation for semantic knowledge acquisition.<sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Evaluation_in_practice\">Evaluation in practice<\/span><\/h2>\n<p>We ran into many problems concerning alternative representations of the archetype and the inability to express some of the constraints in different knowledge representation languages. We detail these problems as a cautionary tale to others planning to use pre-existing archetypes for semantic interoperability, as a list of issues to consider when describing concepts formally in any language, and as a collection of criteria for evaluating alternative representations.\n<\/p><p>The three best-suited knowledge formalisms\u2014ADL, XML, and OWL\u2014for archetype representation have been evaluated for the features mentioned in the paper through the experimental setup KnowledgeRep. The ADL formalism has been compared with XML and OWL to find the suitable role of these formalisms in a working semantic interoperable system.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"KnowledgeRep:_Simulation\">KnowledgeRep: Simulation<\/span><\/h3>\n<p>Various knowledge formalisms used in different EHR standards for obtaining semantic interoperability have been examined in current research with the openEHR standard. The underlying Java Reference Implementation<sup id=\"rdp-ebb-cite_ref-:5_19-1\" class=\"reference\"><a href=\"#cite_note-:5-19\">[19]<\/a><\/sup> of openEHR has been used, referred to as KnowledgeRep. It is an evaluation setup for examining various archetype representations for EHR concepts. Figure 2, shows an application GUI (graphical user interface), the knowledge representations, and the communication classes. The application GUI represents various system interactions between the users and the EHR system. It is responsible for multiple calls to the utility and server-side classes to perform the formatting and transformations of the data and extract relevant data. It comprises the following modules: the form presented to the user, the template mechanism required to create the template corresponding to the EHR system, the data binding module, and the result viewer, which represents the report desired by the user. GWT (Google Web Toolkit) facilitates all these modules. It introduces the necessary flexibility into the model-driven approach of standard-based EHR system development.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Sachdeva_Information22_13-2.png\" class=\"image wiki-link\" data-key=\"8130634ab6bc9b6e20f41a0f46c781b3\"><img alt=\"Fig2 Sachdeva Information22 13-2.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/b\/bc\/Fig2_Sachdeva_Information22_13-2.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> KnowledgeRep: Evaluation setup for various archetype representations for EHR concepts<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The knowledge representation (archetypes) in ADL, XML, and OWL formalisms and the communication classes are shown in the second part of the diagram. It contains components that are responsible for communication. It also contains logic that connects the GUI with the underlying Java Reference Implementation of openEHR. The entire set of knowledge is parsed from ADL\/XML\/OWL files using the classes of RM and mapped to the GUI (form). The knowledge representation and communication part of the setup comprises the <<tt>ArchetypeWrapper<\/tt> and <tt>DatabaseWrapper<\/tt> classes, which act as the communication nodes. <tt>ArchetypeDAO<\/tt> maps the database and the basic RM data types. The clinical software database is shown (the details are beyond the scope of the current research).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Methodology\">Methodology<\/span><\/h3>\n<p>Here we describe the analysis procedure applied for each formalism, ADL, XML, and OWL. The archetypes used for the analysis have been downloaded from Clinical Knowledge Manager (CKM)<sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup>, Appendix C. Each knowledge representation has been analyzed from the perspective of how strong it is to support the client side and the server side of the EHR system. In other words, we have tried to explore knowledge representation from a user\u2019s perspective and the machine\u2019s perspective.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Representation_in_ADL\">Representation in ADL<\/span><\/h4>\n<p>The analysis of ADL was performed as given. A user selects a form to make a data entry, the corresponding .adl file is picked up from the archetype repository, it is parsed to extract all the node paths of the mandatory fields, and then a form is generated. When the user enters the value of any of the fields in the archetype, they are bonded with the exact path in the .adl file. We see that the ADL formalism is a powerful knowledge representation that can act as a GUI generator. At the same time, when the data are to be persisted, a user inputs to the corresponding archetype are mapped to the RM data types by intermediate classes and stored in the database. Along with the data type and the data value, the path of the node in the .adl file and the name of the .adl file are also persisted\u2014this aids in the retrieval of the data from the database. Whenever the data are to be represented as a report, the data value is picked, mapped to the node whose path corresponds to it in the database, and then represented in the form corresponding to the archetype. Thus, ADL formalism plays a major role in data persistence in this case. From the above analysis, we can conclude that ADL, on the one hand, provides the object-oriented semantics and, on the other hand, is machine-processable; thus, it plays a significant role in both the client side and backend of an EHR system, making it a powerful knowledge formalism.\n<\/p><p>However, parsing of the ADL archetype returns objects according to the archetype object model (AOM). AOM is the definitive formal representation of archetype semantics. It is independent of syntax. The primary goal of the AOM specification is to tell developers how to build archetype tools and EHR components that utilize archetypes. It can be used to generate the output side of parsers that process archetypes in a linguistic format, such as the openEHR ADL. The semantics defined in the AOM is used to express the object structures of archetypes. These objects are equivalent to a syntax tree. The AOM can be thought of as a model of an in-memory archetype or template, or as a standard syntax tree for any serialized format\u2014not only ADL. An archetype\u2019s canonical abstract syntactic form is ADL, although it may also be parsed from and serialized to XML, JSON, or any other format. Calls to an appropriate AOM construction API from an archetype or template editing tool can also produce the in-memory archetype representation. This model is common to all dual-model-based standards; it will have no information about the particular RM for which the archetype was built. Thus, the obtained objects cannot be used to perform any semantic activity such as comparison, selection, or classification.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Representation_in_XML\">Representation in XML<\/span><\/h4>\n<p>For experimental analysis, an XML representation automatically generated by the archetype editor is being used. This XML format conforms to the archetype constraint classes defined in the openEHR RM, and it can be directly imported into the oenEHR RM to initialize the relevant archetypes. Thus, the XML format is again generated via the archetype editor from a corresponding ADL counterpart. Each piece of data can subsequently be referenced using its XML path. For example, the patient\u2019s first name (Paul) could be referenced as \u201c\/record\/name\/firstname.\u201d The drawback of this formalism can be tracked in its inefficiency to represent the archetype constraints completely. It is, however, a suitable formalism for transforming and exchanging data from one form to another.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Representation_in_OWL\">Representation in OWL<\/span><\/h4>\n<p>The semantic web enables greater access not only to content but also to services on the web.<sup id=\"rdp-ebb-cite_ref-:10_39-0\" class=\"reference\"><a href=\"#cite_note-:10-39\">[39]<\/a><\/sup> Users and software agents should discover, invoke, compose, and monitor web resources offering particular services and having specific properties. They should be able to do so with a high degree of automation if desired. Powerful tools should be enabled by service descriptions across the web service lifecycle. OWL-S (formerly DAML-S)<sup id=\"rdp-ebb-cite_ref-:10_39-1\" class=\"reference\"><a href=\"#cite_note-:10-39\">[39]<\/a><\/sup> is an ontology of services that makes these functionalities possible.\n<\/p><p>Since the experiment used the openEHR Java Reference Implementation of RM, it has been found that in order to use OWL formalism, the RM (i.e., information model) should be transformed into OWL statements (OWL is found to be at a more abstract level as compared to ADL, XML, and XML schema). As such, there exists a method for binding terminology to the EHR system with OWL as a bridging technology, given that the terminology is expressible in OWL.\n<\/p><p>Recent research<sup id=\"rdp-ebb-cite_ref-:14_40-0\" class=\"reference\"><a href=\"#cite_note-:14-40\">[40]<\/a><\/sup> describes the ADL-to-OWL translation approach, describes the techniques to map archetypes to formal ontologies, and demonstrates how rules can be applied to the resulting representation. It translates definitions expressed in the openEHR ADL to a formal representation expressed using OWL. The formal representations are then integrated with rules expressed with Semantic Web Rule Language (SWRL)<sup id=\"rdp-ebb-cite_ref-:15_41-0\" class=\"reference\"><a href=\"#cite_note-:15-41\">[41]<\/a><\/sup> expressions, providing an approach to apply the SWRL rules to concrete instances of clinical data. Sharing the knowledge expressed in rules is consistent with the philosophy of open sharing, encouraged by archetypes. The approach also allows the reuse of formal knowledge, expressed through ontologies, and extends reuse to propositions of declarative knowledge, such as those encoded in clinical guidelines.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Findings\">Findings<\/span><\/h3>\n<p>To the best of the authors' knowledge, KnowledgeRep has investigated the suitability of various formalisms in the context of archetypes, using the specific semantics of their underlying RMs and hierarchical structure (tree) of archetype definitions. It examines whether currently available archetype languages provide direct support for mapping to formal ontologies and then exploiting reasoning on clinical knowledge, which are critical ingredients of full semantic interoperability.\n<\/p><p>Through KnowledgeRep, various comparisons, presented in Table 1, have been obtained. The conclusions of various results are also shown in Table 2 and Table 3.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"6\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Comparative analysis of various knowledge representations (in context to archetype)\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Features\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">ADL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">XML\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">OWL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">OCL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">KIF\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Domain Modeling<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Archetype Description Language (ADL)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Web document model\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Web-enabled ontologies for building the semantic web\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Constraints on object models (not on data) can describe archetypes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Formal semantics (sharable among software entities)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Reference Model (RM) with object-oriented semantics<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL syntax adheres to object-oriented RMs (expressed in UML for constraints)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XML and XML schema languages do not follow object-oriented semantics\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Requires explicit expression of an RM in OWL to represent archetype constraints\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">All statements are FOPL statements; it is impossible to express an archetype in a structural way\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Existing information model and terminologies have to be converted to KIF statements to describe archetypes\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Constraint Representation<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL enables constraints to be expressed in a structural and nested way for archetypes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Strict rules in XML schema cannot express archetype constraints\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Inconvenient in OWL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">OCL constraint types include function pre- and post-conditions, and class variants\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Path Traceability<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL has a path syntax based on XPath (openEHR path) to deal with heavily nested structures\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Inbuilt Xpath mechanism\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No inbuilt path mechanism\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">The OCL syntax for paths (that traverse associations) is similar to XPath\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No inbuilt path mechanism\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Inbuilt Ontology Section<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL provides independence from natural language and terminology issues by having a separate ontology per archetype, containing \"bindings\" and language-specific translations\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No built-in syntax\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No built-in syntax and requires the semantics to be represented from first principles\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No built-in syntax\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No built-in syntax\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Suitability of ADL, XML, and OWL\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Various formalisms\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Suitability\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Representation of archetypes\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XML\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Information interchange\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">OWL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Semantic activities and transformation among archetypes\n<\/td><\/tr><\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"5\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> Summary of transformation of ADL with other formalisms\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Task\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">XML\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">OCL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">OWL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">KIF\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Transformation of ADL archetypes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes (GEHR Project)<sup id=\"rdp-ebb-cite_ref-:8_27-1\" class=\"reference\"><a href=\"#cite_note-:8-27\">[27]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">No\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes (Poseacle Convertor, ARTEMIS project, Archetype Ontologiser, LinkEHR project)<sup id=\"rdp-ebb-cite_ref-:13_35-1\" class=\"reference\"><a href=\"#cite_note-:13-35\">[35]<\/a><\/sup>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes <sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>From Table 1 we infer that ADL best represents archetypes definitions. The XML schema languages were not able to specify the archetype constraints; therefore, the XML-encoded EHR data and archetype definitions will be read into the EHR system, which will validate the EHR data against the archetype constraints programmatically. XML has a role in the exchange requirement over the web. OWL would not be a suitable representation for storing the EHR data itself. It is designed on a mathematical base specifically for reasoning. Thus, it is suitable for semantic activities such as classification, comparing, reasoning, and transformation.\n<\/p><p>Table 3 presents a consolidated view of the possibility of transformation of ADL archetypes. Thus, the XML archetypes are serialized instances of the parse tree obtained from ADL parser. Expressing archetypes using OWL\/KIF requires the existing information model and relevant terminologies to be converted to OWL\/KIF statements. Valuing data using OWL expressed archetypes requires massive amounts of data to be converted to OWL statements; however, OWL plays a significant role in ontology mapping, which permits the exchange of information among healthcare information systems conforming to different standards. The transformation to OCL is impossible, but the ADL syntax includes assertion language based on OCL.\n<\/p><p>However, OWL is not suitable for representing conditional expressions used in representing constraints and rules. Some researchers have proposed ways to represent such richer expressions, for example, by adopting rule languages (e.g., RuleML) into RDF and OWL representations.<sup id=\"rdp-ebb-cite_ref-:10_39-2\" class=\"reference\"><a href=\"#cite_note-:10-39\">[39]<\/a><\/sup> RuleML is a family of languages whose modular system of XML schemas permits high-precision web rule interchange.<sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[43]<\/a><\/sup> Recent work<sup id=\"rdp-ebb-cite_ref-:14_40-1\" class=\"reference\"><a href=\"#cite_note-:14-40\">[40]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup> makes a case for the potential of combining the translated openEHR Archetype Definitions with a rule-based approach using SWRL<sup id=\"rdp-ebb-cite_ref-:15_41-1\" class=\"reference\"><a href=\"#cite_note-:15-41\">[41]<\/a><\/sup> rules. El Hajjamy <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:16_45-0\" class=\"reference\"><a href=\"#cite_note-:16-45\">[45]<\/a><\/sup> developed a semi-automatic integration approach for integrating data from traditional information systems to a better ontologies-based system. Different data sources via UML, RDB, and XML are converted into local ontologies (OWL2) in the mentioned approach. Based on semantic, structural, and syntactic similarity measurement, all the local ontologies output then merge into a global ontology.<sup id=\"rdp-ebb-cite_ref-:16_45-1\" class=\"reference\"><a href=\"#cite_note-:16-45\">[45]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>ADL has various advantages and a few disadvantages compared to the other languages, as shown in Table 1. A recent study<sup id=\"rdp-ebb-cite_ref-:4_16-2\" class=\"reference\"><a href=\"#cite_note-:4-16\">[16]<\/a><\/sup> states the difference between openEHR RM\/ADL and XML\/XML schema as:\n<\/p>\n<ol><li>The openEHR RM has a \u201cdomain bias\u201d and is, therefore, more extensive and expressive than XML, a minimal generic model to describe hierarchical textual structures. This means that more has to be expressed in an XML schema in order to obtain a document class that is semantically equivalent to an archetype.<\/li>\n<li>The openEHR RM and AOMs are modeled in UML. There is a direct correspondence between an ADL instance and the AOM. These models have an object-oriented bias, which is beneficial when seen as representations for software systems. They may be further equipped with logical artifacts, such as pre-and post-conditions, loop, and class invariants, and finally, operational implementation artifacts.<\/li><\/ol>\n<p>As such, the XML\/XML schema models can be considered more abstract than the openEHR RM\/AOM\/ADL models, in the sense that the latter is more \u201cimplementation-oriented.\u201d\n<\/p><p>To standardize knowledge representation in the clinical domain, a significant contribution comes from languages such as the RDF schema or OWL.<sup id=\"rdp-ebb-cite_ref-46\" class=\"reference\"><a href=\"#cite_note-46\">[46]<\/a><\/sup> OWL is even more abstract (omitting as much as possible about internal structures and reducing the description to a set of statements about what is true in the description). This minimalism enables formal reasoner engines to operate on the models, assisting us in discovering irregularities and inconsistencies.<sup id=\"rdp-ebb-cite_ref-:4_16-3\" class=\"reference\"><a href=\"#cite_note-:4-16\">[16]<\/a><\/sup>\n<\/p><p>To publish pre-existing ontologies (e.g., UMLS) on the semantic web, there exist several problems concerning alternative interpretations of the semantic network notation and the inability to express some of the interpretations in OWL. Kashyap and Bordiga<sup id=\"rdp-ebb-cite_ref-:17_47-0\" class=\"reference\"><a href=\"#cite_note-:17-47\">[47]<\/a><\/sup> run into several difficulties in this undertaking. Some obstacles were due to ambiguities in the SN notation\u2019s semantics or the notation\u2019s under-specification (e.g., what can be inferred from the absence of edges?). Other problems were the inability to express the SN as OWL axioms that would provide the desired inferences, and the difficulty of making choices among multiple possible representations. The authors encountered obstacles representing the semantics of \u201clinks\u201d in the SN, especially in the context of requirements such as <i>\u03b4\/\u03c1<\/i> inheritance, inheritance blocking, and polymorphism. Thus, OWL language cannot be used to represent some notions in UMLS. <i>\u03b4\/\u03c1<\/i> inheritance is domain and range inheritance. The \u201cis-a\u201d link in SN gives rise to inheritance. Whenever there is a conflict between the placement of types in the SN and the links to be inherited, the SN provides a mechanism to explicitly \u201cblock\u201d inheritance. The relationships whose arguments (i.e., domain and range values) can be instances of multiple classes are called polymorphic relationships. These requirements led Kashyap and Bordiga<sup id=\"rdp-ebb-cite_ref-:17_47-1\" class=\"reference\"><a href=\"#cite_note-:17-47\">[47]<\/a><\/sup> to investigate the possible interpretations and encodings of a \u201clink\u201d in the SN.\n<\/p><p>Codes representing the meanings of nodes and constraints on text or terms, bindings to terminologies such as SNOMED or LOINC, are stated in the ontology section of an archetype. The report<sup id=\"rdp-ebb-cite_ref-:3_15-2\" class=\"reference\"><a href=\"#cite_note-:3-15\">[15]<\/a><\/sup> describes a novel approach to address semantic interoperability in the healthcare domain, taking into account ontology mapping. Archetypes are used to scope the context of the matching process that will allow two independent healthcare providers to interoperate. It structures the matching algorithms at two different levels\u2014terminology and archetype\u2014leveraging the most mature research on ontology matching. The approach identifies relationships between ontological terms that have been embedded in pairs of archetypes as a means of matching these terms. The matched terms can then, in turn, be used to identify similarities between archetypes. The context of the archetype will limit the matching space to allow for more accurate mapping results and, due to the nature of archetypes, ultimately to a very high level of automation. The Simple Knowledge Organization System (SKOS)<sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[48]<\/a><\/sup> is a standard data model for sharing and linking knowledge organization systems via the semantic web. The possibility of exploring SKOS shortly to bridge the gaps among records that have been created by different representation languages or represented on different semantics of terms may be done. da Costa <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:18_49-0\" class=\"reference\"><a href=\"#cite_note-:18-49\">[49]<\/a><\/sup> introduced a method of achieving interoperability heterogeneous health systems through ontologies and rules; that approach used OWL features to map out the balance between openEHR records mixed with HL7. Recent research proposes a semantic ontological framework that might unify several EHR data formats. It takes different data formats as input (ADL, SQL, XML, and CDA) and converts them into an OWL ontology.<sup id=\"rdp-ebb-cite_ref-:18_49-1\" class=\"reference\"><a href=\"#cite_note-:18-49\">[49]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>Semantic interoperability is essential to facilitate the computerized support for alerts, workflow management, and evidence-based healthcare across heterogeneous EHR systems. The archetypes have been presented as a key to knowledge representation and information exchange; however, currently available archetype languages do not provide direct support for mapping to formal ontologies and then exploiting reasoning on clinical knowledge, which are critical ingredients of full semantic interoperability. This study presented various technologies for representing archetypes such as XML, ADL, and OWL through the simulation tool KnowledgeRep. The comparative analysis among formalisms such as OWL, OCL, and KIF were presented (Table 1). The semantic interoperable exchange among different standards requires these formalisms, as is illustrated by recent research projects (Table 3) in the study.\n<\/p><p>The KnowledgeRep study has explored the following objectives:\n<\/p>\n<dl><dd>1. Given an EHR system expressed in OWL (ES<sub>OWL<\/sub>) and a terminology system expressed in OWL (TS<sub>OWL<\/sub>), there exists a method for binding terminology to EHR expressed in OWL (T<sub>OWL<\/sub>). The EHR system here includes the RM and archetype. This enables both the RM and archetypes to be expressed in OWL representation. That is, \u2203 T<sub>OWL<\/sub> (ES<sub>OWL<\/sub>, TS<sub>OWL<\/sub>).<\/dd>\n<dd>2. It has been found that given an EHR system expressed in UML+ADL (ES<sub>UML+ADL<\/sub>) and a terminology system (TS<sub>F<\/sub>) expressed in formalism F, there exists a method for binding terminology to EHR through the \"term binding\" (TB) section of archetype (T<sub>TB<\/sub>). The EHR system here includes the RM (expressed in UML) and archetypes (expressed in ADL representation). The archetypes contain a \"term binding\" section. That is, \u2203 T<sub>TB<\/sub> (ES<sub>UML+ADL<\/sub>, TS<sub>F<\/sub>).<\/dd>\n<dd>3. It has also been found that given an EHR system expressed in XML (ES<sub>XML<\/sub>) and a terminology system expressed in XML (TS<sub>XML<\/sub>), there exists a method for binding terminology to EHR. The EHR system here includes the RM (expressed in XML schema) and Archetypes (represented in XML). That is, \u2203 T<sub>XML<\/sub> (ES<sub>XML<\/sub>, TS<sub>XML<\/sub>).<\/dd><\/dl>\n<p>However, for coping with the semantics, two things are required. First, terminology binding must established through archetypes. Second, mappings between different standardized EHR systems must be established. In other words, data elements of one EHR system need to be transformed to the data elements of another EHR system and vice versa (through various knowledge formalisms, see Table 1).\n<\/p><p>Thus, the paper concludes that ADL is suitable for domain modeling and constraint representation. XML schema do not provide the support for defining archetypes constraints<sup id=\"rdp-ebb-cite_ref-:12_29-1\" class=\"reference\"><a href=\"#cite_note-:12-29\">[29]<\/a><\/sup>; however, XML is the global standard for exchange requirements and is also used for bringing the data from a non-archetype-based EHR system into an archetype-based EHR repository (through XSLT transformations). OWL representation is the best fit for semantic activities, without which the semantic exchange among the three prevalent standards is impossible. The structural components of a knowledge graph have been considered for forming virtual intermediate support for the information exchanges. Current research can contribute to helping EHR system vendors and developers to choose the appropriate technology for the required purpose, keeping in mind semantic interoperability.\n<\/p><p>Note that this study is limited to establishing a comparison between distinct approaches (XML, OWL, OCL, and KIF) to interoperate within domain-specific applications such as healthcare. Tt does not discuss intelligent, semi-auto-constructed knowledge graph framework in the e-health context, a subject requiring further examination. Moreover, the research shows potential for being extended for various knowledge graph problems<sup id=\"rdp-ebb-cite_ref-:11_3-1\" class=\"reference\"><a href=\"#cite_note-:11-3\">[3]<\/a><\/sup> such as data insufficiency, explainability, incomplete and incorrect knowledge, inconsistencies, and integration of knowledge.\n<\/p>\n<h2><span id=\"rdp-ebb-Abbreviations,_acronyms,_and_initialisms\"><\/span><span class=\"mw-headline\" id=\"Abbreviations.2C_acronyms.2C_and_initialisms\">Abbreviations, acronyms, and initialisms<\/span><\/h2>\n<p><b>ADL<\/b>: Archetype Definition Language\n<\/p><p><b>AM<\/b>: archetype model\n<\/p><p><b>AOM<\/b>: archetype object model\n<\/p><p><b>CCR<\/b>: Continuity of Care Record\n<\/p><p><b>CDA<\/b>: Clinical Document Architecture\n<\/p><p><b>CEN<\/b>: European Committee for Standardization\n<\/p><p><b>CKM<\/b>: Clinical Knowledge Manager\n<\/p><p><b>DL<\/b>: description logic\n<\/p><p><b>EHR<\/b>: electronic health record\n<\/p><p><b>GEHR<\/b>: Good Electronic Health Record\n<\/p><p><b>GWT<\/b>: Google Web Toolkit\n<\/p><p><b>HL7<\/b>: Health Level 7\n<\/p><p><b>ISO<\/b>: International Organization for Standardization \n<\/p><p><b>KG<\/b>: knowledge graph\n<\/p><p><b>KIF<\/b>: Knowledge Interchange Format\n<\/p><p><b>MeSH<\/b>: Medical Subject Heading\n<\/p><p><b>NCI<\/b>: National Cancer Institute\n<\/p><p><b>OCL<\/b>: Object Constraint Language\n<\/p><p><b>OWL<\/b>: Web Ontology Language\n<\/p><p><b>RDF<\/b>: Resource Description Framework\n<\/p><p><b>RIM<\/b>: Reference Information Model\n<\/p><p><b>RM<\/b>: reference model\n<\/p><p><b>SKOS<\/b>: Simple Knowledge Organization System\n<\/p><p><b>SWRL<\/b>: Semantic Web Rule Language\n<\/p><p><b>UML<\/b>: Unified Modeling Language\n<\/p><p><b>UMLS<\/b>: Unified Medical Language System\n<\/p><p><b>XML<\/b>: Extensible Markup Language\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Appendices\">Appendices<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Appendix_A._Parameter_Heart_rate_as_an_archetype\">Appendix A. Parameter Heart_rate as an archetype<\/span><\/h3>\n<p>The structure of an archetype is given in Figure A1.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:FigA1_Sachdeva_Information22_13-2.png\" class=\"image wiki-link\" data-key=\"2c241b6d864d1c9c62dc863057a1868d\"><img alt=\"FigA1 Sachdeva Information22 13-2.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f1\/FigA1_Sachdeva_Information22_13-2.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. A1<\/b> Parameter Heart_rate as an archetype.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Appendix_B._Comparison_of_ADL_and_XML\">Appendix B. Comparison of ADL and XML<\/span><\/h3>\n<p>The comparison of ADL and XML is given in Table A1.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table A1.<\/b> Comparison of ADL and XML\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Properties\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">ADL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">XML\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Machine-processable<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Human-readable<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sometimes unreadable (e.g., XML schema instance, OWL-RDF ontologies)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Leaf data types<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">More comprehensive set, including interval of numerics and date\/time types\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">String data; with XML String data; schema option- more comprehensive set\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Structure<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Universal schema for temporal database (EHRs) (history database)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Semi-structured data (rooted acyclic graph with unique path from root to leaf)\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Adhering to object-oriented semantics<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Yes, particularly for container types\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XML schema languages do not follow object-oriented semantics\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Ontological reference<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Domain entities\/archetypes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Global terms\/concepts\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Representation of object properties<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Uses attributes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Uses attributes and sub-elements\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Space (for storage)<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Uses nearly half of space for tags\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">May have data redundancy in contents\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Efficiency<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Is a domain specific language (sufficiently rich to capture and model medical domain)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Good for web document modeling with limited ability to represent database contents\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Example (Archetype)<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ADL representation of Heart_rate (Appendix D)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">XML representation of Heart_rate (Appendix D)\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Appendix_C._List_of_archetypes\">Appendix C. List of archetypes<\/span><\/h3>\n<ol><li>openEHR-EHR-ITEM_TREE.medication.v1<\/li>\n<li>openEHR-EHR-OBSERVATION.heart_rate.v1<\/li>\n<li>openEHR-EHR-OBSERVATION.blood_pressure.v1<\/li>\n<li>openEHR-EHR-COMPOSITION.report.v1<\/li>\n<li>openEHR-EHR-OBSERVATION.body_weight.v1<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"Appendix_D._XML_and_ADL_representation_of_Heart_rate\">Appendix D. XML and ADL representation of Heart_rate<\/span><\/h3>\n<p>The XML and ADL representation of the Heart_rate archetype is given in Table A2.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table A2.<\/b> XML and ADL representation of Heart_rate\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">XML representation\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">ADL representation\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><tt><?xml version=\"1.0\" encoding=\"UTF-8\"?>\n<p><archetype xmlns=\"<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/schemas.openehr.org\/v1\" target=\"_blank\">http:\/\/schemas.openehr.org\/v1<\/a>\" xmlns:xsi=\"<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.w3.org\/2001\/XMLSchema-instance\" target=\"_blank\">http:\/\/www.w3.org\/2001\/XMLSchema-instance<\/a>\" xmlns:xsd=\"<a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.w3.org\/2001\/XMLSchema\" target=\"_blank\">http:\/\/www.w3.org\/2001\/XMLSchema<\/a>\">\n.<br \/>\n.<br \/>\n.<br \/>\n<ontology><br \/>\n<term_definitions language=\"ar-sy\"><br \/>\n<items code=\"at0000\">\n<\/p>\n<dl><dd><items id=\"text\">*Pulse\/Heart beat(en)<\/items><\/dd>\n<dd><items id=\"description\">*The rate and associated attributes for a pulse or heart beat. (en)<\/items><\/dd>\n<dd><\/items><\/dd><\/dl>\n<p><items code=\"at1037\">\n<\/p>\n<dl><dd><items id=\"text\">*Body site(en)<\/items><\/dd>\n<dd><items id=\"description\">*Body site where the pulse or heart beat were observed.(en)<\/items><\/dd>\n<dd><\/items><\/dd><\/dl>\n<p><items code=\"at1005\">\n<\/p>\n<dl><dd><items id=\"text\">*Presence(en)<\/items><\/dd>\n<dd><items id=\"description\">*Presence of a pulse or heart beat.(en)<\/items><\/dd>\n<dd><items id=\"comment\">*It can be implied that the pulse or heart beat is present if Rate >0 \/min. (en)<\/items><\/dd>\n<dd><\/items><\/dd><\/dl>\n<p><items code=\"at1013\">\n<\/p>\n<dl><dd><items id=\"text\">*Device(en)<\/items><\/dd>\n<dd><items id=\"description\">*Details about the device used to measure the pulse rate or heart rate.(en)<\/items><\/dd>\n<dd><\/items><\/dd><\/dl>\n<p><items code=\"at0013\">\n<\/p>\n<dl><dd><items id=\"text\">*Position(en)<\/items><\/dd>\n<dd><items id=\"description\">*The body position of the subject during the observation.(en)<\/items><\/dd>\n<dd><\/items><\/dd><\/dl>\n<\/tt><p><tt>.<br \/>\n.<br \/>\n.<br \/>\n<\/ontology><br \/>\n<\/archetype>\n<\/tt>\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><tt>archetype (adl_version=1.4; uid=566c355d-9e8f-473d-a80d-90fcd8d61414)\n<dl><dd>openEHR-EHR-OBSERVATION.pulse.v2<\/dd><\/dl>\n<p>.<br \/>\n.<br \/>\n.<br \/>\nontology\n<\/p>\n<dl><dd>term_definitions = <\n<dl><dd>[\"ar-sy\"] = <<\/dd>\n<dd>items = <[\"at0000\"] = <<\/dd>\n<dd>text = <\"*Pulse\/Heart beat(en)\"><\/dd>\n<dd>description = <\"*The rate and associated attributes for a pulse or heart beat. (en)\"><\/dd><\/dl><\/dd><\/dl>\n<dl><dd><dl><dd><dl><dd>[\"at1037\"] = <<\/dd>\n<dd>text = <\"*Body site(en)\"><\/dd>\n<dd>description = <\"*Body site where the pulse or heart beat were observed.(en)\"><\/dd><\/dl><\/dd><\/dl><\/dd><\/dl>\n<dl><dd><dl><dd><dl><dd>[\"at1005\"] = <<\/dd>\n<dd>text = <\"*Presence(en)\"><\/dd>\n<dd>description = <\"*Presence of a pulse or heart beat.(en)\"><\/dd>\n<dd>comment = <\"*It can be implied that the pulse or heart beat is present if Rate >0 \/min. (en)\"><\/dd><\/dl><\/dd><\/dl><\/dd><\/dl>\n<dl><dd><dl><dd><dl><dd>[\"at1013\"] = <<\/dd>\n<dd>text = <\"*Device(en)\"><\/dd>\n<dd>description = <\"*Details about the device used to measure the pulse rate or heart rate.(en)\"><\/dd><\/dl><\/dd><\/dl><\/dd><\/dl>\n<dl><dd><dl><dd><dl><dd>[\"at0013\"] = <<\/dd>\n<dd>text = <\"*Position(en)\"><\/dd>\n<dd>description = <\"*The body position of the subject during the observation.(en)\"><\/dd><\/dl><\/dd><\/dl><\/dd><\/dl>\n<p>>      ><br \/>\n.<br \/>\n.<br \/>\n.<br \/>\n<\/p>\n<dl><dd>><\/dd><\/dl>\n<\/tt><p><tt>><\/tt>\n<\/p>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>S.S. and S.B. conceived, formulated, and verified the formalisms for archetypes. S.S. and S.B. analyzed the results, proofread the manuscript, and corrected the manuscript. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This research received no external funding.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-:0-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_1-0\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-1\">1.1<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-2\">1.2<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-3\">1.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">openEHR Foundation (15 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/specifications.openehr.org\/releases\/BASE\/Release-1.0.3\/architecture_overview.html\" target=\"_blank\">\"openEHR Architecture Overview\"<\/a>. <i>BASE Release-1.0.3<\/i>. openEHR Foundation<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/specifications.openehr.org\/releases\/BASE\/Release-1.0.3\/architecture_overview.html\" target=\"_blank\">https:\/\/specifications.openehr.org\/releases\/BASE\/Release-1.0.3\/architecture_overview.html<\/a><\/span><span class=\"reference-accessdate\">. 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Retrieved 06 September 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=HL7+Reference+Information+Model&rft.atitle=&rft.aulast=Beeler%2C+G.%3B+Duteau%2C+J.-H.%3B+Grieve%2C+G.+et+al.&rft.au=Beeler%2C+G.%3B+Duteau%2C+J.-H.%3B+Grieve%2C+G.+et+al.&rft.date=September+2014&rft.pub=Health+Level+7&rft_id=http%3A%2F%2Fwww.hl7.org%2Fv3ballotarchive%2Fv3ballot%2Fhtml%2Finfrastructure%2Frim%2Frim.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Dolin, R.H.; Alschuler, L.; Boyer, S. et al. (2 April 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.hl7.org\/v3ballotarchive\/v3ballot\/html\/infrastructure\/cda\/cda.html\" target=\"_blank\">\"Clinical Document Architecture, Release 2\"<\/a>. Health Level 7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.hl7.org\/v3ballotarchive\/v3ballot\/html\/infrastructure\/cda\/cda.html\" target=\"_blank\">http:\/\/www.hl7.org\/v3ballotarchive\/v3ballot\/html\/infrastructure\/cda\/cda.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 06 September 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Clinical+Document+Architecture%2C+Release+2&rft.atitle=&rft.aulast=Dolin%2C+R.H.%3B+Alschuler%2C+L.%3B+Boyer%2C+S.+et+al.&rft.au=Dolin%2C+R.H.%3B+Alschuler%2C+L.%3B+Boyer%2C+S.+et+al.&rft.date=2+April+2018&rft.pub=Health+Level+7&rft_id=http%3A%2F%2Fwww.hl7.org%2Fv3ballotarchive%2Fv3ballot%2Fhtml%2Finfrastructure%2Fcda%2Fcda.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-15\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_15-0\">15.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_15-1\">15.1<\/a><\/sup> <sup><a href=\"#cite_ref-:3_15-2\">15.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bisbal, J.; Berry, D. (2009). <a rel=\"nofollow\" class=\"external text\" href=\"#BisbalB09\">\"Archetype Alignment - A Two-level Driven Semantic Matching Approach to Interoperability in the Clinical Domain\"<\/a>. <i>Proceedings of the Second International Conference on Health Informatics, HEALTHINF 2009<\/i>: 216\u201321. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5220%2F0001541502160221\" target=\"_blank\">10.5220\/0001541502160221<\/a><span class=\"printonly\">. <a rel=\"nofollow\" class=\"external free\" href=\"#BisbalB09\">https:\/\/dblp.uni-trier.de\/db\/conf\/biostec\/healthinf2009.html#BisbalB09<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Archetype+Alignment+-+A+Two-level+Driven+Semantic+Matching+Approach+to+Interoperability+in+the+Clinical+Domain&rft.jtitle=Proceedings+of+the+Second+International+Conference+on+Health+Informatics%2C+HEALTHINF+2009&rft.aulast=Bisbal%2C+J.%3B+Berry%2C+D.&rft.au=Bisbal%2C+J.%3B+Berry%2C+D.&rft.date=2009&rft.pages=216%E2%80%9321&rft_id=info:doi\/10.5220%2F0001541502160221&rft_id=https%3A%2F%2Fdblp.uni-trier.de%2Fdb%2Fconf%2Fbiostec%2Fhealthinf2009.html%23BisbalB09&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-16\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_16-0\">16.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_16-1\">16.1<\/a><\/sup> <sup><a href=\"#cite_ref-:4_16-2\">16.2<\/a><\/sup> <sup><a href=\"#cite_ref-:4_16-3\">16.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Hedayat, R. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/uu.diva-portal.org\/smash\/record.jsf?pid=diva2%3A310787&dswid=9043\" target=\"_blank\">\"Semantic Web Technologies in the Quest for Compatible Distributed Health Records\"<\/a>. Uppsala Universitet<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/uu.diva-portal.org\/smash\/record.jsf?pid=diva2%3A310787&dswid=9043\" target=\"_blank\">http:\/\/uu.diva-portal.org\/smash\/record.jsf?pid=diva2%3A310787&dswid=9043<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Semantic+Web+Technologies+in+the+Quest+for+Compatible+Distributed+Health+Records&rft.atitle=&rft.aulast=Hedayat%2C+R.&rft.au=Hedayat%2C+R.&rft.date=2010&rft.pub=Uppsala+Universitet&rft_id=http%3A%2F%2Fuu.diva-portal.org%2Fsmash%2Frecord.jsf%3Fpid%3Ddiva2%253A310787%26dswid%3D9043&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Maldonado, Jos\u00e9 Alberto; Costa, Catalina Mart\u00ednez; Moner, David; Men\u00e1rguez-Tortosa, Marcos; Bosc\u00e1, Diego; Mi\u00f1arro Gim\u00e9nez, Jos\u00e9 Antonio; Fern\u00e1ndez-Breis, Jesualdo Tom\u00e1s; Robles, Montserrat (1 August 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046411001924\" target=\"_blank\">\"Using the ResearchEHR platform to facilitate the practical application of the EHR standards\"<\/a> (in en). <i>Journal of Biomedical Informatics<\/i> <b>45<\/b> (4): 746\u2013762. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbi.2011.11.004\" target=\"_blank\">10.1016\/j.jbi.2011.11.004<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046411001924\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046411001924<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Using+the+ResearchEHR+platform+to+facilitate+the+practical+application+of+the+EHR+standards&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Maldonado&rft.aufirst=Jos%C3%A9+Alberto&rft.au=Maldonado%2C%26%2332%3BJos%C3%A9+Alberto&rft.au=Costa%2C%26%2332%3BCatalina+Mart%C3%ADnez&rft.au=Moner%2C%26%2332%3BDavid&rft.au=Men%C3%A1rguez-Tortosa%2C%26%2332%3BMarcos&rft.au=Bosc%C3%A1%2C%26%2332%3BDiego&rft.au=Mi%C3%B1arro+Gim%C3%A9nez%2C%26%2332%3BJos%C3%A9+Antonio&rft.au=Fern%C3%A1ndez-Breis%2C%26%2332%3BJesualdo+Tom%C3%A1s&rft.au=Robles%2C%26%2332%3BMontserrat&rft.date=1+August+2012&rft.volume=45&rft.issue=4&rft.pages=746%E2%80%93762&rft_id=info:doi\/10.1016%2Fj.jbi.2011.11.004&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046411001924&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Breis, J.T.F.; Tortosa, M.M.; Martinez-Costa, C.. <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/web.archive.org\/web\/20120626121900\/http:\/\/miuras.inf.um.es:9080\/PoseacleConverter\/\" target=\"_blank\">\"POSEACLE Converter\"<\/a>. Universidad de Murcia. Archived from <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/miuras.inf.um.es\/~researchehr\/ISO13606-OpenEHR-Mappings.html\" target=\"_blank\">the original<\/a> on 26 June 2012<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/web.archive.org\/web\/20120626121900\/http:\/\/miuras.inf.um.es:9080\/PoseacleConverter\/\" target=\"_blank\">https:\/\/web.archive.org\/web\/20120626121900\/http:\/\/miuras.inf.um.es:9080\/PoseacleConverter\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=POSEACLE+Converter&rft.atitle=&rft.aulast=Breis%2C+J.T.F.%3B+Tortosa%2C+M.M.%3B+Martinez-Costa%2C+C.&rft.au=Breis%2C+J.T.F.%3B+Tortosa%2C+M.M.%3B+Martinez-Costa%2C+C.&rft.pub=Universidad+de+Murcia&rft_id=https%3A%2F%2Fweb.archive.org%2Fweb%2F20120626121900%2Fhttp%3A%2F%2Fmiuras.inf.um.es%3A9080%2FPoseacleConverter%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-19\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_19-0\">19.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_19-1\">19.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chen, Rong; Klein, Gunnar (2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/17911678\" target=\"_blank\">\"The openEHR Java reference implementation project\"<\/a>. <i>Studies in Health Technology and Informatics<\/i> <b>129<\/b> (Pt 1): 58\u201362. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0926-9630\" target=\"_blank\">0926-9630<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17911678\" target=\"_blank\">17911678<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/17911678\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/17911678<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+openEHR+Java+reference+implementation+project&rft.jtitle=Studies+in+Health+Technology+and+Informatics&rft.aulast=Chen&rft.aufirst=Rong&rft.au=Chen%2C%26%2332%3BRong&rft.au=Klein%2C%26%2332%3BGunnar&rft.date=2007&rft.volume=129&rft.issue=Pt+1&rft.pages=58%E2%80%9362&rft.issn=0926-9630&rft_id=info:pmid\/17911678&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F17911678&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-20\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Adel, Ebtsam; El-sappagh, Shaker; Elmogy, Mohammed; Barakat, Sherif; Kwak, Kyung-Sup (2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/autosoftjournal.net\/paperShow.php?paper=100000151\" target=\"_blank\">\"A Fuzzy Ontological Infrastructure for Semantic Interoperability in Distributed Electronic Health Record\"<\/a> (in en). <i>Intelligent Automation and Soft Computing<\/i>: \u20131\u2013-1. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.31209%2F2019.100000151\" target=\"_blank\">10.31209\/2019.100000151<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1079-8587\" target=\"_blank\">1079-8587<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/autosoftjournal.net\/paperShow.php?paper=100000151\" target=\"_blank\">http:\/\/autosoftjournal.net\/paperShow.php?paper=100000151<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Fuzzy+Ontological+Infrastructure+for+Semantic+Interoperability+in+Distributed+Electronic+Health+Record&rft.jtitle=Intelligent+Automation+and+Soft+Computing&rft.aulast=Adel&rft.aufirst=Ebtsam&rft.au=Adel%2C%26%2332%3BEbtsam&rft.au=El-sappagh%2C%26%2332%3BShaker&rft.au=Elmogy%2C%26%2332%3BMohammed&rft.au=Barakat%2C%26%2332%3BSherif&rft.au=Kwak%2C%26%2332%3BKyung-Sup&rft.date=2019&rft.pages=%E2%80%931%E2%80%93-1&rft_id=info:doi\/10.31209%2F2019.100000151&rft.issn=1079-8587&rft_id=http%3A%2F%2Fautosoftjournal.net%2FpaperShow.php%3Fpaper%3D100000151&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-21\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_21-0\">21.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_21-1\">21.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFMartinez-CostaMenarguez-TortosaAlbertoTomas2010\">Martinez-Costa, Catalina; Menarguez-Tortosa, Marcos; Alberto, Jose; Tomas, Jesualdo (1 January 2010), Wu, Gang, ed., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.intechopen.com\/books\/semantic-web\/semantic-web-technologies-for-managing-ehr-related-clinical-knowledge\" target=\"_blank\">\"Semantic Web Technologies for Managing EHR-related Clinical Knowledge\"<\/a> (in en), <i>Semantic Web<\/i> (InTech), <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5772%2F7298\" target=\"_blank\">10.5772\/7298<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-953-7619-54-1<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.intechopen.com\/books\/semantic-web\/semantic-web-technologies-for-managing-ehr-related-clinical-knowledge\" target=\"_blank\">http:\/\/www.intechopen.com\/books\/semantic-web\/semantic-web-technologies-for-managing-ehr-related-clinical-knowledge<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-06-12<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Semantic+Web+Technologies+for+Managing+EHR-related+Clinical+Knowledge&rft.jtitle=Semantic+Web&rft.aulast=Martinez-Costa&rft.aufirst=Catalina&rft.au=Martinez-Costa%2C%26%2332%3BCatalina&rft.au=Menarguez-Tortosa%2C%26%2332%3BMarcos&rft.au=Alberto%2C%26%2332%3BJose&rft.au=Tomas%2C%26%2332%3BJesualdo&rft.date=1+January+2010&rft.pub=InTech&rft_id=info:doi\/10.5772%2F7298&rft.isbn=978-953-7619-54-1&rft_id=http%3A%2F%2Fwww.intechopen.com%2Fbooks%2Fsemantic-web%2Fsemantic-web-technologies-for-managing-ehr-related-clinical-knowledge&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Roehrs, Alex; da Costa, Cristiano Andre; da Rosa Righi, Rodrigo; Rigo, Sandro Jose; Wichman, Matheus Henrique (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8358689\/\" target=\"_blank\">\"Toward a Model for Personal Health Record Interoperability\"<\/a>. <i>IEEE Journal of Biomedical and Health Informatics<\/i> <b>23<\/b> (2): 867\u2013873. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJBHI.2018.2836138\" target=\"_blank\">10.1109\/JBHI.2018.2836138<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2168-2194\" target=\"_blank\">2168-2194<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/8358689\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/8358689\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Toward+a+Model+for+Personal+Health+Record+Interoperability&rft.jtitle=IEEE+Journal+of+Biomedical+and+Health+Informatics&rft.aulast=Roehrs&rft.aufirst=Alex&rft.au=Roehrs%2C%26%2332%3BAlex&rft.au=da+Costa%2C%26%2332%3BCristiano+Andre&rft.au=da+Rosa+Righi%2C%26%2332%3BRodrigo&rft.au=Rigo%2C%26%2332%3BSandro+Jose&rft.au=Wichman%2C%26%2332%3BMatheus+Henrique&rft.date=1+March+2019&rft.volume=23&rft.issue=2&rft.pages=867%E2%80%93873&rft_id=info:doi\/10.1109%2FJBHI.2018.2836138&rft.issn=2168-2194&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F8358689%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nicholson, David N.; Greene, Casey S. 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Peleg, Mor; ten Teije, Annette (1 September 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0933365719304531\" target=\"_blank\">\"Ten years of knowledge representation for health care (2009\u20132018): Topics, trends, and challenges\"<\/a> (in en). <i>Artificial Intelligence in Medicine<\/i> <b>100<\/b>: 101713. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.artmed.2019.101713\" target=\"_blank\">10.1016\/j.artmed.2019.101713<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0933365719304531\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0933365719304531<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ten+years+of+knowledge+representation+for+health+care+%282009%E2%80%932018%29%3A+Topics%2C+trends%2C+and+challenges&rft.jtitle=Artificial+Intelligence+in+Medicine&rft.aulast=Ria%C3%B1o&rft.aufirst=David&rft.au=Ria%C3%B1o%2C%26%2332%3BDavid&rft.au=Peleg%2C%26%2332%3BMor&rft.au=ten+Teije%2C%26%2332%3BAnnette&rft.date=1+September+2019&rft.volume=100&rft.pages=101713&rft_id=info:doi\/10.1016%2Fj.artmed.2019.101713&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0933365719304531&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Blobel, Bernd (2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23542959\" target=\"_blank\">\"Knowledge representation and management enabling intelligent interoperability - principles and standards\"<\/a>. <i>Studies in Health Technology and Informatics<\/i> <b>186<\/b>: 3\u201321. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0926-9630\" target=\"_blank\">0926-9630<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23542959\" target=\"_blank\">23542959<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23542959\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/23542959<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Knowledge+representation+and+management+enabling+intelligent+interoperability+-+principles+and+standards&rft.jtitle=Studies+in+Health+Technology+and+Informatics&rft.aulast=Blobel&rft.aufirst=Bernd&rft.au=Blobel%2C%26%2332%3BBernd&rft.date=2013&rft.volume=186&rft.pages=3%E2%80%9321&rft.issn=0926-9630&rft_id=info:pmid\/23542959&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23542959&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-26\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Ocean Informatics (15 February 2006). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/specifications.openehr.org\/releases\/1.0.2\/its\/XML-schema\/index.html\" target=\"_blank\">\"openEHR XML-schemas - Release 1.0.2\"<\/a>. openEHR Foundation<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/specifications.openehr.org\/releases\/1.0.2\/its\/XML-schema\/index.html\" target=\"_blank\">https:\/\/specifications.openehr.org\/releases\/1.0.2\/its\/XML-schema\/index.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 08 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=openEHR+XML-schemas+-+Release+1.0.2&rft.atitle=&rft.aulast=Ocean+Informatics&rft.au=Ocean+Informatics&rft.date=15+February+2006&rft.pub=openEHR+Foundation&rft_id=https%3A%2F%2Fspecifications.openehr.org%2Freleases%2F1.0.2%2Fits%2FXML-schema%2Findex.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-27\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_27-0\">27.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_27-1\">27.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">St. Bartholomew's Hospital Medical College (23 June 1994). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/cordis.europa.eu\/project\/id\/A2014\" target=\"_blank\">\"The Good European Health Record\"<\/a>. <i>CORDIS<\/i>. 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Retrieved 09 January 2022<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+Good+European+Health+Record&rft.atitle=CORDIS&rft.aulast=St.+Bartholomew%27s+Hospital+Medical+College&rft.au=St.+Bartholomew%27s+Hospital+Medical+College&rft.date=23+June+1994&rft.pub=European+Commission&rft_id=https%3A%2F%2Fcordis.europa.eu%2Fproject%2Fid%2FA2014&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-28\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_28-0\">28.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_28-1\">28.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rinner, C.; Janzek-Hawlat, S.; Sibinovic, S.; Duftschmid, G. (2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME09-02-0027\" target=\"_blank\">\"Semantic Validation of Standard-based Electronic Health Record Documents with W3C XML Schema\"<\/a> (in en). <i>Methods of Information in Medicine<\/i> <b>49<\/b> (03): 271\u2013280. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3414%2FME09-02-0027\" target=\"_blank\">10.3414\/ME09-02-0027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0026-1270\" target=\"_blank\">0026-1270<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME09-02-0027\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.3414\/ME09-02-0027<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Semantic+Validation+of+Standard-based+Electronic+Health+Record+Documents+with+W3C+XML+Schema&rft.jtitle=Methods+of+Information+in+Medicine&rft.aulast=Rinner&rft.aufirst=C.&rft.au=Rinner%2C%26%2332%3BC.&rft.au=Janzek-Hawlat%2C%26%2332%3BS.&rft.au=Sibinovic%2C%26%2332%3BS.&rft.au=Duftschmid%2C%26%2332%3BG.&rft.date=2010&rft.volume=49&rft.issue=03&rft.pages=271%E2%80%93280&rft_id=info:doi\/10.3414%2FME09-02-0027&rft.issn=0026-1270&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.3414%2FME09-02-0027&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-29\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_29-0\">29.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_29-1\">29.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Tun, Z.; Bird, L.J.; Goodchild, A. 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Retrieved 06 November 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=OWL-S%3A+Semantic+Markup+for+Web+Services&rft.atitle=&rft.aulast=Martin%2C+D.%3B+Burstein%2C+M.%3B+Hobbs%2C+J.+et+al.&rft.au=Martin%2C+D.%3B+Burstein%2C+M.%3B+Hobbs%2C+J.+et+al.&rft.date=22+November+2004&rft.pub=W3C&rft_id=https%3A%2F%2Fwww.w3.org%2FSubmission%2FOWL-S%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:14-40\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:14_40-0\">40.0<\/a><\/sup> <sup><a href=\"#cite_ref-:14_40-1\">40.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lezcano, Leonardo; Sicilia, Miguel-Angel; Rodr\u00edguez-Solano, Carlos (1 April 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046410001711\" target=\"_blank\">\"Integrating reasoning and clinical archetypes using OWL ontologies and SWRL rules\"<\/a> (in en). <i>Journal of Biomedical Informatics<\/i> <b>44<\/b> (2): 343\u2013353. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbi.2010.11.005\" target=\"_blank\">10.1016\/j.jbi.2010.11.005<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046410001711\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046410001711<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Integrating+reasoning+and+clinical+archetypes+using+OWL+ontologies+and+SWRL+rules&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Lezcano&rft.aufirst=Leonardo&rft.au=Lezcano%2C%26%2332%3BLeonardo&rft.au=Sicilia%2C%26%2332%3BMiguel-Angel&rft.au=Rodr%C3%ADguez-Solano%2C%26%2332%3BCarlos&rft.date=1+April+2011&rft.volume=44&rft.issue=2&rft.pages=343%E2%80%93353&rft_id=info:doi\/10.1016%2Fj.jbi.2010.11.005&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046410001711&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:15-41\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:15_41-0\">41.0<\/a><\/sup> <sup><a href=\"#cite_ref-:15_41-1\">41.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Horrocks, I.; Patel-Schneider, P.F.; Boley, H. et al. (21 May 2004). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/Submission\/SWRL\/\" target=\"_blank\">\"SWRL: A Semantic Web Rule Language Combining OWL and RuleML\"<\/a>. W3C<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.w3.org\/Submission\/SWRL\/\" target=\"_blank\">https:\/\/www.w3.org\/Submission\/SWRL\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 06 November 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=SWRL%3A+A+Semantic+Web+Rule+Language+Combining+OWL+and+RuleML&rft.atitle=&rft.aulast=Horrocks%2C+I.%3B+Patel-Schneider%2C+P.F.%3B+Boley%2C+H.+et+al.&rft.au=Horrocks%2C+I.%3B+Patel-Schneider%2C+P.F.%3B+Boley%2C+H.+et+al.&rft.date=21+May+2004&rft.pub=W3C&rft_id=https%3A%2F%2Fwww.w3.org%2FSubmission%2FSWRL%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Knowledge Systems, AI Laboratory. <a rel=\"nofollow\" class=\"external text\" href=\"#other\">\"Knowledge Interchange Format (KIF)\"<\/a>. Stanford University<span class=\"printonly\">. <a rel=\"nofollow\" class=\"external free\" href=\"#other\">http:\/\/www-ksl.stanford.edu\/knowledge-sharing\/kif\/#other<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 06 September 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Knowledge+Interchange+Format+%28KIF%29&rft.atitle=&rft.aulast=Knowledge+Systems%2C+AI+Laboratory&rft.au=Knowledge+Systems%2C+AI+Laboratory&rft.pub=Stanford+University&rft_id=http%3A%2F%2Fwww-ksl.stanford.edu%2Fknowledge-sharing%2Fkif%2F%23other&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFBoleyPaschkeShafiq2010\">Boley, Harold; Paschke, Adrian; Shafiq, Omair (2010), Dean, Mike; Hall, John; Rotolo, Antonino <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-16289-3_15\" target=\"_blank\">\"RuleML 1.0: The Overarching Specification of Web Rules\"<\/a>, <i>Semantic Web Rules<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>6403<\/b>: 162\u2013178, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-642-16289-3_15\" target=\"_blank\">10.1007\/978-3-642-16289-3_15<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-642-16288-6<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-16289-3_15\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-642-16289-3_15<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-06-12<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=RuleML+1.0%3A+The+Overarching+Specification+of+Web+Rules&rft.jtitle=Semantic+Web+Rules&rft.aulast=Boley&rft.aufirst=Harold&rft.au=Boley%2C%26%2332%3BHarold&rft.au=Paschke%2C%26%2332%3BAdrian&rft.au=Shafiq%2C%26%2332%3BOmair&rft.date=2010&rft.volume=6403&rft.pages=162%E2%80%93178&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-642-16289-3_15&rft.isbn=978-3-642-16288-6&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-642-16289-3_15&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFLezcanoSiciliaSerrano-Balazote2008\">Lezcano, Leonardo; Sicilia, Miguel-Angel; Serrano-Balazote, Pablo (2008), Lytras, Miltiadis D.; Carroll, John M.; Damiani, Ernesto <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-87781-3_9\" target=\"_blank\">\"Combining OpenEHR Archetype Definitions with SWRL Rules \u2013 A Translation Approach\"<\/a> (in en), <i>Emerging Technologies and Information Systems for the Knowledge Society<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>5288<\/b>: 79\u201387, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-540-87781-3_9\" target=\"_blank\">10.1007\/978-3-540-87781-3_9<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-540-87780-6<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-87781-3_9\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-540-87781-3_9<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-06-12<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Combining+OpenEHR+Archetype+Definitions+with+SWRL+Rules+%E2%80%93+A+Translation+Approach&rft.jtitle=Emerging+Technologies+and+Information+Systems+for+the+Knowledge+Society&rft.aulast=Lezcano&rft.aufirst=Leonardo&rft.au=Lezcano%2C%26%2332%3BLeonardo&rft.au=Sicilia%2C%26%2332%3BMiguel-Angel&rft.au=Serrano-Balazote%2C%26%2332%3BPablo&rft.date=2008&rft.volume=5288&rft.pages=79%E2%80%9387&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-540-87781-3_9&rft.isbn=978-3-540-87780-6&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-540-87781-3_9&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:16-45\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:16_45-0\">45.0<\/a><\/sup> <sup><a href=\"#cite_ref-:16_45-1\">45.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFEl_HajjamyAlaouiBahaj2018\">El Hajjamy, Oussama; Alaoui, Larbi; Bahaj, Mohamed (2018), Tabii, Youness; Lazaar, Mohamed; Al Achhab, Mohammed <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-96292-4_33\" target=\"_blank\">\"Integration of Heterogeneous Classical Data Sources in an Ontological Database\"<\/a> (in en), <i>Big Data, Cloud and Applications<\/i> (Cham: Springer International Publishing) <b>872<\/b>: 417\u2013432, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-96292-4_33\" target=\"_blank\">10.1007\/978-3-319-96292-4_33<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-96291-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-96292-4_33\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-96292-4_33<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-06-12<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Integration+of+Heterogeneous+Classical+Data+Sources+in+an+Ontological+Database&rft.jtitle=Big+Data%2C+Cloud+and+Applications&rft.aulast=El+Hajjamy&rft.aufirst=Oussama&rft.au=El+Hajjamy%2C%26%2332%3BOussama&rft.au=Alaoui%2C%26%2332%3BLarbi&rft.au=Bahaj%2C%26%2332%3BMohamed&rft.date=2018&rft.volume=872&rft.pages=417%E2%80%93432&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-96292-4_33&rft.isbn=978-3-319-96291-7&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-96292-4_33&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-46\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-46\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gatta, Roberto; Vallati, Mauro; Cappelli, Carlo; De Bari, Berardino; Salvetti, Massimo; Finardi, Silvio; Muiesan, Maria Lorenza; Valentini, Vincenzo <i>et al.<\/i> (2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.scitepress.org\/DigitalLibrary\/Link.aspx?doi=10.5220\/0005648801590165\" target=\"_blank\">\"Bridging the Gap between Knowledge Representation and Electronic Health Records:\"<\/a>. <i>Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies<\/i> (Rome, Italy: SCITEPRESS - Science and and Technology Publications): 159\u2013165. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5220%2F0005648801590165\" target=\"_blank\">10.5220\/0005648801590165<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-989-758-170-0<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.scitepress.org\/DigitalLibrary\/Link.aspx?doi=10.5220\/0005648801590165\" target=\"_blank\">http:\/\/www.scitepress.org\/DigitalLibrary\/Link.aspx?doi=10.5220\/0005648801590165<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bridging+the+Gap+between+Knowledge+Representation+and+Electronic+Health+Records%3A&rft.jtitle=Proceedings+of+the+9th+International+Joint+Conference+on+Biomedical+Engineering+Systems+and+Technologies&rft.aulast=Gatta&rft.aufirst=Roberto&rft.au=Gatta%2C%26%2332%3BRoberto&rft.au=Vallati%2C%26%2332%3BMauro&rft.au=Cappelli%2C%26%2332%3BCarlo&rft.au=De+Bari%2C%26%2332%3BBerardino&rft.au=Salvetti%2C%26%2332%3BMassimo&rft.au=Finardi%2C%26%2332%3BSilvio&rft.au=Muiesan%2C%26%2332%3BMaria+Lorenza&rft.au=Valentini%2C%26%2332%3BVincenzo&rft.au=Castellano%2C%26%2332%3BMaurizio&rft.date=2016&rft.pages=159%E2%80%93165&rft.place=Rome%2C+Italy&rft.pub=SCITEPRESS+-+Science+and+and+Technology+Publications&rft_id=info:doi\/10.5220%2F0005648801590165&rft.isbn=978-989-758-170-0&rft_id=http%3A%2F%2Fwww.scitepress.org%2FDigitalLibrary%2FLink.aspx%3Fdoi%3D10.5220%2F0005648801590165&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:17-47\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:17_47-0\">47.0<\/a><\/sup> <sup><a href=\"#cite_ref-:17_47-1\">47.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFKashyapBorgida2003\">Kashyap, Vipul; Borgida, Alex (2003), Fensel, Dieter; Sycara, Katia; Mylopoulos, John, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-39718-2_1\" target=\"_blank\">\"Representing the UMLS\u00ae Semantic Network Using OWL\"<\/a>, <i>The Semantic Web - ISWC 2003<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>2870<\/b>: 1\u201316, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-540-39718-2_1\" target=\"_blank\">10.1007\/978-3-540-39718-2_1<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-540-20362-9<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-540-39718-2_1\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-540-39718-2_1<\/a><\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Representing+the+UMLS%C2%AE+Semantic+Network+Using+OWL&rft.jtitle=The+Semantic+Web+-+ISWC+2003&rft.aulast=Kashyap&rft.aufirst=Vipul&rft.au=Kashyap%2C%26%2332%3BVipul&rft.au=Borgida%2C%26%2332%3BAlex&rft.date=2003&rft.volume=2870&rft.pages=1%E2%80%9316&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-540-39718-2_1&rft.isbn=978-3-540-20362-9&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-540-39718-2_1&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Miles, A.; Bechhofer, S. (20 August 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.w3.org\/TR\/2008\/WD-skos-reference-20080829\/skos.html\" target=\"_blank\">\"SKOS Simple Knowledge Organization System RDF Schema\"<\/a>. WC3<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.w3.org\/TR\/2008\/WD-skos-reference-20080829\/skos.html\" target=\"_blank\">https:\/\/www.w3.org\/TR\/2008\/WD-skos-reference-20080829\/skos.html<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 06 November 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=SKOS+Simple+Knowledge+Organization+System+RDF+Schema&rft.atitle=&rft.aulast=Miles%2C+A.%3B+Bechhofer%2C+S.&rft.au=Miles%2C+A.%3B+Bechhofer%2C+S.&rft.date=20+August+2008&rft.pub=WC3&rft_id=https%3A%2F%2Fwww.w3.org%2FTR%2F2008%2FWD-skos-reference-20080829%2Fskos.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:18-49\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:18_49-0\">49.0<\/a><\/sup> <sup><a href=\"#cite_ref-:18_49-1\">49.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">da Costa, C.A.; Wichman, M.H.; Righi, R.R. et al. (2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/public.eblib.com\/choice\/PublicFullRecord.aspx?p=6143762\" target=\"_blank\">\"Ontology-based Model for Interoperability between openEHR and HL7 Health Applications\"<\/a>. In Arabnia, H.R.; Deligiannidis, L.; Tinetti, F.G. et al. (in English). <i>HIMS'19 proceedings of the 2019 International Conference on Health Informatics and Medical Systems<\/i>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-68392-570-5. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/1151199195\" target=\"_blank\">1151199195<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/public.eblib.com\/choice\/PublicFullRecord.aspx?p=6143762\" target=\"_blank\">http:\/\/public.eblib.com\/choice\/PublicFullRecord.aspx?p=6143762<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Ontology-based+Model+for+Interoperability+between+openEHR+and+HL7+Health+Applications&rft.atitle=HIMS%2719+proceedings+of+the+2019+International+Conference+on+Health+Informatics+and+Medical+Systems&rft.aulast=da+Costa%2C+C.A.%3B+Wichman%2C+M.H.%3B+Righi%2C+R.R.+et+al.&rft.au=da+Costa%2C+C.A.%3B+Wichman%2C+M.H.%3B+Righi%2C+R.R.+et+al.&rft.date=2019&rft.isbn=978-1-68392-570-5&rft_id=info:oclcnum\/1151199195&rft_id=http%3A%2F%2Fpublic.eblib.com%2Fchoice%2FPublicFullRecord.aspx%3Fp%3D6143762&rfr_id=info:sid\/en.wikipedia.org:Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. The original references are in alphabetical order; this version places them in or order of appearance, by design. The original gives the same citation for both 35 and 50; for this version, only one instance is used. \n<\/p><p>|}\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628181027\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.490 seconds\nReal time usage: 0.921 seconds\nPreprocessor visited node count: 42742\/1000000\nPost\u2010expand include size: 340953\/2097152 bytes\nTemplate argument size: 111310\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 100290\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 429.003 1 -total\n 86.65% 371.711 1 Template:Reflist\n 66.85% 286.803 49 Template:Citation\/core\n 31.53% 135.281 19 Template:Cite_journal\n 28.23% 121.112 23 Template:Cite_web\n 11.00% 47.181 6 Template:Citation\n 10.63% 45.614 40 Template:Date\n 6.21% 26.661 1 Template:Infobox_journal_article\n 5.06% 21.716 45 Template:Citation\/identifier\n 4.75% 20.379 1 Template:Infobox\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13359-0!canonical and timestamp 20220628181026 and revision id 48313. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges\">https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","5c4c23816cc524a349b691a9b6846809_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6e\/Fig1_Sachdeva_Information22_13-2.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/b\/bc\/Fig2_Sachdeva_Information22_13-2.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/f\/f1\/FigA1_Sachdeva_Information22_13-2.png"],"5c4c23816cc524a349b691a9b6846809_timestamp":1656439826,"c4564a9f0e02ca2559e204e61f391fbd_type":"article","c4564a9f0e02ca2559e204e61f391fbd_title":"Health informatics: Engaging modern healthcare units: A brief overview (Yogesh and Karthikeyan 2022)","c4564a9f0e02ca2559e204e61f391fbd_url":"https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview","c4564a9f0e02ca2559e204e61f391fbd_plaintext":"\n\nJournal:Health informatics: Engaging modern healthcare units: A brief overviewFrom LIMSWikiJump to navigationJump to searchFull article title\n \nHealth informatics: Engaging modern healthcare units: A brief overviewJournal\n \nFrontiers in Public HealthAuthor(s)\n \nYogesh, M.J.; Karthikeyan, J.Author affiliation(s)\n \nVellore Institute of TechnologyPrimary contact\n \nEmail: yogeshmj dot nie at gmail dot comYear published\n \n2022Volume and issue\n \n10Article #\n \n854688DOI\n \n10.3389\/fpubh.2022.854688ISSN\n \n2296-2565Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.854688\/fullDownload\n \nhttps:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2022.854688\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Related work \n4 Introduction to HL7 FHIR architecture \n\n4.1 FHIR for patient access to medical records \n4.2 FHIR resources \n4.3 Workflow description \n\n4.3.1 Workflow state and relationships \n\n\n\n\n5 Overview of health informatics \n\n5.1 Informatics approaches \n\n\n6 Status QUO in health informatics: An Indian perspective \n\n6.1 Health care delivery systems \n6.2 Applications of health informatics \n6.3 Future trends and directions in health informatics \n\n\n7 Challenges in health informatics \n\n7.1 Health data standards challenges and possible solutions to them \n\n\n8 Conclusion \n9 Acknowledgements \n\n9.1 Author contributions \n9.2 Conflict of interest \n\n\n10 References \n11 Notes \n\n\n\nAbstract \nWith a large amount of unstructured data finding its way into health systems, health informatics implementations are currently gaining traction, allowing healthcare units to leverage and make meaningful insights for doctors and decision makers using relevant information to scale operations and predict the future view of treatments via information systems communication. Now, around the world, massive amounts of data are being collected and analyzed for better patient diagnosis and treatment, improving public health systems and assisting government agencies in designing and implementing public health policies, while also instilling confidence in future generations who want to use better public health systems. \nThis article provides an overview of the Health Level 7 FHIR architecture, including the workflow state, linkages, and various informatics approaches used in healthcare units. The article also discusses future trends and directions in health informatics and its successful application to benefiting public health safety. With the advancement of health informatics technologies, however, healthcare units face new issues that must be addressed with appropriate adoption policies and standards.\nKeywords: health informatics, public health, information systems, health policy, public health systems\n\nIntroduction \nMachine learning is the fastest-growing topic in computer science today, and with it a health informatics implementation of ML is one of the more difficult problems to solve.[1][2]\nEmerging economies are increasing their investments in healthcare, which makes sense and encourages health professionals to adopt sound frameworks and regulatory standards, as well as health IT, to improve the quality and efficacy of care.[3] In this expanding field, new age occupations can be established. This new field has the potential to be a lucrative career path in the future. With a clear flow of information across many medical subsystems, adoption of electronic health record systems (EHRs) will improve the health care system going forward.[4]\nBig data is frequently employed in the field of health informatics, as new data is constantly pouring into the system, requiring analysis and interpretation in order to make rational decisions.[5][6] This big data has ushered in a new era for healthcare companies to improve decision-making through the comprehensive integration of data from a range of sources, allowing for much faster and more effective decision making.[7] As such, within and outside of the medical industry, computational health informatics has become an emerging field of study.[7][8][9]\nIn recent years, the healthcare industry has seen a rapid growth in medical and healthcare data, which can be used to improve facilities and public healthcare utilization and implementation using novel treatment and diagnosis methodologies. In turn, this more efficient use of healthcare data gives patients confidence in using the best public healthcare services available and aids governments in developing better healthcare policies.[10] \nIn today's increasingly complex social and economic environment, at hand is the vital issue of improving quality of offered healthcare services while lowering prices. This is largely what health informatics has attempted to solve. The major purpose of health informatics is to increase our understanding of medicine and medical practice by using real-world medical data. In the scope of healthcare, health informatics is practically a blend of information science and computer science.[11]\nAt the core of health informatics has historically been a collection of computerized systems for assisting patient analysis and diagnosis. More recent technologies have emerged that make it even easier for clinicians to make better healthcare decisions.[12][13] As health informatics continues to evolve, it promises to improve public health activities through the advanced application of information and communication technologies (ICT).[14] ICTs have been shown to help healthcare systems increase productivity, which has resulted in significant cost savings in operations and service delivery. For administrative and healthcare objectives, ICTs have already proven to be quite effective. Additionally, new prospects for new medical equipment and systems are opening up as ICTs become smaller, quicker, wireless, and remotely controlled.\nThe internet and web have recently brought up new possibilities for increasing the response time of healthcare services, while also lowering costs. It is clear that we are in the early stages of a new era that will fundamentally alter the way healthcare services are provided. This will help us acquire the public's trust in using high-quality healthcare services. However, new e-Health services and technology must still be researched, developed, promoted, and disseminated with significant effort. With the COVID-19 pandemic presently sweeping the globe, increasing ICT use has demonstrated that healthcare can and will become more contactless in the future, with fresh means of treating patients and providing healthcare services emerging. This is a popular yet difficult research subject since it necessitates interdisciplinary competence.[15] \nAdditionally, as big data continues to increasingly find its way into healthcare, additional challenges exist in the effective use of big data within ICT frameworks. For example, big data in healthcare is intimidating not only because of its sheer magnitude, but also due to the variety of data types and the pace with which it must be managed. To gain people' trust and give quality healthcare services, all health service providers are now putting in extra effort to use the most up-to-date technologies to effectively use big data to provide quality health services and advanced treatments.\nVarious requirements drive innovation in this industry, such as finding appropriate accommodation with standardization and coordinating the acquisition and implementation of newer healthcare systems and services on a national\/international level. With COVID-19 still threatening disruption in the healthcare sector, investments in this sector are gaining steam with new-age healthcare units in many nations, and growing economies such as India and China will continue to play a vital role in providing quality healthcare services to its citizens in the future. At the same time, those new-age healthcare units and systems will aid in dramatically lowering costs, making public healthcare systems more dependable, and instilling citizens' confidence in using inexpensive, high-quality healthcare.\n\nRelated work \n\"Big data\" is a term used to describe a significant volume of data that is collected and stored yet has outgrown standard data management and analysis solutions. Solutions like Hadoop and Spark, according to Roger Fyre and Mark McKenney, have arisen to solve some of these big data concerns.[16] For example, researchers have used Hadoop to implement a variety of parallel processing algorithms to efficiently handle geographical data.[17][18] Multistage map and reduce algorithms, which generate on-demand indexes and retain persistent indexes, are the end result of these techniques.[19]\nOther techniques such as predictive analytics and data mining have also been employed. Much of the current work on predictive analytics, particularly in clinical contexts, is aimed at improving health and financial outcomes, which will aid in making better decisions.[20] Data mining, which is defined as the processing and modeling of huge amounts of medical\/health data to identify previously unknown patterns or associations, is another important machine learning approach.[21][22] Data mining has been used, for example, in the collection of data for diseases such as cancer and neurological disorders in order to improve disease prognosis.[23][24] Cancer detection and diagnosis, as well as other health-related issues, have been made possible because to these breakthroughs.[25] Machine learning is also crucial in the testing and development of various models that take into account clinical and other important medical characteristics for decision making.\nDeep learning is now also being used to solve more difficult problems in the arena of health informatics.[26][27] For example, advances in medical imaging and its data management have made positive contributions to decision making. Today, medical imaging incorporates capabilities such as image segmentation, image registration, annotation, and database retrieval, holding greater promise for decision makers. As such, new deep learning and machine learning models can be employed with medical imaging for speedier decision making.[26] However, this means researchers in the fields of data science, machine learning, and deep learning remain in high demand for developing effective algorithms that adapt to changing data.\nHolzinger et al.[28] examined many approaches to developing an explainable prediction model for the medical domain. Prediction explanations can be useful in a variety of situations, including teaching, learning, research, and even the courtroom. Similarly, the demand for interpretable and explainable models is growing in the medical field. However, these models must be able to re-enact the decision-making and knowledge-extraction processes. Ribeiro et al.[29] have emphasized this requirement, discussing how machine learning models are essentially black boxes. Understanding the reasons for predictions can help to build trust, better assess model performance, and construct better, more accurate, and correct models by providing insights into the model. They propose the LIME algorithm[29] for explaining predictions of any model. Similarly, though dealing with neural machine translation, the proposed model of Bahdanau et al.[30] can be used in a variety of other applications such as healthcare.\n\nIntroduction to HL7 FHIR architecture \nIn the last two decades, EHRs have been widely implemented in the United States to improve healthcare quality, increase patient happiness, and reduce healthcare costs.[31][32][33] As growing countries such as India, China, and Bangladesh experiment with innovative ways to establish EHR systems, they will significantly aid in the development of effective public health systems in those countries. In all cases, at the core of most effective EHRs is Health Level 7's (HL7's) Fast Health Interoperability Resources (FHIR) architecture.\nThe basic idea behind HL7's FHIR (pronounced \u201cfire\u201d) was to create a set of resources and then create HTTP-based REST application programming interfaces (APIs) to access and use these resources. FHIR uses components called \"resources\" to access and perform operations on patient's health data at the granular level. This feature distinguishes FHIR from all other standards because it was not present in any earlier version of HL7 (v2, v3) or the HL7 clinical document architecture (CDA).[34]\nThe fundamental building blocks of FHIR are the so-called resources, which are generic definitions of common health care categories (e.g., patient, observation, practitioner, device, condition). For data interchange and resource serialization, FHIR employs JavaScript object syntax and XML structures. FHIR not only supports RESTful resource exchange but also manages and documents an interoperability paradigm.\nFHIR has grown in popularity and is being increasingly used by the healthcare industry since its inception. In 2018, six major technology companies\u2014including Microsoft, IBM, Amazon, and Google\u2014vowed to remove barriers to healthcare interoperability and signed a statement mentioning FHIR as an emerging standard for the interchange of health data. With the incorporation of Substitutable Medical Applications Reusable Technologies (SMART), a platform for interoperable applications[35], FHIR can be expected to attract even more attention to digital health tools in the future. As is, the use of FHIR for medical data transmission has the potential to deliver benefits in a wide range of disciplines, including mobile health apps, EHRs, precision medicine, wearable devices, big data analytics, and clinical decision support.\nThe primary goal of FHIR is to reduce implementation complexity while maintaining information integrity. Furthermore, this new standard integrates the benefits of existing HL7 standards (v2, v3, and CDA) and is projected to overcome their drawbacks. FHIR enables developers to create standardized browser applications that allow users to access clinical data from any healthcare system, regardless of the operating systems and devices used. Figure 1 represents the general architecture of FHIR.[34]\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. General architecture of the Fast Health Interoperability Resources (FHIR) standard[34]\n\n\n\nFHIR for patient access to medical records \nFHIR is an HL7 standard for electronically transferring healthcare information. The Centers for Medicare and Medicaid Services (CMS) Interoperability and Patient Access final regulation, announced in 2020, mandates all CMS-regulated payers to use FHIR version 4. Unlike earlier releases, the fourth iteration is backward compatible, ensuring that software suppliers' solutions will not become obsolete when a new FHIR version is released.\nThe FHIR standard defines a collection of HTTP-based RESTful APIs that allow healthcare platforms to exchange and share data in XML or JSON format. FHIR offers mobile apps, which users can obtain from the Apple App Store or Google Play in order to access their medical records and claims data.\nFHIR's basic exchangeable data piece is known as a resource. Each resource is formatted similarly and contains roughly the same amount of data. Each resource offers information about patient demographics, diagnosis, prescriptions, allergies, care plans, family history, claims, and so on, depending on the kind. They span the complete healthcare workflow and can be used independently or as part of a larger document.\nEach resource is given a unique ID, and many health systems, insurers, patients, and software developers can access the underlying data element using an API. Figure 2 represents the data layers and resources of FHIR.[34]\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. FHIR data layers and resources[34]\n\n\n\nFHIR resources \nA resource is the smallest discrete concept that can be independently maintained and is the lowest feasible unit of a FHIR-based transaction.[36] As a result, a resource is a known identity that provides useful data. Each resource has distinct bounds and differs from all others. A resource should be provided in sufficient depth to specify and enable the process's medical data interchange. The FHIR community has specified over 150 resources to date, according to the most recent FHIR version (R4).[37]\nThere are five key categories in which these resources can be found: \n\nAdministrative: location, organization, device, patient, and group\nClinical: CarePan, diagnostics, medication, allergy, and family history\nFinancial: billing, payment, and support\nInfrastructure: conformance, document, and message profile\nWorkflow: encounter, scheduling, and order\nFHIR is fast gaining popularity due to its dynamic properties. FHIR is projected to quickly become a symbol for clinical data interchange in the healthcare industry.\n\nWorkflow description \nWorkflow is a critical component of healthcare; orders, care regimens, and referrals drive the majority of activity in inpatient settings, as well as a significant amount of activity in community care. FHIR is concerned with workflow when it is necessary to share information about workflow state or relationships, when it is necessary to coordinate or drive the execution of workflow across systems, and when it is necessary to specify permissible actions, dependencies, and behavior requirements.\n\nWorkflow state and relationships \nFHIR does not have to be used for workflow execution. Orders, care plans, test findings, hospital admissions, claim payments, and other documents can all be exchanged utilizing FHIR resources without the need for a FHIR transaction to solicit fulfillment of those orders or request payment of those claims. Because it necessitates a greater level of standardization, interoperable support for workflow execution is a more advanced FHIR activity. Interoperable workflow execution necessitates the standardization of processes, roles, and activities across multiple systems, rather than just the data to be exchanged.\nEven if FHIR is not used for workflow execution, there is still a requirement to standardize workflow data elements: how does an event or a result point to the order that allowed it? How are parent and child steps tied together? How does a care plan know which protocol it is following?\nFHIR distinguishes three types of resources engaged in activities: requests, events, and definitions. Each of these categories is associated with a \u201cpattern.\u201d Resources in that category are encouraged to follow their specific pattern. These patterns provide conventional elements that are common to the majority of resources in each category. Work groups are anticipated to align with common domain behavior, and requirements as more authoritative than \u201cdesired\u201d architectural patterns, and as such, strict conformance is not necessary. When a pattern capability is assessed to be \u201cnot common, but nonetheless relevant\u201d for a given resource, it may be supplied through extensions rather than core parts. Figure 3 represents the workflow relations of the FHIR standard.[38]\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. Workflow relations with the FHIR standard[38]\n\n\n\nOverview of health informatics \nHealth informatics involves more than merely automating routine tasks. With contemporary technology developments in machine learning and deep learning, it is possible to redesign systems using methodologies that were previously impossible or not even considered.[26] Machine learning and deep learning are computationally expensive, however, though they can now be handled by the latest IBM POWER9 processors with GPU capabilities, which was previously impossible because the data was not available in electronic form and the number of possible symptoms\/incident patterns was too big to manage. Early detection of patterns that can anticipate what kind of treatment or diagnosis can be offered to such patients has improved dramatically.[39]\nIn the future, modern healthcare units will make use of such a framework for successful delivery of treatments for society as a whole, making effective use of data obtained from such systems by extracting insights that assist decision makers such as doctors, hospital owners, and health policymakers. However, classification and regression tree (CART) components are required for successful clinical decision support. For example, vital signs must be clearly classified to be applied to prediction.[40][41] From there, the prediction of a patient's breathing rate obtained from sensors acts as an example of regression.[42] In the future, this sort of CART-based Bayesian inference will be used to make better predictions in the domain of health informatics.\nHowever, several not-so-commonly employed principles will have to first be implemented in informatics systems in order to answer some the most pressing future difficulties in health informatics:\n\nMulti-task learning: Traditional machine learning frameworks consider only one learner attempting to solve a single task. However, in many applications, there are multiple tasks that label the same data instances differently. When the tasks are related, the information learned from each task can be used to improve learning of other tasks. Learning relevant tasks concurrently, rather than learning each task independently, is thus advantageous. Multi-task learning makes use of the intrinsic relationships between multiple tasks to improve generalization performance. It benefits all tasks by leveraging task relatedness and shared information across relevant tasks.[43]\nTransfer learning: Traditional machine learning technology has had a lot of success and has been used in many practical applications, but it still has certain limits in some real-world settings. Machine learning works best when there are a lot of labeled training cases with the same distribution as the test data. In many cases, however, gathering sufficient training data is costly, time-consuming, or even impossible. Semi-supervised learning can help to alleviate this difficulty by removing the requirement for large amounts of labeled data. A semi-supervised approach typically requires a small amount of labeled data and a large amount of unlabeled data to improve learning accuracy. However, in many cases, unlabeled instances are difficult to collect, making the resulting traditional models unsatisfactory.[44]\nMulti-agent hybrid systems: Multi-agent systems are networks of interconnected autonomous agents in which the behavior of neighboring agents influences the dynamics of each agent. Because of the increasing importance of multi-agent systems, there is a growing interest in coordination control to ensure consensus, flocking, containment, formation, rendezvous, and so on. To better understand multi-agent coordination, a variety of dynamic models of agents have been developed over the last two decades. Furthermore, many mathematical methods are used in the analysis and control of multi-agent systems. For more information, see research by Qin et al.[45] and the references within the research of Zheng et al.[46]\nRepresentation learning: Patient-specific data such as vital signs, medications, laboratory measures, observations, clinical notes, fluid balance, procedure codes, diagnostic codes, and so on are all included in modern EHR systems. Clinicians originally employed the codes and their hierarchies, as well as their associated ontologies, for internal administrative and invoicing functions. Recent deep learning algorithms, on the other hand, have attempted to project discrete codes into vector space, identify intrinsic commonalities between medical concepts, more accurately depict patients' health, and perform more precise predicting tasks. Word embedding and unsupervised learning have been used to examine medical concepts and patient representations in general.[47]\nHealth informatics has a number of long-term benefits in terms of research and healthcare delivery that can be used to create a sustainable ecosystem. ICTs aid in the enrichment of relevant data for analysis and decision making by health professionals. Following the COVID-19 pandemic, new-age healthcare units will arise, with increased investment and research spending, making public healthcare more accessible. As a result, solutions are required to manage the massive amounts of data created by medical equipment and healthcare systems, allowing for effective storage and retrieval in real-time data analysis and decision making.\n\nInformatics approaches \nTo make electronic health data more easily usable for research, recent publications have identified the need for effective adoption and use of standards, essential data and research services, clear and consistent policies regarding data access and use, and transparent and effective governance structures.[48][49]\nTo achieve data quality criteria, electronic health data utilized in research frequently require standardized ontologies, additional contextual information, field transformations, and missing or contradictory data to be handled.[50] For research-related data or functions, such as cohort identification and repeated extracts of source data over time, system development is frequently required.[49] Organizations with expertise utilizing and enhancing their health IT infrastructure for research have shared their lessons learned in these areas, adding value to organizations with similar goals but less experience or resources.[51]\nFor example, when preparing data for research use, organizations must understand the clinical context and structure of electronic health data, just as they do for other data uses such as decision support or population health. Individual researchers and data analysts can be relieved of their load by informatics support that spans research and operational usage of data. It is vital to evaluate and develop informatics tools and approaches by establishing processes that allow for coordinated governance and decisions informed by research users.\nInvesting in infrastructure to enable the use of electronic health data for research has also been shown to be beneficial to researchers by providing them with the necessary tools and expertise, to patients by providing clinical trial participation opportunities, to clinicians by enabling more rapid translation of research into practice, and to population health analysts by facilitating patient cohort views. In order to reduce project-specific IT costs, using health IT to assist research necessitates greater flexibility, increasing use of standards, and reusable ways for getting, preparing, and evaluating data.[52]\nAny use of operational data in research necessitates the establishment of a privacy and security framework, as well as data governance monitoring. Two initiatives\u2014Informatics for Integrating Biology and the Bedside (i2b2) and Observational Health Data Sciences and Informatics (OHDSI)\u2014have developed informatics tools and approaches that allow researchers to query organizational participants and support transformation or analytics of relevant data to facilitate research.[53][54]\nSpecifically, i2b2 has standardized data models and distributed computational tools that enable for the anonymous identification of potential genomic study participants at the institution level. OHDSI also employs a single data model, which incorporates information such as health economics and health systems. The methodologies utilized in these programs demonstrate the kind of functionality that may be required in health IT systems to better support research, as well as the types of concerns with the quality of electronic health data that regularly arise.\n\nStatus QUO in health informatics: An Indian perspective \nHealth care delivery systems \nDespite having a solid telecommunication infrastructure, many existing healthcare systems are based on manual record keeping. It would seem the value of health informatics in healthcare delivery has yet to be recognized by many policymakers.[55]\nIn countries such as India, health informatics is a new and emerging discipline. Its future prospects are very bright, thanks to the development of excellent infrastructure here. However, in order to implement a robust framework, this necessitates a multidisciplinary interaction with various stakeholders.\nInformation systems development could be another area where research is being conducted to improve the way data flows from various sources such as devices and medical equipment, allowing doctors and decision makers to make rational decisions on critical cases or equipment purchases in the future.\nDigitizing all medical data also aids in the creation of a structure for patient-related data in a hospital that can be easily retrieved and searched. Finally, the development of some kind of EHR can be accomplished through the development of information systems.[56]\n\nApplications of health informatics \nHealth informatics in India can become cost-effective and ensure proper service delivery, which aids in beneficial behavioral change through the use of ICTs.[57] We can create novel applications that can be used effectively by utilizing local talent and effective use of ICT in remote parts of India.[58] Various governance issues can be addressed in the future with certain checks and balances in the data collection and analysis process.[59] The following are some of the areas where health informatics can be used:\n\nEpidemiological disease prediction\nDisaster management\nAwareness in healthcare processes\nHealthcare in remote areas\nEHRs and their linkages with health systems\nHealth statistics\nEducation and training\nDevelopment of clinical decision support systems (CDSS)\nPublic health research\nVisualization tools for doctors\nRecommendation systems for health informatics\nPrecision drug prediction\nThe potential of this emerging area has far-reaching benefits over a long period of time, and new and novel solutions can be built using various machine\/deep learning models. There is a lot of work to be done in this area where we can use cutting-edge technology to aid\/assist in the development of robust products and frameworks for public health policy.[60][61][62][63]\n\nFuture trends and directions in health informatics \nThere are many current trends in the field of health informatics that can be used to develop sustainable products, services, and health-related policies for effective implementation across the country and internationally. A few of them are listed below, and many more trends may emerge in the near future as a result of discussions with multiple stakeholders.\n\nData standards and Interoperability\nProcesses to transform medical\/clinical data\nToolkits and pipelines for data management\nStandardized reporting methodologies\nAppropriate use of informatics expertise\nMore trends may emerge in the future, taking into account the most recent technological advancements. Because health informatics is a new and emerging field, more research challenges may emerge, bringing forth newer perspectives. To solve more difficult problems in this area, future researchers will likely prefer machine\/deep learning methods\/models.[26] There are numerous other research directions being pursued in relation to various aspects of healthcare data such as quality, veracity, privacy, and timeliness. The following are some of the most notable data characteristics of healthcare data[9][64]:\n1. Complexity and noise: Because healthcare data is multisource and multimodal, it has a high level of complexity and noise. Furthermore, there are issues with impurity and missing values in high-volume data. It is difficult to deal with all of these issues, both in terms of scale and accuracy, despite the fact that a number of methods have been developed to improve data accuracy and usability.[65] Because the quality of data dictates the quality of information, which in turn affects decision-making, it is vital to develop efficient big data cleansing ways to improve data quality in order to make effective and correct decisions.[66]\n2. Heterogeneity: Traditional healthcare data is frequently fragmented into multiple forms due to a lack of standardization. As a result, it is both reasonable and important to investigate and adopt universal data standards. However, due to the complexity of developing universal data standards, it is a difficult undertaking. Not only is healthcare data diverse, but there are also numerous technical challenges to integrating that data for specific purposes.[67] Even with standardized data formats, the multi-modal character of data makes efficient fusion difficult[68], necessitating the development of advanced analytics that cope with vast amounts of multi-modal data. The integration and synthesis of multi-source and multi-modal healthcare data on a larger scale would be a significant issue.\n3. Longitudinal analysis: Longitudinal data is the collection of repeated measurements of participant outcomes and possibly treatments or exposures[69], which means that \"the outcome variable is repeatedly measured on the same individual on multiple occasions.\"[70] In recent decades, longitudinal data analysis, particularly statistical longitudinal data analysis, has gotten a lot of attention. Longitudinal studies are used to characterize normal growth and aging, as well as to evaluate the effectiveness of risk factors and therapies. It is extremely important in epidemiology, clinical research, and therapeutic evaluation. With big data analytic tools, it is possible to perform longitudinal care analysis across patients and diagnoses to identify the optimal care options.\n4. Scale: Healthcare data is continuously expanding in quantity and scope.[68] The fact that data volume is growing faster than processing power is a significant challenge in managing vast amounts of data. Several fundamental adjustments are occurring to handle this enormous transition.[71] First, in recent years, CPU technology has increasingly turned its focus to parallel data processing within nodes and the packing of numerous sockets. Second, the shift to cloud computing allows for information sharing and the consolidation of multiple workloads into large-scale clusters. Third, the transformation of the traditional I\/O subsystem from hard disk drives (HDDs) to solid-state drives (SSDs), as well as other storage technologies, is reforming data processing system design and operation.\n5. Real-time requirement: The velocity of big data in health informatics reflects not only the rate of data collecting and processing, but also the timeliness of replies. There are various instances that call for a quick choice. For example, it would be immensely desirable to monitor and analyze a person's health condition in real time or near real time in order to predict potential disease. It would also be critical to raise the alert for a potential influenza outbreak by examining public health statistics. Although real-time analytic applications are still in their infancy in the big data era, they represent the strongest trend and most promising direction in health informatics' future.[72]\n6. Privacy: Data privacy is another major worry for future big data analytics in health informatics.[73] Although strong laws control more formalized EHR data, extra attention should be taken and standards should be enforced to regularize the use and dissemination of personal and sensitive information obtained from diverse sources. In addition to data privacy, there are a number of other challenges\u2014 such as data protection, data security, data safety, and the protection of doctors from liability resulting from manipulated data\u2014that necessitate the use of specialized big data analytics to address these complicated constraints.[73][74]\n7. Visualization: The visualization of healthcare data is crucial for exploratory or discovery analytics, which aim to investigate and discover elements that are hidden or encrypted in the data.[75] Effective visualization tools will enable clinicians and physicians to explore data without the need for IT assistance.[72]\n8. Multidisciplinary and human-computer interaction: Big data in health informatics is expected to be a multidisciplinary job requiring ongoing contributions from multiple topic experts.[76] They include, but are not limited to, engineering scientists who provide basic big data infrastructure to collect, store, share, and manage big data; computer science data scientists who provide solutions for processing and analyzing high-volume, high-velocity healthcare data using a variety of data mining and machine-learning techniques; and clinicians and physicians from the medical domain who provide professional healthcare data analysis, personalized care, and make recommendations. Computer algorithms can struggle to find patterns and interpret results at times; consequently, it is a desirable feature for an advanced big data analysis system to be able to enable input from numerous human specialists, exchange of viewpoints, and collaborative exploration of outcomes. Furthermore, in the health sector, we sometimes do not have massive data: we are confronted with a small number of datasets or unusual events, where, for example, machine-learning algorithms suffer from insufficient training samples. In such circumstances, we require more than just automatic machine learning; we also require a person in the loop. In other words, interactive machine learning (iML) or \u201chuman in the loop\u201d techniques can be used in health informatics when automatic machine learning algorithms cannot handle rare occurrences on their own and a human expert is required to interact in the learning process.[77] The interplay between computer algorithms and human specialists has the potential to improve the learning process.\n\nChallenges in health informatics \nThere are numerous challenges in this area, particularly in a country like India, where a large population is denied affordable healthcare. This can serve as a starting point for developing and implementing robust health informatics applications, products, and research and development investments. The start-up\/venture costs, people, and equipment are very high, and it is a niche sector in which many people are hesitant to venture into; however, such a space\/sector can be leveraged, making very good business sense.[78]\nTo improve the way health services are delivered and implemented to the public, a multidisciplinary approach involving various sectors\/stakeholders is required. These informatics systems can be used for a variety of purposes. Medical\/healthcare data will be more structured and democratized by competent authorities. The advancement of EHRs and web-based health monitoring systems will also aid in rational decision making and policy framework implementation.[12] \nHowever, there may be numerous bottlenecks in the development of ICT systems for health informatics.[55][79] For example, the majority of stakeholders are unconvinced about the benefits of internet technologies in health care and are unfamiliar with how to use such new technology.[80] Concerns about security and privacy may also arise as robust healthcare systems are developed in the future.[12]\nProper techniques are essential to ensure patient data confidentiality, and system security may become a concern when data policy standardization increases. Many new challenges can be encountered while developing novel and innovative ways to promote public health through the use of information technology (IT) and other computing technological advances such as cloud computing, data visualization, and health informatics innovations. Future research is required because the health informatics domain is still in its early stages, where more difficult problems can be solved and newer products and services can be spawned as a business venture. Additionally, deep learning in health informatics has its own set of challenges.[26]\nAdditionally, despite significant investments in information technology, patient safety and productivity have not improved. Preventable medical errors are the third leading cause of death in the United States, after heart disease and cancer, killing over 400,000 people each year. These blunders cost the United States over one trillion dollars per year. To combat this problem, the federal government has mandated that the healthcare industry transition to electronic health records (EHRs) and use these records to improve patient processes and outcomes (i.e., meaningful use). Emerging economies have to allocate and give incentives to healthcare units\/organizations to promote the use of EHRs.\nThe COVID-19 pandemic has also revealed challenges in maintaining quality patient outcomes through health information management and health informatics. Roadblocks have included a lack of standards for information exchange between providers and PHAs (public health authorities); issues with data collection and data quality, particularly in terms of completeness and timeliness; and gaps in effectiveness of governance, public policies, and regulations. \nThe latter in particular highlights a lack of procedures to support efficient data sharing, contact tracing, and data governance, as well as providers' concerns about privacy regulations, which resulted in insufficient data sharing. Governance and public policy hurdles stem from chronic underfunding of public health infrastructure, as well as a lack of adequate investments in resources (particularly qualified employees) and facilities. A key difficulty is also found in the lack of international coordination. Many overlapping and interrelated legal, ethical, scientific, technical, technological, health equality, and privacy elements have influenced how health information has been managed or mismanaged during the COVID-19 pandemic. Other long-standing systemic difficulties in health information management will need to be addressed in order to operationalize many of the data and information system recommendations.[81]\nAnother challenge in effectively implementing health informatics rests in the financial investment required to design, execute, and sustain e-health programs. For example, Anderson cited a lack of financial backing and high initial expenses as hurdles to implementing ICT in health care.[82] While health informaticians and information professionals may see future benefits from investments in ICTs, health professionals and managers may be skeptical, especially if they are satisfied with current methods of working and wish to maintain the status quo; they may see such initiatives as diverting financial resources away from under-resourced clinical care.[83]\nContinued resistance to the establishment of ICT systems by health professionals and managers can lead to further issues once the systems are in place, and the restricted adoption of health informatics applications has meant that their potential is not always achieved. Decision support systems, for example, may be ignored or overridden, and evidence-based information may have limited applicability for an individual patient. Clinicians make life-changing judgments or act in life-threatening situations, and if they don't comprehend the reasons behind the decisions behind a CDSS, they won't trust it or use it effectively.[84] This highlights the importance of not only involving physicians and healthcare professionals in the construction of systems and the interpretation of outcomes, but also of providing adequate explanation and information at the point of care for healthcare practitioners to trust such systems.[84]\nAs previously stated, identifying the types of information that clinicians require, as well as the methods by which they access and utilize information, is critical in ensuring that developments not only meet the needs of the users, but are also perceived to be valuable, so that health professionals and other users will want to maximize their potential. Addressing healthcare professionals', patients', and the public's concerns about data security, as well as threats to patient privacy and confidentiality, will be critical in developing online access to patient records.[85] Greater security measures integrated into system design will help boost system confidence; however, the chance of third parties getting access to sensitive patient-identifiable data remains a danger.[82]\nAnother challenge that can stall the creation and execution of health informatics efforts is quality. The real and perceived quality of data entered into systems and then used for health care is vital not only for assuring system use, but also for the safety and well-being of patients. If data is not input, or is not entered correctly, the buildup of missing or low quality data discourages others from using the system and creates additional suspicion and skepticism about future advancements. The importance of accurate and correct data will grow as lifelong electronic records are established[84], both prospectively as individuals are born and retrospectively using data acquired over an existing person's lifetime to date.\nAs previously noted, the earlier development of small-scale information systems within individual departments or hospitals resulted in system incompatibility and difficulties communicating or transferring data when larger-scale systems were later built. One approach to addressing this issue is to increase interoperability and employ known electronic record architectures in the creation of new systems. In addition, the lack of data standards in health presents additional challenges for moving and sharing data between systems.[82] Attempts to address these issues include the creation of information management standards such as Digital Imaging and Communications in Medicine (DICOM), HL7, and terminologies and coding systems like the International Classification of Diseases (ICD) and SNOMED CT to standardize the ways in which medical conditions and diseases are represented in computer-based systems and codify the natural language used by medical staff. In particular, the ICD was created to provide a standard method of classifying medical diagnoses for epidemiology and healthcare purposes. Initially, it only included causes of death, but more recent versions have included causes of morbidity, and it is now in its eleventh version.[86] \n\nHealth data standards challenges and possible solutions to them \nClearly, data standards are not lacking in the healthcare industry. Standard development organizations have created a plethora of them to address nearly every facet of communication between diverse health systems. However, the simple fact that they exist and are available does not address all of the issues surrounding interoperability. What follows are some of the more difficult standards issues, as well as potential solutions.\n1. Medical coding speed and accuracy issues: The manual work required to convert diagnoses, treatments, services, treatment plans, and other concepts into medical codes is undertaken by professionally qualified individuals. Computer-assisted coding systems are now used by coders. However, the translation process' speed and precision are far from flawless. To that aim, high hopes are placed on AI-powered tools capable of identifying proper codes and recommending them for expert evaluation. Currently, such intelligent systems speed up coding, but they cannot completely replace humans and automate the entire process.\n2. Need for mapping between codes: Each code in healthcare serves a specific purpose. SNOMED allows physicians to provide a thorough clinical picture of a patient being treated, whereas ICD-10 presents diagnoses quickly and CPT summarizes services. However, there are times when translation from one code system to another is required. As previously stated, SNOMED cannot be used for billing reasons and must be translated to ICD-10-CT. To overcome mapping issues, standard development organizations continue to research various approaches.\n3. Lack of compatibility between old and new standards: To comply with existing interoperability regulations, hospitals must make content described by USCDI available via FHIR-based APIs. However, most older EHR systems were designed with previous standards in mind. Some of them are only capable of importing and exporting HL7 v2 messages. Others rely heavily on C-CDA materials. Neither v2 nor C-CDA are compatible with granular USCDI data elements or FHIR basic interchangeable data block resources. As a result, hospitals will require additional digital technologies and human resources to extract data from legacy formats and convert it into FHIR- and USCDI-compliant formats.\n4. No two-way communication between patients and EHRs: The FHIR standard enables patients to access health data through apps of their choice. However, because EHRs largely limit access to their systems as read-only, this more often than not becomes a one-way street. The software allows users to request information but does not allow them to modify or change it. Many industry experts believe that the next major difficulty for healthcare is a lack of two-way communication between medical apps and EHR systems. And, sooner or later, it will need the development of new data standards.[87]\n\nConclusion \nContinued research in the domain of health informatics is vital, driving new discoveries that can be realized effectively and via rigorous testing. There are no proven design blueprints for such a comprehensive infrastructure, and the goal is always shifting due to the nature of real-time patient, medical, and equipment data collection from a variety of sources. The future of health informatics lies in the creation of novel algorithms, models, and an ecosystem that is conducive to health professionals and decision makers.\nSome of the advantages that will result from innovation in this emerging area will be critical, including the:\n\ndevelopment of case- and incident-related health information standards and services;\nimprovement in professionalism among healthcare units;\ncreation of various innovative industrial processes;\nenhancement of research collaboration both nationally and internationally;\ndevelopment of better data visualization tools;\ndevelopment of novel prediction models using machine learning, deep learning, and reinforcement learning;\ncreation of new products and services related to healthcare and health informatics;\nimprovement of storage and retrieval mechanisms associated with health data; and\ndevelopment of curated, novel datasets for research communities.\nCurrent cutting-edge health informatics research projects aim to discover new condition onset behaviors that are visible in physiological data streams earlier than traditional condition detection in critical care data.[88] Cloud computing has attracted a lot of research attention, but only a small portion of the work done so far has addressed performance issues, and only a few examinations have used a rigorous analytical approach.[89][90][91][92]\nBig data is also playing an important role in health informatics, where a large amount of data related to healthcare is generated, assisting doctors and decision makers in making rational decisions regarding patient treatment and diagnosis. Newer computational technologies may emerge that will improve the way healthcare is delivered and implemented in the future, thereby vastly improving the public healthcare system. Policymakers can propose tried-and-true use cases that can be transformed into a meaningful framework in which all stakeholders can deliberate and decide on the best model for improving the public health care system.\nHealth informatics is a new field, with many stakeholders involved in the design and implementation of sustainable public health systems and policies for the benefit of society as a whole.\n\nAcknowledgements \nAuthor contributions \nMY has written the manuscript with relevant information from the literature regarding the major challenges and gaps that the present health informatics system and public health system are undergoing. The manuscript was reviewed and inputs were given by JK to focus on health informatics and policy framework. 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Elets Technomedia Pvt. Ltd. https:\/\/ehealth.eletsonline.com\/2008\/06\/universalising-healthcare-through-telemedicine\/ .   \n \n\n\u2191 Saxena, G.; Singh, J.P. (2003). \"E-medicine in India: Hurdles and future prospects\". https:\/\/www.themanager.org\/Resources\/Telemed.pdf .   \n \n\n\u2191 Massoudi, Barbara L.; Sobolevskaia, Diana (1 August 2021). \"Keep Moving Forward: Health Informatics and Information Management beyond the COVID-19 Pandemic\" (in en). Yearbook of Medical Informatics 30 (01): 075\u2013083. doi:10.1055\/s-0041-1726499. ISSN 0943-4747. PMC PMC8416200. PMID 34479380. http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1726499 .   \n \n\n\u2191 82.0 82.1 82.2 Anderson, James G. (1 May 2007). \"Social, ethical and legal barriers to e-health\". International Journal of Medical Informatics 76 (5-6): 480\u2013483. doi:10.1016\/j.ijmedinf.2006.09.016. ISSN 1386-5056. PMID 17064955. https:\/\/pubmed.ncbi.nlm.nih.gov\/17064955 .   \n \n\n\u2191 Wyatt, J. C (9 June 2001). \"The new NHS information technology strategy\". BMJ 322 (7299): 1378\u20131379. doi:10.1136\/bmj.322.7299.1378. PMC PMC1120460. PMID 11397729. https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.322.7299.1378 .   \n \n\n\u2191 84.0 84.1 84.2 Berner, Eta S.; Moss, Jacqueline (1 November 2005). \"Informatics Challenges for the Impending Patient Information Explosion\" (in en). Journal of the American Medical Informatics Association 12 (6): 614\u2013617. doi:10.1197\/jamia.M1873. ISSN 1067-5027. PMC PMC1294032. PMID 16049224. https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1197\/jamia.M1873 .   \n \n\n\u2191 Becker, Moritz Y. (1 May 2007). \"Information governance in NHS's NPfIT: A case for policy specification\" (in en). International Journal of Medical Informatics 76 (5-6): 432\u2013437. doi:10.1016\/j.ijmedinf.2006.09.008. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002139 .   \n \n\n\u2191 \"International Statistical Classification of Diseases and Related Health Problems (ICD)\". World Health Organization. https:\/\/www.who.int\/standards\/classifications\/classification-of-diseases .   \n \n\n\u2191 \"Data Standards in Healthcare: Codes, Documents, and Exchange Formats\". Altexsoft Blog. Altexsoft. 23 October 2020. https:\/\/www.altexsoft.com\/blog\/data-standards-healthcare\/ .   \n \n\n\u2191 McGregor, Carolyn (1 June 2013). \"Big Data in Neonatal Intensive Care\". Computer 46 (6): 54\u201359. doi:10.1109\/MC.2013.157. ISSN 0018-9162. http:\/\/ieeexplore.ieee.org\/document\/6513228\/ .   \n \n\n\u2191 Iosup, A; Ostermann, S; Yigitbasi, M N; Prodan, R; Fahringer, T; Epema, D H J (1 June 2011). \"Performance Analysis of Cloud Computing Services for Many-Tasks Scientific Computing\". IEEE Transactions on Parallel and Distributed Systems 22 (6): 931\u2013945. doi:10.1109\/TPDS.2011.66. ISSN 1045-9219. http:\/\/ieeexplore.ieee.org\/document\/5719609\/ .   \n \n\n\u2191 Deelman, Ewa; Singh, Gurmeet; Livny, Miron; Berriman, Bruce; Good, John (1 November 2008). \"The cost of doing science on the cloud: The Montage example\". 2008 SC - International Conference for High Performance Computing, Networking, Storage and Analysis (Austin, TX, USA: IEEE): 1\u201312. doi:10.1109\/SC.2008.5217932. ISBN 978-1-4244-2834-2. http:\/\/ieeexplore.ieee.org\/document\/5217932\/ .   \n \n\n\u2191 Wang, Lei; Zhan, Jianfeng; Shi, Weisong; Liang, Yi; Yuan, Lin (2009). \"In cloud, do MTC or HTC service providers benefit from the economies of scale?\" (in en). Proceedings of the 2nd Workshop on Many-Task Computing on Grids and Supercomputers - MTAGS '09 (Portland, Oregon: ACM Press): 1\u201310. doi:10.1145\/1646468.1646475. ISBN 978-1-60558-714-1. http:\/\/portal.acm.org\/citation.cfm?doid=1646468.1646475 .   \n \n\n\u2191 Alam, S.; Barrett, R.; Bast, M.; Fahey, M.R.; Kuehn, J.; McCurdy, C.; Rogers, J.; Roth, P. et al. (1 November 2008). \"Early evaluation of IBM BlueGene\/P\". 2008 SC - International Conference for High Performance Computing, Networking, Storage and Analysis (Austin, TX: IEEE): 1\u201312. doi:10.1109\/SC.2008.5214725. ISBN 978-1-4244-2834-2. http:\/\/ieeexplore.ieee.org\/document\/5214725\/ .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Some grammar and sentence placement was cleaned up for better readability. A few sentences and citations were removed for their lack of relevance to the topic.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\">https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on health informaticsNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 16 May 2022, at 21:11.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 209 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","c4564a9f0e02ca2559e204e61f391fbd_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_Health_informatics_Engaging_modern_healthcare_units_A_brief_overview rootpage-Journal_Health_informatics_Engaging_modern_healthcare_units_A_brief_overview skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Health informatics: Engaging modern healthcare units: A brief overview<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>With a large amount of unstructured data finding its way into health systems, <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_informatics\" title=\"Health informatics\" class=\"wiki-link\" data-key=\"055eb51f53cfdbacc08ed150b266c9f4\">health informatics<\/a> implementations are currently gaining traction, allowing healthcare units to leverage and make meaningful insights for doctors and decision makers using relevant <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> to scale operations and predict the future view of treatments via information systems communication. Now, around the world, massive amounts of data are being collected and analyzed for better patient diagnosis and treatment, improving <a href=\"https:\/\/www.limswiki.org\/index.php\/Public_health\" title=\"Public health\" class=\"wiki-link\" data-key=\"81092e25c0bd359cedd1b9f9dc350c86\">public health<\/a> systems and assisting government agencies in designing and implementing public health policies, while also instilling confidence in future generations who want to use better public health systems. \n<\/p><p>This article provides an overview of the <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_7#Fast_Healthcare_Interoperability_Resources_.28FHIR.29\" title=\"Health Level 7\" class=\"wiki-link\" data-key=\"ce348e672e47598e4b42cbd03c292ec4\">Health Level 7 FHIR<\/a> architecture, including the <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> state, linkages, and various <a href=\"https:\/\/www.limswiki.org\/index.php\/Informatics_(academic_field)\" title=\"Informatics (academic field)\" class=\"wiki-link\" data-key=\"0391318826a5d9f9a1a1bcc88394739f\">informatics<\/a> approaches used in healthcare units. The article also discusses future trends and directions in health informatics and its successful application to benefiting public health safety. With the advancement of health informatics technologies, however, healthcare units face new issues that must be addressed with appropriate adoption policies and standards.\n<\/p><p><b>Keywords<\/b>: health informatics, public health, information systems, health policy, public health systems\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">Machine learning<\/a> is the fastest-growing topic in computer science today, and with it a <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_informatics\" title=\"Health informatics\" class=\"wiki-link\" data-key=\"055eb51f53cfdbacc08ed150b266c9f4\">health informatics<\/a> implementation of ML is one of the more difficult problems to solve.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup>\n<\/p><p>Emerging economies are increasing their investments in healthcare, which makes sense and encourages health professionals to adopt sound frameworks and regulatory standards, as well as health IT, to improve the quality and efficacy of care.<sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup> In this expanding field, new age occupations can be established. This new field has the potential to be a lucrative career path in the future. With a clear flow of <a href=\"https:\/\/www.limswiki.org\/index.php\/Information\" title=\"Information\" class=\"wiki-link\" data-key=\"6300a14d9c2776dcca0999b5ed940e7d\">information<\/a> across many medical subsystems, adoption of <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">electronic health record<\/a> systems (EHRs) will improve the health care system going forward.<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup>\n<\/p><p>Big data is frequently employed in the field of health informatics, as new data is constantly pouring into the system, requiring analysis and interpretation in order to make rational decisions.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup> This big data has ushered in a new era for healthcare companies to improve decision-making through the comprehensive integration of data from a range of sources, allowing for much faster and more effective decision making.<sup id=\"rdp-ebb-cite_ref-:0_7-0\" class=\"reference\"><a href=\"#cite_note-:0-7\">[7]<\/a><\/sup> As such, within and outside of the medical industry, computational health informatics has become an emerging field of study.<sup id=\"rdp-ebb-cite_ref-:0_7-1\" class=\"reference\"><a href=\"#cite_note-:0-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_9-0\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup>\n<\/p><p>In recent years, the healthcare industry has seen a rapid growth in medical and healthcare data, which can be used to improve facilities and public healthcare utilization and implementation using novel treatment and diagnosis methodologies. In turn, this more efficient use of healthcare data gives patients confidence in using the best public healthcare services available and aids governments in developing better healthcare policies.<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup> \n<\/p><p>In today's increasingly complex social and economic environment, at hand is the vital issue of improving quality of offered healthcare services while lowering prices. This is largely what health informatics has attempted to solve. The major purpose of health informatics is to increase our understanding of medicine and medical practice by using real-world medical data. In the scope of healthcare, health informatics is practically a blend of information science and computer science.<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup>\n<\/p><p>At the core of health informatics has historically been a collection of computerized systems for assisting patient analysis and diagnosis. More recent technologies have emerged that make it even easier for clinicians to make better healthcare decisions.<sup id=\"rdp-ebb-cite_ref-:6_12-0\" class=\"reference\"><a href=\"#cite_note-:6-12\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup> As health informatics continues to evolve, it promises to improve <a href=\"https:\/\/www.limswiki.org\/index.php\/Public_health\" title=\"Public health\" class=\"wiki-link\" data-key=\"81092e25c0bd359cedd1b9f9dc350c86\">public health<\/a> activities through the advanced application of information and communication technologies (ICT).<sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup> ICTs have been shown to help healthcare systems increase productivity, which has resulted in significant cost savings in operations and service delivery. For administrative and healthcare objectives, ICTs have already proven to be quite effective. Additionally, new prospects for new medical equipment and systems are opening up as ICTs become smaller, quicker, wireless, and remotely controlled.\n<\/p><p>The internet and web have recently brought up new possibilities for increasing the response time of healthcare services, while also lowering costs. It is clear that we are in the early stages of a new era that will fundamentally alter the way healthcare services are provided. This will help us acquire the public's trust in using high-quality healthcare services. However, new e-Health services and technology must still be researched, developed, promoted, and disseminated with significant effort. With the <a href=\"https:\/\/www.limswiki.org\/index.php\/COVID-19\" class=\"mw-redirect wiki-link\" title=\"COVID-19\" data-key=\"da9bd20c492b2a17074ad66c2fe25652\">COVID-19<\/a> <a href=\"https:\/\/www.limswiki.org\/index.php\/Pandemic\" title=\"Pandemic\" class=\"wiki-link\" data-key=\"bd9a48e6c6e41b6d603ee703836b01f1\">pandemic<\/a> presently sweeping the globe, increasing ICT use has demonstrated that healthcare can and will become more contactless in the future, with fresh means of treating patients and providing healthcare services emerging. This is a popular yet difficult research subject since it necessitates interdisciplinary competence.<sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup> \n<\/p><p>Additionally, as big data continues to increasingly find its way into healthcare, additional challenges exist in the effective use of big data within ICT frameworks. For example, big data in healthcare is intimidating not only because of its sheer magnitude, but also due to the variety of data types and the pace with which it must be managed. To gain people' trust and give quality healthcare services, all health service providers are now putting in extra effort to use the most up-to-date technologies to effectively use big data to provide quality health services and advanced treatments.\n<\/p><p>Various requirements drive innovation in this industry, such as finding appropriate accommodation with standardization and coordinating the acquisition and implementation of newer healthcare systems and services on a national\/international level. With COVID-19 still threatening disruption in the healthcare sector, investments in this sector are gaining steam with new-age healthcare units in many nations, and growing economies such as India and China will continue to play a vital role in providing quality healthcare services to its citizens in the future. At the same time, those new-age healthcare units and systems will aid in dramatically lowering costs, making public healthcare systems more dependable, and instilling citizens' confidence in using inexpensive, high-quality healthcare.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Related_work\">Related work<\/span><\/h2>\n<p>\"Big data\" is a term used to describe a significant volume of data that is collected and stored yet has outgrown standard data management and analysis solutions. Solutions like Hadoop and Spark, according to Roger Fyre and Mark McKenney, have arisen to solve some of these big data concerns.<sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[16]<\/a><\/sup> For example, researchers have used Hadoop to implement a variety of parallel processing algorithms to efficiently handle geographical data.<sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup> Multistage map and reduce algorithms, which generate on-demand indexes and retain persistent indexes, are the end result of these techniques.<sup id=\"rdp-ebb-cite_ref-19\" class=\"reference\"><a href=\"#cite_note-19\">[19]<\/a><\/sup>\n<\/p><p>Other techniques such as predictive analytics and <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_mining\" title=\"Data mining\" class=\"wiki-link\" data-key=\"be09d3680fe1608addedf6f62692ee47\">data mining<\/a> have also been employed. Much of the current work on predictive analytics, particularly in clinical contexts, is aimed at improving health and financial outcomes, which will aid in making better decisions.<sup id=\"rdp-ebb-cite_ref-20\" class=\"reference\"><a href=\"#cite_note-20\">[20]<\/a><\/sup> Data mining, which is defined as the processing and modeling of huge amounts of medical\/health data to identify previously unknown patterns or associations, is another important machine learning approach.<sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup> Data mining has been used, for example, in the collection of data for diseases such as cancer and neurological disorders in order to improve disease prognosis.<sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup> Cancer detection and diagnosis, as well as other health-related issues, have been made possible because to these breakthroughs.<sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[25]<\/a><\/sup> Machine learning is also crucial in the testing and development of various models that take into account clinical and other important medical characteristics for decision making.\n<\/p><p>Deep learning is now also being used to solve more difficult problems in the arena of health informatics.<sup id=\"rdp-ebb-cite_ref-:1_26-0\" class=\"reference\"><a href=\"#cite_note-:1-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup> For example, advances in medical imaging and its <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">data management<\/a> have made positive contributions to decision making. Today, medical imaging incorporates capabilities such as image segmentation, image registration, annotation, and database retrieval, holding greater promise for decision makers. As such, new deep learning and machine learning models can be employed with medical imaging for speedier decision making.<sup id=\"rdp-ebb-cite_ref-:1_26-1\" class=\"reference\"><a href=\"#cite_note-:1-26\">[26]<\/a><\/sup> However, this means researchers in the fields of data science, machine learning, and deep learning remain in high demand for developing effective algorithms that adapt to changing data.\n<\/p><p>Holzinger <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-28\" class=\"reference\"><a href=\"#cite_note-28\">[28]<\/a><\/sup> examined many approaches to developing an explainable prediction model for the medical domain. Prediction explanations can be useful in a variety of situations, including teaching, learning, research, and even the courtroom. Similarly, the demand for interpretable and explainable models is growing in the medical field. However, these models must be able to re-enact the decision-making and knowledge-extraction processes. Ribeiro <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:2_29-0\" class=\"reference\"><a href=\"#cite_note-:2-29\">[29]<\/a><\/sup> have emphasized this requirement, discussing how machine learning models are essentially black boxes. Understanding the reasons for predictions can help to build trust, better assess model performance, and construct better, more accurate, and correct models by providing insights into the model. They propose the LIME algorithm<sup id=\"rdp-ebb-cite_ref-:2_29-1\" class=\"reference\"><a href=\"#cite_note-:2-29\">[29]<\/a><\/sup> for explaining predictions of any model. Similarly, though dealing with neural machine translation, the proposed model of Bahdanau <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup> can be used in a variety of other applications such as healthcare.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction_to_HL7_FHIR_architecture\">Introduction to HL7 FHIR architecture<\/span><\/h2>\n<p>In the last two decades, EHRs have been widely implemented in the United States to improve healthcare quality, increase patient happiness, and reduce healthcare costs.<sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup> As growing countries such as India, China, and Bangladesh experiment with innovative ways to establish EHR systems, they will significantly aid in the development of effective public health systems in those countries. In all cases, at the core of most effective EHRs is Health Level 7's (HL7's) <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_7#Fast_Healthcare_Interoperability_Resources_.28FHIR.29\" title=\"Health Level 7\" class=\"wiki-link\" data-key=\"ce348e672e47598e4b42cbd03c292ec4\">Fast Health Interoperability Resources (FHIR) architecture<\/a>.\n<\/p><p>The basic idea behind HL7's FHIR (pronounced \u201cfire\u201d) was to create a set of resources and then create HTTP-based REST <a href=\"https:\/\/www.limswiki.org\/index.php\/Application_programming_interface\" title=\"Application programming interface\" class=\"wiki-link\" data-key=\"36fc319869eba4613cb0854b421b0934\">application programming interfaces<\/a> (APIs) to access and use these resources. FHIR uses components called \"resources\" to access and perform operations on patient's health data at the granular level. This feature distinguishes FHIR from all other standards because it was not present in any earlier version of HL7 (v2, v3) or the HL7 clinical document architecture (CDA).<sup id=\"rdp-ebb-cite_ref-:3_34-0\" class=\"reference\"><a href=\"#cite_note-:3-34\">[34]<\/a><\/sup>\n<\/p><p>The fundamental building blocks of FHIR are the so-called resources, which are generic definitions of common health care categories (e.g., patient, observation, practitioner, device, condition). For data interchange and resource serialization, FHIR employs JavaScript object syntax and XML structures. FHIR not only supports RESTful resource exchange but also manages and documents an interoperability paradigm.\n<\/p><p>FHIR has grown in popularity and is being increasingly used by the healthcare industry since its inception. In 2018, six major technology companies\u2014including Microsoft, IBM, Amazon, and Google\u2014vowed to remove barriers to healthcare interoperability and signed a statement mentioning FHIR as an emerging standard for the interchange of health data. With the incorporation of Substitutable Medical Applications Reusable Technologies (SMART), a platform for interoperable applications<sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup>, FHIR can be expected to attract even more attention to digital health tools in the future. As is, the use of FHIR for medical data transmission has the potential to deliver benefits in a wide range of disciplines, including mobile health apps, EHRs, precision medicine, wearable devices, big data analytics, and clinical decision support.\n<\/p><p>The primary goal of FHIR is to reduce implementation complexity while maintaining information integrity. Furthermore, this new standard integrates the benefits of existing HL7 standards (v2, v3, and CDA) and is projected to overcome their drawbacks. FHIR enables developers to create standardized browser applications that allow users to access clinical data from any healthcare system, regardless of the operating systems and devices used. Figure 1 represents the general architecture of FHIR.<sup id=\"rdp-ebb-cite_ref-:3_34-1\" class=\"reference\"><a href=\"#cite_note-:3-34\">[34]<\/a><\/sup>\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Yogesh_FrontPubHlth2022_10.jpg\" class=\"image wiki-link\" data-key=\"848fb90d3d970a736d5c0d2e489eaba1\"><img alt=\"Fig1 Yogesh FrontPubHlth2022 10.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/29\/Fig1_Yogesh_FrontPubHlth2022_10.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> General architecture of the Fast Health Interoperability Resources (FHIR) standard<sup id=\"rdp-ebb-cite_ref-:3_34-2\" class=\"reference\"><a href=\"#cite_note-:3-34\">[34]<\/a><\/sup><\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"FHIR_for_patient_access_to_medical_records\">FHIR for patient access to medical records<\/span><\/h3>\n<p>FHIR is an HL7 standard for electronically transferring healthcare information. The Centers for Medicare and Medicaid Services (CMS) Interoperability and Patient Access final regulation, announced in 2020, mandates all CMS-regulated payers to use FHIR version 4. Unlike earlier releases, the fourth iteration is backward compatible, ensuring that software suppliers' solutions will not become obsolete when a new FHIR version is released.\n<\/p><p>The FHIR standard defines a collection of HTTP-based RESTful APIs that allow healthcare platforms to exchange and share data in XML or JSON format. FHIR offers mobile apps, which users can obtain from the Apple App Store or Google Play in order to access their medical records and claims data.\n<\/p><p>FHIR's basic exchangeable data piece is known as a resource. Each resource is formatted similarly and contains roughly the same amount of data. Each resource offers information about patient demographics, diagnosis, prescriptions, allergies, care plans, family history, claims, and so on, depending on the kind. They span the complete healthcare <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> and can be used independently or as part of a larger document.\n<\/p><p>Each resource is given a unique ID, and many health systems, insurers, patients, and software developers can access the underlying data element using an API. Figure 2 represents the data layers and resources of FHIR.<sup id=\"rdp-ebb-cite_ref-:3_34-3\" class=\"reference\"><a href=\"#cite_note-:3-34\">[34]<\/a><\/sup>\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Yogesh_FrontPubHlth2022_10.jpg\" class=\"image wiki-link\" data-key=\"46a85f85e127ac98c3f854609685de17\"><img alt=\"Fig2 Yogesh FrontPubHlth2022 10.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a1\/Fig2_Yogesh_FrontPubHlth2022_10.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> FHIR data layers and resources<sup id=\"rdp-ebb-cite_ref-:3_34-4\" class=\"reference\"><a href=\"#cite_note-:3-34\">[34]<\/a><\/sup><\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"FHIR_resources\">FHIR resources<\/span><\/h3>\n<p>A resource is the smallest discrete concept that can be independently maintained and is the lowest feasible unit of a FHIR-based transaction.<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup> As a result, a resource is a known identity that provides useful data. Each resource has distinct bounds and differs from all others. A resource should be provided in sufficient depth to specify and enable the process's medical data interchange. The FHIR community has specified over 150 resources to date, according to the most recent FHIR version (R4).<sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup>\n<\/p><p>There are five key categories in which these resources can be found: \n<\/p>\n<ol><li><b>Administrative<\/b>: location, organization, device, patient, and group<\/li>\n<li><b>Clinical<\/b>: CarePan, diagnostics, medication, allergy, and family history<\/li>\n<li><b>Financial<\/b>: billing, payment, and support<\/li>\n<li><b>Infrastructure<\/b>: conformance, document, and message profile<\/li>\n<li><b>Workflow<\/b>: encounter, scheduling, and order<\/li><\/ol>\n<p>FHIR is fast gaining popularity due to its dynamic properties. FHIR is projected to quickly become a symbol for clinical data interchange in the healthcare industry.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Workflow_description\">Workflow description<\/span><\/h3>\n<p>Workflow is a critical component of healthcare; orders, care regimens, and referrals drive the majority of activity in inpatient settings, as well as a significant amount of activity in community care. FHIR is concerned with workflow when it is necessary to share information about workflow state or relationships, when it is necessary to coordinate or drive the execution of workflow across systems, and when it is necessary to specify permissible actions, dependencies, and behavior requirements.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Workflow_state_and_relationships\">Workflow state and relationships<\/span><\/h4>\n<p>FHIR does not have to be used for workflow execution. Orders, care plans, test findings, <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospital<\/a> admissions, claim payments, and other documents can all be exchanged utilizing FHIR resources without the need for a FHIR transaction to solicit fulfillment of those orders or request payment of those claims. Because it necessitates a greater level of standardization, interoperable support for workflow execution is a more advanced FHIR activity. Interoperable workflow execution necessitates the standardization of processes, roles, and activities across multiple systems, rather than just the data to be exchanged.\n<\/p><p>Even if FHIR is not used for workflow execution, there is still a requirement to standardize workflow data elements: how does an event or a result point to the order that allowed it? How are parent and child steps tied together? How does a care plan know which protocol it is following?\n<\/p><p>FHIR distinguishes three types of resources engaged in activities: requests, events, and definitions. Each of these categories is associated with a \u201cpattern.\u201d Resources in that category are encouraged to follow their specific pattern. These patterns provide conventional elements that are common to the majority of resources in each category. Work groups are anticipated to align with common domain behavior, and requirements as more authoritative than \u201cdesired\u201d architectural patterns, and as such, strict conformance is not necessary. When a pattern capability is assessed to be \u201cnot common, but nonetheless relevant\u201d for a given resource, it may be supplied through extensions rather than core parts. Figure 3 represents the workflow relations of the FHIR standard.<sup id=\"rdp-ebb-cite_ref-:4_38-0\" class=\"reference\"><a href=\"#cite_note-:4-38\">[38]<\/a><\/sup>\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Yogesh_FrontPubHlth2022_10.jpg\" class=\"image wiki-link\" data-key=\"0105941df45041eb886f294b7b304f86\"><img alt=\"Fig3 Yogesh FrontPubHlth2022 10.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7d\/Fig3_Yogesh_FrontPubHlth2022_10.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> Workflow relations with the FHIR standard<sup id=\"rdp-ebb-cite_ref-:4_38-1\" class=\"reference\"><a href=\"#cite_note-:4-38\">[38]<\/a><\/sup><\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Overview_of_health_informatics\">Overview of health informatics<\/span><\/h2>\n<p>Health informatics involves more than merely automating routine tasks. With contemporary technology developments in machine learning and deep learning, it is possible to redesign systems using methodologies that were previously impossible or not even considered.<sup id=\"rdp-ebb-cite_ref-:1_26-2\" class=\"reference\"><a href=\"#cite_note-:1-26\">[26]<\/a><\/sup> Machine learning and deep learning are computationally expensive, however, though they can now be handled by the latest IBM POWER9 processors with GPU capabilities, which was previously impossible because the data was not available in electronic form and the number of possible symptoms\/incident patterns was too big to manage. Early detection of patterns that can anticipate what kind of treatment or diagnosis can be offered to such patients has improved dramatically.<sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup>\n<\/p><p>In the future, modern healthcare units will make use of such a framework for successful delivery of treatments for society as a whole, making effective use of data obtained from such systems by extracting insights that assist decision makers such as doctors, hospital owners, and health policymakers. However, classification and regression tree (CART) components are required for successful clinical decision support. For example, vital signs must be clearly classified to be applied to prediction.<sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[41]<\/a><\/sup> From there, the prediction of a patient's breathing rate obtained from sensors acts as an example of regression.<sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup> In the future, this sort of CART-based Bayesian inference will be used to make better predictions in the domain of health informatics.\n<\/p><p>However, several not-so-commonly employed principles will have to first be implemented in informatics systems in order to answer some the most pressing future difficulties in health informatics:\n<\/p>\n<ul><li><b>Multi-task learning<\/b>: Traditional machine learning frameworks consider only one learner attempting to solve a single task. However, in many applications, there are multiple tasks that label the same data instances differently. When the tasks are related, the information learned from each task can be used to improve learning of other tasks. Learning relevant tasks concurrently, rather than learning each task independently, is thus advantageous. Multi-task learning makes use of the intrinsic relationships between multiple tasks to improve generalization performance. It benefits all tasks by leveraging task relatedness and shared information across relevant tasks.<sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[43]<\/a><\/sup><\/li>\n<li><b>Transfer learning<\/b>: Traditional machine learning technology has had a lot of success and has been used in many practical applications, but it still has certain limits in some real-world settings. Machine learning works best when there are a lot of labeled training cases with the same distribution as the test data. In many cases, however, gathering sufficient training data is costly, time-consuming, or even impossible. Semi-supervised learning can help to alleviate this difficulty by removing the requirement for large amounts of labeled data. A semi-supervised approach typically requires a small amount of labeled data and a large amount of unlabeled data to improve learning accuracy. However, in many cases, unlabeled instances are difficult to collect, making the resulting traditional models unsatisfactory.<sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup><\/li>\n<li><b>Multi-agent hybrid systems<\/b>: Multi-agent systems are networks of interconnected autonomous agents in which the behavior of neighboring agents influences the dynamics of each agent. Because of the increasing importance of multi-agent systems, there is a growing interest in coordination control to ensure consensus, flocking, containment, formation, rendezvous, and so on. To better understand multi-agent coordination, a variety of dynamic models of agents have been developed over the last two decades. Furthermore, many mathematical methods are used in the analysis and control of multi-agent systems. For more information, see research by Qin <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[45]<\/a><\/sup> and the references within the research of Zheng <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-46\" class=\"reference\"><a href=\"#cite_note-46\">[46]<\/a><\/sup><\/li>\n<li><b>Representation learning<\/b>: Patient-specific data such as vital signs, medications, <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratory<\/a> measures, observations, clinical notes, fluid balance, procedure codes, diagnostic codes, and so on are all included in modern EHR systems. Clinicians originally employed the codes and their hierarchies, as well as their associated <a href=\"https:\/\/www.limswiki.org\/index.php\/Ontology_(information_science)\" title=\"Ontology (information science)\" class=\"wiki-link\" data-key=\"52d0664bde4b458e81fbc128b911a4a6\">ontologies<\/a>, for internal administrative and invoicing functions. Recent deep learning algorithms, on the other hand, have attempted to project discrete codes into vector space, identify intrinsic commonalities between medical concepts, more accurately depict patients' health, and perform more precise predicting tasks. Word embedding and unsupervised learning have been used to examine medical concepts and patient representations in general.<sup id=\"rdp-ebb-cite_ref-47\" class=\"reference\"><a href=\"#cite_note-47\">[47]<\/a><\/sup><\/li><\/ul>\n<p>Health informatics has a number of long-term benefits in terms of research and healthcare delivery that can be used to create a sustainable ecosystem. ICTs aid in the enrichment of relevant data for analysis and decision making by health professionals. Following the COVID-19 pandemic, new-age healthcare units will arise, with increased investment and research spending, making public healthcare more accessible. As a result, solutions are required to manage the massive amounts of data created by medical equipment and healthcare systems, allowing for effective storage and retrieval in real-time data analysis and decision making.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Informatics_approaches\">Informatics approaches<\/span><\/h3>\n<p>To make electronic health data more easily usable for research, recent publications have identified the need for effective adoption and use of standards, essential data and research services, clear and consistent policies regarding data access and use, and transparent and effective governance structures.<sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[48]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:7_49-0\" class=\"reference\"><a href=\"#cite_note-:7-49\">[49]<\/a><\/sup>\n<\/p><p>To achieve data quality criteria, electronic health data utilized in research frequently require standardized ontologies, additional contextual information, field transformations, and missing or contradictory data to be handled.<sup id=\"rdp-ebb-cite_ref-50\" class=\"reference\"><a href=\"#cite_note-50\">[50]<\/a><\/sup> For research-related data or functions, such as cohort identification and repeated extracts of source data over time, system development is frequently required.<sup id=\"rdp-ebb-cite_ref-:7_49-1\" class=\"reference\"><a href=\"#cite_note-:7-49\">[49]<\/a><\/sup> Organizations with expertise utilizing and enhancing their health IT infrastructure for research have shared their lessons learned in these areas, adding value to organizations with similar goals but less experience or resources.<sup id=\"rdp-ebb-cite_ref-51\" class=\"reference\"><a href=\"#cite_note-51\">[51]<\/a><\/sup>\n<\/p><p>For example, when preparing data for research use, organizations must understand the clinical context and structure of electronic health data, just as they do for other data uses such as decision support or population health. Individual researchers and data analysts can be relieved of their load by informatics support that spans research and operational usage of data. It is vital to evaluate and develop informatics tools and approaches by establishing processes that allow for coordinated governance and decisions informed by research users.\n<\/p><p>Investing in infrastructure to enable the use of electronic health data for research has also been shown to be beneficial to researchers by providing them with the necessary tools and expertise, to patients by providing clinical trial participation opportunities, to clinicians by enabling more rapid translation of research into practice, and to population health analysts by facilitating patient cohort views. In order to reduce project-specific IT costs, using health IT to assist research necessitates greater flexibility, increasing use of standards, and reusable ways for getting, preparing, and evaluating data.<sup id=\"rdp-ebb-cite_ref-52\" class=\"reference\"><a href=\"#cite_note-52\">[52]<\/a><\/sup>\n<\/p><p>Any use of operational data in research necessitates the establishment of a privacy and security framework, as well as data governance monitoring. Two initiatives\u2014Informatics for Integrating Biology and the Bedside (i2b2) and Observational Health Data Sciences and Informatics (OHDSI)\u2014have developed informatics tools and approaches that allow researchers to query organizational participants and support transformation or analytics of relevant data to facilitate research.<sup id=\"rdp-ebb-cite_ref-53\" class=\"reference\"><a href=\"#cite_note-53\">[53]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-54\" class=\"reference\"><a href=\"#cite_note-54\">[54]<\/a><\/sup>\n<\/p><p>Specifically, i2b2 has standardized data models and distributed computational tools that enable for the anonymous identification of potential genomic study participants at the institution level. OHDSI also employs a single data model, which incorporates information such as health economics and health systems. The methodologies utilized in these programs demonstrate the kind of functionality that may be required in health IT systems to better support research, as well as the types of concerns with the quality of electronic health data that regularly arise.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Status_QUO_in_health_informatics:_An_Indian_perspective\">Status QUO in health informatics: An Indian perspective<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Health_care_delivery_systems\">Health care delivery systems<\/span><\/h3>\n<p>Despite having a solid telecommunication infrastructure, many existing healthcare systems are based on manual record keeping. It would seem the value of health informatics in healthcare delivery has yet to be recognized by many policymakers.<sup id=\"rdp-ebb-cite_ref-:8_55-0\" class=\"reference\"><a href=\"#cite_note-:8-55\">[55]<\/a><\/sup>\n<\/p><p>In countries such as India, health informatics is a new and emerging discipline. Its future prospects are very bright, thanks to the development of excellent infrastructure here. However, in order to implement a robust framework, this necessitates a multidisciplinary interaction with various stakeholders.\n<\/p><p>Information systems development could be another area where research is being conducted to improve the way data flows from various sources such as devices and medical equipment, allowing doctors and decision makers to make rational decisions on critical cases or equipment purchases in the future.\n<\/p><p>Digitizing all medical data also aids in the creation of a structure for patient-related data in a hospital that can be easily retrieved and searched. Finally, the development of some kind of EHR can be accomplished through the development of information systems.<sup id=\"rdp-ebb-cite_ref-56\" class=\"reference\"><a href=\"#cite_note-56\">[56]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Applications_of_health_informatics\">Applications of health informatics<\/span><\/h3>\n<p>Health informatics in India can become cost-effective and ensure proper service delivery, which aids in beneficial behavioral change through the use of ICTs.<sup id=\"rdp-ebb-cite_ref-57\" class=\"reference\"><a href=\"#cite_note-57\">[57]<\/a><\/sup> We can create novel applications that can be used effectively by utilizing local talent and effective use of ICT in remote parts of India.<sup id=\"rdp-ebb-cite_ref-58\" class=\"reference\"><a href=\"#cite_note-58\">[58]<\/a><\/sup> Various governance issues can be addressed in the future with certain checks and balances in the data collection and analysis process.<sup id=\"rdp-ebb-cite_ref-59\" class=\"reference\"><a href=\"#cite_note-59\">[59]<\/a><\/sup> The following are some of the areas where health informatics can be used:\n<\/p>\n<ul><li>Epidemiological disease prediction<\/li>\n<li>Disaster management<\/li>\n<li>Awareness in healthcare processes<\/li>\n<li>Healthcare in remote areas<\/li>\n<li>EHRs and their linkages with health systems<\/li>\n<li>Health statistics<\/li>\n<li>Education and training<\/li>\n<li>Development of <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_decision_support_system\" title=\"Clinical decision support system\" class=\"wiki-link\" data-key=\"095141425468d057aa977016869ca37d\">clinical decision support systems<\/a> (CDSS)<\/li>\n<li>Public health research<\/li>\n<li>Visualization tools for doctors<\/li>\n<li>Recommendation systems for health informatics<\/li>\n<li>Precision drug prediction<\/li><\/ul>\n<p>The potential of this emerging area has far-reaching benefits over a long period of time, and new and novel solutions can be built using various machine\/deep learning models. There is a lot of work to be done in this area where we can use cutting-edge technology to aid\/assist in the development of robust products and frameworks for public health policy.<sup id=\"rdp-ebb-cite_ref-60\" class=\"reference\"><a href=\"#cite_note-60\">[60]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-61\" class=\"reference\"><a href=\"#cite_note-61\">[61]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-62\" class=\"reference\"><a href=\"#cite_note-62\">[62]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[63]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Future_trends_and_directions_in_health_informatics\">Future trends and directions in health informatics<\/span><\/h3>\n<p>There are many current trends in the field of health informatics that can be used to develop sustainable products, services, and health-related policies for effective implementation across the country and internationally. A few of them are listed below, and many more trends may emerge in the near future as a result of discussions with multiple stakeholders.\n<\/p>\n<ul><li>Data standards and Interoperability<\/li>\n<li>Processes to transform medical\/clinical data<\/li>\n<li>Toolkits and pipelines for data management<\/li>\n<li>Standardized reporting methodologies<\/li>\n<li>Appropriate use of informatics expertise<\/li><\/ul>\n<p>More trends may emerge in the future, taking into account the most recent technological advancements. Because health informatics is a new and emerging field, more research challenges may emerge, bringing forth newer perspectives. To solve more difficult problems in this area, future researchers will likely prefer machine\/deep learning methods\/models.<sup id=\"rdp-ebb-cite_ref-:1_26-3\" class=\"reference\"><a href=\"#cite_note-:1-26\">[26]<\/a><\/sup> There are numerous other research directions being pursued in relation to various aspects of healthcare data such as quality, veracity, privacy, and timeliness. The following are some of the most notable data characteristics of healthcare data<sup id=\"rdp-ebb-cite_ref-:5_9-1\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-64\" class=\"reference\"><a href=\"#cite_note-64\">[64]<\/a><\/sup>:\n<\/p><p>1. <b>Complexity and noise<\/b>: Because healthcare data is multisource and multimodal, it has a high level of complexity and noise. Furthermore, there are issues with impurity and missing values in high-volume data. It is difficult to deal with all of these issues, both in terms of scale and accuracy, despite the fact that a number of methods have been developed to improve data accuracy and usability.<sup id=\"rdp-ebb-cite_ref-65\" class=\"reference\"><a href=\"#cite_note-65\">[65]<\/a><\/sup> Because the quality of data dictates the quality of information, which in turn affects decision-making, it is vital to develop efficient big data cleansing ways to improve data quality in order to make effective and correct decisions.<sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[66]<\/a><\/sup>\n<\/p><p>2. <b>Heterogeneity<\/b>: Traditional healthcare data is frequently fragmented into multiple forms due to a lack of standardization. As a result, it is both reasonable and important to investigate and adopt universal data standards. However, due to the complexity of developing universal data standards, it is a difficult undertaking. Not only is healthcare data diverse, but there are also numerous technical challenges to integrating that data for specific purposes.<sup id=\"rdp-ebb-cite_ref-67\" class=\"reference\"><a href=\"#cite_note-67\">[67]<\/a><\/sup> Even with standardized data formats, the multi-modal character of data makes efficient fusion difficult<sup id=\"rdp-ebb-cite_ref-:9_68-0\" class=\"reference\"><a href=\"#cite_note-:9-68\">[68]<\/a><\/sup>, necessitating the development of advanced analytics that cope with vast amounts of multi-modal data. The integration and synthesis of multi-source and multi-modal healthcare data on a larger scale would be a significant issue.\n<\/p><p>3. <b>Longitudinal analysis<\/b>: Longitudinal data is the collection of repeated measurements of participant outcomes and possibly treatments or exposures<sup id=\"rdp-ebb-cite_ref-69\" class=\"reference\"><a href=\"#cite_note-69\">[69]<\/a><\/sup>, which means that \"the outcome variable is repeatedly measured on the same individual on multiple occasions.\"<sup id=\"rdp-ebb-cite_ref-70\" class=\"reference\"><a href=\"#cite_note-70\">[70]<\/a><\/sup> In recent decades, longitudinal data analysis, particularly statistical longitudinal data analysis, has gotten a lot of attention. Longitudinal studies are used to characterize normal growth and aging, as well as to evaluate the effectiveness of risk factors and therapies. It is extremely important in <a href=\"https:\/\/www.limswiki.org\/index.php\/Epidemiology\" title=\"Epidemiology\" class=\"wiki-link\" data-key=\"123badb8bf0b37a513182dbcfc3875bc\">epidemiology<\/a>, clinical research, and therapeutic evaluation. With big data analytic tools, it is possible to perform longitudinal care analysis across patients and diagnoses to identify the optimal care options.\n<\/p><p>4. <b>Scale<\/b>: Healthcare data is continuously expanding in quantity and scope.<sup id=\"rdp-ebb-cite_ref-:9_68-1\" class=\"reference\"><a href=\"#cite_note-:9-68\">[68]<\/a><\/sup> The fact that data volume is growing faster than processing power is a significant challenge in managing vast amounts of data. Several fundamental adjustments are occurring to handle this enormous transition.<sup id=\"rdp-ebb-cite_ref-71\" class=\"reference\"><a href=\"#cite_note-71\">[71]<\/a><\/sup> First, in recent years, CPU technology has increasingly turned its focus to parallel data processing within nodes and the packing of numerous sockets. Second, the shift to <a href=\"https:\/\/www.limswiki.org\/index.php\/Cloud_computing\" title=\"Cloud computing\" class=\"wiki-link\" data-key=\"fcfe5882eaa018d920cedb88398b604f\">cloud computing<\/a> allows for information sharing and the consolidation of multiple workloads into large-scale clusters. Third, the transformation of the traditional I\/O subsystem from hard disk drives (HDDs) to solid-state drives (SSDs), as well as other storage technologies, is reforming data processing system design and operation.\n<\/p><p>5. <b>Real-time requirement<\/b>: The velocity of big data in health informatics reflects not only the rate of data collecting and processing, but also the timeliness of replies. There are various instances that call for a quick choice. For example, it would be immensely desirable to monitor and analyze a person's health condition in real time or near real time in order to predict potential disease. It would also be critical to raise the alert for a potential influenza outbreak by examining public health statistics. Although real-time analytic applications are still in their infancy in the big data era, they represent the strongest trend and most promising direction in health informatics' future.<sup id=\"rdp-ebb-cite_ref-:10_72-0\" class=\"reference\"><a href=\"#cite_note-:10-72\">[72]<\/a><\/sup>\n<\/p><p>6. <b>Privacy<\/b>: Data privacy is another major worry for future big data analytics in health informatics.<sup id=\"rdp-ebb-cite_ref-:11_73-0\" class=\"reference\"><a href=\"#cite_note-:11-73\">[73]<\/a><\/sup> Although strong laws control more formalized EHR data, extra attention should be taken and standards should be enforced to regularize the use and dissemination of personal and sensitive information obtained from diverse sources. In addition to data privacy, there are a number of other challenges\u2014 such as data protection, data security, data safety, and the protection of doctors from liability resulting from manipulated data\u2014that necessitate the use of specialized big data analytics to address these complicated constraints.<sup id=\"rdp-ebb-cite_ref-:11_73-1\" class=\"reference\"><a href=\"#cite_note-:11-73\">[73]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-74\" class=\"reference\"><a href=\"#cite_note-74\">[74]<\/a><\/sup>\n<\/p><p>7. <b>Visualization<\/b>: The visualization of healthcare data is crucial for exploratory or discovery analytics, which aim to investigate and discover elements that are hidden or encrypted in the data.<sup id=\"rdp-ebb-cite_ref-75\" class=\"reference\"><a href=\"#cite_note-75\">[75]<\/a><\/sup> Effective visualization tools will enable clinicians and physicians to explore data without the need for IT assistance.<sup id=\"rdp-ebb-cite_ref-:10_72-1\" class=\"reference\"><a href=\"#cite_note-:10-72\">[72]<\/a><\/sup>\n<\/p><p>8. <b>Multidisciplinary and human-computer interaction<\/b>: Big data in health informatics is expected to be a multidisciplinary job requiring ongoing contributions from multiple topic experts.<sup id=\"rdp-ebb-cite_ref-76\" class=\"reference\"><a href=\"#cite_note-76\">[76]<\/a><\/sup> They include, but are not limited to, engineering scientists who provide basic big data infrastructure to collect, store, share, and manage big data; computer science data scientists who provide solutions for processing and analyzing high-volume, high-velocity healthcare data using a variety of data mining and machine-learning techniques; and clinicians and physicians from the medical domain who provide professional healthcare data analysis, personalized care, and make recommendations. Computer algorithms can struggle to find patterns and interpret results at times; consequently, it is a desirable feature for an advanced big data analysis system to be able to enable input from numerous human specialists, exchange of viewpoints, and collaborative exploration of outcomes. Furthermore, in the health sector, we sometimes do not have massive data: we are confronted with a small number of datasets or unusual events, where, for example, machine-learning algorithms suffer from insufficient training samples. In such circumstances, we require more than just automatic machine learning; we also require a person in the loop. In other words, interactive machine learning (iML) or \u201chuman in the loop\u201d techniques can be used in health informatics when automatic machine learning algorithms cannot handle rare occurrences on their own and a human expert is required to interact in the learning process.<sup id=\"rdp-ebb-cite_ref-77\" class=\"reference\"><a href=\"#cite_note-77\">[77]<\/a><\/sup> The interplay between computer algorithms and human specialists has the potential to improve the learning process.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Challenges_in_health_informatics\">Challenges in health informatics<\/span><\/h2>\n<p>There are numerous challenges in this area, particularly in a country like India, where a large population is denied affordable healthcare. This can serve as a starting point for developing and implementing robust health informatics applications, products, and research and development investments. The start-up\/venture costs, people, and equipment are very high, and it is a niche sector in which many people are hesitant to venture into; however, such a space\/sector can be leveraged, making very good business sense.<sup id=\"rdp-ebb-cite_ref-78\" class=\"reference\"><a href=\"#cite_note-78\">[78]<\/a><\/sup>\n<\/p><p>To improve the way health services are delivered and implemented to the public, a multidisciplinary approach involving various sectors\/stakeholders is required. These informatics systems can be used for a variety of purposes. Medical\/healthcare data will be more structured and democratized by competent authorities. The advancement of EHRs and web-based health monitoring systems will also aid in rational decision making and policy framework implementation.<sup id=\"rdp-ebb-cite_ref-:6_12-1\" class=\"reference\"><a href=\"#cite_note-:6-12\">[12]<\/a><\/sup> \n<\/p><p>However, there may be numerous bottlenecks in the development of ICT systems for health informatics.<sup id=\"rdp-ebb-cite_ref-:8_55-1\" class=\"reference\"><a href=\"#cite_note-:8-55\">[55]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-79\" class=\"reference\"><a href=\"#cite_note-79\">[79]<\/a><\/sup> For example, the majority of stakeholders are unconvinced about the benefits of internet technologies in health care and are unfamiliar with how to use such new technology.<sup id=\"rdp-ebb-cite_ref-80\" class=\"reference\"><a href=\"#cite_note-80\">[80]<\/a><\/sup> Concerns about security and privacy may also arise as robust healthcare systems are developed in the future.<sup id=\"rdp-ebb-cite_ref-:6_12-2\" class=\"reference\"><a href=\"#cite_note-:6-12\">[12]<\/a><\/sup>\n<\/p><p>Proper techniques are essential to ensure patient data confidentiality, and system security may become a concern when data policy standardization increases. Many new challenges can be encountered while developing novel and innovative ways to promote public health through the use of information technology (IT) and other computing technological advances such as cloud computing, <a href=\"https:\/\/www.limswiki.org\/index.php\/Data_visualization\" title=\"Data visualization\" class=\"wiki-link\" data-key=\"4a3b86cba74bc7bb7471aa3fc2fcccc3\">data visualization<\/a>, and health informatics innovations. Future research is required because the health informatics domain is still in its early stages, where more difficult problems can be solved and newer products and services can be spawned as a business venture. Additionally, deep learning in health informatics has its own set of challenges.<sup id=\"rdp-ebb-cite_ref-:1_26-4\" class=\"reference\"><a href=\"#cite_note-:1-26\">[26]<\/a><\/sup>\n<\/p><p>Additionally, despite significant investments in information technology, patient safety and productivity have not improved. Preventable medical errors are the third leading cause of death in the United States, after heart disease and cancer, killing over 400,000 people each year. These blunders cost the United States over one trillion dollars per year. To combat this problem, the federal government has mandated that the healthcare industry transition to electronic health records (EHRs) and use these records to improve patient processes and outcomes (i.e., meaningful use). Emerging economies have to allocate and give incentives to healthcare units\/organizations to promote the use of EHRs.\n<\/p><p>The COVID-19 pandemic has also revealed challenges in maintaining quality patient outcomes through health information management and health informatics. Roadblocks have included a lack of standards for information exchange between providers and PHAs (public health authorities); issues with data collection and data quality, particularly in terms of completeness and timeliness; and gaps in effectiveness of governance, public policies, and regulations. \n<\/p><p>The latter in particular highlights a lack of procedures to support efficient data sharing, <a href=\"https:\/\/www.limswiki.org\/index.php\/Contact_tracing\" title=\"Contact tracing\" class=\"wiki-link\" data-key=\"6527a70b24b6f9b489bcec301240b0d8\">contact tracing<\/a>, and data governance, as well as providers' concerns about privacy regulations, which resulted in insufficient data sharing. Governance and public policy hurdles stem from chronic underfunding of public health infrastructure, as well as a lack of adequate investments in resources (particularly qualified employees) and facilities. A key difficulty is also found in the lack of international coordination. Many overlapping and interrelated legal, ethical, scientific, technical, technological, health equality, and privacy elements have influenced how health information has been managed or mismanaged during the COVID-19 pandemic. Other long-standing systemic difficulties in health information management will need to be addressed in order to operationalize many of the data and information system recommendations.<sup id=\"rdp-ebb-cite_ref-81\" class=\"reference\"><a href=\"#cite_note-81\">[81]<\/a><\/sup>\n<\/p><p>Another challenge in effectively implementing health informatics rests in the financial investment required to design, execute, and sustain e-health programs. For example, Anderson cited a lack of financial backing and high initial expenses as hurdles to implementing ICT in health care.<sup id=\"rdp-ebb-cite_ref-:12_82-0\" class=\"reference\"><a href=\"#cite_note-:12-82\">[82]<\/a><\/sup> While health informaticians and information professionals may see future benefits from investments in ICTs, health professionals and managers may be skeptical, especially if they are satisfied with current methods of working and wish to maintain the status quo; they may see such initiatives as diverting financial resources away from under-resourced clinical care.<sup id=\"rdp-ebb-cite_ref-83\" class=\"reference\"><a href=\"#cite_note-83\">[83]<\/a><\/sup>\n<\/p><p>Continued resistance to the establishment of ICT systems by health professionals and managers can lead to further issues once the systems are in place, and the restricted adoption of health informatics applications has meant that their potential is not always achieved. Decision support systems, for example, may be ignored or overridden, and evidence-based information may have limited applicability for an individual patient. Clinicians make life-changing judgments or act in life-threatening situations, and if they don't comprehend the reasons behind the decisions behind a CDSS, they won't trust it or use it effectively.<sup id=\"rdp-ebb-cite_ref-:13_84-0\" class=\"reference\"><a href=\"#cite_note-:13-84\">[84]<\/a><\/sup> This highlights the importance of not only involving physicians and healthcare professionals in the construction of systems and the interpretation of outcomes, but also of providing adequate explanation and information at the point of care for healthcare practitioners to trust such systems.<sup id=\"rdp-ebb-cite_ref-:13_84-1\" class=\"reference\"><a href=\"#cite_note-:13-84\">[84]<\/a><\/sup>\n<\/p><p>As previously stated, identifying the types of information that clinicians require, as well as the methods by which they access and utilize information, is critical in ensuring that developments not only meet the needs of the users, but are also perceived to be valuable, so that health professionals and other users will want to maximize their potential. Addressing healthcare professionals', patients', and the public's concerns about data security, as well as threats to patient privacy and confidentiality, will be critical in developing online access to patient records.<sup id=\"rdp-ebb-cite_ref-85\" class=\"reference\"><a href=\"#cite_note-85\">[85]<\/a><\/sup> Greater security measures integrated into system design will help boost system confidence; however, the chance of third parties getting access to sensitive patient-identifiable data remains a danger.<sup id=\"rdp-ebb-cite_ref-:12_82-1\" class=\"reference\"><a href=\"#cite_note-:12-82\">[82]<\/a><\/sup>\n<\/p><p>Another challenge that can stall the creation and execution of health informatics efforts is quality. The real and perceived quality of data entered into systems and then used for health care is vital not only for assuring system use, but also for the safety and well-being of patients. If data is not input, or is not entered correctly, the buildup of missing or low quality data discourages others from using the system and creates additional suspicion and skepticism about future advancements. The importance of accurate and correct data will grow as lifelong electronic records are established<sup id=\"rdp-ebb-cite_ref-:13_84-2\" class=\"reference\"><a href=\"#cite_note-:13-84\">[84]<\/a><\/sup>, both prospectively as individuals are born and retrospectively using data acquired over an existing person's lifetime to date.\n<\/p><p>As previously noted, the earlier development of small-scale information systems within individual departments or hospitals resulted in system incompatibility and difficulties communicating or transferring data when larger-scale systems were later built. One approach to addressing this issue is to increase interoperability and employ known electronic record architectures in the creation of new systems. In addition, the lack of data standards in health presents additional challenges for moving and sharing data between systems.<sup id=\"rdp-ebb-cite_ref-:12_82-2\" class=\"reference\"><a href=\"#cite_note-:12-82\">[82]<\/a><\/sup> Attempts to address these issues include the creation of information management standards such as <a href=\"https:\/\/www.limswiki.org\/index.php\/DICOM\" title=\"DICOM\" class=\"wiki-link\" data-key=\"f0c7c747895286ff8785b6ed4dbc7ec0\">Digital Imaging and Communications in Medicine<\/a> (DICOM), HL7, and terminologies and coding systems like the <a href=\"https:\/\/www.limswiki.org\/index.php\/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems\" title=\"International Statistical Classification of Diseases and Related Health Problems\" class=\"wiki-link\" data-key=\"1de9af67005dfe2895e5d8cf6de57d4a\">International Classification of Diseases<\/a> (ICD) and <a href=\"https:\/\/www.limswiki.org\/index.php\/SNOMED_CT\" title=\"SNOMED CT\" class=\"wiki-link\" data-key=\"a04000c818ae954bf52cfea5efdf020d\">SNOMED CT<\/a> to standardize the ways in which medical conditions and diseases are represented in computer-based systems and codify the natural language used by medical staff. In particular, the ICD was created to provide a standard method of classifying medical diagnoses for epidemiology and healthcare purposes. Initially, it only included causes of death, but more recent versions have included causes of morbidity, and it is now in its eleventh version.<sup id=\"rdp-ebb-cite_ref-86\" class=\"reference\"><a href=\"#cite_note-86\">[86]<\/a><\/sup> \n<\/p>\n<h3><span class=\"mw-headline\" id=\"Health_data_standards_challenges_and_possible_solutions_to_them\">Health data standards challenges and possible solutions to them<\/span><\/h3>\n<p>Clearly, data standards are not lacking in the healthcare industry. Standard development organizations have created a plethora of them to address nearly every facet of communication between diverse health systems. However, the simple fact that they exist and are available does not address all of the issues surrounding interoperability. What follows are some of the more difficult standards issues, as well as potential solutions.\n<\/p><p>1. <b>Medical coding speed and accuracy issues<\/b>: The manual work required to convert diagnoses, treatments, services, treatment plans, and other concepts into medical codes is undertaken by professionally qualified individuals. Computer-assisted coding systems are now used by coders. However, the translation process' speed and precision are far from flawless. To that aim, high hopes are placed on AI-powered tools capable of identifying proper codes and recommending them for expert evaluation. Currently, such intelligent systems speed up coding, but they cannot completely replace humans and automate the entire process.\n<\/p><p>2. <b>Need for mapping between codes<\/b>: Each code in healthcare serves a specific purpose. SNOMED allows physicians to provide a thorough clinical picture of a patient being treated, whereas ICD-10 presents diagnoses quickly and CPT summarizes services. However, there are times when translation from one code system to another is required. As previously stated, SNOMED cannot be used for billing reasons and must be translated to ICD-10-CT. To overcome mapping issues, standard development organizations continue to research various approaches.\n<\/p><p>3. <b>Lack of compatibility between old and new standards<\/b>: To comply with existing interoperability regulations, hospitals must make content described by USCDI available via FHIR-based APIs. However, most older EHR systems were designed with previous standards in mind. Some of them are only capable of importing and exporting HL7 v2 messages. Others rely heavily on C-CDA materials. Neither v2 nor C-CDA are compatible with granular USCDI data elements or FHIR basic interchangeable data block resources. As a result, hospitals will require additional digital technologies and human resources to extract data from legacy formats and convert it into FHIR- and USCDI-compliant formats.\n<\/p><p>4. <b>No two-way communication between patients and EHRs<\/b>: The FHIR standard enables patients to access health data through apps of their choice. However, because EHRs largely limit access to their systems as read-only, this more often than not becomes a one-way street. The software allows users to request information but does not allow them to modify or change it. Many industry experts believe that the next major difficulty for healthcare is a lack of two-way communication between medical apps and EHR systems. And, sooner or later, it will need the development of new data standards.<sup id=\"rdp-ebb-cite_ref-87\" class=\"reference\"><a href=\"#cite_note-87\">[87]<\/a><\/sup>\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion\">Conclusion<\/span><\/h2>\n<p>Continued research in the domain of health informatics is vital, driving new discoveries that can be realized effectively and via rigorous testing. There are no proven design blueprints for such a comprehensive infrastructure, and the goal is always shifting due to the nature of real-time patient, medical, and equipment data collection from a variety of sources. The future of health informatics lies in the creation of novel algorithms, models, and an ecosystem that is conducive to health professionals and decision makers.\n<\/p><p>Some of the advantages that will result from innovation in this emerging area will be critical, including the:\n<\/p>\n<ul><li>development of case- and incident-related health information standards and services;<\/li>\n<li>improvement in professionalism among healthcare units;<\/li>\n<li>creation of various innovative industrial processes;<\/li>\n<li>enhancement of research collaboration both nationally and internationally;<\/li>\n<li>development of better data visualization tools;<\/li>\n<li>development of novel prediction models using machine learning, deep learning, and reinforcement learning;<\/li>\n<li>creation of new products and services related to healthcare and health informatics;<\/li>\n<li>improvement of storage and retrieval mechanisms associated with health data; and<\/li>\n<li>development of curated, novel datasets for research communities.<\/li><\/ul>\n<p>Current cutting-edge health informatics research projects aim to discover new condition onset behaviors that are visible in physiological data streams earlier than traditional condition detection in critical care data.<sup id=\"rdp-ebb-cite_ref-88\" class=\"reference\"><a href=\"#cite_note-88\">[88]<\/a><\/sup> Cloud computing has attracted a lot of research attention, but only a small portion of the work done so far has addressed performance issues, and only a few examinations have used a rigorous analytical approach.<sup id=\"rdp-ebb-cite_ref-89\" class=\"reference\"><a href=\"#cite_note-89\">[89]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-90\" class=\"reference\"><a href=\"#cite_note-90\">[90]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-91\" class=\"reference\"><a href=\"#cite_note-91\">[91]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-92\" class=\"reference\"><a href=\"#cite_note-92\">[92]<\/a><\/sup>\n<\/p><p>Big data is also playing an important role in health informatics, where a large amount of data related to healthcare is generated, assisting doctors and decision makers in making rational decisions regarding patient treatment and diagnosis. Newer computational technologies may emerge that will improve the way healthcare is delivered and implemented in the future, thereby vastly improving the public healthcare system. Policymakers can propose tried-and-true use cases that can be transformed into a meaningful framework in which all stakeholders can deliberate and decide on the best model for improving the public health care system.\n<\/p><p>Health informatics is a new field, with many stakeholders involved in the design and implementation of sustainable public health systems and policies for the benefit of society as a whole.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>MY has written the manuscript with relevant information from the literature regarding the major challenges and gaps that the present health informatics system and public health system are undergoing. The manuscript was reviewed and inputs were given by JK to focus on health informatics and policy framework. All authors contributed to the article and approved the submitted version.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jordan, M. I.; Mitchell, T. M. 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(28 July 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2932707\" target=\"_blank\">\"Computational Health Informatics in the Big Data Age: A Survey\"<\/a> (in en). <i>ACM Computing Surveys<\/i> <b>49<\/b> (1): 1\u201336. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2932707\" target=\"_blank\">10.1145\/2932707<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0360-0300\" target=\"_blank\">0360-0300<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2932707\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/2932707<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Computational+Health+Informatics+in+the+Big+Data+Age%3A+A+Survey&rft.jtitle=ACM+Computing+Surveys&rft.aulast=Fang&rft.aufirst=Ruogu&rft.au=Fang%2C%26%2332%3BRuogu&rft.au=Pouyanfar%2C%26%2332%3BSamira&rft.au=Yang%2C%26%2332%3BYimin&rft.au=Chen%2C%26%2332%3BShu-Ching&rft.au=Iyengar%2C%26%2332%3BS.+S.&rft.date=28+July+2016&rft.volume=49&rft.issue=1&rft.pages=1%E2%80%9336&rft_id=info:doi\/10.1145%2F2932707&rft.issn=0360-0300&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F2932707&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Institute of Medicine (U.S.), ed. (1988). <i>The future of public health<\/i>. Washington, D.C: National Academy Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-309-03830-0.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+future+of+public+health&rft.date=1988&rft.place=Washington%2C+D.C&rft.pub=National+Academy+Press&rft.isbn=978-0-309-03830-0&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chen, Jiajia; Qian, Fuliang; Yan, Wenying; Shen, Bairong (2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.hindawi.com\/journals\/bmri\/2013\/658925\/\" target=\"_blank\">\"Translational Biomedical Informatics in the Cloud: Present and Future\"<\/a> (in en). <i>BioMed Research International<\/i> <b>2013<\/b>: 1\u20138. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1155%2F2013%2F658925\" target=\"_blank\">10.1155\/2013\/658925<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2314-6133\" target=\"_blank\">2314-6133<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3613081\/\" target=\"_blank\">PMC3613081<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23586054\" target=\"_blank\">23586054<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.hindawi.com\/journals\/bmri\/2013\/658925\/\" target=\"_blank\">http:\/\/www.hindawi.com\/journals\/bmri\/2013\/658925\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Translational+Biomedical+Informatics+in+the+Cloud%3A+Present+and+Future&rft.jtitle=BioMed+Research+International&rft.aulast=Chen&rft.aufirst=Jiajia&rft.au=Chen%2C%26%2332%3BJiajia&rft.au=Qian%2C%26%2332%3BFuliang&rft.au=Yan%2C%26%2332%3BWenying&rft.au=Shen%2C%26%2332%3BBairong&rft.date=2013&rft.volume=2013&rft.pages=1%E2%80%938&rft_id=info:doi\/10.1155%2F2013%2F658925&rft.issn=2314-6133&rft_id=info:pmc\/PMC3613081&rft_id=info:pmid\/23586054&rft_id=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fbmri%2F2013%2F658925%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-12\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_12-0\">12.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_12-1\">12.1<\/a><\/sup> <sup><a href=\"#cite_ref-:6_12-2\">12.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yasnoff, William A.; O\u02bcCarroll, Patrick W.; Koo, Denise; Linkins, Robert W.; Kilbourne, Edwin M. (2000). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.lww.com\/00124784-200006060-00010\" target=\"_blank\">\"Public Health Informatics: Improving and Transforming Public Health in the Information Age:\"<\/a> (in en). <i>Journal of Public Health Management and Practice<\/i> <b>6<\/b> (6): 67\u201375. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2F00124784-200006060-00010\" target=\"_blank\">10.1097\/00124784-200006060-00010<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1078-4659\" target=\"_blank\">1078-4659<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.lww.com\/00124784-200006060-00010\" target=\"_blank\">http:\/\/journals.lww.com\/00124784-200006060-00010<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Public+Health+Informatics%3A+Improving+and+Transforming+Public+Health+in+the+Information+Age%3A&rft.jtitle=Journal+of+Public+Health+Management+and+Practice&rft.aulast=Yasnoff&rft.aufirst=William+A.&rft.au=Yasnoff%2C%26%2332%3BWilliam+A.&rft.au=O%CA%BCCarroll%2C%26%2332%3BPatrick+W.&rft.au=Koo%2C%26%2332%3BDenise&rft.au=Linkins%2C%26%2332%3BRobert+W.&rft.au=Kilbourne%2C%26%2332%3BEdwin+M.&rft.date=2000&rft.volume=6&rft.issue=6&rft.pages=67%E2%80%9375&rft_id=info:doi\/10.1097%2F00124784-200006060-00010&rft.issn=1078-4659&rft_id=http%3A%2F%2Fjournals.lww.com%2F00124784-200006060-00010&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gable, Carol Brignoli (1 March 1990). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/aje\/article\/63855\/A\" target=\"_blank\">\"A COMPENDIUM OF PUBLIC HEALTH DATA SOURCES\"<\/a> (in en). <i>American Journal of Epidemiology<\/i> <b>131<\/b> (3): 381\u2013394. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Foxfordjournals.aje.a115513\" target=\"_blank\">10.1093\/oxfordjournals.aje.a115513<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1476-6256\" target=\"_blank\">1476-6256<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/aje\/article\/63855\/A\" target=\"_blank\">https:\/\/academic.oup.com\/aje\/article\/63855\/A<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+COMPENDIUM+OF+PUBLIC+HEALTH+DATA+SOURCES&rft.jtitle=American+Journal+of+Epidemiology&rft.aulast=Gable&rft.aufirst=Carol+Brignoli&rft.au=Gable%2C%26%2332%3BCarol+Brignoli&rft.date=1+March+1990&rft.volume=131&rft.issue=3&rft.pages=381%E2%80%93394&rft_id=info:doi\/10.1093%2Foxfordjournals.aje.a115513&rft.issn=1476-6256&rft_id=https%3A%2F%2Facademic.oup.com%2Faje%2Farticle%2F63855%2FA&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Institute of Medicine (U.S.), ed. (2003). <i>The future of the public's health in the 21st century<\/i>. Washington, D.C: National Academies Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-309-08704-9.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+future+of+the+public%27s+health+in+the+21st+century&rft.date=2003&rft.place=Washington%2C+D.C&rft.pub=National+Academies+Press&rft.isbn=978-0-309-08704-9&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Patel, Shyamal; Park, Hyung; Bonato, Paolo; Chan, Leighton; Rodgers, Mary (1 December 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/jneuroengrehab.biomedcentral.com\/articles\/10.1186\/1743-0003-9-21\" target=\"_blank\">\"A review of wearable sensors and systems with application in rehabilitation\"<\/a> (in en). <i>Journal of NeuroEngineering and Rehabilitation<\/i> <b>9<\/b> (1): 21. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F1743-0003-9-21\" target=\"_blank\">10.1186\/1743-0003-9-21<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1743-0003\" target=\"_blank\">1743-0003<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3354997\/\" target=\"_blank\">PMC3354997<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22520559\" target=\"_blank\">22520559<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/jneuroengrehab.biomedcentral.com\/articles\/10.1186\/1743-0003-9-21\" target=\"_blank\">https:\/\/jneuroengrehab.biomedcentral.com\/articles\/10.1186\/1743-0003-9-21<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+review+of+wearable+sensors+and+systems+with+application+in+rehabilitation&rft.jtitle=Journal+of+NeuroEngineering+and+Rehabilitation&rft.aulast=Patel&rft.aufirst=Shyamal&rft.au=Patel%2C%26%2332%3BShyamal&rft.au=Park%2C%26%2332%3BHyung&rft.au=Bonato%2C%26%2332%3BPaolo&rft.au=Chan%2C%26%2332%3BLeighton&rft.au=Rodgers%2C%26%2332%3BMary&rft.date=1+December+2012&rft.volume=9&rft.issue=1&rft.pages=21&rft_id=info:doi\/10.1186%2F1743-0003-9-21&rft.issn=1743-0003&rft_id=info:pmc\/PMC3354997&rft_id=info:pmid\/22520559&rft_id=https%3A%2F%2Fjneuroengrehab.biomedcentral.com%2Farticles%2F10.1186%2F1743-0003-9-21&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-16\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Pedrycz, Witold; Chen, Shyi-Ming, eds. (2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-08254-7\" target=\"_blank\"><i>Information Granularity, Big Data, and Computational Intelligence<\/i><\/a>. Studies in Big Data. <b>8<\/b>. Cham: Springer International Publishing. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-08254-7\" target=\"_blank\">10.1007\/978-3-319-08254-7<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-08253-0<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-08254-7\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-08254-7<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Information+Granularity%2C+Big+Data%2C+and+Computational+Intelligence&rft.date=2015&rft.series=Studies+in+Big+Data&rft.volume=8&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-08254-7&rft.isbn=978-3-319-08253-0&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-08254-7&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wu,P.Y.; Cheng, C.W.; Kaddi, C.D. et al. (1 February 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7587347\/\" target=\"_blank\">\"\u2013Omic and Electronic Health Record Big Data Analytics for Precision Medicine\"<\/a>. <i>IEEE Transactions on Biomedical Engineering<\/i> <b>64<\/b> (2): 263\u2013273. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTBME.2016.2573285\" target=\"_blank\">10.1109\/TBME.2016.2573285<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0018-9294\" target=\"_blank\">0018-9294<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5859562\/\" target=\"_blank\">PMC5859562<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27740470\" target=\"_blank\">27740470<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/7587347\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/7587347\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%E2%80%93Omic+and+Electronic+Health+Record+Big+Data+Analytics+for+Precision+Medicine&rft.jtitle=IEEE+Transactions+on+Biomedical+Engineering&rft.aulast=Wu%2CP.Y.%3B+Cheng%2C+C.W.%3B+Kaddi%2C+C.D.+et+al.&rft.au=Wu%2CP.Y.%3B+Cheng%2C+C.W.%3B+Kaddi%2C+C.D.+et+al.&rft.date=1+February+2017&rft.volume=64&rft.issue=2&rft.pages=263%E2%80%93273&rft_id=info:doi\/10.1109%2FTBME.2016.2573285&rft.issn=0018-9294&rft_id=info:pmc\/PMC5859562&rft_id=info:pmid\/27740470&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7587347%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yang, Hung-chih; Dasdan, Ali; Hsiao, Ruey-Lung; Parker, D. Stott (2007). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1247480.1247602\" target=\"_blank\">\"Map-reduce-merge: simplified relational data processing on large clusters\"<\/a> (in en). <i>Proceedings of the 2007 ACM SIGMOD international conference on Management of data - SIGMOD '07<\/i> (Beijing, China: ACM Press): 1029\u201340. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1247480.1247602\" target=\"_blank\">10.1145\/1247480.1247602<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-59593-686-8<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1247480.1247602\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=1247480.1247602<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Map-reduce-merge%3A+simplified+relational+data+processing+on+large+clusters&rft.jtitle=Proceedings+of+the+2007+ACM+SIGMOD+international+conference+on+Management+of+data++-+SIGMOD+%2707&rft.aulast=Yang&rft.aufirst=Hung-chih&rft.au=Yang%2C%26%2332%3BHung-chih&rft.au=Dasdan%2C%26%2332%3BAli&rft.au=Hsiao%2C%26%2332%3BRuey-Lung&rft.au=Parker%2C%26%2332%3BD.+Stott&rft.date=2007&rft.pages=1029%E2%80%9340&rft.place=Beijing%2C+China&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F1247480.1247602&rft.isbn=978-1-59593-686-8&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D1247480.1247602&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-19\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kala Karun, A.; Chitharanjan, K. (1 April 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6558077\/\" target=\"_blank\">\"A review on hadoop — HDFS infrastructure extensions\"<\/a>. <i>2013 IEEE CONFERENCE ON INFORMATION AND COMMUNICATION TECHNOLOGIES<\/i> (Thuckalay, Tamil Nadu, India: IEEE): 132\u2013137. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FCICT.2013.6558077\" target=\"_blank\">10.1109\/CICT.2013.6558077<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4673-5758-6<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6558077\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/6558077\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+review+on+hadoop+%26%23x2014%3B+HDFS+infrastructure+extensions&rft.jtitle=2013+IEEE+CONFERENCE+ON+INFORMATION+AND+COMMUNICATION+TECHNOLOGIES&rft.aulast=Kala+Karun&rft.aufirst=A.&rft.au=Kala+Karun%2C%26%2332%3BA.&rft.au=Chitharanjan%2C%26%2332%3BK.&rft.date=1+April+2013&rft.pages=132%E2%80%93137&rft.place=Thuckalay%2C+Tamil+Nadu%2C+India&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FCICT.2013.6558077&rft.isbn=978-1-4673-5758-6&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6558077%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-20\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Mohri, Mehryar; Rostamizadeh, Afshin; Talwalkar, Ameet (2012). <i>Foundations of machine learning<\/i>. Adaptive computation and machine learning series. Cambridge, MA: MIT Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-262-01825-8.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Foundations+of+machine+learning&rft.aulast=Mohri&rft.aufirst=Mehryar&rft.au=Mohri%2C%26%2332%3BMehryar&rft.au=Rostamizadeh%2C%26%2332%3BAfshin&rft.au=Talwalkar%2C%26%2332%3BAmeet&rft.date=2012&rft.series=Adaptive+computation+and+machine+learning+series&rft.place=Cambridge%2C+MA&rft.pub=MIT+Press&rft.isbn=978-0-262-01825-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bellazzi, R; Zupan, B (1 February 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002747\" target=\"_blank\">\"Predictive data mining in clinical medicine: Current issues and guidelines\"<\/a> (in en). <i>International Journal of Medical Informatics<\/i> <b>77<\/b> (2): 81\u201397. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.ijmedinf.2006.11.006\" target=\"_blank\">10.1016\/j.ijmedinf.2006.11.006<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002747\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002747<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Predictive+data+mining+in+clinical+medicine%3A+Current+issues+and+guidelines&rft.jtitle=International+Journal+of+Medical+Informatics&rft.aulast=Bellazzi&rft.aufirst=R&rft.au=Bellazzi%2C%26%2332%3BR&rft.au=Zupan%2C%26%2332%3BB&rft.date=1+February+2008&rft.volume=77&rft.issue=2&rft.pages=81%E2%80%9397&rft_id=info:doi\/10.1016%2Fj.ijmedinf.2006.11.006&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1386505606002747&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cohen, A. M. (1 January 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/doi.org\/10.1093\/bib\/6.1.57\" target=\"_blank\">\"A survey of current work in biomedical text mining\"<\/a>. <i>Briefings in Bioinformatics<\/i> <b>6<\/b> (1): 57\u201371. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbib%2F6.1.57\" target=\"_blank\">10.1093\/bib\/6.1.57<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1467-5463\" target=\"_blank\">1467-5463<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/doi.org\/10.1093\/bib\/6.1.57\" target=\"_blank\">https:\/\/doi.org\/10.1093\/bib\/6.1.57<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+survey+of+current+work+in+biomedical+text+mining&rft.jtitle=Briefings+in+Bioinformatics&rft.aulast=Cohen&rft.aufirst=A.+M.&rft.au=Cohen%2C%26%2332%3BA.+M.&rft.date=1+January+2005&rft.volume=6&rft.issue=1&rft.pages=57%E2%80%9371&rft_id=info:doi\/10.1093%2Fbib%2F6.1.57&rft.issn=1467-5463&rft_id=https%3A%2F%2Fdoi.org%2F10.1093%2Fbib%2F6.1.57&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bedard, Noah; Pierce, Mark; El-Naggar, Adel; Anandasabapathy, S.; Gillenwater, Ann; Richards-Kortum, R. (1 April 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/153303461000900210\" target=\"_blank\">\"Emerging Roles for Multimodal Optical Imaging in Early Cancer Detection: A Global Challenge\"<\/a> (in en). <i>Technology in Cancer Research & Treatment<\/i> <b>9<\/b> (2): 211\u2013217. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F153303461000900210\" target=\"_blank\">10.1177\/153303461000900210<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1533-0346\" target=\"_blank\">1533-0346<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2906814\/\" target=\"_blank\">PMC2906814<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20218743\" target=\"_blank\">20218743<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/153303461000900210\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/153303461000900210<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Emerging+Roles+for+Multimodal+Optical+Imaging+in+Early+Cancer+Detection%3A+A+Global+Challenge&rft.jtitle=Technology+in+Cancer+Research+%26+Treatment&rft.aulast=Bedard&rft.aufirst=Noah&rft.au=Bedard%2C%26%2332%3BNoah&rft.au=Pierce%2C%26%2332%3BMark&rft.au=El-Naggar%2C%26%2332%3BAdel&rft.au=Anandasabapathy%2C%26%2332%3BS.&rft.au=Gillenwater%2C%26%2332%3BAnn&rft.au=Richards-Kortum%2C%26%2332%3BR.&rft.date=1+April+2010&rft.volume=9&rft.issue=2&rft.pages=211%E2%80%93217&rft_id=info:doi\/10.1177%2F153303461000900210&rft.issn=1533-0346&rft_id=info:pmc\/PMC2906814&rft_id=info:pmid\/20218743&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F153303461000900210&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Weissleder, Ralph; Pittet, Mikael J. (3 April 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.nature.com\/articles\/nature06917\" target=\"_blank\">\"Imaging in the era of molecular oncology\"<\/a> (in en). <i>Nature<\/i> <b>452<\/b> (7187): 580\u2013589. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fnature06917\" target=\"_blank\">10.1038\/nature06917<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0028-0836\" target=\"_blank\">0028-0836<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2708079\/\" target=\"_blank\">PMC2708079<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18385732\" target=\"_blank\">18385732<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.nature.com\/articles\/nature06917\" target=\"_blank\">https:\/\/www.nature.com\/articles\/nature06917<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Imaging+in+the+era+of+molecular+oncology&rft.jtitle=Nature&rft.aulast=Weissleder&rft.aufirst=Ralph&rft.au=Weissleder%2C%26%2332%3BRalph&rft.au=Pittet%2C%26%2332%3BMikael+J.&rft.date=3+April+2008&rft.volume=452&rft.issue=7187&rft.pages=580%E2%80%93589&rft_id=info:doi\/10.1038%2Fnature06917&rft.issn=0028-0836&rft_id=info:pmc\/PMC2708079&rft_id=info:pmid\/18385732&rft_id=https%3A%2F%2Fwww.nature.com%2Farticles%2Fnature06917&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pierce, Mark C.; Javier, David J.; Richards-Kortum, Rebecca (1 November 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23858\" target=\"_blank\">\"Optical contrast agents and imaging systems for detection and diagnosis of cancer\"<\/a> (in en). <i>International Journal of Cancer<\/i> <b>123<\/b> (9): 1979\u20131990. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fijc.23858\" target=\"_blank\">10.1002\/ijc.23858<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2902964\/\" target=\"_blank\">PMC2902964<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18712733\" target=\"_blank\">18712733<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23858\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23858<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Optical+contrast+agents+and+imaging+systems+for+detection+and+diagnosis+of+cancer&rft.jtitle=International+Journal+of+Cancer&rft.aulast=Pierce&rft.aufirst=Mark+C.&rft.au=Pierce%2C%26%2332%3BMark+C.&rft.au=Javier%2C%26%2332%3BDavid+J.&rft.au=Richards-Kortum%2C%26%2332%3BRebecca&rft.date=1+November+2008&rft.volume=123&rft.issue=9&rft.pages=1979%E2%80%931990&rft_id=info:doi\/10.1002%2Fijc.23858&rft_id=info:pmc\/PMC2902964&rft_id=info:pmid\/18712733&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fijc.23858&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-26\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_26-0\">26.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_26-1\">26.1<\/a><\/sup> <sup><a href=\"#cite_ref-:1_26-2\">26.2<\/a><\/sup> <sup><a href=\"#cite_ref-:1_26-3\">26.3<\/a><\/sup> <sup><a href=\"#cite_ref-:1_26-4\">26.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ravi, Daniele; Wong, Charence; Deligianni, Fani; Berthelot, Melissa; Andreu-Perez, Javier; Lo, Benny; Yang, Guang-Zhong (1 January 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7801947\/\" target=\"_blank\">\"Deep Learning for Health Informatics\"<\/a>. <i>IEEE Journal of Biomedical and Health Informatics<\/i> <b>21<\/b> (1): 4\u201321. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJBHI.2016.2636665\" target=\"_blank\">10.1109\/JBHI.2016.2636665<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2168-2194\" target=\"_blank\">2168-2194<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7801947\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7801947\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Deep+Learning+for+Health+Informatics&rft.jtitle=IEEE+Journal+of+Biomedical+and+Health+Informatics&rft.aulast=Ravi&rft.aufirst=Daniele&rft.au=Ravi%2C%26%2332%3BDaniele&rft.au=Wong%2C%26%2332%3BCharence&rft.au=Deligianni%2C%26%2332%3BFani&rft.au=Berthelot%2C%26%2332%3BMelissa&rft.au=Andreu-Perez%2C%26%2332%3BJavier&rft.au=Lo%2C%26%2332%3BBenny&rft.au=Yang%2C%26%2332%3BGuang-Zhong&rft.date=1+January+2017&rft.volume=21&rft.issue=1&rft.pages=4%E2%80%9321&rft_id=info:doi\/10.1109%2FJBHI.2016.2636665&rft.issn=2168-2194&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7801947%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Suzuki, Kenji; Yan, Pingkun; Wang, Fei; Shen, Dinggang (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.hindawi.com\/journals\/ijbi\/2012\/123727\/\" target=\"_blank\">\"Machine Learning in Medical Imaging\"<\/a> (in en). <i>International Journal of Biomedical Imaging<\/i> <b>2012<\/b>: 1\u20132. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1155%2F2012%2F123727\" target=\"_blank\">10.1155\/2012\/123727<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1687-4188\" target=\"_blank\">1687-4188<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3303553\/\" target=\"_blank\">PMC3303553<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22481902\" target=\"_blank\">22481902<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.hindawi.com\/journals\/ijbi\/2012\/123727\/\" target=\"_blank\">http:\/\/www.hindawi.com\/journals\/ijbi\/2012\/123727\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Machine+Learning+in+Medical+Imaging&rft.jtitle=International+Journal+of+Biomedical+Imaging&rft.aulast=Suzuki&rft.aufirst=Kenji&rft.au=Suzuki%2C%26%2332%3BKenji&rft.au=Yan%2C%26%2332%3BPingkun&rft.au=Wang%2C%26%2332%3BFei&rft.au=Shen%2C%26%2332%3BDinggang&rft.date=2012&rft.volume=2012&rft.pages=1%E2%80%932&rft_id=info:doi\/10.1155%2F2012%2F123727&rft.issn=1687-4188&rft_id=info:pmc\/PMC3303553&rft_id=info:pmid\/22481902&rft_id=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fijbi%2F2012%2F123727%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-28\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-28\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Holzinger, Andreas; Biemann, Chris; Pattichis, Constantinos S.; Kell, Douglas B. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1712.09923\" target=\"_blank\"><i>What do we need to build explainable AI systems for the medical domain?<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.48550%2FARXIV.1712.09923\" target=\"_blank\">10.48550\/ARXIV.1712.09923<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1712.09923\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1712.09923<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=What+do+we+need+to+build+explainable+AI+systems+for+the+medical+domain%3F&rft.aulast=Holzinger&rft.aufirst=Andreas&rft.au=Holzinger%2C%26%2332%3BAndreas&rft.au=Biemann%2C%26%2332%3BChris&rft.au=Pattichis%2C%26%2332%3BConstantinos+S.&rft.au=Kell%2C%26%2332%3BDouglas+B.&rft.date=2017&rft_id=info:doi\/10.48550%2FARXIV.1712.09923&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1712.09923&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-29\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_29-0\">29.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_29-1\">29.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ribeiro, Marco Tulio; Singh, Sameer; Guestrin, Carlos (13 August 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2939672.2939778\" target=\"_blank\">\"\"Why Should I Trust You?\": Explaining the Predictions of Any Classifier\"<\/a> (in en). <i>Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining<\/i> (San Francisco California USA: ACM): 1135\u20131144. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F2939672.2939778\" target=\"_blank\">10.1145\/2939672.2939778<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4503-4232-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.1145\/2939672.2939778\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.1145\/2939672.2939778<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%22Why+Should+I+Trust+You%3F%22%3A+Explaining+the+Predictions+of+Any+Classifier&rft.jtitle=Proceedings+of+the+22nd+ACM+SIGKDD+International+Conference+on+Knowledge+Discovery+and+Data+Mining&rft.aulast=Ribeiro&rft.aufirst=Marco+Tulio&rft.au=Ribeiro%2C%26%2332%3BMarco+Tulio&rft.au=Singh%2C%26%2332%3BSameer&rft.au=Guestrin%2C%26%2332%3BCarlos&rft.date=13+August+2016&rft.pages=1135%E2%80%931144&rft.place=San+Francisco+California+USA&rft.pub=ACM&rft_id=info:doi\/10.1145%2F2939672.2939778&rft.isbn=978-1-4503-4232-2&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.1145%2F2939672.2939778&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bahdanau, Dzmitry; Cho, Kyunghyun; Bengio, Yoshua (2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1409.0473\" target=\"_blank\"><i>Neural Machine Translation by Jointly Learning to Align and Translate<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.48550%2FARXIV.1409.0473\" target=\"_blank\">10.48550\/ARXIV.1409.0473<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1409.0473\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1409.0473<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Neural+Machine+Translation+by+Jointly+Learning+to+Align+and+Translate&rft.aulast=Bahdanau&rft.aufirst=Dzmitry&rft.au=Bahdanau%2C%26%2332%3BDzmitry&rft.au=Cho%2C%26%2332%3BKyunghyun&rft.au=Bengio%2C%26%2332%3BYoshua&rft.date=2014&rft_id=info:doi\/10.48550%2FARXIV.1409.0473&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1409.0473&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Buntin, Melinda Beeuwkes; Burke, Matthew F.; Hoaglin, Michael C.; Blumenthal, David (1 March 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2011.0178\" target=\"_blank\">\"The Benefits Of Health Information Technology: A Review Of The Recent Literature Shows Predominantly Positive Results\"<\/a> (in en). <i>Health Affairs<\/i> <b>30<\/b> (3): 464\u2013471. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1377%2Fhlthaff.2011.0178\" target=\"_blank\">10.1377\/hlthaff.2011.0178<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0278-2715\" target=\"_blank\">0278-2715<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2011.0178\" target=\"_blank\">http:\/\/www.healthaffairs.org\/doi\/10.1377\/hlthaff.2011.0178<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Benefits+Of+Health+Information+Technology%3A+A+Review+Of+The+Recent+Literature+Shows+Predominantly+Positive+Results&rft.jtitle=Health+Affairs&rft.aulast=Buntin&rft.aufirst=Melinda+Beeuwkes&rft.au=Buntin%2C%26%2332%3BMelinda+Beeuwkes&rft.au=Burke%2C%26%2332%3BMatthew+F.&rft.au=Hoaglin%2C%26%2332%3BMichael+C.&rft.au=Blumenthal%2C%26%2332%3BDavid&rft.date=1+March+2011&rft.volume=30&rft.issue=3&rft.pages=464%E2%80%93471&rft_id=info:doi\/10.1377%2Fhlthaff.2011.0178&rft.issn=0278-2715&rft_id=http%3A%2F%2Fwww.healthaffairs.org%2Fdoi%2F10.1377%2Fhlthaff.2011.0178&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-32\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Menachemi, Nir; Brooks, Robert G. (1 June 2006). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-005-7988-x\" target=\"_blank\">\"Reviewing the Benefits and Costs of Electronic Health Records and Associated Patient Safety Technologies\"<\/a> (in en). <i>Journal of Medical Systems<\/i> <b>30<\/b> (3): 159\u2013168. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10916-005-7988-x\" target=\"_blank\">10.1007\/s10916-005-7988-x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0148-5598\" target=\"_blank\">0148-5598<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-005-7988-x\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10916-005-7988-x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reviewing+the+Benefits+and+Costs+of+Electronic+Health+Records+and+Associated+Patient+Safety+Technologies&rft.jtitle=Journal+of+Medical+Systems&rft.aulast=Menachemi&rft.aufirst=Nir&rft.au=Menachemi%2C%26%2332%3BNir&rft.au=Brooks%2C%26%2332%3BRobert+G.&rft.date=1+June+2006&rft.volume=30&rft.issue=3&rft.pages=159%E2%80%93168&rft_id=info:doi\/10.1007%2Fs10916-005-7988-x&rft.issn=0148-5598&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10916-005-7988-x&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-33\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">King, Jennifer; Patel, Vaishali; Jamoom, Eric W.; Furukawa, Michael F. (1 February 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1475-6773.12135\" target=\"_blank\">\"Clinical Benefits of Electronic Health Record Use: National Findings\"<\/a> (in en). <i>Health Services Research<\/i> <b>49<\/b> (1pt2): 392\u2013404. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2F1475-6773.12135\" target=\"_blank\">10.1111\/1475-6773.12135<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3925409\/\" target=\"_blank\">PMC3925409<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24359580\" target=\"_blank\">24359580<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1475-6773.12135\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1475-6773.12135<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+Benefits+of+Electronic+Health+Record+Use%3A+National+Findings&rft.jtitle=Health+Services+Research&rft.aulast=King&rft.aufirst=Jennifer&rft.au=King%2C%26%2332%3BJennifer&rft.au=Patel%2C%26%2332%3BVaishali&rft.au=Jamoom%2C%26%2332%3BEric+W.&rft.au=Furukawa%2C%26%2332%3BMichael+F.&rft.date=1+February+2014&rft.volume=49&rft.issue=1pt2&rft.pages=392%E2%80%93404&rft_id=info:doi\/10.1111%2F1475-6773.12135&rft_id=info:pmc\/PMC3925409&rft_id=info:pmid\/24359580&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2F1475-6773.12135&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-34\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_34-0\">34.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_34-1\">34.1<\/a><\/sup> <sup><a href=\"#cite_ref-:3_34-2\">34.2<\/a><\/sup> <sup><a href=\"#cite_ref-:3_34-3\">34.3<\/a><\/sup> <sup><a href=\"#cite_ref-:3_34-4\">34.4<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hl7.org\/fhir\/overview-arch.html\" target=\"_blank\">\"2.16 FHIR Overview - Architects\"<\/a>. Health Level 7. 1 November 2019<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hl7.org\/fhir\/overview-arch.html\" target=\"_blank\">https:\/\/www.hl7.org\/fhir\/overview-arch.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=2.16+FHIR+Overview+-+Architects&rft.atitle=&rft.date=1+November+2019&rft.pub=Health+Level+7&rft_id=https%3A%2F%2Fwww.hl7.org%2Ffhir%2Foverview-arch.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mandel, Joshua C; Kreda, David A; Mandl, Kenneth D; Kohane, Isaac S; Ramoni, Rachel B (1 September 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article\/23\/5\/899\/2379865\" target=\"_blank\">\"SMART on FHIR: a standards-based, interoperable apps platform for electronic health records\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>23<\/b> (5): 899\u2013908. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fjamia%2Focv189\" target=\"_blank\">10.1093\/jamia\/ocv189<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1527-974X\" target=\"_blank\">1527-974X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4997036\/\" target=\"_blank\">PMC4997036<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26911829\" target=\"_blank\">26911829<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article\/23\/5\/899\/2379865\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article\/23\/5\/899\/2379865<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SMART+on+FHIR%3A+a+standards-based%2C+interoperable+apps+platform+for+electronic+health+records&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Mandel&rft.aufirst=Joshua+C&rft.au=Mandel%2C%26%2332%3BJoshua+C&rft.au=Kreda%2C%26%2332%3BDavid+A&rft.au=Mandl%2C%26%2332%3BKenneth+D&rft.au=Kohane%2C%26%2332%3BIsaac+S&rft.au=Ramoni%2C%26%2332%3BRachel+B&rft.date=1+September+2016&rft.volume=23&rft.issue=5&rft.pages=899%E2%80%93908&rft_id=info:doi\/10.1093%2Fjamia%2Focv189&rft.issn=1527-974X&rft_id=info:pmc\/PMC4997036&rft_id=info:pmid\/26911829&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle%2F23%2F5%2F899%2F2379865&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Yan, Hangcheng; Xiao, Liang; Tian, Jingbai (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.atlantis-press.com\/php\/paper-details.php?id=25876700\" target=\"_blank\">\"Clinical Decision Support Based on FHIR Data Exchange Standard\"<\/a> (in en). <i>Proceedings of the 2nd International Conference on Mechatronics Engineering and Information Technology (ICMEIT 2017)<\/i> (Dalian, China: Atlantis Press). <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2991%2Ficmeit-17.2017.96\" target=\"_blank\">10.2991\/icmeit-17.2017.96<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-94-6252-338-8<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.atlantis-press.com\/php\/paper-details.php?id=25876700\" target=\"_blank\">http:\/\/www.atlantis-press.com\/php\/paper-details.php?id=25876700<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+Decision+Support+Based+on+FHIR+Data+Exchange+Standard&rft.jtitle=Proceedings+of+the+2nd+International+Conference+on+Mechatronics+Engineering+and+Information+Technology+%28ICMEIT+2017%29&rft.aulast=Yan&rft.aufirst=Hangcheng&rft.au=Yan%2C%26%2332%3BHangcheng&rft.au=Xiao%2C%26%2332%3BLiang&rft.au=Tian%2C%26%2332%3BJingbai&rft.date=2017&rft.place=Dalian%2C+China&rft.pub=Atlantis+Press&rft_id=info:doi\/10.2991%2Ficmeit-17.2017.96&rft.isbn=978-94-6252-338-8&rft_id=http%3A%2F%2Fwww.atlantis-press.com%2Fphp%2Fpaper-details.php%3Fid%3D25876700&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFSharmaAggarwal2019\">Sharma, Meenakshi; Aggarwal, Himanshu (2019), Krishna, C. Rama; Dutta, Maitreyee; Kumar, Rakesh, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-13-1217-5_87\" target=\"_blank\">\"HL-7 Based Middleware Standard for Healthcare Information System: FHIR\"<\/a>, <i>Proceedings of 2nd International Conference on Communication, Computing and Networking<\/i> (Singapore: Springer Singapore) <b>46<\/b>: 889\u2013899, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-981-13-1217-5_87\" target=\"_blank\">10.1007\/978-981-13-1217-5_87<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-981-13-1216-8<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-981-13-1217-5_87\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-981-13-1217-5_87<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-05-16<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=HL-7+Based+Middleware+Standard+for+Healthcare+Information+System%3A+FHIR&rft.jtitle=Proceedings+of+2nd+International+Conference+on+Communication%2C+Computing+and+Networking&rft.aulast=Sharma&rft.aufirst=Meenakshi&rft.au=Sharma%2C%26%2332%3BMeenakshi&rft.au=Aggarwal%2C%26%2332%3BHimanshu&rft.date=2019&rft.volume=46&rft.pages=889%E2%80%93899&rft.place=Singapore&rft.pub=Springer+Singapore&rft_id=info:doi\/10.1007%2F978-981-13-1217-5_87&rft.isbn=978-981-13-1216-8&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-981-13-1217-5_87&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-38\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_38-0\">38.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_38-1\">38.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hl7.org\/fhir\/workflow.html\" target=\"_blank\">\"12.5 Workflow Description\"<\/a>. Health Level 7. 1 November 2019<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hl7.org\/fhir\/workflow.html\" target=\"_blank\">https:\/\/www.hl7.org\/fhir\/workflow.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=12.5+Workflow+Description&rft.atitle=&rft.date=1+November+2019&rft.pub=Health+Level+7&rft_id=https%3A%2F%2Fwww.hl7.org%2Ffhir%2Fworkflow.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Institute of Medicine (12 February 1999). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nap.edu\/catalog\/6364\" target=\"_blank\"><i>Chemical and Biological Terrorism: Research and Development to Improve Civilian Medical Response<\/i><\/a>. Washington, D.C.: National Academies Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17226%2F6364\" target=\"_blank\">10.17226\/6364<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-309-06195-7<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nap.edu\/catalog\/6364\" target=\"_blank\">http:\/\/www.nap.edu\/catalog\/6364<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Chemical+and+Biological+Terrorism%3A+Research+and+Development+to+Improve+Civilian+Medical+Response&rft.aulast=Institute+of+Medicine&rft.au=Institute+of+Medicine&rft.date=12+February+1999&rft.place=Washington%2C+D.C.&rft.pub=National+Academies+Press&rft_id=info:doi\/10.17226%2F6364&rft.isbn=978-0-309-06195-7&rft_id=http%3A%2F%2Fwww.nap.edu%2Fcatalog%2F6364&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Clifton, David Andrew; Hugueny, Samuel; Tarassenko, Lionel (1 December 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11265-010-0513-6\" target=\"_blank\">\"Novelty Detection with Multivariate Extreme Value Statistics\"<\/a> (in en). <i>Journal of Signal Processing Systems<\/i> <b>65<\/b> (3): 371\u2013389. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11265-010-0513-6\" target=\"_blank\">10.1007\/s11265-010-0513-6<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1939-8018\" target=\"_blank\">1939-8018<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11265-010-0513-6\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11265-010-0513-6<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Novelty+Detection+with+Multivariate+Extreme+Value+Statistics&rft.jtitle=Journal+of+Signal+Processing+Systems&rft.aulast=Clifton&rft.aufirst=David+Andrew&rft.au=Clifton%2C%26%2332%3BDavid+Andrew&rft.au=Hugueny%2C%26%2332%3BSamuel&rft.au=Tarassenko%2C%26%2332%3BLionel&rft.date=1+December+2011&rft.volume=65&rft.issue=3&rft.pages=371%E2%80%93389&rft_id=info:doi\/10.1007%2Fs11265-010-0513-6&rft.issn=1939-8018&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11265-010-0513-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFHuguenyCliftonTarassenko2011\">Hugueny, Samuel; Clifton, David A.; Tarassenko, Lionel (2011), Fred, Ana; Filipe, Joaquim; Gamboa, Hugo, eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-18472-7_16\" target=\"_blank\">\"Probabilistic Patient Monitoring with Multivariate, Multimodal Extreme Value Theory\"<\/a>, <i>Biomedical Engineering Systems and Technologies<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>127<\/b>: 199\u2013211, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-642-18472-7_16\" target=\"_blank\">10.1007\/978-3-642-18472-7_16<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-642-18471-0<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-18472-7_16\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-642-18472-7_16<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-05-16<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Probabilistic+Patient+Monitoring+with+Multivariate%2C+Multimodal+Extreme+Value+Theory&rft.jtitle=Biomedical+Engineering+Systems+and+Technologies&rft.aulast=Hugueny&rft.aufirst=Samuel&rft.au=Hugueny%2C%26%2332%3BSamuel&rft.au=Clifton%2C%26%2332%3BDavid+A.&rft.au=Tarassenko%2C%26%2332%3BLionel&rft.date=2011&rft.volume=127&rft.pages=199%E2%80%93211&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-642-18472-7_16&rft.isbn=978-3-642-18471-0&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-642-18472-7_16&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Meredith, D. J.; Clifton, D.; Charlton, P.; Brooks, J.; Pugh, C. W.; Tarassenko, L. (1 March 2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.tandfonline.com\/doi\/full\/10.3109\/03091902.2011.638965\" target=\"_blank\">\"Photoplethysmographic derivation of respiratory rate: a review of relevant physiology\"<\/a> (in en). <i>Journal of Medical Engineering & Technology<\/i> <b>36<\/b> (1): 1\u20137. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3109%2F03091902.2011.638965\" target=\"_blank\">10.3109\/03091902.2011.638965<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0309-1902\" target=\"_blank\">0309-1902<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.tandfonline.com\/doi\/full\/10.3109\/03091902.2011.638965\" target=\"_blank\">http:\/\/www.tandfonline.com\/doi\/full\/10.3109\/03091902.2011.638965<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Photoplethysmographic+derivation+of+respiratory+rate%3A+a+review+of+relevant+physiology&rft.jtitle=Journal+of+Medical+Engineering+%26+Technology&rft.aulast=Meredith&rft.aufirst=D.+J.&rft.au=Meredith%2C%26%2332%3BD.+J.&rft.au=Clifton%2C%26%2332%3BD.&rft.au=Charlton%2C%26%2332%3BP.&rft.au=Brooks%2C%26%2332%3BJ.&rft.au=Pugh%2C%26%2332%3BC.+W.&rft.au=Tarassenko%2C%26%2332%3BL.&rft.date=1+March+2012&rft.volume=36&rft.issue=1&rft.pages=1%E2%80%937&rft_id=info:doi\/10.3109%2F03091902.2011.638965&rft.issn=0309-1902&rft_id=http%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.3109%2F03091902.2011.638965&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hunt, Xin J.; Emrani, Saba; Kabul, Ilknur Kaynar; Silva, Jorge (2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1807.02442\" target=\"_blank\"><i>Multi-Task Learning with Incomplete Data for Healthcare<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.48550%2FARXIV.1807.02442\" target=\"_blank\">10.48550\/ARXIV.1807.02442<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1807.02442\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1807.02442<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Multi-Task+Learning+with+Incomplete+Data+for+Healthcare&rft.aulast=Hunt&rft.aufirst=Xin+J.&rft.au=Hunt%2C%26%2332%3BXin+J.&rft.au=Emrani%2C%26%2332%3BSaba&rft.au=Kabul%2C%26%2332%3BIlknur+Kaynar&rft.au=Silva%2C%26%2332%3BJorge&rft.date=2018&rft_id=info:doi\/10.48550%2FARXIV.1807.02442&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1807.02442&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zhuang, Fuzhen; Qi, Zhiyuan; Duan, Keyu; Xi, Dongbo; Zhu, Yongchun; Zhu, Hengshu; Xiong, Hui; He, Qing (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ieeexplore.ieee.org\/document\/9134370\/\" target=\"_blank\">\"A Comprehensive Survey on Transfer Learning\"<\/a>. <i>Proceedings of the IEEE<\/i> <b>109<\/b> (1): 43\u201376. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FJPROC.2020.3004555\" target=\"_blank\">10.1109\/JPROC.2020.3004555<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0018-9219\" target=\"_blank\">0018-9219<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ieeexplore.ieee.org\/document\/9134370\/\" target=\"_blank\">https:\/\/ieeexplore.ieee.org\/document\/9134370\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Comprehensive+Survey+on+Transfer+Learning&rft.jtitle=Proceedings+of+the+IEEE&rft.aulast=Zhuang&rft.aufirst=Fuzhen&rft.au=Zhuang%2C%26%2332%3BFuzhen&rft.au=Qi%2C%26%2332%3BZhiyuan&rft.au=Duan%2C%26%2332%3BKeyu&rft.au=Xi%2C%26%2332%3BDongbo&rft.au=Zhu%2C%26%2332%3BYongchun&rft.au=Zhu%2C%26%2332%3BHengshu&rft.au=Xiong%2C%26%2332%3BHui&rft.au=He%2C%26%2332%3BQing&rft.date=1+January+2021&rft.volume=109&rft.issue=1&rft.pages=43%E2%80%9376&rft_id=info:doi\/10.1109%2FJPROC.2020.3004555&rft.issn=0018-9219&rft_id=https%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F9134370%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Qin, Jiahu; Ma, Qichao; Shi, Yang; Wang, Long (1 June 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7776972\/\" target=\"_blank\">\"Recent Advances in Consensus of Multi-Agent Systems: A Brief Survey\"<\/a>. <i>IEEE Transactions on Industrial Electronics<\/i> <b>64<\/b> (6): 4972\u20134983. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTIE.2016.2636810\" target=\"_blank\">10.1109\/TIE.2016.2636810<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0278-0046\" target=\"_blank\">0278-0046<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7776972\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7776972\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Recent+Advances+in+Consensus+of+Multi-Agent+Systems%3A+A+Brief+Survey&rft.jtitle=IEEE+Transactions+on+Industrial+Electronics&rft.aulast=Qin&rft.aufirst=Jiahu&rft.au=Qin%2C%26%2332%3BJiahu&rft.au=Ma%2C%26%2332%3BQichao&rft.au=Shi%2C%26%2332%3BYang&rft.au=Wang%2C%26%2332%3BLong&rft.date=1+June+2017&rft.volume=64&rft.issue=6&rft.pages=4972%E2%80%934983&rft_id=info:doi\/10.1109%2FTIE.2016.2636810&rft.issn=0278-0046&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7776972%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-46\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-46\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zheng, Yuanshi; Zhao, Qi; Ma, Jingying; Wang, Long (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167691119300179\" target=\"_blank\">\"Second-order consensus of hybrid multi-agent systems\"<\/a> (in en). <i>Systems & Control Letters<\/i> <b>125<\/b>: 51\u201358. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.sysconle.2019.01.009\" target=\"_blank\">10.1016\/j.sysconle.2019.01.009<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167691119300179\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167691119300179<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Second-order+consensus+of+hybrid+multi-agent+systems&rft.jtitle=Systems+%26+Control+Letters&rft.aulast=Zheng&rft.aufirst=Yuanshi&rft.au=Zheng%2C%26%2332%3BYuanshi&rft.au=Zhao%2C%26%2332%3BQi&rft.au=Ma%2C%26%2332%3BJingying&rft.au=Wang%2C%26%2332%3BLong&rft.date=1+March+2019&rft.volume=125&rft.pages=51%E2%80%9358&rft_id=info:doi\/10.1016%2Fj.sysconle.2019.01.009&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0167691119300179&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-47\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-47\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kwak, Gloria Hyunjung; Hui, Pan (2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/arxiv.org\/abs\/1909.00384\" target=\"_blank\"><i>DeepHealth: Review and challenges of artificial intelligence in health informatics<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.48550%2FARXIV.1909.00384\" target=\"_blank\">10.48550\/ARXIV.1909.00384<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/arxiv.org\/abs\/1909.00384\" target=\"_blank\">https:\/\/arxiv.org\/abs\/1909.00384<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=DeepHealth%3A+Review+and+challenges+of+artificial+intelligence+in+health+informatics&rft.aulast=Kwak&rft.aufirst=Gloria+Hyunjung&rft.au=Kwak%2C%26%2332%3BGloria+Hyunjung&rft.au=Hui%2C%26%2332%3BPan&rft.date=2019&rft_id=info:doi\/10.48550%2FARXIV.1909.00384&rft_id=https%3A%2F%2Farxiv.org%2Fabs%2F1909.00384&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hersh, William; Cimino, James; Payne, Philip R.O.; Embi, Peter; Logan, Judith; Weiner, Mark; Bernstam, Elmer V.; Lehmann, Harold <i>et al.<\/i> (1 October 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/egems.journal.ubiquity.website\/\/article\/10.13063\/2327-9214.1018\/\" target=\"_blank\">\"Recommendations for the Use of Operational Electronic Health Record Data in Comparative Effectiveness Research\"<\/a>. <i>eGEMs (Generating Evidence & Methods to improve patient outcomes)<\/i> <b>1<\/b> (1): 14. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.13063%2F2327-9214.1018\" target=\"_blank\">10.13063\/2327-9214.1018<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2327-9214\" target=\"_blank\">2327-9214<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4371471\/\" target=\"_blank\">PMC4371471<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25848563\" target=\"_blank\">25848563<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/egems.journal.ubiquity.website\/\/article\/10.13063\/2327-9214.1018\/\" target=\"_blank\">https:\/\/egems.journal.ubiquity.website\/\/article\/10.13063\/2327-9214.1018\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Recommendations+for+the+Use+of+Operational+Electronic+Health+Record+Data+in+Comparative+Effectiveness+Research&rft.jtitle=eGEMs+%28Generating+Evidence+%26+Methods+to+improve+patient+outcomes%29&rft.aulast=Hersh&rft.aufirst=William&rft.au=Hersh%2C%26%2332%3BWilliam&rft.au=Cimino%2C%26%2332%3BJames&rft.au=Payne%2C%26%2332%3BPhilip+R.O.&rft.au=Embi%2C%26%2332%3BPeter&rft.au=Logan%2C%26%2332%3BJudith&rft.au=Weiner%2C%26%2332%3BMark&rft.au=Bernstam%2C%26%2332%3BElmer+V.&rft.au=Lehmann%2C%26%2332%3BHarold&rft.au=Hripcsak%2C%26%2332%3BGeorge&rft.date=1+October+2013&rft.volume=1&rft.issue=1&rft.pages=14&rft_id=info:doi\/10.13063%2F2327-9214.1018&rft.issn=2327-9214&rft_id=info:pmc\/PMC4371471&rft_id=info:pmid\/25848563&rft_id=https%3A%2F%2Fegems.journal.ubiquity.website%2F%2Farticle%2F10.13063%2F2327-9214.1018%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-49\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_49-0\">49.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_49-1\">49.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Amoozegar, J.B.; Blumenfeld, B.H.; Brown, S.L. et al. (2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.rti.org\/publication\/building-data-capacity-patient-centered-outcomes-research-hhs\" target=\"_blank\">\"Building data capacity for patient-centered outcomes research in HHS: A formative evaluation of 2012-2016 projects\"<\/a>. Division of Healthcare Quality and Outcomes Office of Health Policy\/ASPE\/HHS<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.rti.org\/publication\/building-data-capacity-patient-centered-outcomes-research-hhs\" target=\"_blank\">https:\/\/www.rti.org\/publication\/building-data-capacity-patient-centered-outcomes-research-hhs<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Building+data+capacity+for+patient-centered+outcomes+research+in+HHS%3A+A+formative+evaluation+of+2012-2016+projects&rft.atitle=&rft.aulast=Amoozegar%2C+J.B.%3B+Blumenfeld%2C+B.H.%3B+Brown%2C+S.L.+et+al.&rft.au=Amoozegar%2C+J.B.%3B+Blumenfeld%2C+B.H.%3B+Brown%2C+S.L.+et+al.&rft.date=2017&rft.pub=Division+of+Healthcare+Quality+and+Outcomes+Office+of+Health+Policy%2FASPE%2FHHS&rft_id=https%3A%2F%2Fwww.rti.org%2Fpublication%2Fbuilding-data-capacity-patient-centered-outcomes-research-hhs&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-50\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-50\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ogunyemi, Omolola I.; Meeker, Daniella; Kim, Hyeon-Eui; Ashish, Naveen; Farzaneh, Seena; Boxwala, Aziz (1 August 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journals.lww.com\/00005650-201308001-00009\" target=\"_blank\">\"Identifying Appropriate Reference Data Models for Comparative Effectiveness Research (CER) Studies Based on Data from Clinical Information Systems\"<\/a> (in en). <i>Medical Care<\/i> <b>51<\/b> (Supplement 8Suppl 3): S45\u2013S52. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FMLR.0b013e31829b1e0b\" target=\"_blank\">10.1097\/MLR.0b013e31829b1e0b<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0025-7079\" target=\"_blank\">0025-7079<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journals.lww.com\/00005650-201308001-00009\" target=\"_blank\">https:\/\/journals.lww.com\/00005650-201308001-00009<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identifying+Appropriate+Reference+Data+Models+for+Comparative+Effectiveness+Research+%28CER%29+Studies+Based+on+Data+from+Clinical+Information+Systems&rft.jtitle=Medical+Care&rft.aulast=Ogunyemi&rft.aufirst=Omolola+I.&rft.au=Ogunyemi%2C%26%2332%3BOmolola+I.&rft.au=Meeker%2C%26%2332%3BDaniella&rft.au=Kim%2C%26%2332%3BHyeon-Eui&rft.au=Ashish%2C%26%2332%3BNaveen&rft.au=Farzaneh%2C%26%2332%3BSeena&rft.au=Boxwala%2C%26%2332%3BAziz&rft.date=1+August+2013&rft.volume=51&rft.issue=Supplement+8Suppl+3&rft.pages=S45%E2%80%93S52&rft_id=info:doi\/10.1097%2FMLR.0b013e31829b1e0b&rft.issn=0025-7079&rft_id=https%3A%2F%2Fjournals.lww.com%2F00005650-201308001-00009&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-51\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-51\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Danciu, Ioana; Cowan, James D.; Basford, Melissa; Wang, Xiaoming; Saip, Alexander; Osgood, Susan; Shirey-Rice, Jana; Kirby, Jacqueline <i>et al.<\/i> (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046414000392\" target=\"_blank\">\"Secondary use of clinical data: The Vanderbilt approach\"<\/a> (in en). <i>Journal of Biomedical Informatics<\/i> <b>52<\/b>: 28\u201335. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbi.2014.02.003\" target=\"_blank\">10.1016\/j.jbi.2014.02.003<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4133331\/\" target=\"_blank\">PMC4133331<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24534443\" target=\"_blank\">24534443<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046414000392\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1532046414000392<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Secondary+use+of+clinical+data%3A+The+Vanderbilt+approach&rft.jtitle=Journal+of+Biomedical+Informatics&rft.aulast=Danciu&rft.aufirst=Ioana&rft.au=Danciu%2C%26%2332%3BIoana&rft.au=Cowan%2C%26%2332%3BJames+D.&rft.au=Basford%2C%26%2332%3BMelissa&rft.au=Wang%2C%26%2332%3BXiaoming&rft.au=Saip%2C%26%2332%3BAlexander&rft.au=Osgood%2C%26%2332%3BSusan&rft.au=Shirey-Rice%2C%26%2332%3BJana&rft.au=Kirby%2C%26%2332%3BJacqueline&rft.au=Harris%2C%26%2332%3BPaul+A.&rft.date=1+December+2014&rft.volume=52&rft.pages=28%E2%80%9335&rft_id=info:doi\/10.1016%2Fj.jbi.2014.02.003&rft_id=info:pmc\/PMC4133331&rft_id=info:pmid\/24534443&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1532046414000392&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-52\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-52\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Masys, Daniel R.; Harris, Paul A.; Fearn, Paul A.; Kohane, Isaac S. (29 August 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.3004032\" target=\"_blank\">\"Designing a Public Square for Research Computing\"<\/a> (in en). <i>Science Translational Medicine<\/i> <b>4<\/b> (149). <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1126%2Fscitranslmed.3004032\" target=\"_blank\">10.1126\/scitranslmed.3004032<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1946-6234\" target=\"_blank\">1946-6234<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3725749\/\" target=\"_blank\">PMC3725749<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22932220\" target=\"_blank\">22932220<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.3004032\" target=\"_blank\">https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.3004032<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Designing+a+Public+Square+for+Research+Computing&rft.jtitle=Science+Translational+Medicine&rft.aulast=Masys&rft.aufirst=Daniel+R.&rft.au=Masys%2C%26%2332%3BDaniel+R.&rft.au=Harris%2C%26%2332%3BPaul+A.&rft.au=Fearn%2C%26%2332%3BPaul+A.&rft.au=Kohane%2C%26%2332%3BIsaac+S.&rft.date=29+August+2012&rft.volume=4&rft.issue=149&rft_id=info:doi\/10.1126%2Fscitranslmed.3004032&rft.issn=1946-6234&rft_id=info:pmc\/PMC3725749&rft_id=info:pmid\/22932220&rft_id=https%3A%2F%2Fwww.science.org%2Fdoi%2F10.1126%2Fscitranslmed.3004032&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-53\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-53\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Murphy, Shawn; Churchill, Susanne; Bry, Lynn; Chueh, Henry; Weiss, Scott; Lazarus, Ross; Zeng, Qing; Dubey, Anil <i>et al.<\/i> (1 September 2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.094615.109\" target=\"_blank\">\"Instrumenting the health care enterprise for discovery research in the genomic era\"<\/a> (in en). <i>Genome Research<\/i> <b>19<\/b> (9): 1675\u20131681. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1101%2Fgr.094615.109\" target=\"_blank\">10.1101\/gr.094615.109<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1088-9051\" target=\"_blank\">1088-9051<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2752136\/\" target=\"_blank\">PMC2752136<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19602638\" target=\"_blank\">19602638<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.094615.109\" target=\"_blank\">http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.094615.109<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Instrumenting+the+health+care+enterprise+for+discovery+research+in+the+genomic+era&rft.jtitle=Genome+Research&rft.aulast=Murphy&rft.aufirst=Shawn&rft.au=Murphy%2C%26%2332%3BShawn&rft.au=Churchill%2C%26%2332%3BSusanne&rft.au=Bry%2C%26%2332%3BLynn&rft.au=Chueh%2C%26%2332%3BHenry&rft.au=Weiss%2C%26%2332%3BScott&rft.au=Lazarus%2C%26%2332%3BRoss&rft.au=Zeng%2C%26%2332%3BQing&rft.au=Dubey%2C%26%2332%3BAnil&rft.au=Gainer%2C%26%2332%3BVivian&rft.date=1+September+2009&rft.volume=19&rft.issue=9&rft.pages=1675%E2%80%931681&rft_id=info:doi\/10.1101%2Fgr.094615.109&rft.issn=1088-9051&rft_id=info:pmc\/PMC2752136&rft_id=info:pmid\/19602638&rft_id=http%3A%2F%2Fgenome.cshlp.org%2Flookup%2Fdoi%2F10.1101%2Fgr.094615.109&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-54\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-54\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hripcsak, George; Duke, Jon D.; Shah, Nigam H.; Reich, Christian G.; Huser, Vojtech; Schuemie, Martijn J.; Suchard, Marc A.; Park, Rae Woong <i>et al.<\/i> (2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26262116\" target=\"_blank\">\"Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers\"<\/a>. <i>Studies in Health Technology and Informatics<\/i> <b>216<\/b>: 574\u2013578. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1879-8365\" target=\"_blank\">1879-8365<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/4815923\/\" target=\"_blank\">4815923<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26262116\" target=\"_blank\">26262116<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26262116\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/26262116<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Observational+Health+Data+Sciences+and+Informatics+%28OHDSI%29%3A+Opportunities+for+Observational+Researchers&rft.jtitle=Studies+in+Health+Technology+and+Informatics&rft.aulast=Hripcsak&rft.aufirst=George&rft.au=Hripcsak%2C%26%2332%3BGeorge&rft.au=Duke%2C%26%2332%3BJon+D.&rft.au=Shah%2C%26%2332%3BNigam+H.&rft.au=Reich%2C%26%2332%3BChristian+G.&rft.au=Huser%2C%26%2332%3BVojtech&rft.au=Schuemie%2C%26%2332%3BMartijn+J.&rft.au=Suchard%2C%26%2332%3BMarc+A.&rft.au=Park%2C%26%2332%3BRae+Woong&rft.au=Wong%2C%26%2332%3BIan+Chi+Kei&rft.date=2015&rft.volume=216&rft.pages=574%E2%80%93578&rft.issn=1879-8365&rft_id=info:pmc\/4815923&rft_id=info:pmid\/26262116&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26262116&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-55\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_55-0\">55.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_55-1\">55.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Bodavala, R. (1998). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/cdn1.sph.harvard.edu\/wp-content\/uploads\/sites\/114\/2012\/10\/rp176.pdf\" target=\"_blank\">\"Evaluation of Health Management Information System in India: Need for Computerized Databases in HMIS\"<\/a> (PDF). Harvard School of Public Health<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/cdn1.sph.harvard.edu\/wp-content\/uploads\/sites\/114\/2012\/10\/rp176.pdf\" target=\"_blank\">https:\/\/cdn1.sph.harvard.edu\/wp-content\/uploads\/sites\/114\/2012\/10\/rp176.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Evaluation+of+Health+Management+Information+System+in+India%3A+Need+for+Computerized+Databases+in+HMIS&rft.atitle=&rft.aulast=Bodavala%2C+R.&rft.au=Bodavala%2C+R.&rft.date=1998&rft.pub=Harvard+School+of+Public+Health&rft_id=https%3A%2F%2Fcdn1.sph.harvard.edu%2Fwp-content%2Fuploads%2Fsites%2F114%2F2012%2F10%2Frp176.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-56\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-56\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sarbadhikari, Suptendra Nath (1 April 2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-005-3001-y\" target=\"_blank\">\"The State of Medical Informatics in India: A Roadmap for Optimal Organization\"<\/a> (in en). <i>Journal of Medical Systems<\/i> <b>29<\/b> (2): 125\u2013141. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10916-005-3001-y\" target=\"_blank\">10.1007\/s10916-005-3001-y<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0148-5598\" target=\"_blank\">0148-5598<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10916-005-3001-y\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10916-005-3001-y<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+State+of+Medical+Informatics+in+India%3A+A+Roadmap+for+Optimal+Organization&rft.jtitle=Journal+of+Medical+Systems&rft.aulast=Sarbadhikari&rft.aufirst=Suptendra+Nath&rft.au=Sarbadhikari%2C%26%2332%3BSuptendra+Nath&rft.date=1+April+2005&rft.volume=29&rft.issue=2&rft.pages=125%E2%80%93141&rft_id=info:doi\/10.1007%2Fs10916-005-3001-y&rft.issn=0148-5598&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10916-005-3001-y&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-57\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-57\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Singh, A.K.; Kohli, M.; Trell, E.; Wigertz, O.; Kohli, S. (1 April 1997). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505696012518\" target=\"_blank\">\"Bhorugram (India): revisited A 4 year follow-up of a computer-based information system for distributed MCH services\"<\/a> (in en). <i>International Journal of Medical Informatics<\/i> <b>44<\/b> (2): 117\u2013125. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS1386-5056%2896%2901251-8\" target=\"_blank\">10.1016\/S1386-5056(96)01251-8<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505696012518\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505696012518<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bhorugram+%28India%29%3A+revisited+A+4+year+follow-up+of+a+computer-based+information+system+for+distributed+MCH+services&rft.jtitle=International+Journal+of+Medical+Informatics&rft.aulast=Singh&rft.aufirst=A.K.&rft.au=Singh%2C%26%2332%3BA.K.&rft.au=Kohli%2C%26%2332%3BM.&rft.au=Trell%2C%26%2332%3BE.&rft.au=Wigertz%2C%26%2332%3BO.&rft.au=Kohli%2C%26%2332%3BS.&rft.date=1+April+1997&rft.volume=44&rft.issue=2&rft.pages=117%E2%80%93125&rft_id=info:doi\/10.1016%2FS1386-5056%2896%2901251-8&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1386505696012518&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-58\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-58\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chandrasekhar, C. 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(2001). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11584733\" target=\"_blank\">\"Information and communication technologies and health in low income countries: the potential and the constraints\"<\/a>. <i>Bulletin of the World Health Organization<\/i> <b>79<\/b> (9): 850\u2013855. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0042-9686\" target=\"_blank\">0042-9686<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/2566653\/\" target=\"_blank\">2566653<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11584733\" target=\"_blank\">11584733<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/11584733\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/11584733<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Information+and+communication+technologies+and+health+in+low+income+countries%3A+the+potential+and+the+constraints&rft.jtitle=Bulletin+of+the+World+Health+Organization&rft.aulast=Chandrasekhar&rft.aufirst=C.+P.&rft.au=Chandrasekhar%2C%26%2332%3BC.+P.&rft.au=Ghosh%2C%26%2332%3BJ.&rft.date=2001&rft.volume=79&rft.issue=9&rft.pages=850%E2%80%93855&rft.issn=0042-9686&rft_id=info:pmc\/2566653&rft_id=info:pmid\/11584733&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F11584733&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-59\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-59\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zodpey, S. 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Eickholt, Jesse; Cheng, Jianlin (1 January 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6872810\/\" target=\"_blank\">\"A Deep Learning Network Approach to ab initio Protein Secondary Structure Prediction\"<\/a>. <i>IEEE\/ACM Transactions on Computational Biology and Bioinformatics<\/i> <b>12<\/b> (1): 103\u2013112. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTCBB.2014.2343960\" target=\"_blank\">10.1109\/TCBB.2014.2343960<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1545-5963\" target=\"_blank\">1545-5963<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4348072\/\" target=\"_blank\">PMC4348072<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25750595\" target=\"_blank\">25750595<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6872810\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/6872810\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Deep+Learning+Network+Approach+to+ab+initio+Protein+Secondary+Structure+Prediction&rft.jtitle=IEEE%2FACM+Transactions+on+Computational+Biology+and+Bioinformatics&rft.aulast=Spencer&rft.aufirst=Matt&rft.au=Spencer%2C%26%2332%3BMatt&rft.au=Eickholt%2C%26%2332%3BJesse&rft.au=Cheng%2C%26%2332%3BJianlin&rft.date=1+January+2015&rft.volume=12&rft.issue=1&rft.pages=103%E2%80%93112&rft_id=info:doi\/10.1109%2FTCBB.2014.2343960&rft.issn=1545-5963&rft_id=info:pmc\/PMC4348072&rft_id=info:pmid\/25750595&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6872810%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-61\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-61\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Quang, Daniel; Chen, Yifei; Xie, Xiaohui (1 March 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/bioinformatics\/article-lookup\/doi\/10.1093\/bioinformatics\/btu703\" target=\"_blank\">\"DANN: a deep learning approach for annotating the pathogenicity of genetic variants\"<\/a> (in en). <i>Bioinformatics<\/i> <b>31<\/b> (5): 761\u2013763. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fbioinformatics%2Fbtu703\" target=\"_blank\">10.1093\/bioinformatics\/btu703<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1367-4803\" target=\"_blank\">1367-4803<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4341060\/\" target=\"_blank\">PMC4341060<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25338716\" target=\"_blank\">25338716<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/bioinformatics\/article-lookup\/doi\/10.1093\/bioinformatics\/btu703\" target=\"_blank\">https:\/\/academic.oup.com\/bioinformatics\/article-lookup\/doi\/10.1093\/bioinformatics\/btu703<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DANN%3A+a+deep+learning+approach+for+annotating+the+pathogenicity+of+genetic+variants&rft.jtitle=Bioinformatics&rft.aulast=Quang&rft.aufirst=Daniel&rft.au=Quang%2C%26%2332%3BDaniel&rft.au=Chen%2C%26%2332%3BYifei&rft.au=Xie%2C%26%2332%3BXiaohui&rft.date=1+March+2015&rft.volume=31&rft.issue=5&rft.pages=761%E2%80%93763&rft_id=info:doi\/10.1093%2Fbioinformatics%2Fbtu703&rft.issn=1367-4803&rft_id=info:pmc\/PMC4341060&rft_id=info:pmid\/25338716&rft_id=https%3A%2F%2Facademic.oup.com%2Fbioinformatics%2Farticle-lookup%2Fdoi%2F10.1093%2Fbioinformatics%2Fbtu703&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-62\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-62\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zeng, Tao; Li, Rongjian; Mukkamala, Ravi; Ye, Jieping; Ji, Shuiwang (1 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-015-0553-9\" target=\"_blank\">\"Deep convolutional neural networks for annotating gene expression patterns in the mouse brain\"<\/a> (in en). <i>BMC Bioinformatics<\/i> <b>16<\/b> (1): 147. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2Fs12859-015-0553-9\" target=\"_blank\">10.1186\/s12859-015-0553-9<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1471-2105\" target=\"_blank\">1471-2105<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4432953\/\" target=\"_blank\">PMC4432953<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25948335\" target=\"_blank\">25948335<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-015-0553-9\" target=\"_blank\">https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-015-0553-9<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Deep+convolutional+neural+networks+for+annotating+gene+expression+patterns+in+the+mouse+brain&rft.jtitle=BMC+Bioinformatics&rft.aulast=Zeng&rft.aufirst=Tao&rft.au=Zeng%2C%26%2332%3BTao&rft.au=Li%2C%26%2332%3BRongjian&rft.au=Mukkamala%2C%26%2332%3BRavi&rft.au=Ye%2C%26%2332%3BJieping&rft.au=Ji%2C%26%2332%3BShuiwang&rft.date=1+December+2015&rft.volume=16&rft.issue=1&rft.pages=147&rft_id=info:doi\/10.1186%2Fs12859-015-0553-9&rft.issn=1471-2105&rft_id=info:pmc\/PMC4432953&rft_id=info:pmid\/25948335&rft_id=https%3A%2F%2Fbmcbioinformatics.biomedcentral.com%2Farticles%2F10.1186%2Fs12859-015-0553-9&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-63\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-63\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ditzler, Gregory; Polikar, Robi; Rosen, Gail (1 September 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7219432\/\" target=\"_blank\">\"Multi-Layer and Recursive Neural Networks for Metagenomic Classification\"<\/a>. <i>IEEE Transactions on NanoBioscience<\/i> <b>14<\/b> (6): 608\u2013616. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTNB.2015.2461219\" target=\"_blank\">10.1109\/TNB.2015.2461219<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1536-1241\" target=\"_blank\">1536-1241<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/7219432\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/7219432\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Multi-Layer+and+Recursive+Neural+Networks+for+Metagenomic+Classification&rft.jtitle=IEEE+Transactions+on+NanoBioscience&rft.aulast=Ditzler&rft.aufirst=Gregory&rft.au=Ditzler%2C%26%2332%3BGregory&rft.au=Polikar%2C%26%2332%3BRobi&rft.au=Rosen%2C%26%2332%3BGail&rft.date=1+September+2015&rft.volume=14&rft.issue=6&rft.pages=608%E2%80%93616&rft_id=info:doi\/10.1109%2FTNB.2015.2461219&rft.issn=1536-1241&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F7219432%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-64\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-64\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Raghupathi, Wullianallur; Raghupathi, Viju (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1186\/2047-2501-2-3\" target=\"_blank\">\"Big data analytics in healthcare: promise and potential\"<\/a> (in en). <i>Health Information Science and Systems<\/i> <b>2<\/b> (1): 3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1186%2F2047-2501-2-3\" target=\"_blank\">10.1186\/2047-2501-2-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2047-2501\" target=\"_blank\">2047-2501<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4341817\/\" target=\"_blank\">PMC4341817<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25825667\" target=\"_blank\">25825667<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1186\/2047-2501-2-3\" target=\"_blank\">http:\/\/link.springer.com\/10.1186\/2047-2501-2-3<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+data+analytics+in+healthcare%3A+promise+and+potential&rft.jtitle=Health+Information+Science+and+Systems&rft.aulast=Raghupathi&rft.aufirst=Wullianallur&rft.au=Raghupathi%2C%26%2332%3BWullianallur&rft.au=Raghupathi%2C%26%2332%3BViju&rft.date=1+December+2014&rft.volume=2&rft.issue=1&rft.pages=3&rft_id=info:doi\/10.1186%2F2047-2501-2-3&rft.issn=2047-2501&rft_id=info:pmc\/PMC4341817&rft_id=info:pmid\/25825667&rft_id=http%3A%2F%2Flink.springer.com%2F10.1186%2F2047-2501-2-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-65\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-65\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">M\u00fcller, H.; Freytag, J.-C. (2003). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/tarjomefa.com\/wp-content\/uploads\/2015\/06\/3229-English.pdf\" target=\"_blank\">\"Problems, Methods, and Challenges in Comprehensive Data Cleansing\"<\/a> (PDF). Humboldt-Universit\u00e4t zu Berlin zu Berlin<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/tarjomefa.com\/wp-content\/uploads\/2015\/06\/3229-English.pdf\" target=\"_blank\">https:\/\/tarjomefa.com\/wp-content\/uploads\/2015\/06\/3229-English.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Problems%2C+Methods%2C+and+Challenges+in+Comprehensive+Data+Cleansing&rft.atitle=&rft.aulast=M%C3%BCller%2C+H.%3B+Freytag%2C+J.-C.&rft.au=M%C3%BCller%2C+H.%3B+Freytag%2C+J.-C.&rft.date=2003&rft.pub=Humboldt-Universit%C3%A4t+zu+Berlin+zu+Berlin&rft_id=https%3A%2F%2Ftarjomefa.com%2Fwp-content%2Fuploads%2F2015%2F06%2F3229-English.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Holzinger, Andreas; Simonic, Klaus-Martin, eds. (2011) (in en). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-25364-5\" target=\"_blank\"><i>Information Quality in e-Health: 7th Conference of the Workgroup Human-Computer Interaction and Usability Engineering of the Austrian Computer Society, USAB 2011, Graz, Austria, November 25-26, 2011. Proceedings<\/i><\/a>. Lecture Notes in Computer Science. <b>7058<\/b>. Berlin, Heidelberg: Springer Berlin Heidelberg. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-642-25364-5\" target=\"_blank\">10.1007\/978-3-642-25364-5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-642-25363-8<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-25364-5\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-642-25364-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Information+Quality+in+e-Health%3A+7th+Conference+of+the+Workgroup+Human-Computer+Interaction+and+Usability+Engineering+of+the+Austrian+Computer+Society%2C+USAB+2011%2C+Graz%2C+Austria%2C+November+25-26%2C+2011.+Proceedings&rft.date=2011&rft.series=Lecture+Notes+in+Computer+Science&rft.volume=7058&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-642-25364-5&rft.isbn=978-3-642-25363-8&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-642-25364-5&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-67\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-67\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Richesson, Rachel L.; Krischer, Jeffrey (1 November 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article\/14\/6\/687\/750453\" target=\"_blank\">\"Data Standards in Clinical Research: Gaps, Overlaps, Challenges and Future Directions\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>14<\/b> (6): 687\u2013696. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1197%2Fjamia.M2470\" target=\"_blank\">10.1197\/jamia.M2470<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1527-974X\" target=\"_blank\">1527-974X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2213488\/\" target=\"_blank\">PMC2213488<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17712081\" target=\"_blank\">17712081<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article\/14\/6\/687\/750453\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article\/14\/6\/687\/750453<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Data+Standards+in+Clinical+Research%3A+Gaps%2C+Overlaps%2C+Challenges+and+Future+Directions&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Richesson&rft.aufirst=Rachel+L.&rft.au=Richesson%2C%26%2332%3BRachel+L.&rft.au=Krischer%2C%26%2332%3BJeffrey&rft.date=1+November+2007&rft.volume=14&rft.issue=6&rft.pages=687%E2%80%93696&rft_id=info:doi\/10.1197%2Fjamia.M2470&rft.issn=1527-974X&rft_id=info:pmc\/PMC2213488&rft_id=info:pmid\/17712081&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle%2F14%2F6%2F687%2F750453&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-68\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_68-0\">68.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_68-1\">68.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kambatla, Karthik; Kollias, Giorgos; Kumar, Vipin; Grama, Ananth (1 July 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0743731514000057\" target=\"_blank\">\"Trends in big data analytics\"<\/a> (in en). <i>Journal of Parallel and Distributed Computing<\/i> <b>74<\/b> (7): 2561\u20132573. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jpdc.2014.01.003\" target=\"_blank\">10.1016\/j.jpdc.2014.01.003<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0743731514000057\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0743731514000057<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Trends+in+big+data+analytics&rft.jtitle=Journal+of+Parallel+and+Distributed+Computing&rft.aulast=Kambatla&rft.aufirst=Karthik&rft.au=Kambatla%2C%26%2332%3BKarthik&rft.au=Kollias%2C%26%2332%3BGiorgos&rft.au=Kumar%2C%26%2332%3BVipin&rft.au=Grama%2C%26%2332%3BAnanth&rft.date=1+July+2014&rft.volume=74&rft.issue=7&rft.pages=2561%E2%80%932573&rft_id=info:doi\/10.1016%2Fj.jpdc.2014.01.003&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0743731514000057&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-69\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-69\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Fitzmaurice, Garrett M.; Ravichandran, Caitlin (4 November 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.107.714618\" target=\"_blank\">\"A Primer in Longitudinal Data Analysis\"<\/a>. <i>Circulation<\/i> <b>118<\/b> (19): 2005\u20132010. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1161%2FCIRCULATIONAHA.107.714618\" target=\"_blank\">10.1161\/CIRCULATIONAHA.107.714618<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.107.714618\" target=\"_blank\">https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.107.714618<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Primer+in+Longitudinal+Data+Analysis&rft.jtitle=Circulation&rft.aulast=Fitzmaurice&rft.aufirst=Garrett+M.&rft.au=Fitzmaurice%2C%26%2332%3BGarrett+M.&rft.au=Ravichandran%2C%26%2332%3BCaitlin&rft.date=4+November+2008&rft.volume=118&rft.issue=19&rft.pages=2005%E2%80%932010&rft_id=info:doi\/10.1161%2FCIRCULATIONAHA.107.714618&rft_id=https%3A%2F%2Fwww.ahajournals.org%2Fdoi%2F10.1161%2FCIRCULATIONAHA.107.714618&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-70\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-70\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Verhagen, Evert; van der Beek, Allard; Twisk, Jos; Bouter, Lex; Bahr, Roald; van Mechelen, Willem (1 September 2004). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0363546503262177\" target=\"_blank\">\"The Effect of a Proprioceptive Balance Board Training Program for the Prevention of Ankle Sprains: A Prospective Controlled Trial\"<\/a> (in en). <i>The American Journal of Sports Medicine<\/i> <b>32<\/b> (6): 1385\u20131393. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F0363546503262177\" target=\"_blank\">10.1177\/0363546503262177<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0363-5465\" target=\"_blank\">0363-5465<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0363546503262177\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/0363546503262177<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Effect+of+a+Proprioceptive+Balance+Board+Training+Program+for+the+Prevention+of+Ankle+Sprains%3A+A+Prospective+Controlled+Trial&rft.jtitle=The+American+Journal+of+Sports+Medicine&rft.aulast=Verhagen&rft.aufirst=Evert&rft.au=Verhagen%2C%26%2332%3BEvert&rft.au=van+der+Beek%2C%26%2332%3BAllard&rft.au=Twisk%2C%26%2332%3BJos&rft.au=Bouter%2C%26%2332%3BLex&rft.au=Bahr%2C%26%2332%3BRoald&rft.au=van+Mechelen%2C%26%2332%3BWillem&rft.date=1+September+2004&rft.volume=32&rft.issue=6&rft.pages=1385%E2%80%931393&rft_id=info:doi\/10.1177%2F0363546503262177&rft.issn=0363-5465&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F0363546503262177&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-71\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-71\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Labrinidis, Alexandros; Jagadish, H. V. (1 August 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dl.acm.org\/doi\/10.14778\/2367502.2367572\" target=\"_blank\">\"Challenges and opportunities with big data\"<\/a> (in en). <i>Proceedings of the VLDB Endowment<\/i> <b>5<\/b> (12): 2032\u20132033. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.14778%2F2367502.2367572\" target=\"_blank\">10.14778\/2367502.2367572<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2150-8097\" target=\"_blank\">2150-8097<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dl.acm.org\/doi\/10.14778\/2367502.2367572\" target=\"_blank\">https:\/\/dl.acm.org\/doi\/10.14778\/2367502.2367572<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Challenges+and+opportunities+with+big+data&rft.jtitle=Proceedings+of+the+VLDB+Endowment&rft.aulast=Labrinidis&rft.aufirst=Alexandros&rft.au=Labrinidis%2C%26%2332%3BAlexandros&rft.au=Jagadish%2C%26%2332%3BH.+V.&rft.date=1+August+2012&rft.volume=5&rft.issue=12&rft.pages=2032%E2%80%932033&rft_id=info:doi\/10.14778%2F2367502.2367572&rft.issn=2150-8097&rft_id=https%3A%2F%2Fdl.acm.org%2Fdoi%2F10.14778%2F2367502.2367572&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-72\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_72-0\">72.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_72-1\">72.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFElgendyElragal2014\">Elgendy, Nada; Elragal, Ahmed (2014), Perner, Petra, ed., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-08976-8_16\" target=\"_blank\">\"Big Data Analytics: A Literature Review Paper\"<\/a>, <i>Advances in Data Mining. Applications and Theoretical Aspects<\/i> (Cham: Springer International Publishing) <b>8557<\/b>: 214\u2013227, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-08976-8_16\" target=\"_blank\">10.1007\/978-3-319-08976-8_16<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-08975-1<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-08976-8_16\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-08976-8_16<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-05-16<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+Data+Analytics%3A+A+Literature+Review+Paper&rft.jtitle=Advances+in+Data+Mining.+Applications+and+Theoretical+Aspects&rft.aulast=Elgendy&rft.aufirst=Nada&rft.au=Elgendy%2C%26%2332%3BNada&rft.au=Elragal%2C%26%2332%3BAhmed&rft.date=2014&rft.volume=8557&rft.pages=214%E2%80%93227&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-08976-8_16&rft.isbn=978-3-319-08975-1&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-08976-8_16&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-73\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_73-0\">73.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_73-1\">73.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Weippl, Edgar R. (2005). <i>Security in e-learning<\/i>. Advances in information security. New York, NY: Springer. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-387-24341-2.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Security+in+e-learning&rft.aulast=Weippl&rft.aufirst=Edgar+R.&rft.au=Weippl%2C%26%2332%3BEdgar+R.&rft.date=2005&rft.series=Advances+in+information+security&rft.place=New+York%2C+NY&rft.pub=Springer&rft.isbn=978-0-387-24341-2&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-74\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-74\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFKiesebergSchantlFr.C3.BChwirtWeippl2015\">Kieseberg, Peter; Schantl, Johannes; Fr\u00fchwirt, Peter; Weippl, Edgar; Holzinger, Andreas (2015), Guo, Yike; Friston, Karl; Aldo, Faisal <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-23344-4_36\" target=\"_blank\">\"Witnesses for the Doctor in the Loop\"<\/a> (in en), <i>Brain Informatics and Health<\/i> (Cham: Springer International Publishing) <b>9250<\/b>: 369\u2013378, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-23344-4_36\" target=\"_blank\">10.1007\/978-3-319-23344-4_36<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-23343-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-23344-4_36\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-23344-4_36<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-05-16<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Witnesses+for+the+Doctor+in+the+Loop&rft.jtitle=Brain+Informatics+and+Health&rft.aulast=Kieseberg&rft.aufirst=Peter&rft.au=Kieseberg%2C%26%2332%3BPeter&rft.au=Schantl%2C%26%2332%3BJohannes&rft.au=Fr%C3%BChwirt%2C%26%2332%3BPeter&rft.au=Weippl%2C%26%2332%3BEdgar&rft.au=Holzinger%2C%26%2332%3BAndreas&rft.date=2015&rft.volume=9250&rft.pages=369%E2%80%93378&rft.place=Cham&rft.pub=Springer+International+Publishing&rft_id=info:doi\/10.1007%2F978-3-319-23344-4_36&rft.isbn=978-3-319-23343-7&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-319-23344-4_36&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-75\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-75\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFJeanquartierHolzinger2013\">Jeanquartier, Fleur; Holzinger, Andreas (2013), Cuzzocrea, Alfredo; Kittl, Christian; Simos, Dimitris E. <i>et al.<\/i>., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-40511-2_36\" target=\"_blank\">\"On Visual Analytics and Evaluation in Cell Physiology: A Case Study\"<\/a>, <i>Availability, Reliability, and Security in Information Systems and HCI<\/i> (Berlin, Heidelberg: Springer Berlin Heidelberg) <b>8127<\/b>: 495\u2013502, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-642-40511-2_36\" target=\"_blank\">10.1007\/978-3-642-40511-2_36<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-642-40510-5<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-642-40511-2_36\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-642-40511-2_36<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-05-16<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=On+Visual+Analytics+and+Evaluation+in+Cell+Physiology%3A+A+Case+Study&rft.jtitle=Availability%2C+Reliability%2C+and+Security+in+Information+Systems+and+HCI&rft.aulast=Jeanquartier&rft.aufirst=Fleur&rft.au=Jeanquartier%2C%26%2332%3BFleur&rft.au=Holzinger%2C%26%2332%3BAndreas&rft.date=2013&rft.volume=8127&rft.pages=495%E2%80%93502&rft.place=Berlin%2C+Heidelberg&rft.pub=Springer+Berlin+Heidelberg&rft_id=info:doi\/10.1007%2F978-3-642-40511-2_36&rft.isbn=978-3-642-40510-5&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2F978-3-642-40511-2_36&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-76\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-76\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chen, Min; Mao, Shiwen; Liu, Yunhao (1 April 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11036-013-0489-0\" target=\"_blank\">\"Big Data: A Survey\"<\/a> (in en). <i>Mobile Networks and Applications<\/i> <b>19<\/b> (2): 171\u2013209. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11036-013-0489-0\" target=\"_blank\">10.1007\/s11036-013-0489-0<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1383-469X\" target=\"_blank\">1383-469X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11036-013-0489-0\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11036-013-0489-0<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+Data%3A+A+Survey&rft.jtitle=Mobile+Networks+and+Applications&rft.aulast=Chen&rft.aufirst=Min&rft.au=Chen%2C%26%2332%3BMin&rft.au=Mao%2C%26%2332%3BShiwen&rft.au=Liu%2C%26%2332%3BYunhao&rft.date=1+April+2014&rft.volume=19&rft.issue=2&rft.pages=171%E2%80%93209&rft_id=info:doi\/10.1007%2Fs11036-013-0489-0&rft.issn=1383-469X&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11036-013-0489-0&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-77\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-77\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Holzinger, Andreas (1 June 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s40708-016-0042-6\" target=\"_blank\">\"Interactive machine learning for health informatics: when do we need the human-in-the-loop?\"<\/a> (in en). <i>Brain Informatics<\/i> <b>3<\/b> (2): 119\u2013131. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs40708-016-0042-6\" target=\"_blank\">10.1007\/s40708-016-0042-6<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2198-4018\" target=\"_blank\">2198-4018<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4883171\/\" target=\"_blank\">PMC4883171<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27747607\" target=\"_blank\">27747607<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s40708-016-0042-6\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s40708-016-0042-6<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Interactive+machine+learning+for+health+informatics%3A+when+do+we+need+the+human-in-the-loop%3F&rft.jtitle=Brain+Informatics&rft.aulast=Holzinger&rft.aufirst=Andreas&rft.au=Holzinger%2C%26%2332%3BAndreas&rft.date=1+June+2016&rft.volume=3&rft.issue=2&rft.pages=119%E2%80%93131&rft_id=info:doi\/10.1007%2Fs40708-016-0042-6&rft.issn=2198-4018&rft_id=info:pmc\/PMC4883171&rft_id=info:pmid\/27747607&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs40708-016-0042-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-78\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-78\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Solberg, Kristin Elisabeth (1 January 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0140673608600525\" target=\"_blank\">\"Telemedicine set to grow in India over the next 5 years\"<\/a> (in en). <i>The Lancet<\/i> <b>371<\/b> (9606): 17\u201318. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0140-6736%2808%2960052-5\" target=\"_blank\">10.1016\/S0140-6736(08)60052-5<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0140673608600525\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0140673608600525<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Telemedicine+set+to+grow+in+India+over+the+next+5+years&rft.jtitle=The+Lancet&rft.aulast=Solberg&rft.aufirst=Kristin+Elisabeth&rft.au=Solberg%2C%26%2332%3BKristin+Elisabeth&rft.date=1+January+2008&rft.volume=371&rft.issue=9606&rft.pages=17%E2%80%9318&rft_id=info:doi\/10.1016%2FS0140-6736%2808%2960052-5&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673608600525&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-79\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-79\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">eHealth Network (June 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ehealth.eletsonline.com\/2008\/06\/universalising-healthcare-through-telemedicine\/\" target=\"_blank\">\"Universalising healthcare through telemedicine\"<\/a>. <i>eHealth<\/i>. Elets Technomedia Pvt. Ltd<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/ehealth.eletsonline.com\/2008\/06\/universalising-healthcare-through-telemedicine\/\" target=\"_blank\">https:\/\/ehealth.eletsonline.com\/2008\/06\/universalising-healthcare-through-telemedicine\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Universalising+healthcare+through+telemedicine&rft.atitle=eHealth&rft.aulast=eHealth+Network&rft.au=eHealth+Network&rft.date=June+2008&rft.pub=Elets+Technomedia+Pvt.+Ltd&rft_id=https%3A%2F%2Fehealth.eletsonline.com%2F2008%2F06%2Funiversalising-healthcare-through-telemedicine%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-80\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-80\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Saxena, G.; Singh, J.P. (2003). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.themanager.org\/Resources\/Telemed.pdf\" target=\"_blank\">\"E-medicine in India: Hurdles and future prospects\"<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.themanager.org\/Resources\/Telemed.pdf\" target=\"_blank\">https:\/\/www.themanager.org\/Resources\/Telemed.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=E-medicine+in+India%3A+Hurdles+and+future+prospects&rft.atitle=&rft.aulast=Saxena%2C+G.%3B+Singh%2C+J.P.&rft.au=Saxena%2C+G.%3B+Singh%2C+J.P.&rft.date=2003&rft_id=https%3A%2F%2Fwww.themanager.org%2FResources%2FTelemed.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-81\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-81\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Massoudi, Barbara L.; Sobolevskaia, Diana (1 August 2021). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1726499\" target=\"_blank\">\"Keep Moving Forward: Health Informatics and Information Management beyond the COVID-19 Pandemic\"<\/a> (in en). <i>Yearbook of Medical Informatics<\/i> <b>30<\/b> (01): 075\u2013083. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1055%2Fs-0041-1726499\" target=\"_blank\">10.1055\/s-0041-1726499<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0943-4747\" target=\"_blank\">0943-4747<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8416200\/\" target=\"_blank\">PMC8416200<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34479380\" target=\"_blank\">34479380<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1726499\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1726499<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Keep+Moving+Forward%3A+Health+Informatics+and+Information+Management+beyond+the+COVID-19+Pandemic&rft.jtitle=Yearbook+of+Medical+Informatics&rft.aulast=Massoudi&rft.aufirst=Barbara+L.&rft.au=Massoudi%2C%26%2332%3BBarbara+L.&rft.au=Sobolevskaia%2C%26%2332%3BDiana&rft.date=1+August+2021&rft.volume=30&rft.issue=01&rft.pages=075%E2%80%93083&rft_id=info:doi\/10.1055%2Fs-0041-1726499&rft.issn=0943-4747&rft_id=info:pmc\/PMC8416200&rft_id=info:pmid\/34479380&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.1055%2Fs-0041-1726499&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-82\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_82-0\">82.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_82-1\">82.1<\/a><\/sup> <sup><a href=\"#cite_ref-:12_82-2\">82.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Anderson, James G. (1 May 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/17064955\" target=\"_blank\">\"Social, ethical and legal barriers to e-health\"<\/a>. <i>International Journal of Medical Informatics<\/i> <b>76<\/b> (5-6): 480\u2013483. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.ijmedinf.2006.09.016\" target=\"_blank\">10.1016\/j.ijmedinf.2006.09.016<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1386-5056\" target=\"_blank\">1386-5056<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17064955\" target=\"_blank\">17064955<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/17064955\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/17064955<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Social%2C+ethical+and+legal+barriers+to+e-health&rft.jtitle=International+Journal+of+Medical+Informatics&rft.aulast=Anderson&rft.aufirst=James+G.&rft.au=Anderson%2C%26%2332%3BJames+G.&rft.date=1+May+2007&rft.volume=76&rft.issue=5-6&rft.pages=480%E2%80%93483&rft_id=info:doi\/10.1016%2Fj.ijmedinf.2006.09.016&rft.issn=1386-5056&rft_id=info:pmid\/17064955&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F17064955&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-83\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-83\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wyatt, J. C (9 June 2001). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.322.7299.1378\" target=\"_blank\">\"The new NHS information technology strategy\"<\/a>. <i>BMJ<\/i> <b>322<\/b> (7299): 1378\u20131379. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fbmj.322.7299.1378\" target=\"_blank\">10.1136\/bmj.322.7299.1378<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1120460\/\" target=\"_blank\">PMC1120460<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11397729\" target=\"_blank\">11397729<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.322.7299.1378\" target=\"_blank\">https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.322.7299.1378<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+new+NHS+information+technology+strategy&rft.jtitle=BMJ&rft.aulast=Wyatt&rft.aufirst=J.+C&rft.au=Wyatt%2C%26%2332%3BJ.+C&rft.date=9+June+2001&rft.volume=322&rft.issue=7299&rft.pages=1378%E2%80%931379&rft_id=info:doi\/10.1136%2Fbmj.322.7299.1378&rft_id=info:pmc\/PMC1120460&rft_id=info:pmid\/11397729&rft_id=https%3A%2F%2Fwww.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fbmj.322.7299.1378&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:13-84\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:13_84-0\">84.0<\/a><\/sup> <sup><a href=\"#cite_ref-:13_84-1\">84.1<\/a><\/sup> <sup><a href=\"#cite_ref-:13_84-2\">84.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Berner, Eta S.; Moss, Jacqueline (1 November 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1197\/jamia.M1873\" target=\"_blank\">\"Informatics Challenges for the Impending Patient Information Explosion\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>12<\/b> (6): 614\u2013617. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1197%2Fjamia.M1873\" target=\"_blank\">10.1197\/jamia.M1873<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1067-5027\" target=\"_blank\">1067-5027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1294032\/\" target=\"_blank\">PMC1294032<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16049224\" target=\"_blank\">16049224<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1197\/jamia.M1873\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article-lookup\/doi\/10.1197\/jamia.M1873<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Informatics+Challenges+for+the+Impending+Patient+Information+Explosion&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Berner&rft.aufirst=Eta+S.&rft.au=Berner%2C%26%2332%3BEta+S.&rft.au=Moss%2C%26%2332%3BJacqueline&rft.date=1+November+2005&rft.volume=12&rft.issue=6&rft.pages=614%E2%80%93617&rft_id=info:doi\/10.1197%2Fjamia.M1873&rft.issn=1067-5027&rft_id=info:pmc\/PMC1294032&rft_id=info:pmid\/16049224&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle-lookup%2Fdoi%2F10.1197%2Fjamia.M1873&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-85\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-85\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Becker, Moritz Y. (1 May 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002139\" target=\"_blank\">\"Information governance in NHS's NPfIT: A case for policy specification\"<\/a> (in en). <i>International Journal of Medical Informatics<\/i> <b>76<\/b> (5-6): 432\u2013437. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.ijmedinf.2006.09.008\" target=\"_blank\">10.1016\/j.ijmedinf.2006.09.008<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002139\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386505606002139<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Information+governance+in+NHS%27s+NPfIT%3A+A+case+for+policy+specification&rft.jtitle=International+Journal+of+Medical+Informatics&rft.aulast=Becker&rft.aufirst=Moritz+Y.&rft.au=Becker%2C%26%2332%3BMoritz+Y.&rft.date=1+May+2007&rft.volume=76&rft.issue=5-6&rft.pages=432%E2%80%93437&rft_id=info:doi\/10.1016%2Fj.ijmedinf.2006.09.008&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1386505606002139&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-86\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-86\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.who.int\/standards\/classifications\/classification-of-diseases\" target=\"_blank\">\"International Statistical Classification of Diseases and Related Health Problems (ICD)\"<\/a>. World Health Organization<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.who.int\/standards\/classifications\/classification-of-diseases\" target=\"_blank\">https:\/\/www.who.int\/standards\/classifications\/classification-of-diseases<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=International+Statistical+Classification+of+Diseases+and+Related+Health+Problems+%28ICD%29&rft.atitle=&rft.pub=World+Health+Organization&rft_id=https%3A%2F%2Fwww.who.int%2Fstandards%2Fclassifications%2Fclassification-of-diseases&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-87\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-87\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.altexsoft.com\/blog\/data-standards-healthcare\/\" target=\"_blank\">\"Data Standards in Healthcare: Codes, Documents, and Exchange Formats\"<\/a>. <i>Altexsoft Blog<\/i>. Altexsoft. 23 October 2020<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.altexsoft.com\/blog\/data-standards-healthcare\/\" target=\"_blank\">https:\/\/www.altexsoft.com\/blog\/data-standards-healthcare\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Data+Standards+in+Healthcare%3A+Codes%2C+Documents%2C+and+Exchange+Formats&rft.atitle=Altexsoft+Blog&rft.date=23+October+2020&rft.pub=Altexsoft&rft_id=https%3A%2F%2Fwww.altexsoft.com%2Fblog%2Fdata-standards-healthcare%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-88\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-88\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">McGregor, Carolyn (1 June 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6513228\/\" target=\"_blank\">\"Big Data in Neonatal Intensive Care\"<\/a>. <i>Computer<\/i> <b>46<\/b> (6): 54\u201359. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FMC.2013.157\" target=\"_blank\">10.1109\/MC.2013.157<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0018-9162\" target=\"_blank\">0018-9162<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/6513228\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/6513228\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Big+Data+in+Neonatal+Intensive+Care&rft.jtitle=Computer&rft.aulast=McGregor&rft.aufirst=Carolyn&rft.au=McGregor%2C%26%2332%3BCarolyn&rft.date=1+June+2013&rft.volume=46&rft.issue=6&rft.pages=54%E2%80%9359&rft_id=info:doi\/10.1109%2FMC.2013.157&rft.issn=0018-9162&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F6513228%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-89\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-89\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Iosup, A; Ostermann, S; Yigitbasi, M N; Prodan, R; Fahringer, T; Epema, D H J (1 June 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5719609\/\" target=\"_blank\">\"Performance Analysis of Cloud Computing Services for Many-Tasks Scientific Computing\"<\/a>. <i>IEEE Transactions on Parallel and Distributed Systems<\/i> <b>22<\/b> (6): 931\u2013945. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FTPDS.2011.66\" target=\"_blank\">10.1109\/TPDS.2011.66<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1045-9219\" target=\"_blank\">1045-9219<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5719609\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/5719609\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Performance+Analysis+of+Cloud+Computing+Services+for+Many-Tasks+Scientific+Computing&rft.jtitle=IEEE+Transactions+on+Parallel+and+Distributed+Systems&rft.aulast=Iosup&rft.aufirst=A&rft.au=Iosup%2C%26%2332%3BA&rft.au=Ostermann%2C%26%2332%3BS&rft.au=Yigitbasi%2C%26%2332%3BM+N&rft.au=Prodan%2C%26%2332%3BR&rft.au=Fahringer%2C%26%2332%3BT&rft.au=Epema%2C%26%2332%3BD+H+J&rft.date=1+June+2011&rft.volume=22&rft.issue=6&rft.pages=931%E2%80%93945&rft_id=info:doi\/10.1109%2FTPDS.2011.66&rft.issn=1045-9219&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F5719609%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-90\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-90\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Deelman, Ewa; Singh, Gurmeet; Livny, Miron; Berriman, Bruce; Good, John (1 November 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5217932\/\" target=\"_blank\">\"The cost of doing science on the cloud: The Montage example\"<\/a>. <i>2008 SC - International Conference for High Performance Computing, Networking, Storage and Analysis<\/i> (Austin, TX, USA: IEEE): 1\u201312. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FSC.2008.5217932\" target=\"_blank\">10.1109\/SC.2008.5217932<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4244-2834-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5217932\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/5217932\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+cost+of+doing+science+on+the+cloud%3A+The+Montage+example&rft.jtitle=2008+SC+-+International+Conference+for+High+Performance+Computing%2C+Networking%2C+Storage+and+Analysis&rft.aulast=Deelman&rft.aufirst=Ewa&rft.au=Deelman%2C%26%2332%3BEwa&rft.au=Singh%2C%26%2332%3BGurmeet&rft.au=Livny%2C%26%2332%3BMiron&rft.au=Berriman%2C%26%2332%3BBruce&rft.au=Good%2C%26%2332%3BJohn&rft.date=1+November+2008&rft.pages=1%E2%80%9312&rft.place=Austin%2C+TX%2C+USA&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FSC.2008.5217932&rft.isbn=978-1-4244-2834-2&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F5217932%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-91\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-91\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wang, Lei; Zhan, Jianfeng; Shi, Weisong; Liang, Yi; Yuan, Lin (2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1646468.1646475\" target=\"_blank\">\"In cloud, do MTC or HTC service providers benefit from the economies of scale?\"<\/a> (in en). <i>Proceedings of the 2nd Workshop on Many-Task Computing on Grids and Supercomputers - MTAGS '09<\/i> (Portland, Oregon: ACM Press): 1\u201310. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1145%2F1646468.1646475\" target=\"_blank\">10.1145\/1646468.1646475<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-60558-714-1<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/portal.acm.org\/citation.cfm?doid=1646468.1646475\" target=\"_blank\">http:\/\/portal.acm.org\/citation.cfm?doid=1646468.1646475<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=In+cloud%2C+do+MTC+or+HTC+service+providers+benefit+from+the+economies+of+scale%3F&rft.jtitle=Proceedings+of+the+2nd+Workshop+on+Many-Task+Computing+on+Grids+and+Supercomputers+-+MTAGS+%2709&rft.aulast=Wang&rft.aufirst=Lei&rft.au=Wang%2C%26%2332%3BLei&rft.au=Zhan%2C%26%2332%3BJianfeng&rft.au=Shi%2C%26%2332%3BWeisong&rft.au=Liang%2C%26%2332%3BYi&rft.au=Yuan%2C%26%2332%3BLin&rft.date=2009&rft.pages=1%E2%80%9310&rft.place=Portland%2C+Oregon&rft.pub=ACM+Press&rft_id=info:doi\/10.1145%2F1646468.1646475&rft.isbn=978-1-60558-714-1&rft_id=http%3A%2F%2Fportal.acm.org%2Fcitation.cfm%3Fdoid%3D1646468.1646475&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-92\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-92\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alam, S.; Barrett, R.; Bast, M.; Fahey, M.R.; Kuehn, J.; McCurdy, C.; Rogers, J.; Roth, P. <i>et al.<\/i> (1 November 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5214725\/\" target=\"_blank\">\"Early evaluation of IBM BlueGene\/P\"<\/a>. <i>2008 SC - International Conference for High Performance Computing, Networking, Storage and Analysis<\/i> (Austin, TX: IEEE): 1\u201312. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1109%2FSC.2008.5214725\" target=\"_blank\">10.1109\/SC.2008.5214725<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4244-2834-2<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ieeexplore.ieee.org\/document\/5214725\/\" target=\"_blank\">http:\/\/ieeexplore.ieee.org\/document\/5214725\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Early+evaluation+of+IBM+BlueGene%2FP&rft.jtitle=2008+SC+-+International+Conference+for+High+Performance+Computing%2C+Networking%2C+Storage+and+Analysis&rft.aulast=Alam&rft.aufirst=S.&rft.au=Alam%2C%26%2332%3BS.&rft.au=Barrett%2C%26%2332%3BR.&rft.au=Bast%2C%26%2332%3BM.&rft.au=Fahey%2C%26%2332%3BM.R.&rft.au=Kuehn%2C%26%2332%3BJ.&rft.au=McCurdy%2C%26%2332%3BC.&rft.au=Rogers%2C%26%2332%3BJ.&rft.au=Roth%2C%26%2332%3BP.&rft.au=Sankaran%2C%26%2332%3BR.&rft.date=1+November+2008&rft.pages=1%E2%80%9312&rft.place=Austin%2C+TX&rft.pub=IEEE&rft_id=info:doi\/10.1109%2FSC.2008.5214725&rft.isbn=978-1-4244-2834-2&rft_id=http%3A%2F%2Fieeexplore.ieee.org%2Fdocument%2F5214725%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Some grammar and sentence placement was cleaned up for better readability. A few sentences and citations were removed for their lack of relevance to the topic.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628175445\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.889 seconds\nReal time usage: 1.149 seconds\nPreprocessor visited node count: 89648\/1000000\nPost\u2010expand include size: 750501\/2097152 bytes\nTemplate argument size: 226334\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 217471\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 811.357 1 -total\n 90.59% 735.041 1 Template:Reflist\n 74.77% 606.666 92 Template:Citation\/core\n 62.49% 507.018 70 Template:Cite_journal\n 12.28% 99.630 90 Template:Date\n 9.89% 80.260 194 Template:Citation\/identifier\n 6.32% 51.273 7 Template:Cite_book\n 6.23% 50.564 10 Template:Cite_web\n 4.89% 39.703 5 Template:Citation\n 3.84% 31.131 1 Template:Infobox_journal_article\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13241-0!canonical and timestamp 20220628175444 and revision id 47871. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview\">https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","c4564a9f0e02ca2559e204e61f391fbd_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/29\/Fig1_Yogesh_FrontPubHlth2022_10.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a1\/Fig2_Yogesh_FrontPubHlth2022_10.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/7\/7d\/Fig3_Yogesh_FrontPubHlth2022_10.jpg"],"c4564a9f0e02ca2559e204e61f391fbd_timestamp":1656439825,"215d8425e45c087c83287d3b78268e65_type":"article","215d8425e45c087c83287d3b78268e65_title":"A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operations (Tomlinson et al. 2022)","215d8425e45c087c83287d3b78268e65_url":"https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations","215d8425e45c087c83287d3b78268e65_plaintext":"\n\nJournal:A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operationsFrom LIMSWikiJump to navigationJump to searchFull article title\n \nA model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operationsJournal\n \nThe Journal of Molecular DiagnosticsAuthor(s)\n \nTomlinson, Eban; Goodman, Jennifer; Loftus, Margaret; Bitto, Stephen; Carpenter, Erica; Oddo, Richard; Judis, LuAnn; Ali, Shabab; Robinson, Wyatt E.; Carver, Miranda; Ganea, Mariana; McDonnell, Kristen; O'Neill, Diane; Starbuck, Jennifer; Johnson, Eric; Meister, Erik; Pohl, Jonathan; Spildener, Jessica; Shurtleff, Sheila; Sovie, Sheryl; Melendez, Cathleen; Krebs, Pamela; Riley, Jacquelyn D.; Wensel, Christine; Astbury, Caroline; Azzato, Elizabeth M.; Bosler, David S.; Brock, Jay E.; Cook, James R.; Cheng, Yu-Weu; Tu, Zheng J.; Cruise, M.; Henricks, Walter H.; Farkas, Daniel H.Author affiliation(s)\n \nSemaphore Solutions, Cleveland ClinicPrimary contact\n \nEmail: farkasd2 at ccf dot orgYear published\n \n2022Volume and issue\n \nS1525-1578(22)Page(s)\n \n00012-5DOI\n \n10.1016\/j.jmoldx.2022.01.002ISSN\n \n1525-1578Distribution license\n \nCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalWebsite\n \nhttps:\/\/www.jmdjournal.org\/article\/S1525-1578(22)00012-5\/fulltextDownload\n \nhttps:\/\/www.jmdjournal.org\/action\/showPdf?pii=S1525-1578%2822%2900012-5 (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Materials and methods \n\n3.1 Scope definition \n3.2 Needs assessment and partner selection \n3.3 Technology platforms and software tools \n3.4 Project management \n3.5 Key roles \n3.6 Key activities \n\n3.6.1 Development\/Validation Phase 1: Requirements elicitation \n3.6.2 Development\/Validation Phase 2: Software development \n3.6.3 Development\/Validation Phase 3: User acceptance testing \n3.6.4 Development\/Validation Phase 4: Preproduction runs, progression to user-accepted version, and deployment \n\n\n\n\n4 Results \n\n4.1 System design: Workflow analysis and support \n4.2 System features and integration \n\n4.2.1 LIS\u2013HL7 interface for sample accessioning \n4.2.2 Instrumentation \n\n\n4.3 Clinical reporting application \n4.4 Resulting end-to-end software solution \n\n\n5 Discussion \n\n5.1 Limitations, lessons learned, and future work \n\n\n6 Acknowledgements \n\n6.1 Funding \n6.2 Conflict of interest \n\n\n7 References \n8 Notes \n\n\n\nAbstract \nThe Molecular Pathology Section of Cleveland Clinic (Cleveland, OH) has undergone enhancement of its testing portfolio and processes. An electronic- and paper-based data management system was replaced with a commercially available laboratory information management system (LIMS) solution, a separate bioinformatics platform, customized test-interpretation applications, a dedicated accessioning service, and a results-releasing solution. The LIMS solution manages complex workflows, large-scale data packets, and process automation. However, a customized approach was required for the LIMS since a survey of commercially available off-the-shelf (COTS) software solutions revealed none met the diverse and complex needs of Cleveland Clinic's molecular pathology service. The project utilized the expertise of clinical laboratorians, pathologists, genetics counselors, bioinformaticians, and systems analysts in partnering with software-engineering consultants to design and implement a solution. Concurrently, Agile software development best practices were formulated, which may be emulated for scalable and cost-effective laboratory-authored software.\nKeywords: molecular pathology, laboratory information management system, LIMS, bioinformatics, software development, Agile-Scrum\n\nIntroduction \nData management needs in clinical molecular pathology laboratories differ in substantive ways from those in other clinical laboratories and anatomical pathology labs.[1][2][3][4] Conventional laboratory information systems (LISs) historically have not inherently supported the needs of molecular pathology laboratories to the extent that they have in other laboratory disciplines and operations.[2] Molecular pathology laboratories have often relied on a combination of manual methods, spreadsheets, and nonintegrated and\/or modular software to meet data management and operational needs.\nSuch was the situation in the Molecular Pathology Section, Pathology & Laboratory Medicine Institute, Cleveland Clinic (Cleveland, OH) in early 2017. A revitalization and growth plan for the section\u2014which included expansion of personnel, equipment, testing platforms, and test development\u2014was undertaken. An improvement deemed fundamental to this re-invention process was a new laboratory information management system (LIMS) to reduce and eventually replace the outdated, largely paper- and electronic spreadsheet\u2013based information and workflow management system.\nWhile the overhaul of the laboratory service was substantial, the focus of this report is limited to a description of a replicable process for the modernization of information and workflow management specific to a clinical molecular pathology laboratory. The process employed a customer\u2013vendor relationship. Out of necessity, the relationship was a partnership due to the complementary and nontechnical skill sets of each party. The overall goal was to digitize workflow based on paper and Excel (Microsoft, Redmond, WA) across a complex, multidisciplinary molecular pathology and cytogenomics clinical laboratory service. This digitization was accomplished through a custom-architected software solution.\nThis article describes a model for the design and implementation of a LIMS that meets the diverse information management needs of a full-service clinical molecular pathology laboratory, emphasizes the integral importance of a well-structured development process, and describes a novel application of modern software-based project management methods and third-party partnerships for building and deploying a LIMS suitable for a modern molecular pathology laboratory.\n\nMaterials and methods \nScope definition \nThe goal of the project was to deploy a LIMS to modernize data and workflow management of the clinical molecular pathology laboratory, including cytogenomics workflows. The project encompassed a complete overhaul of paper and electronic spreadsheet\u2013based data handling methods into a comprehensive, integrated electronic platform. Objectives were identified to define the scope and focus priorities of the project:\n\nDesign and implement an electronic information system to support the specialized requirements and workflow of a full-service clinical molecular pathology laboratory, and to fulfill needs unmet by conventional LISs.\nSupport the range of clinical testing performed, including adult, pediatric, and somatic mutation detection in tumor tissues, blood, and bone marrow; chromosome analysis; germline genetic testing for diagnosis and\/or carrier screening; and pharmacogenomics.\nSupport the range of complex data management of analytical methods (and applications) in use, including polymerase chain reaction (PCR); reverse transcription polymerase chain reaction (RT-PCR); next-generation sequencing (NGS); B- and T-cell gene rearrangement (PCR + capillary electrophoresis); chromosomal microarray analysis; fluorescence in situ hybridization (FISH); cytogenetic testing; and (genotyping by) mass spectrometry.\nIntegrate into the information technology (IT) environment of the institution for accessioning and resulting, particularly the electronic health record (EHR) system and the conventional clinical laboratory and anatomical pathology information systems. (More specifically, Cleveland Clinic was using Sunquest Laboratory version 7.2 [Sunquest Information Systems, Tucson, AZ] and CoPathPlus version 2014 [Cerner, N. Kansas City, MO] at the time, but these are now in the process of being replaced by Epic Beaker version November 2020 [Epic Systems, Verona, WI].)\nNeeds assessment and partner selection \nGiven the complexity and multifaceted nature of the project, two key needs were recognized: professional project management guided by domain expertise in molecular testing laboratories, and experienced and expert software development professionals who could bring to bear state-of-the-art software development tools and techniques. Between two and four software developers were dedicated to the project at various stages. One business-based quality assurance analyst was included, who served as the conduit for the translation of laboratory-specific requirements into software requirements. A Ph.D.-level molecular biologist with project management expertise was hired to apply process rigor and organization to direct LIMS development and implementation (among other projects).[5] Laboratory-based personnel participated in their various subject matter domains as their primary responsibilities to patient care allowed. Partnership with a team of software engineers was established. This team worked with molecular pathologists and laboratory personnel (subject matter experts) to design and build the full software solution. Peer-to-peer relationships were formed between the clinical laboratory project manager and software project managers as control points for the project.\nPrior to the beginning of this extensive development project, due diligence was undertaken to evaluate whether, or to what extent, commercially available information systems could meet the needs at hand. This assessment indicated that some systems on the market could provide some of the functional requirements, and that development entirely from scratch was not required. NGS\u2013centric LIMS software was selected for licensure (BaseSpace Clarity LIMS by Illumina, San Diego, CA). As licensed, this software was focused narrowly on supporting particular elements of NGS workflows. Its distinguishing characteristics were customizability and extensibility that could ultimately support the objectives of the laboratory, including a wide portfolio of molecular diagnostics tests performed and the need for systems integration. Compatibility with the third-party commercial bioinformatics software that the laboratory had previously chosen (Clinical Genomics Workspace version 6.15.1 by PierianDx, Creve Couer, MO) was another key deciding criterion.\n\nTechnology platforms and software tools \nThe software engineering team used Jira and Confluence web-based software (Atlassian, San Francisco, CA) to organize development tasks and to project documentation, respectively. Version control was implemented in the web-based GitHub software host (San Francisco, CA). A continuous-integration pipeline (Table 1) was built using TeamCity software version 2019.1 (JetBrains, Prague, Czech Republic). The PyCharm version 2019.1 (JetBrains), Docker Desktop Community version 2.1.0.5 (Docker, Palo Alto, CA), VirtualBox version 6.1 (Oracle, Austin, TX), and Postman version 8.1 (Postman, San Francisco, CA) software solutions were used to facilitate local testing and development.\n\n\n\n\n\n\n\nTable 1. Definitions of terms for the Agile-Scrum software development method applied.\n\n\nTerm\n\nDefinition\n\n\nStakeholders\n\nThe group of individuals who work with, and would be impacted by, the software system being developed (i.e., laboratory and medical directors, laboratory managers, laboratory supervisors, medical\/laboratory technologists, pathologists, geneticists, bioinformaticians, staff scientists, clinical systems analysts, and a revolving cast from the larger Cleveland Clinic information-technology group).\n\n\nAgile project management\n\nA system of practice to manage project delivery using an iterative approach. Optimization is achieved via continuous releases that include changes based on stakeholder review at each iteration. The process is useful for addressing highly complex problems in a mechanistic, incremental way.\n\n\nScrum\n\nAgile framework that encourages cross-functional team progress through short, measured iterations. Each problem is addressed in focused iterations called sprints, in which engineering management and build practices are used for addressing the complexity at hand. Outcomes are predicted and control of risk is assessed incrementally and via empirical observation.\n\n\nLIMS workflow\n\nClinical laboratory test workflows have three components: i) pre-analytical, ii) analytical, and iii) post-analytical. A LIMS, or other supporting software, digitally models test workflows, storing and classifying large volumes of laboratory workflow data, while also automating laborious, repetitive workflow tasks that risk compounding human error. The term \"LIMS workflow\" alludes to customized, digital workflow models that span the pre-analytical, analytical, and post-analytical stages.\n\n\nExternal program plug-in (EPP)\n\nA Clarity LIMS\u2013specific term that refers to a standalone script file accessible within the LIMS to perform calculations, transformations, or integrations too complex or cumbersome to configure within the LIMS itself.\n\n\nApplication programming interface (API)\n\nSoftware intermediary that serves to connect multiple applications, allowing them to exchange information. An API dictates what information can be sent and received by a given application and may add security restrictions. It also abstracts underlying code when interacting with other software. An analogy is a person (application A) ordering at a restaurant (application B); the menu represents the API.\n\n\nContinuous integration (CI) pipeline\n\nThe practice of automating the grouping of changes (typically software code, but also software build pipelines and automated tests) from multiple contributors into a single software project; this is software industry best practice, allowing developers to incorporate code changes into a central repository where builds and tests can be run more frequently and easily.\n\n\nDevelopment environment\n\nSystem in which new features are actively developed.\n\n\nTest environment\n\nSystem in which newly developed features are tested. User-acceptance testing occurs in this environment; if the test fails, the software goes back to development, and if it passes, it is promoted to staging.\n\n\nStaging environment\n\nSystem used for validating changes prior to promotion to production. The system should mirror production in all ways except those new changes to be tested.\n\n\nProduction environment\n\nThe active system processing patient samples. This environment processes protected health information (PHI) and needs to be treated in accordance with HIPAA regulations.\n\n\n\nPython (Python Software Foundation, Wilmington, DE), a popular, general-purpose, high-level programming language with well-documented, well-supported engineering standards, was used to develop external program plug-ins, automated test scripts, report templates, and other services. A report-generation and sign-out application named AVRO (analytically validated reporting object; see subsequent sections) was built on a Python server with an Angular JavaScript front-end. For LIMS workflows, the open-source Python S4-Clarity library[6] was used to support batch-analyte data (spreadsheet-formatted) parsing, laboratory instrument integrations, complex library pooling, de-multiplexing, and other computations on analytes. The Jinja web-based template engine library[7] was used for default report-content templating to support clinical interpretation and clinical report generation in AVRO.\n\nProject management \nThe general project management process used was Agile-Scrum in Jira, chosen by the owner of the critical path for project completion (i.e., the software development team). In the project, Agile-Scrum was supplemented with additional roles and processes tailored to work in the hybrid clinical laboratory service\/software development consultant environment. It became obvious that definitions and vocabulary differed between these two groups of subject matter experts (i.e., clinical laboratory and software engineering professionals). Selected terms are defined in Table 1. Key roles and activities of the Agile-Scrum development process, as applied in this project, are described in the next subsection.\n\nKey roles \nFour key roles corresponding to major development and validation phases were identified as gatekeepers of the development process. These gatekeepers controlled the promotion of a deliverable through the process and, thus, control of a rapidly evolving process was retained. The subject matter experts in these roles worked in tight collaboration to ensure that the highest possible quality was achieved. Note that at relevant steps, bioinformatics professionals, Ph.D.-level laboratory director-designees, and\/or M.D.-level pathologists reviewed and approved changes as appropriate.\n Key Role 1: Business Analyst (Extant within Software Development Team)\nThe business analyst assumed responsibility and accountability for the elicitation and decomposition of requirements into granular requirements that were logically defined and complete. This work output was added to the stakeholder consensus process.\nKey Role 2: Software Development Team\nThe software development team was the consumer of approved granular requirements and the developer of software designed to meet those requirements. This team was involved in developing automated tests to validate that the software written did in fact meet the granular requirements as specified. This work output was collected into a release candidate and, upon passing the automated tests, was released into Phase 3, user acceptance testing. This team was self-organizing and chose the Scrum framework to align themselves into two-week iterations (.e., sprints).\nKey Role 3: Clinical Systems Analyst (Extant within Laboratory Team)\nThe clinical systems analyst served as the first round of testing for the laboratory service, owing to the proximity of the role to the laboratory and to the expertise in the laboratory's process and informatics architecture. The work assigned to this role was to coordinate and, in some cases, to perform the tasks in development\/validation (Phase 3), user acceptance testing. The output of this work was a pass\/fail decision that either sent the release candidate back to development or promoted the release candidate to staging.\nKey Role 4: Laboratory Manager\nThe laboratory manager signed documentation approving the release candidate for promotion to the production environment after review of successful pre-production runs that were performed using test samples in the laboratory and after verification that all test plans and checklists were completed.\n\nKey activities \nThe major phases of software development and validation are shown in Figure 1. All activities were coordinated utilizing a series of modular processes that worked together to produce a performant and validated software installation consisting of licensed software, configuration of that software, and customized software to supplement the licensed software (e.g., AVRO and the Health Level 7 (HL7) version 2.3 [Health Level Seven International, Ann Arbor, MI] interface.)\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. Representation of the four major phases of software validation and development.\n\n\n\nThe highest-order process consisted of four development\/validation phases:\n\nPhase 1: Identify requirements and group them into architecturally independent release candidates logically small enough to enable rapid development (requirements elicitation).\nPhase 2: Monitor and facilitate the development of automated testing and peer-review process on release candidates (software development).\nPhase 3: Coordinate the promotion of release candidates from the development environment to the testing environment (user acceptance testing).\nPhase 4: Coordinate the promotion of the release candidate from the testing environment to the staging environment for preproduction run, and subsequently to the production in silico environments in such a way as to avoid patient-care impacts (preproduction runs, progression to user-accepted version, and deployment).\n Development\/Validation Phase 1: Requirements elicitation \nThe project consumed hundreds of person hours in elicitation meetings, the goals of which were to:\n\nEstablish the location of relevant domain knowledge.\nEstablish detailed requirements and shared terminology.\nAchieve stakeholder group consensus on each granular requirement.\nPromote granular requirements to the approved backlog of work.\nTranslation of end-user system functionality into workable development items was a task shared between the laboratory and software teams. The laboratory team solicited input from subject matter experts and prepared documentation. The software business analyst then used that documentation to produce software development work items that fulfilled the final system requirements specified by the laboratory team. System requirements documentation included written requirements, text-based documents, logic tables (e.g., user-role permission maps, diagrams, and flowcharts), spreadsheets, native-instrument data files, laboratory standard operating procedures, and test validation plans.\nSoftware deliverables were detailed and tracked in Jira. Laboratory objectives were described in common language, then passed to the software team for decomposition. Software development tasks were identified during decomposition and completed by the software team using Scrum. The percentage of completion reports for each objective were tracked using Jira and reviewed weekly by the joint project management group. Impediments to progress were identified and delegated to the appropriate team members for resolution. Common impediments included:\n\nlanguage ambiguity of requirements,\ntechnical difficulty in mapping laboratory requirements to the software, and\nrequirements without a test plan or for which generating a test plan to be used in practice was challenging.\n Development\/Validation Phase 2: Software development \nSoftware development proceeded in two-week iteration cycles (sprints). Members of the clinical laboratory and software engineering teams continuously evaluated and improved the software development processes throughout the project. The teams incorporated the requirements of the Health Insurance Portability and Accountability Act (HIPAA) to ensure that protected health information was handled appropriately. For example, scripting of mock samples was developed with convincing, yet mock, data. This scripting enabled the engineering team to test the system in a realistic fashion without the use of patient information.\nThe engineering team adhered to the following technical process while working within sprints:\n\nA team member chose a development task from the approved requirements to work on during the current iteration (sprint backlog).\nOnce completed, each development task was peer-reviewed by other software engineers prior to inclusion in the master codebase, an industry-standard quality assurance practice.\nAutomated tests were generated during development and run before and after each development task was committed to the master codebase, to identify problems in the task and in the integration of the task into the codebase, respectively. Automated tests generally consisted of scripts that generated representative mock samples and utilized the Clarity LIMS application programming interface to move those mock samples through the workflow while replicating user interaction at each step, again using the API.\nWhen the development of a full software deliverable was completed (release candidate), it was assembled atop all previous deliverables on a replica LIMS (test server).\nThe release candidate was tested for both successful and potentially erroneous scenarios, in accordance with the requirement specification(s).\n Development\/Validation Phase 3: User acceptance testing \nIn Phase 3 of software validation, functional testing was performed by the laboratory team and led by the clinical systems analyst, who reported results and discrepancies back to the software team at each stage for collaborative triage. A go\/no-go decision was made based on the severity of the discrepancy and the viability of a workaround being utilized until the next release candidate could be deployed. Discrepancies were addressed by the software team in order of priority and redeployed through reiteration of the above process.\n\n Development\/Validation Phase 4: Preproduction runs, progression to user-accepted version, and deployment \nThe following process was used for preproduction runs, progression to user-accepted version, and deployment:\n\nAfter all tests were passed, the software vendor deployed the validated release candidate to the staging environment of the laboratory.\nSuccessful execution of the user acceptance testing phase triggered full system\u2013level preproduction runs by laboratory personnel in the staging environment.\nSuccessful preproduction run completion was followed by scheduled deployment of the release candidate to the production environment, which, in some cases, constituted several releases at once.\nFull deployment was facilitated jointly by software and laboratory IT personnel. Full system\u2013level tests, as well as preproduction run checklists and end-to-end testing scripts, were utilized to validate the performant nature of the final deployment(s).\nResults \nSystem design: Workflow analysis and support \nThe LIMS organizes and handles the workflows of the clinical laboratory, from specimen accessioning through to laboratory analysis and issuing reports to ordering physicians. The system also coordinates tasks among staff. The LIMS automates several laboratory processes, such as spreadsheet parsing or container tracking, and is compatible with laboratory instrumentation, such as automated liquid handlers and quality control instruments, either through an off-the-shelf or custom-built integration. Substantial customized LIMS workflow design and engineering were required to model the testing procedures of the laboratory and to organize the constituent processes, including sample accessioning, nucleic acid (i.e., DNA, RNA, or total nucleic acid) purification, direct PCR testing, genotyping by mass spectrometry, sequencing, chromosome testing, data analysis, and all associated quality control steps.\nA key project requirement was organization and refinement of workflows within the LIMS. Wherever possible, shared processes were identified and excluded from test-specific workflow building. For example, sample accessioning and DNA extraction were built out as shared protocols. Templating (sharing) at the step and protocol layers were combined with unique elements to generate end-to-end workflows specific to each test.\nThe LIMS was engineered to support the build of workflows in a hierarchical fashion in which workflows contain protocols which, in turn, contain steps (Table 2). In steps, the work of the end user is performed, on either a single sample or a batch of samples. Protocols are a collection of steps organized around the standard operating procedures of a laboratory, and workflows comprise the protocols required to execute a test. Custom-built workflows are shown in Table 3.\n\n\n\n\n\n\n\nTable 2. Test component organization.\n\n\nLIMS component\n\nExample\n\nScope\n\n\nStep\n\nDNA extraction\n\nSingle wet laboratory process contained in a single work session, in one physical location\n\n\nProtocol\n\nSample extraction\n\nCollection of steps that facilitate one stage of the workflow\n\n\nWorkflow\n\nFragile X carrier screening\n\nEnd-to-end sample processing, from accessioning to report issuance\n\n\n\n\n\n\n\n\n\nTable 3. Shared workflow components. \u2217 Indicates universally shared component. Note that pre-analytics was able to be shared across all workflows, while sample preparation extraction was shared, but only within the MDx group of tests.\n\n\nLIMS workflow\n\nWorkflow components\n\n\nCytogenetics (CytoG)\n\nPre-analytics\u2217 > (CytoG) wet laboratory sample extraction > wet laboratory analysis > clinical reporting > long-term data archiving\u2217\n\n\nChromosomal microarray (CMA)\n\nPre-analytics\u2217 > (CMA) wet laboratory sample preparation > wet laboratory analysis > clinical reporting > long-term data archiving\u2217\n\n\nCarrier screening\n\nPre-analytics\u2217 > sample preparation extraction\u2217 > (carrier screening) wet laboratory analysis (per test code) > clinical reporting > MDx long-term data archiving\u2217\n\n\nMolecular diagnostics (MDx)\n\nPreanalytics\u2217 > samplepreparation extraction\u2217 > wet laboratory analysis (per test code) > clinical reporting > MDx long-term data archiving\u2217\n\n\n\nSystem features and integration \n LIS\u2013HL7 interface for sample accessioning \nLIS applications typically connect to other patient health care applications such as health insurance policy administration systems and EHRs.[8] To function effectively, an LIS must be interoperable with these health care record systems through the adoption of a common standard.[2] The HL7 standard was utilized as the form of communication between the LIS and the LIMS through a customized interface (Figure 2).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. A laboratory information management system (LIMS) supports clinical laboratory test workflows, systems interfacing, and traceability by classifying and storing laboratory workflow data like accessioning, pre-analytics, analytical wet bench, and analytical interpretation paired to clinical interpretation (i.e., results reporting). Traceability refers to the record keeping in each of the systems shown above (i.e., data received, sent, and transformed, that happen in between). AVRO, analytically validated reporting object; EPP, external program plug-in; LIS, laboratory information system. CoPathPlus, Cerner (N. Kansas City, MO); Epic Beaker version November 2020, Epic Systems (Verona, WI); HL7, Health Level Seven International version 2.3, Health Level Seven International (Ann Arbor, MI); Sunquest software version 7.2, Sunquest Information Systems (Tucson, AZ).\n\n\n\nThe interface between the existing Sunquest Laboratory and CoPathPlus LISs of the laboratory and the new LIMS streamlined the flow of patient data received from the health care record systems into sample accessioning. A customized HL7 listener service was built and configured to interface with the LIS. This service verifies whether the HL7 message received is valid and, if so, generates a sample with all required sample information fields and accessions it directly into the LIMS. Required sample fields including, but not limited to, medical record number, last name, and collection date are extracted from the HL7 message and mapped to user-defined LIMS fields to preserve vital information for mapping test results to the correct patient downstream. The original inbound HL7 message was preserved on the sample to resolve any ambiguous data mapping in the LIMS. Error logs are generated for review when HL7 messages either cannot be processed or produce errors.\nThe LIS application was integrated with the HL7 interface while its essential functionality and interoperable links were preserved. After software build, the LISs still collected and organized patient health care data. However, software management of the clinical test workflows and process automation were improved with LIMS implementation.\n\nInstrumentation \nIntegration with nucleic acid purification robotics and spectrophotometers (pre-analytical) and molecular diagnostics\u2013related analytical platforms were facilitated through file transfer systems built on shared network locations. Integrations followed the same process:\n\nA plate map was generated and displayed to laboratory personnel at the appropriate LIMS workflow step.\nAfter the requisite samples were plated and the instrument completed its full cycle, an output file was directed to a shared network location available at each LIMS workstation.\nLaboratory personnel uploaded the output file to the appropriate (usually next) step in the LIMS workflow.\nAn external program plug-in parsed data from the output file and saved discrete pieces to user-defined fields on the sample in the LIMS.\nClinical reporting application \nTo address the ultimate goal of every high-complexity clinical laboratory test (i.e., the issuance of a patient report for the physician who ordered the test), the customized AVRO was built. AVRO serves as an interface to manage the interpretation (post-analytical) component of laboratory test workflows. AVRO utilizes the authentication system of the LIMS, and therefore only LIMS users with the correct permission setting can access AVRO. AVRO runs on its own server, links directly to the LIMS, and polls specific steps to import reporting objects. It then determines which report template to assign based on the test code and displays test data to professional staff reviewers. This reporting application generates standards-compliant clinical reports for annotation and sign-out by molecular pathology professional staff. Upon sign-out, AVRO sends text reports to the automated clinical results\u2013releasing service, which submits HL7-formatted data and issues a text-based copy of the report to the appropriate recipient.\nAVRO was designed and implemented to harmonize results reporting and formatting within a dynamic multicomponent system of EMRs and LISs (Epic Beaker, Sunquest Laboratory, CoPathPlus, and Rhapsody version 6.6 [Lyniate, Boston, MA]) while maintaining a flexible LIMS configuration. (Rhapsody is an interface engine that sits between Epic and ancillary systems, e.g., Sunquest Laboratory, CoPathPlus.) Given that report fields are populated directly from LIMS user-defined fields, all LIMS data are available to the report template. Using Jinja2 Python templating enabled a programmatic approach to reporting (i.e., rules can be applied to text and data formatting). AVRO uses the LIMS application data layer and the LIMS-managed user credentials that can be integrated with Lightweight Directory Access Protocol (LDAP) systems to support data provenance and added security. This approach obviated the architectural generation of a separate database and the duplication of user credentials. AVRO thus facilitates professional actions on samples that exist entirely within the LIMS.\nThe concept of report-based content defaults was identified from feedback after early implementations had been tested by the reporting professional staff. Reporting templates were customized for each test and then served the correct template by mapping test codes to those templates. Templates could be mapped to multiple test codes and were maintained independently for maximum flexibility in content.\nOpening a report in AVRO presents a template based on the above logic, populated with interpretation text derived from the results interpretation code applied in the analysis portion of the workflow. The molecular pathologist user is able to modify and customize all of the populated content prior to sign-out. At any point during the report-building process, AVRO allows the user to preview the report.\nA customized results\u2013releasing service was built into the LIMS as a set of external program plug-ins for report release. This step was designed such that the system monitors for newly signed-out reports in AVRO every 30 seconds via the AVRO API. The report is generated and sent back to the LIS, and then the report file(s) are attached to the completed step in the LIMS.\nAudit trails were available as base functionality in the LIMS and did not require customization. Building AVRO atop the audit trail data layer facilitated auditing through the reporting process up until submission of the outbound HL7 message. HIPAA compliance as implemented in the LIMS thus persisted through the reporting process, an efficiency afforded by leveraging of the existing software validation work extant in the off-the-shelf product. The LIMS tracks all of the elements specified by audit trail-related items per the College of American Pathologists Laboratory General Accreditation Checklist.\n\nResulting end-to-end software solution \nThe test management software system of the LIMS and AVRO interfaced with the pre-existing LIS architecture via customized software services, an HL7-bridged laboratory sample accessioning service, and an automated clinical results\u2013releasing service through the LIMS. The newly integrated solutions automated the full end-to-end process of the molecular pathology laboratory, from sample accessioning to the issuance of final patient reports. These services eliminated the use of paper to track analytics data and mitigated the risks for bottlenecks and human error that tend to result from manual control of laboratory input and output processes. For example, accessioning bottlenecks have been mitigated by streamlining accessioning through the LIS\u2013HL7 interface, and human errors due to data transcription have been reduced through data tracking in the LIMS and subsequent automated exchange of data between the LIMS, AVRO, and LIS.\nAn important predictor of success was the selection of a LIMS with robust API and customization support in order to address the significant \u0394 between off-the-shelf functionality[2] and the functionality required by the molecular service via the only pathway remaining, custom software engineering. Software engineers worked in virtual instances of the software environment to enable rapid revisions within existing and relevant system parameters. Imagining, designing, testing, and implementing the information management system described required significant human and financial resources. A list of advantages that have been accrued by this clinical laboratory, or that are anticipated in the near future, is shown in Table 4. Specific examples of the benefits the laboratory has experienced since LIMS implementation are listed in Table 5.\n\n\n\n\n\n\n\nTable 4. Benefits accruing to a clinical laboratory from a LIMS. CPT, Current Procedural Terminology; CS, customer service; Fin, financial; Ops, operations; PC, patient care; Q, quality; Reg, regulatory.\n\n\nItem\n\nCategory\n\n\nCS\n\nFin\n\nOps\n\nPC\n\nQ\n\nReg\n\n\nInventory management and control; optimize reagent purchasing to just-in-time model, thereby improving cash flow\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nReduce time needed for retrieval of archived specimens\n\n\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\nReduce paper consumption\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nMonitor process activities: track\/locate a specimen as it moves through testing process, waiting times, bottlenecks, and instrument usage; assess percentages of instrument capacity being used, idle versus active time, batch sizes\n\n\n\n\n\n\u2713\n\n\n\n\n\n\n\n\nReduce opportunities for human error\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nPrevent use of expired reagents\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\u2713\n\n\nMonitor waste, rework, delayed turnaround times\n\n\u2713\n\n\n\n\u2713\n\n\n\n\n\n\n\n\nOptimize use of laboratory human resources; monitor individual clinical laboratory scientist productivity by tracking work units\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nAudit trail\n\n\n\n\n\n\n\n\n\n\n\n\u2713\n\n\nTroubleshoot bottlenecks in testing progress; simplification of root cause analysis\n\n\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\u2713\n\n\nReal-time opportunities for investigation of failures (reagents, instruments, human) and identification of patterns\n\n\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\u2713\n\n\nCapacity to rapidly identify specimens associated with a problematic reagent, instrument, or run\n\n\n\n\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\nSimplification of monitoring instrument calibration and verification\n\n\n\n\n\n\u2713\n\n\n\n\n\n\u2713\n\n\nCapacity to upload supporting documentation so that all data are centralized and not in separate logs\n\n\n\n\n\n\u2713\n\n\n\n\n\n\n\n\nMonitor volumes by client\/physician\n\n\u2713\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nCorrelate testing with environment (e.g., temperature, humidity)\n\n\n\n\n\n\u2713\n\n\n\n\n\n\u2713\n\n\nCorrelate technologist training and competence with testing\n\n\n\n\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\nCentralize instrument maintenance and service agreements\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nOpportunity to learn true cost of testing\n\n\n\n\u2713\n\n\n\n\n\n\n\n\n\n\nCorrelate testing done with and without payer preauthorization\n\n\n\n\u2713\n\n\n\n\n\n\n\n\n\n\nTrack test volumes by variables (e.g., test code, CPT code, shift)\n\n\n\n\u2713\n\n\u2713\n\n\n\n\n\n\n\n\nReduce the time that medical technologists invest in performing clerical tasks (e.g., pre- and post-analytical clerical tasks, accessioning exceptions, data transcription)\n\n\n\n\n\n\u2713\n\n\n\n\n\n\n\n\nSimplified, standardized results reporting across all tests\n\n\u2713\n\n\n\n\u2713\n\n\n\n\n\n\n\n\nReduce time spent on regulatory submissions associated with software\n\n\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\u2713\n\n\nReduce documentation errors associated with instrument function and verification, as well as workspace decontamination\n\n\n\n\n\n\u2713\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nTable 5. Examples of LIMS benefits. FISH, fluorescence in situ hybridization; TAT, turnaround time.\n\n\nItem\n\nBenefit(s)\n\nSupporting metric(s)\n\n\nSpecimen demographic information interfaces directly from extant LIS to LIMS-based analytics workflows\n\n\n1. Pre-analytics and analytics technicians no longer need to manually transcribe specimen demographic information into Excel logs and workbooks\r\n2. Eliminated time-consuming clerical duties from pre-analytics and analytics technicians\r\n3. Eliminated transcription errors that result in discordant specimen demographic information between systems\n\n\n\n1. Time-savings, measurements in progress\r\n2. Twenty-four Excel logs used for specimen data storage eliminated and archived\n\n\n\nNucleic acid quantification values and quality metrics parsed directly from NanoDrop (Thermo Fisher Scientific, Waltham, MA) files into LIMS-based analytical workflows\n\n\n1. Analytics technicians no longer need to manually transcribe quantification data into Excel logs\r\n2. Eliminated time-consuming data transcription duties from analytics technicians\r\n3. Eliminated data transcription errors\r\n4. LIMS-based automations perform quality metrics calculations previously performed by Excel macro\n\n\n\n1. Time-savings, measurements in progress\r\n2. One Excel macro eliminated and archived\n\n\n\nNucleic acid extraction reagent and data tracking now completely LIMS-based; previous state required manual completion and archiving of physical worksheets\n\n\n1. Analytics technicians no longer need to manually transcribe reagent lot information\r\n2. Reduced paper consumption\r\n3. Reduced physical document storage\n\n\n1. Ten high-use nucleic acid extraction documents eliminated and archived\n\n\nConsolidation of specimen tracking history from multiple systems into one searchable database\n\n\n1. Higher-resolution specimen tracking enables users to pinpoint specimen location at any step of pre-analytical, analytical, and post-analytical processes\r\n2. Expanded and available user-defined fields in extraction workflow reveal whether additional material is available for re-extraction\/retesting, i.e., computer-based query versus manual search and review in the laboratory\r\n3.\nReduced interruption of pre-analytics and analytics technicians for specimen data interrogation\r\n4. Improved troubleshooting and trend identification\n\n\n1. Time-savings; measurements in progress\n\n\nLIMS-based workflow steps include performing technologist, date, and time stamps\n\n1. Provides high-resolution data previously unavailable to the laboratory, which can be used for the identification of technique variation among techs\n\nN\/A\n\n\nSpecimen analytical results parsed directly from analytical Excel workbooks into LIMS, which transmits directly to reporting LIS\n\n\n1. Analytics technicians no longer need to manually transcribe result codes into reporting LIS\r\n2. Reduced data-transcription errors\n\n\n1. Time-savings, measurements in progress\n\n\nConsolidation of reporting system from CoPathPlus, Sunquest Laboratory, and ePath Logic web-based software (ePath Logic, Highland, MI) to one universal reporting product (AVRO)\n\n\n1. Standardized reporting process across testing platforms\r\n2. Reduced LIS access and training requirements for analytics technicians\n\n\n1. Reporting LIS reduction from three systems to one\n\n\nLIMS transmits data directly to Tableau\n\n1. Enables more sophisticated queries and data analysis for quality metrics reporting and troubleshooting\n\nN\/A\n\n\nAutomated calculation for reagent addition in FISH\n\n\n1. Saves time\r\n2. Eliminates arithmetic errors\r\n3. Automates recording of probe(s) used, lot numbers, expiration dates\n\n\n1. Time-savings, measurements in progress\n\n\nCase tracking (FISH laboratory)\n\n\n1. TAT tracking automated\r\n2. Rush samples or samples approaching TAT limit more easily sorted and found\r\n3. Facilitates case assignment to technologists\n\n\n1. Time-savings, measurements in progress\n\n\n\nDiscussion \nThe Molecular Pathology Section, Pathology & Laboratory Medicine Institute, Cleveland Clinic performs high-complexity clinical laboratory testing in support of the practice of genomic medicine. A revitalization and modernization program, begun in 2016, established the need for improvements in laboratory data management. Organization of clinical laboratory testing workflows in the twenty-first century is best matched to modern software and information management tools, not tools from the previous century (i.e., paper, Excel, flash drives). Education was pivotal in accelerating the project toward success. Educating all members in this team-based approach in respective domains led to the acknowledgment that both software development and molecular pathology (with inherent regulation) were of equal importance in the LIMS development process. Education, not unlike the build process itself, was accomplished iteratively and continually throughout the project. The more that subject matter experts from all disciplines understood each other, the better the team was able to optimize and improve each build iteration and, subsequently, execute the shared process successfully. The importance of partnership between the laboratory and software engineering teams was a lesson well learned.\nModeling clinical laboratory test workflows digitally and integrating a LIMS into the clinical hardware and software architectures of the laboratory required a significant amount of customized software engineering. Most commercial LIMS are touted as configurable. Principles and practices from the domains of computer science and software engineering were required to produce a maintainable and scalable LIMS implementation, alongside a greater set of laboratory software services and applications. Laboratories often do not have the resources in-house to integrate such a solution into their existing system(s). Software and process engineers were required to build effective customized test-workflow models in silico that automated processes and managed the inherent workflow data. Their role also included installing and successfully integrating the LIMS application alongside other supporting software that existed in the clinical informatics architecture. By employing a team-based collaborative approach between the clinical laboratory and software engineers, the existing software system was significantly upgraded, the use of paper and electronic spreadsheets was reduced (with the eventual goal of the complete elimination of paper), and efficiency was increased, putting the laboratory in a better position to scale up throughput and manage complex data.\nThe results reporting environment is complex; here we show one of the benefits of the LIMS implementation. The Pathology & Laboratory Medicine Institute (composed of two departments: anatomical pathology and laboratory medicine) uses Sunquest Laboratory to output test results. CoPathPlus is used to report anatomic pathology results and additional associated testing of tissue, cytology, and bone marrow specimens (i.e., special stains, FISH, cytogenetics, PCR, and NGS testing). Clarity LIMS streamlined reporting so that all molecular pathology tests are now reported back to Sunquest Laboratory and posted as a discrete item in the patient's EHR in Epic for the specific test. Tests that must be reported as part of an anatomic pathology report are sent back to CoPathPlus from Sunquest Laboratory so that clinicians may view a comprehensive report on that specimen.\nFormulating an effective software development framework was important, considering the challenges in generating and operating customized clinical laboratory software. Such software must address testing intricacies and diverse molecular technologies within a complex clinical laboratory architecture. Rigorous building methods and techniques were needed to ensure build quality and maintenance sustainability.\nScrum best practices are valuable in the modernization of clinical laboratory information management workflows via custom software development. Scrum best practices are demonstrated to be extensible, scalable, and cost-effective. It is crucial that any given Scrum format be lightweight, with clearly defined roles and responsibilities of the participants; be comprehensively simple; and assume room for improvement.\nNotably, a laboratory science framework for molecular biology research, termed LabScrum, has gained support in research-oriented molecular biology laboratories. LabScrum emulates the principles of Scrum software development. The writers of LabScrum illustrated three critical principles of the Scrum framework's utility in research laboratories.[9] These principles are valid for building customized information management software in the setting of clinical laboratory testing.\nThe adoption of some form of Scrum in developing customized laboratory software should focus on three essential components: transparency, inspection, and adaptation. LabScrum proponents have argued that a management framework based on empiricism is highly consistent with the scientific method.[9] Anecdotally, research scientists rigorously apply empiricism and the scientific method for results, or product, but often do not think empirically about tasks, techniques, or processes. Generating process visibility and analysis utilizing a framework for ongoing improvement can improve the quality of the science (i.e., more rigorous science), the quantity of the science (i.e., more productive science), and the quality of life of scientists (i.e., more sustainable science). In effect, to run a modern clinical laboratory necessitates having a laboratory function to interact with the processes of configuring or generating customized software, because, by definition, this software does not yet exist or, more accurately, must be customized for use in every clinical laboratory.\n\n Limitations, lessons learned, and future work \nThe inability of the LIMS implementation to store unique patients in their own table with a one-to-many relationship between the patients table and the specimens table in the database is a limitation of the existing system. The system is maintained via IT department personnel, two full-time laboratorian, and one part-time laboratorian.\nAn important lesson learned in executing the LIMS project was the concept of a minimally viable product (MVP). Early in the project, the laboratory team was excited about the flexibility and customizability of the chosen LIMS product. In understanding what was possible and what was needed to elevate the laboratory's capabilities, overreaching and unrealistic goals were imagined. The team grew too ambitious, frustration accompanied scope creep, and project velocity decreased. Once it became clear that an MVP was, by definition, good enough, goals became simultaneously more modest and attainable. Thus the project's progress toward full execution accelerated over the last approximately 12 months of a 30-month effort from late 2017 to early 2020. \nWith LIMS launch, experience using the LIMS, and newly acquired local skills and knowledge, the laboratory team looks forward to independently adding more functionality via new customizations.\n\nAcknowledgements \nWe thank Gordon Meyer, Justin Chant, Emily Wong, Jeremy Snell, Danny Hopkins, Mark Swinkels, Mark Luszniak, and the rest of the Semaphore team for their technical expertise; Wendy Nedlik for organizational management expertise, Hillard Meade for project management expertise; James Fenske for software implementation assistance; Michael Reese for financial analysis; Eric D. Hsi, MD, for leadership; and Jacqueline Urankar and Susan Brennan for excellent administrative support.\n\nFunding \nSupported by the Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic.\n\nConflict of interest \nE.T., S.A., W.E.R., and C.M. are full-time employees of Semaphore Solutions, the vendor retained by Cleveland Clinic in the development and launch of the LIMS described in this article.\n\nReferences \n\n\n\u2191 Kang, Wenjun; Kadri, Sabah; Puranik, Rutika; Wurst, Michelle N.; Patil, Sushant A.; Mujacic, Ibro; Benhamed, Sonia; Niu, Nifang et al. (1 July 2018). \"System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management\". The Journal of molecular diagnostics: JMD 20 (4): 522\u2013532. doi:10.1016\/j.jmoldx.2018.03.008. ISSN 1943-7811. PMC 6039793. PMID 29698836. https:\/\/pubmed.ncbi.nlm.nih.gov\/29698836 .   \n \n\n\u2191 2.0 2.1 2.2 2.3 Myers, Charles; Swadley, Matthew; Carter, Alexis B. (1 September 2018). \"Laboratory Information Systems and Instrument Software Lack Basic Functionality for Molecular Laboratories\". The Journal of molecular diagnostics: JMD 20 (5): 591\u2013599. doi:10.1016\/j.jmoldx.2018.05.011. ISSN 1943-7811. PMID 30146005. https:\/\/pubmed.ncbi.nlm.nih.gov\/30146005 .   \n \n\n\u2191 Lee, Roy E.; Henricks, Walter H.; Sirintrapun, Sahussapont J. (1 March 2016). \"Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different\". Advances in Anatomic Pathology 23 (2): 125\u2013133. doi:10.1097\/PAP.0000000000000109. ISSN 1533-4031. PMID 26849819. https:\/\/pubmed.ncbi.nlm.nih.gov\/26849819 .   \n \n\n\u2191 Campbell, Walter S.; Carter, Alexis B.; Cushman-Vokoun, Allison M.; Greiner, Timothy C.; Dash, Rajesh C.; Routbort, Mark; de Baca, Monica E.; Campbell, James R. (1 May 2019). \"A Model Information Management Plan for Molecular Pathology Sequence Data Using Standards: From Sequencer to Electronic Health Record\". The Journal of molecular diagnostics: JMD 21 (3): 408\u2013417. doi:10.1016\/j.jmoldx.2018.12.002. ISSN 1943-7811. PMC 6521887. PMID 30797065. https:\/\/pubmed.ncbi.nlm.nih.gov\/30797065 .   \n \n\n\u2191 Brock, J.; Nedlik, W.; Farkas, D.H. (1 November 2018). \"AMP Abstracts - TT002. A Process for New Clinical Laboratory Test Implementation\" (in en). The Journal of Molecular Diagnostics 20 (6): 1016. doi:10.1016\/S1525-1578(18)30401-X. PMC PMC7130024. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S152515781830401X .   \n \n\n\u2191 Semaphore Solutions (6 April 2021). \"SemaphoreSolutions \/ s4-clarity-lib\". GitHub. https:\/\/github.com\/SemaphoreSolutions\/s4-clarity-lib . Retrieved 04 August 2021 .   \n \n\n\u2191 Ronacher, A. (18 May 2021). \"pallets \/ jinja\". GitHub. https:\/\/github.com\/pallets\/jinja . Retrieved 04 August 2021 .   \n \n\n\u2191 Sinard, John H.; Gershkovich, Peter (2012). \"Custom software development for use in a clinical laboratory\". Journal of Pathology Informatics 3: 44\u201353. doi:10.4103\/2153-3539.104906. ISSN 2153-3539. PMC 3551490. PMID 23372985. https:\/\/pubmed.ncbi.nlm.nih.gov\/23372985 .   \n \n\n\u2191 9.0 9.1 May, L.; Runyon, T. (25 June 2019). \"LabScrum: A Case Study for Agility in Academic Research Labs\". Cutter. https:\/\/www.cutter.com\/article\/labscrum-case-study-agility-academic-research-labs-504061 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with minor changes to presentation, grammar, and punctuation. In some cases, important information was missing from the references, and that information was added. Everything else remains true to the original article, per the \"NoDerivatives\" portion of the distribution license.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\">https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on laboratory informaticsLIMSwiki journal articles on softwareNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 16 April 2022, at 20:32.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 236 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","215d8425e45c087c83287d3b78268e65_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations rootpage-Journal_A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operations<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>The Molecular Pathology Section of Cleveland Clinic (Cleveland, OH) has undergone enhancement of its testing portfolio and processes. An electronic- and paper-based <a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">data management<\/a> system was replaced with a commercially available <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management system<\/a> (LIMS) solution, a separate <a href=\"https:\/\/www.limswiki.org\/index.php\/Bioinformatics\" title=\"Bioinformatics\" class=\"wiki-link\" data-key=\"8f506695fdbb26e3f314da308f8c053b\">bioinformatics<\/a> platform, customized test-interpretation applications, a dedicated <a href=\"https:\/\/www.limswiki.org\/index.php\/Accessioning_(medical)\" title=\"Accessioning (medical)\" class=\"wiki-link\" data-key=\"d3a1f1a5d35fd9152d82893878bf9aa1\">accessioning<\/a> service, and a results-releasing solution. The LIMS solution manages complex <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflows<\/a>, large-scale data packets, and process automation. However, a customized approach was required for the LIMS since a survey of commercially available off-the-shelf (COTS) software solutions revealed none met the diverse and complex needs of Cleveland Clinic's <a href=\"https:\/\/www.limswiki.org\/index.php\/Molecular_pathology\" title=\"Molecular pathology\" class=\"wiki-link\" data-key=\"1b14edce41827d8dbb3399291087e507\">molecular pathology<\/a> service. The project utilized the expertise of clinical laboratorians, pathologists, genetics counselors, bioinformaticians, and systems analysts in partnering with software-engineering consultants to design and implement a solution. Concurrently, Agile <a href=\"https:\/\/www.limswiki.org\/index.php\/Software_quality_management\" title=\"Software quality management\" class=\"wiki-link\" data-key=\"8c8c0fa8a260bb5dc333e053bde4c420\">software development best practices<\/a> were formulated, which may be emulated for scalable and cost-effective laboratory-authored software.\n<\/p><p><b>Keywords<\/b>: molecular pathology, laboratory information management system, LIMS, bioinformatics, software development, Agile-Scrum\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/Information_management\" title=\"Information management\" class=\"wiki-link\" data-key=\"f8672d270c0750a858ed940158ca0a73\">Data management<\/a> needs in clinical <a href=\"https:\/\/www.limswiki.org\/index.php\/Molecular_pathology\" title=\"Molecular pathology\" class=\"wiki-link\" data-key=\"1b14edce41827d8dbb3399291087e507\">molecular pathology<\/a> <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a> differ in substantive ways from those in other <a href=\"https:\/\/www.limswiki.org\/index.php\/Clinical_laboratory\" title=\"Clinical laboratory\" class=\"wiki-link\" data-key=\"307bcdf1bdbcd1bb167cee435b7a5463\">clinical laboratories<\/a> and <a href=\"https:\/\/www.limswiki.org\/index.php\/Anatomical_pathology\" title=\"Anatomical pathology\" class=\"wiki-link\" data-key=\"5668db6faf37e8c1432a1d7953f30cb7\">anatomical pathology<\/a> labs.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:0_2-0\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> Conventional <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_system\" title=\"Laboratory information system\" class=\"wiki-link\" data-key=\"37add65b4d1c678b382a7d4817a9cf64\">laboratory information systems<\/a> (LISs) historically have not inherently supported the needs of molecular pathology laboratories to the extent that they have in other laboratory disciplines and operations.<sup id=\"rdp-ebb-cite_ref-:0_2-1\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup> Molecular pathology laboratories have often relied on a combination of manual methods, spreadsheets, and nonintegrated and\/or modular software to meet data management and operational needs.\n<\/p><p>Such was the situation in the Molecular Pathology Section, Pathology & Laboratory Medicine Institute, Cleveland Clinic (Cleveland, OH) in early 2017. A revitalization and growth plan for the section\u2014which included expansion of personnel, equipment, testing platforms, and test development\u2014was undertaken. An improvement deemed fundamental to this re-invention process was a new <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_management_system\" title=\"Laboratory information management system\" class=\"wiki-link\" data-key=\"8ff56a51d34c9b1806fcebdcde634d00\">laboratory information management system<\/a> (LIMS) to reduce and eventually replace the outdated, largely paper- and electronic spreadsheet\u2013based information and <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflow<\/a> management system.\n<\/p><p>While the overhaul of the laboratory service was substantial, the focus of this report is limited to a description of a replicable process for the modernization of information and workflow management specific to a clinical molecular pathology laboratory. The process employed a customer\u2013vendor relationship. Out of necessity, the relationship was a partnership due to the complementary and nontechnical skill sets of each party. The overall goal was to digitize workflow based on paper and Excel (Microsoft, Redmond, WA) across a complex, multidisciplinary molecular pathology and <a href=\"https:\/\/www.limswiki.org\/index.php\/Cytogenetics\" title=\"Cytogenetics\" class=\"wiki-link\" data-key=\"1aecffd165a1f02c974609562fff4449\">cytogenomics<\/a> clinical laboratory service. This digitization was accomplished through a custom-architected software solution.\n<\/p><p>This article describes a model for the design and implementation of a LIMS that meets the diverse information management needs of a full-service clinical molecular pathology laboratory, emphasizes the integral importance of a well-structured development process, and describes a novel application of modern software-based <a href=\"https:\/\/www.limswiki.org\/index.php\/Project_management\" title=\"Project management\" class=\"wiki-link\" data-key=\"22354fe89d01353b2ac2b467aadee84b\">project management<\/a> methods and third-party partnerships for building and deploying a LIMS suitable for a modern molecular pathology laboratory.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Scope_definition\">Scope definition<\/span><\/h3>\n<p>The goal of the project was to deploy a LIMS to modernize data and workflow management of the clinical molecular pathology laboratory, including cytogenomics workflows. The project encompassed a complete overhaul of paper and electronic spreadsheet\u2013based data handling methods into a comprehensive, integrated electronic platform. Objectives were identified to define the scope and focus priorities of the project:\n<\/p>\n<ol><li>Design and implement an electronic information system to support the specialized requirements and workflow of a full-service clinical molecular pathology laboratory, and to fulfill needs unmet by conventional LISs.<\/li>\n<li>Support the range of clinical testing performed, including adult, pediatric, and somatic mutation detection in tumor tissues, blood, and bone marrow; chromosome analysis; germline genetic testing for diagnosis and\/or carrier screening; and pharmacogenomics.<\/li>\n<li>Support the range of complex data management of analytical methods (and applications) in use, including <a href=\"https:\/\/www.limswiki.org\/index.php\/Polymerase_chain_reaction\" title=\"Polymerase chain reaction\" class=\"wiki-link\" data-key=\"f6569fb01ef396379f9f4efa4527e715\">polymerase chain reaction<\/a> (PCR); <a href=\"https:\/\/www.limswiki.org\/index.php\/Reverse_transcription_polymerase_chain_reaction\" title=\"Reverse transcription polymerase chain reaction\" class=\"wiki-link\" data-key=\"bb69657b45c41e6345baf4c8067c7aa3\">reverse transcription polymerase chain reaction<\/a> (RT-PCR); <a href=\"https:\/\/www.limswiki.org\/index.php\/Next-generation_sequencing\" class=\"mw-redirect wiki-link\" title=\"Next-generation sequencing\" data-key=\"c9d965c11eed1543f2a7e5f1abed4bb7\">next-generation sequencing<\/a> (NGS); B- and T-cell gene rearrangement (PCR + <a href=\"https:\/\/www.limswiki.org\/index.php\/Capillary_electrophoresis\" title=\"Capillary electrophoresis\" class=\"wiki-link\" data-key=\"b87d4130c405efb11ae34f19d4abb28c\">capillary electrophoresis<\/a>); chromosomal microarray analysis; fluorescence <i>in situ<\/i> hybridization (FISH); cytogenetic testing; and (genotyping by) <a href=\"https:\/\/www.limswiki.org\/index.php\/Mass_spectrometry\" title=\"Mass spectrometry\" class=\"wiki-link\" data-key=\"fb548eafe2596c35d7ea741849aa83d4\">mass spectrometry<\/a>.<\/li>\n<li>Integrate into the information technology (IT) environment of the institution for <a href=\"https:\/\/www.limswiki.org\/index.php\/Accessioning_(medical)\" title=\"Accessioning (medical)\" class=\"wiki-link\" data-key=\"d3a1f1a5d35fd9152d82893878bf9aa1\">accessioning<\/a> and resulting, particularly the <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">electronic health record<\/a> (EHR) system and the conventional clinical laboratory and anatomical pathology information systems. (More specifically, Cleveland Clinic was using <a href=\"https:\/\/www.limswiki.org\/index.php\/Sunquest_Information_Systems,_Inc.\" title=\"Sunquest Information Systems, Inc.\" class=\"wiki-link\" data-key=\"f4a9158f6e03a611d3ceec4b5ff31702\">Sunquest Laboratory<\/a> version 7.2 [Sunquest Information Systems, Tucson, AZ] and <a href=\"https:\/\/www.limswiki.org\/index.php\/Cerner_Corporation\" title=\"Cerner Corporation\" class=\"wiki-link\" data-key=\"44b952d5fb439af88c84f5ad453fee3f\">CoPathPlus<\/a> version 2014 [Cerner, N. Kansas City, MO] at the time, but these are now in the process of being replaced by Epic Beaker version November 2020 [Epic Systems, Verona, WI].)<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"Needs_assessment_and_partner_selection\">Needs assessment and partner selection<\/span><\/h3>\n<p>Given the complexity and multifaceted nature of the project, two key needs were recognized: professional project management guided by domain expertise in molecular testing laboratories, and experienced and expert software development professionals who could bring to bear state-of-the-art <a href=\"https:\/\/www.limswiki.org\/index.php\/Software_quality_management\" title=\"Software quality management\" class=\"wiki-link\" data-key=\"8c8c0fa8a260bb5dc333e053bde4c420\">software development tools and techniques<\/a>. Between two and four software developers were dedicated to the project at various stages. One business-based <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_assurance\" title=\"Quality assurance\" class=\"wiki-link\" data-key=\"2ede4490f0ea707b14456f44439c0984\">quality assurance<\/a> analyst was included, who served as the conduit for the translation of laboratory-specific requirements into software requirements. A Ph.D.-level molecular biologist with project management expertise was hired to apply process rigor and organization to direct LIMS development and implementation (among other projects).<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> Laboratory-based personnel participated in their various subject matter domains as their primary responsibilities to patient care allowed. Partnership with a team of software engineers was established. This team worked with molecular pathologists and laboratory personnel (subject matter experts) to design and build the full software solution. Peer-to-peer relationships were formed between the clinical laboratory project manager and software project managers as control points for the project.\n<\/p><p>Prior to the beginning of this extensive development project, due diligence was undertaken to evaluate whether, or to what extent, commercially available information systems could meet the needs at hand. This assessment indicated that some systems on the market could provide some of the functional requirements, and that development entirely from scratch was not required. NGS\u2013centric LIMS software was selected for licensure (<a href=\"https:\/\/www.limswiki.org\/index.php\/Illumina,_Inc.\" title=\"Illumina, Inc.\" class=\"wiki-link\" data-key=\"ca3eee9e7b220194a53536295b15ba2b\">BaseSpace Clarity LIMS<\/a> by Illumina, San Diego, CA). As licensed, this software was focused narrowly on supporting particular elements of NGS workflows. Its distinguishing characteristics were customizability and extensibility that could ultimately support the objectives of the laboratory, including a wide portfolio of <a href=\"https:\/\/www.limswiki.org\/index.php\/Molecular_diagnostics\" title=\"Molecular diagnostics\" class=\"wiki-link\" data-key=\"8fc14cae7a6fbac9a53fae1394fae7ee\">molecular diagnostics<\/a> tests performed and the need for systems integration. Compatibility with the third-party commercial <a href=\"https:\/\/www.limswiki.org\/index.php\/Bioinformatics\" title=\"Bioinformatics\" class=\"wiki-link\" data-key=\"8f506695fdbb26e3f314da308f8c053b\">bioinformatics<\/a> software that the laboratory had previously chosen (Clinical Genomics Workspace version 6.15.1 by PierianDx, Creve Couer, MO) was another key deciding criterion.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Technology_platforms_and_software_tools\">Technology platforms and software tools<\/span><\/h3>\n<p>The software engineering team used Jira and Confluence web-based software (Atlassian, San Francisco, CA) to organize development tasks and to project documentation, respectively. Version control was implemented in the web-based GitHub software host (San Francisco, CA). A continuous-integration pipeline (Table 1) was built using TeamCity software version 2019.1 (JetBrains, Prague, Czech Republic). The PyCharm version 2019.1 (JetBrains), Docker Desktop Community version 2.1.0.5 (Docker, Palo Alto, CA), VirtualBox version 6.1 (Oracle, Austin, TX), and Postman version 8.1 (Postman, San Francisco, CA) software solutions were used to facilitate local testing and development.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Definitions of terms for the Agile-Scrum software development method applied.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Term\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Definition\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Stakeholders<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">The group of individuals who work with, and would be impacted by, the software system being developed (i.e., laboratory and medical directors, laboratory managers, laboratory supervisors, medical\/laboratory technologists, pathologists, geneticists, bioinformaticians, staff scientists, clinical systems analysts, and a revolving cast from the larger Cleveland Clinic information-technology group).\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Agile project management<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">A system of practice to manage project delivery using an iterative approach. Optimization is achieved via continuous releases that include changes based on stakeholder review at each iteration. The process is useful for addressing highly complex problems in a mechanistic, incremental way.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Scrum<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Agile framework that encourages cross-functional team progress through short, measured iterations. Each problem is addressed in focused iterations called sprints, in which engineering management and build practices are used for addressing the complexity at hand. Outcomes are predicted and control of risk is assessed incrementally and via empirical observation.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>LIMS workflow<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Clinical laboratory test workflows have three components: i) pre-analytical, ii) analytical, and iii) post-analytical. A LIMS, or other supporting software, digitally models test workflows, storing and classifying large volumes of laboratory workflow data, while also automating laborious, repetitive workflow tasks that risk compounding human error. The term \"LIMS workflow\" alludes to customized, digital workflow models that span the pre-analytical, analytical, and post-analytical stages.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>External program plug-in (EPP)<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">A Clarity LIMS\u2013specific term that refers to a standalone script file accessible within the LIMS to perform calculations, transformations, or integrations too complex or cumbersome to configure within the LIMS itself.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Application programming interface (API)<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Software intermediary that serves to connect multiple applications, allowing them to exchange information. An <a href=\"https:\/\/www.limswiki.org\/index.php\/Application_programming_interface\" title=\"Application programming interface\" class=\"wiki-link\" data-key=\"36fc319869eba4613cb0854b421b0934\">API<\/a> dictates what information can be sent and received by a given application and may add security restrictions. It also abstracts underlying code when interacting with other software. An analogy is a person (application A) ordering at a restaurant (application B); the menu represents the API.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Continuous integration (CI) pipeline<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">The practice of automating the grouping of changes (typically software code, but also software build pipelines and automated tests) from multiple contributors into a single software project; this is software industry best practice, allowing developers to incorporate code changes into a central repository where builds and tests can be run more frequently and easily.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Development environment<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">System in which new features are actively developed.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Test environment<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">System in which newly developed features are tested. User-acceptance testing occurs in this environment; if the test fails, the software goes back to development, and if it passes, it is promoted to staging.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Staging environment<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">System used for validating changes prior to promotion to production. The system should mirror production in all ways except those new changes to be tested.\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><i>Production environment<\/i>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">The active system processing patient samples. This environment processes <a href=\"https:\/\/www.limswiki.org\/index.php\/Protected_health_information\" title=\"Protected health information\" class=\"wiki-link\" data-key=\"eca2f6661b6896668bd523e640e12499\">protected health information<\/a> (PHI) and needs to be treated in accordance with <a href=\"https:\/\/www.limswiki.org\/index.php\/HIPAA\" class=\"mw-redirect wiki-link\" title=\"HIPAA\" data-key=\"70050974d1eda9ff8cf9ecf7e4fcd015\">HIPAA<\/a> regulations.\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><a href=\"https:\/\/www.limswiki.org\/index.php\/Python_(programming_language)\" title=\"Python (programming language)\" class=\"wiki-link\" data-key=\"ef6905a29cbb75d3c71e6bdf6e2915dd\">Python<\/a> (Python Software Foundation, Wilmington, DE), a popular, general-purpose, high-level programming language with well-documented, well-supported engineering standards, was used to develop external program plug-ins, automated test scripts, report templates, and other services. A report-generation and sign-out application named AVRO (analytically validated reporting object; see subsequent sections) was built on a Python server with an Angular JavaScript front-end. For LIMS workflows, the open-source Python S4-Clarity library<sup id=\"rdp-ebb-cite_ref-GHS4_6-0\" class=\"reference\"><a href=\"#cite_note-GHS4-6\">[6]<\/a><\/sup> was used to support batch-analyte data (spreadsheet-formatted) parsing, laboratory instrument integrations, complex library pooling, de-multiplexing, and other computations on analytes. The Jinja web-based template engine library<sup id=\"rdp-ebb-cite_ref-GHJinja_7-0\" class=\"reference\"><a href=\"#cite_note-GHJinja-7\">[7]<\/a><\/sup> was used for default report-content templating to support clinical interpretation and clinical report generation in AVRO.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Project_management\">Project management<\/span><\/h3>\n<p>The general project management process used was Agile-Scrum in Jira, chosen by the owner of the critical path for project completion (i.e., the software development team). In the project, Agile-Scrum was supplemented with additional roles and processes tailored to work in the hybrid clinical laboratory service\/software development consultant environment. It became obvious that definitions and vocabulary differed between these two groups of subject matter experts (i.e., clinical laboratory and software engineering professionals). Selected terms are defined in Table 1. Key roles and activities of the Agile-Scrum development process, as applied in this project, are described in the next subsection.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Key_roles\">Key roles<\/span><\/h3>\n<p>Four key roles corresponding to major development and validation phases were identified as gatekeepers of the development process. These gatekeepers controlled the promotion of a deliverable through the process and, thus, control of a rapidly evolving process was retained. The subject matter experts in these roles worked in tight collaboration to ensure that the highest possible quality was achieved. Note that at relevant steps, bioinformatics professionals, Ph.D.-level laboratory director-designees, and\/or M.D.-level pathologists reviewed and approved changes as appropriate.\n<\/p><p><b> Key Role 1: Business Analyst (Extant within Software Development Team)<\/b>\n<\/p><p>The business analyst assumed responsibility and accountability for the elicitation and decomposition of requirements into granular requirements that were logically defined and complete. This work output was added to the stakeholder consensus process.\n<\/p><p><b>Key Role 2: Software Development Team<\/b>\n<\/p><p>The software development team was the consumer of approved granular requirements and the developer of software designed to meet those requirements. This team was involved in developing automated tests to validate that the software written did in fact meet the granular requirements as specified. This work output was collected into a release candidate and, upon passing the automated tests, was released into Phase 3, user acceptance testing. This team was self-organizing and chose the Scrum framework to align themselves into two-week iterations (.e., sprints).\n<\/p><p><b>Key Role 3: Clinical Systems Analyst (Extant within Laboratory Team)<\/b>\n<\/p><p>The clinical systems analyst served as the first round of testing for the laboratory service, owing to the proximity of the role to the laboratory and to the expertise in the laboratory's process and informatics architecture. The work assigned to this role was to coordinate and, in some cases, to perform the tasks in development\/validation (Phase 3), user acceptance testing. The output of this work was a pass\/fail decision that either sent the release candidate back to development or promoted the release candidate to staging.\n<\/p><p><b>Key Role 4: Laboratory Manager<\/b>\n<\/p><p>The laboratory manager signed documentation approving the release candidate for promotion to the production environment after review of successful pre-production runs that were performed using test samples in the laboratory and after verification that all test plans and checklists were completed.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Key_activities\">Key activities<\/span><\/h3>\n<p>The major phases of software development and <a href=\"https:\/\/www.limswiki.org\/index.php\/Software_verification_and_validation\" title=\"Software verification and validation\" class=\"wiki-link\" data-key=\"14bdd953b2bde31c520ba57b1002195e\">validation<\/a> are shown in Figure 1. All activities were coordinated utilizing a series of modular processes that worked together to produce a performant and validated software installation consisting of licensed software, configuration of that software, and customized software to supplement the licensed software (e.g., AVRO and the <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Level_7\" title=\"Health Level 7\" class=\"wiki-link\" data-key=\"e0bf845fb58d2bae05a846b47629e86f\">Health Level 7<\/a> (HL7) version 2.3 [Health Level Seven International, Ann Arbor, MI] interface.)\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg\" class=\"image wiki-link\" data-key=\"bfb5d8e39037a41ac4d989b10154e18d\"><img alt=\"Fig1 Tomlinson JofMolDiag2022 S1525-1578-22.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/0\/0d\/Fig1_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> Representation of the four major phases of software validation and development.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The highest-order process consisted of four development\/validation phases:\n<\/p>\n<ul><li>Phase 1: Identify requirements and group them into architecturally independent release candidates logically small enough to enable rapid development (requirements elicitation).<\/li>\n<li>Phase 2: Monitor and facilitate the development of automated testing and peer-review process on release candidates (software development).<\/li>\n<li>Phase 3: Coordinate the promotion of release candidates from the development environment to the testing environment (user acceptance testing).<\/li>\n<li>Phase 4: Coordinate the promotion of the release candidate from the testing environment to the staging environment for preproduction run, and subsequently to the production <i>in silico<\/i> environments in such a way as to avoid patient-care impacts (preproduction runs, progression to user-accepted version, and deployment).<\/li><\/ul>\n<h4><span id=\"rdp-ebb-Development\/Validation_Phase_1:_Requirements_elicitation\"><\/span><span class=\"mw-headline\" id=\"Development.2FValidation_Phase_1:_Requirements_elicitation\">Development\/Validation Phase 1: Requirements elicitation<\/span><\/h4>\n<p>The project consumed hundreds of person hours in elicitation meetings, the goals of which were to:\n<\/p>\n<ol><li>Establish the location of relevant domain knowledge.<\/li>\n<li>Establish detailed requirements and shared terminology.<\/li>\n<li>Achieve stakeholder group consensus on each granular requirement.<\/li>\n<li>Promote granular requirements to the approved backlog of work.<\/li><\/ol>\n<p>Translation of end-user system functionality into workable development items was a task shared between the laboratory and software teams. The laboratory team solicited input from subject matter experts and prepared documentation. The software business analyst then used that documentation to produce software development work items that fulfilled the final system requirements specified by the laboratory team. System requirements documentation included written requirements, text-based documents, logic tables (e.g., user-role permission maps, diagrams, and flowcharts), spreadsheets, native-instrument data files, laboratory standard operating procedures, and test validation plans.\n<\/p><p>Software deliverables were detailed and tracked in Jira. Laboratory objectives were described in common language, then passed to the software team for decomposition. Software development tasks were identified during decomposition and completed by the software team using Scrum. The percentage of completion reports for each objective were tracked using Jira and reviewed weekly by the joint project management group. Impediments to progress were identified and delegated to the appropriate team members for resolution. Common impediments included:\n<\/p>\n<ul><li>language ambiguity of requirements,<\/li>\n<li>technical difficulty in mapping laboratory requirements to the software, and<\/li>\n<li>requirements without a test plan or for which generating a test plan to be used in practice was challenging.<\/li><\/ul>\n<h4><span id=\"rdp-ebb-Development\/Validation_Phase_2:_Software_development\"><\/span><span class=\"mw-headline\" id=\"Development.2FValidation_Phase_2:_Software_development\">Development\/Validation Phase 2: Software development<\/span><\/h4>\n<p>Software development proceeded in two-week iteration cycles (sprints). Members of the clinical laboratory and software engineering teams continuously evaluated and improved the software development processes throughout the project. The teams incorporated the requirements of the <a href=\"https:\/\/www.limswiki.org\/index.php\/Health_Insurance_Portability_and_Accountability_Act\" title=\"Health Insurance Portability and Accountability Act\" class=\"wiki-link\" data-key=\"b70673a0117c21576016cb7498867153\">Health Insurance Portability and Accountability Act<\/a> (HIPAA) to ensure that protected health information was handled appropriately. For example, scripting of mock samples was developed with convincing, yet mock, data. This scripting enabled the engineering team to test the system in a realistic fashion without the use of patient information.\n<\/p><p>The engineering team adhered to the following technical process while working within sprints:\n<\/p>\n<ol><li>A team member chose a development task from the approved requirements to work on during the current iteration (sprint backlog).<\/li>\n<li>Once completed, each development task was peer-reviewed by other software engineers prior to inclusion in the master codebase, an industry-standard quality assurance practice.<\/li>\n<li>Automated tests were generated during development and run before and after each development task was committed to the master codebase, to identify problems in the task and in the integration of the task into the codebase, respectively. Automated tests generally consisted of scripts that generated representative mock samples and utilized the Clarity LIMS application programming interface to move those mock samples through the workflow while replicating user interaction at each step, again using the API.<\/li>\n<li>When the development of a full software deliverable was completed (release candidate), it was assembled atop all previous deliverables on a replica LIMS (test server).<\/li>\n<li>The release candidate was tested for both successful and potentially erroneous scenarios, in accordance with the requirement specification(s).<\/li><\/ol>\n<h4><span id=\"rdp-ebb-Development\/Validation_Phase_3:_User_acceptance_testing\"><\/span><span class=\"mw-headline\" id=\"Development.2FValidation_Phase_3:_User_acceptance_testing\">Development\/Validation Phase 3: User acceptance testing<\/span><\/h4>\n<p>In Phase 3 of software validation, functional testing was performed by the laboratory team and led by the clinical systems analyst, who reported results and discrepancies back to the software team at each stage for collaborative triage. A go\/no-go decision was made based on the severity of the discrepancy and the viability of a workaround being utilized until the next release candidate could be deployed. Discrepancies were addressed by the software team in order of priority and redeployed through reiteration of the above process.\n<\/p>\n<h4><span id=\"rdp-ebb-Development\/Validation_Phase_4:_Preproduction_runs,_progression_to_user-accepted_version,_and_deployment\"><\/span><span class=\"mw-headline\" id=\"Development.2FValidation_Phase_4:_Preproduction_runs.2C_progression_to_user-accepted_version.2C_and_deployment\">Development\/Validation Phase 4: Preproduction runs, progression to user-accepted version, and deployment<\/span><\/h4>\n<p>The following process was used for preproduction runs, progression to user-accepted version, and deployment:\n<\/p>\n<ol><li>After all tests were passed, the software vendor deployed the validated release candidate to the staging environment of the laboratory.<\/li>\n<li>Successful execution of the user acceptance testing phase triggered full system\u2013level preproduction runs by laboratory personnel in the staging environment.<\/li>\n<li>Successful preproduction run completion was followed by scheduled deployment of the release candidate to the production environment, which, in some cases, constituted several releases at once.<\/li>\n<li>Full deployment was facilitated jointly by software and laboratory IT personnel. Full system\u2013level tests, as well as preproduction run checklists and end-to-end testing scripts, were utilized to validate the performant nature of the final deployment(s).<\/li><\/ol>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"System_design:_Workflow_analysis_and_support\">System design: Workflow analysis and support<\/span><\/h3>\n<p>The LIMS organizes and handles the workflows of the clinical laboratory, from specimen accessioning through to laboratory analysis and issuing reports to ordering physicians. The system also coordinates tasks among staff. The LIMS automates several laboratory processes, such as spreadsheet parsing or container tracking, and is compatible with laboratory instrumentation, such as automated liquid handlers and <a href=\"https:\/\/www.limswiki.org\/index.php\/Quality_control\" title=\"Quality control\" class=\"wiki-link\" data-key=\"1e0e0c2eb3e45aff02f5d61799821f0f\">quality control<\/a> instruments, either through an off-the-shelf or custom-built integration. Substantial customized LIMS workflow design and engineering were required to model the testing procedures of the laboratory and to organize the constituent processes, including sample accessioning, nucleic acid (i.e., DNA, RNA, or total nucleic acid) purification, direct PCR testing, genotyping by mass spectrometry, sequencing, chromosome testing, data analysis, and all associated quality control steps.\n<\/p><p>A key project requirement was organization and refinement of workflows within the LIMS. Wherever possible, shared processes were identified and excluded from test-specific workflow building. For example, sample accessioning and DNA extraction were built out as shared protocols. Templating (sharing) at the step and protocol layers were combined with unique elements to generate end-to-end workflows specific to each test.\n<\/p><p>The LIMS was engineered to support the build of workflows in a hierarchical fashion in which workflows contain protocols which, in turn, contain steps (Table 2). In steps, the work of the end user is performed, on either a single sample or a batch of samples. Protocols are a collection of steps organized around the standard operating procedures of a laboratory, and workflows comprise the protocols required to execute a test. Custom-built workflows are shown in Table 3.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Test component organization.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LIMS component\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Example\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Scope\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Step\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">DNA extraction\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Single wet laboratory process contained in a single work session, in one physical location\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Protocol\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Sample extraction\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Collection of steps that facilitate one stage of the workflow\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Workflow\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Fragile X carrier screening\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">End-to-end sample processing, from accessioning to report issuance\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> Shared workflow components. <sup>\u2217<\/sup> Indicates universally shared component. Note that pre-analytics was able to be shared across all workflows, while sample preparation extraction was shared, but only within the MDx group of tests.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LIMS workflow\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Workflow components\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Cytogenetics (CytoG)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Pre-analytics<sup>\u2217<\/sup> > (CytoG) wet laboratory sample extraction > wet laboratory analysis > clinical reporting > long-term data archiving<sup>\u2217<\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Chromosomal microarray (CMA)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Pre-analytics<sup>\u2217<\/sup> > (CMA) wet laboratory sample preparation > wet laboratory analysis > clinical reporting > long-term data archiving<sup>\u2217<\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Carrier screening\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Pre-analytics<sup>\u2217<\/sup> > sample preparation extraction<sup>\u2217<\/sup> > (carrier screening) wet laboratory analysis (per test code) > clinical reporting > MDx long-term data archiving<sup>\u2217<\/sup>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Molecular diagnostics (MDx)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Preanalytics<sup>\u2217<\/sup> > samplepreparation extraction<sup>\u2217<\/sup> > wet laboratory analysis (per test code) > clinical reporting > MDx long-term data archiving<sup>\u2217<\/sup>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"System_features_and_integration\">System features and integration<\/span><\/h3>\n<h4><span id=\"rdp-ebb-LIS\u2013HL7_interface_for_sample_accessioning\"><\/span><span class=\"mw-headline\" id=\"LIS.E2.80.93HL7_interface_for_sample_accessioning\">LIS\u2013HL7 interface for sample accessioning<\/span><\/h4>\n<p>LIS applications typically connect to other patient health care applications such as health insurance policy administration systems and EHRs.<sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup> To function effectively, an LIS must be interoperable with these health care record systems through the adoption of a common standard.<sup id=\"rdp-ebb-cite_ref-:0_2-2\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup> The HL7 standard was utilized as the form of communication between the LIS and the LIMS through a customized interface (Figure 2).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg\" class=\"image wiki-link\" data-key=\"d73f846893cc0428df66ba3f7c7bb172\"><img alt=\"Fig2 Tomlinson JofMolDiag2022 S1525-1578-22.jpg\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6e\/Fig2_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> A laboratory information management system (LIMS) supports clinical laboratory test workflows, systems interfacing, and traceability by classifying and storing laboratory workflow data like accessioning, pre-analytics, analytical wet bench, and analytical interpretation paired to clinical interpretation (i.e., results reporting). Traceability refers to the record keeping in each of the systems shown above (i.e., data received, sent, and transformed, that happen in between). AVRO, analytically validated reporting object; EPP, external program plug-in; LIS, laboratory information system. CoPathPlus, Cerner (N. Kansas City, MO); Epic Beaker version November 2020, Epic Systems (Verona, WI); HL7, Health Level Seven International version 2.3, Health Level Seven International (Ann Arbor, MI); Sunquest software version 7.2, Sunquest Information Systems (Tucson, AZ).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The interface between the existing Sunquest Laboratory and CoPathPlus LISs of the laboratory and the new LIMS streamlined the flow of patient data received from the health care record systems into sample accessioning. A customized HL7 listener service was built and configured to interface with the LIS. This service verifies whether the HL7 message received is valid and, if so, generates a sample with all required sample information fields and accessions it directly into the LIMS. Required sample fields including, but not limited to, medical record number, last name, and collection date are extracted from the HL7 message and mapped to user-defined LIMS fields to preserve vital information for mapping test results to the correct patient downstream. The original inbound HL7 message was preserved on the sample to resolve any ambiguous data mapping in the LIMS. Error logs are generated for review when HL7 messages either cannot be processed or produce errors.\n<\/p><p>The LIS application was integrated with the HL7 interface while its essential functionality and interoperable links were preserved. After software build, the LISs still collected and organized patient health care data. However, software management of the clinical test workflows and process automation were improved with LIMS implementation.\n<\/p>\n<h4><span class=\"mw-headline\" id=\"Instrumentation\">Instrumentation<\/span><\/h4>\n<p>Integration with nucleic acid purification robotics and spectrophotometers (pre-analytical) and molecular diagnostics\u2013related analytical platforms were facilitated through file transfer systems built on shared network locations. Integrations followed the same process:\n<\/p>\n<ol><li>A plate map was generated and displayed to laboratory personnel at the appropriate LIMS workflow step.<\/li>\n<li>After the requisite samples were plated and the instrument completed its full cycle, an output file was directed to a shared network location available at each LIMS workstation.<\/li>\n<li>Laboratory personnel uploaded the output file to the appropriate (usually next) step in the LIMS workflow.<\/li>\n<li>An external program plug-in parsed data from the output file and saved discrete pieces to user-defined fields on the sample in the LIMS.<\/li><\/ol>\n<h3><span class=\"mw-headline\" id=\"Clinical_reporting_application\">Clinical reporting application<\/span><\/h3>\n<p>To address the ultimate goal of every high-complexity clinical laboratory test (i.e., the issuance of a patient report for the physician who ordered the test), the customized AVRO was built. AVRO serves as an interface to manage the interpretation (post-analytical) component of laboratory test workflows. AVRO utilizes the authentication system of the LIMS, and therefore only LIMS users with the correct permission setting can access AVRO. AVRO runs on its own server, links directly to the LIMS, and polls specific steps to import reporting objects. It then determines which report template to assign based on the test code and displays test data to professional staff reviewers. This reporting application generates standards-compliant clinical reports for annotation and sign-out by molecular pathology professional staff. Upon sign-out, AVRO sends text reports to the automated clinical results\u2013releasing service, which submits HL7-formatted data and issues a text-based copy of the report to the appropriate recipient.\n<\/p><p>AVRO was designed and implemented to harmonize results reporting and formatting within a dynamic multicomponent system of EMRs and LISs (Epic Beaker, Sunquest Laboratory, CoPathPlus, and Rhapsody version 6.6 [Lyniate, Boston, MA]) while maintaining a flexible LIMS configuration. (Rhapsody is an interface engine that sits between Epic and ancillary systems, e.g., Sunquest Laboratory, CoPathPlus.) Given that report fields are populated directly from LIMS user-defined fields, all LIMS data are available to the report template. Using Jinja2 Python templating enabled a programmatic approach to reporting (i.e., rules can be applied to text and data formatting). AVRO uses the LIMS application data layer and the LIMS-managed user credentials that can be integrated with Lightweight Directory Access Protocol (LDAP) systems to support data provenance and added security. This approach obviated the architectural generation of a separate database and the duplication of user credentials. AVRO thus facilitates professional actions on samples that exist entirely within the LIMS.\n<\/p><p>The concept of report-based content defaults was identified from feedback after early implementations had been tested by the reporting professional staff. Reporting templates were customized for each test and then served the correct template by mapping test codes to those templates. Templates could be mapped to multiple test codes and were maintained independently for maximum flexibility in content.\n<\/p><p>Opening a report in AVRO presents a template based on the above logic, populated with interpretation text derived from the results interpretation code applied in the analysis portion of the workflow. The molecular pathologist user is able to modify and customize all of the populated content prior to sign-out. At any point during the report-building process, AVRO allows the user to preview the report.\n<\/p><p>A customized results\u2013releasing service was built into the LIMS as a set of external program plug-ins for report release. This step was designed such that the system monitors for newly signed-out reports in AVRO every 30 seconds via the AVRO API. The report is generated and sent back to the LIS, and then the report file(s) are attached to the completed step in the LIMS.\n<\/p><p><a href=\"https:\/\/www.limswiki.org\/index.php\/Audit_trail\" title=\"Audit trail\" class=\"wiki-link\" data-key=\"96a617b543c5b2f26617288ba923c0f0\">Audit trails<\/a> were available as base functionality in the LIMS and did not require customization. Building AVRO atop the audit trail data layer facilitated auditing through the reporting process up until submission of the outbound HL7 message. HIPAA compliance as implemented in the LIMS thus persisted through the reporting process, an efficiency afforded by leveraging of the existing software validation work extant in the off-the-shelf product. The LIMS tracks all of the elements specified by audit trail-related items per the College of American Pathologists Laboratory General Accreditation Checklist.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Resulting_end-to-end_software_solution\">Resulting end-to-end software solution<\/span><\/h3>\n<p>The test management software system of the LIMS and AVRO interfaced with the pre-existing LIS architecture via customized software services, an HL7-bridged laboratory sample accessioning service, and an automated clinical results\u2013releasing service through the LIMS. The newly integrated solutions automated the full end-to-end process of the molecular pathology laboratory, from sample accessioning to the issuance of final patient reports. These services eliminated the use of paper to track analytics data and mitigated the risks for bottlenecks and human error that tend to result from manual control of laboratory input and output processes. For example, accessioning bottlenecks have been mitigated by streamlining accessioning through the LIS\u2013HL7 interface, and human errors due to data transcription have been reduced through data tracking in the LIMS and subsequent automated exchange of data between the LIMS, AVRO, and LIS.\n<\/p><p>An important predictor of success was the selection of a LIMS with robust API and customization support in order to address the significant \u0394 between off-the-shelf functionality<sup id=\"rdp-ebb-cite_ref-:0_2-3\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup> and the functionality required by the molecular service via the only pathway remaining, custom software engineering. Software engineers worked in virtual instances of the software environment to enable rapid revisions within existing and relevant system parameters. Imagining, designing, testing, and implementing the information management system described required significant human and financial resources. A list of advantages that have been accrued by this clinical laboratory, or that are anticipated in the near future, is shown in Table 4. Specific examples of the benefits the laboratory has experienced since LIMS implementation are listed in Table 5.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"7\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 4.<\/b> Benefits accruing to a clinical laboratory from a LIMS. CPT, Current Procedural Terminology; CS, customer service; Fin, financial; Ops, operations; PC, patient care; Q, quality; Reg, regulatory.\n<\/td><\/tr>\n<tr>\n<th rowspan=\"2\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Item\n<\/th>\n<th colspan=\"6\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Category\n<\/th><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">CS\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Fin\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Ops\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">PC\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Q\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Reg\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Inventory management and control; optimize reagent purchasing to just-in-time model, thereby improving cash flow\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce time needed for retrieval of archived specimens\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce paper consumption\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Monitor process activities: track\/locate a specimen as it moves through testing process, waiting times, bottlenecks, and instrument usage; assess percentages of instrument capacity being used, idle versus active time, batch sizes\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce opportunities for human error\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Prevent use of expired reagents\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Monitor waste, rework, delayed turnaround times\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Optimize use of laboratory human resources; monitor individual clinical laboratory scientist productivity by tracking work units\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Audit trail\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Troubleshoot bottlenecks in testing progress; simplification of root cause analysis\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Real-time opportunities for investigation of failures (reagents, instruments, human) and identification of patterns\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Capacity to rapidly identify specimens associated with a problematic reagent, instrument, or run\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Simplification of monitoring instrument calibration and verification\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Capacity to upload supporting documentation so that all data are centralized and not in separate logs\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Monitor volumes by client\/physician\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Correlate testing with environment (e.g., temperature, humidity)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Correlate technologist training and competence with testing\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Centralize instrument maintenance and service agreements\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Opportunity to learn true cost of testing\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Correlate testing done with and without payer preauthorization\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Track test volumes by variables (e.g., test code, CPT code, shift)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce the time that medical technologists invest in performing clerical tasks (e.g., pre- and post-analytical clerical tasks, accessioning exceptions, data transcription)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Simplified, standardized results reporting across all tests\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce time spent on regulatory submissions associated with software\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Reduce documentation errors associated with instrument function and verification, as well as workspace decontamination\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 5.<\/b> Examples of LIMS benefits. FISH, fluorescence <i>in situ<\/i> hybridization; TAT, turnaround time.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Item\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Benefit(s)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Supporting metric(s)\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Specimen demographic information interfaces directly from extant LIS to LIMS-based analytics workflows\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Pre-analytics and analytics technicians no longer need to manually transcribe specimen demographic information into Excel logs and workbooks<br \/><b>2.<\/b> Eliminated time-consuming clerical duties from pre-analytics and analytics technicians<br \/><b>3.<\/b> Eliminated transcription errors that result in discordant specimen demographic information between systems\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Time-savings, measurements in progress<br \/><b>2.<\/b> Twenty-four Excel logs used for specimen data storage eliminated and archived\n<\/p>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Nucleic acid quantification values and quality metrics parsed directly from NanoDrop (Thermo Fisher Scientific, Waltham, MA) files into LIMS-based analytical workflows\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Analytics technicians no longer need to manually transcribe quantification data into Excel logs<br \/><b>2.<\/b> Eliminated time-consuming data transcription duties from analytics technicians<br \/><b>3.<\/b> Eliminated data transcription errors<br \/><b>4.<\/b> LIMS-based automations perform quality metrics calculations previously performed by Excel macro\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Time-savings, measurements in progress<br \/><b>2.<\/b> One Excel macro eliminated and archived\n<\/p>\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Nucleic acid extraction reagent and data tracking now completely LIMS-based; previous state required manual completion and archiving of physical worksheets\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Analytics technicians no longer need to manually transcribe reagent lot information<br \/><b>2.<\/b> Reduced paper consumption<br \/><b>3.<\/b> Reduced physical document storage\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Ten high-use nucleic acid extraction documents eliminated and archived\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Consolidation of specimen tracking history from multiple systems into one searchable database\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Higher-resolution specimen tracking enables users to pinpoint specimen location at any step of pre-analytical, analytical, and post-analytical processes<br \/><b>2.<\/b> Expanded and available user-defined fields in extraction workflow reveal whether additional material is available for re-extraction\/retesting, i.e., computer-based query versus manual search and review in the laboratory<br \/><b>3.<\/b>\nReduced interruption of pre-analytics and analytics technicians for specimen data interrogation<br \/><b>4.<\/b> Improved troubleshooting and trend identification\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Time-savings; measurements in progress\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LIMS-based workflow steps include performing technologist, date, and time stamps\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Provides high-resolution data previously unavailable to the laboratory, which can be used for the identification of technique variation among techs\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\/A\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Specimen analytical results parsed directly from analytical Excel workbooks into LIMS, which transmits directly to reporting LIS\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Analytics technicians no longer need to manually transcribe result codes into reporting LIS<br \/><b>2.<\/b> Reduced data-transcription errors\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Time-savings, measurements in progress\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Consolidation of reporting system from CoPathPlus, Sunquest Laboratory, and ePath Logic web-based software (ePath Logic, Highland, MI) to one universal reporting product (AVRO)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Standardized reporting process across testing platforms<br \/><b>2.<\/b> Reduced LIS access and training requirements for analytics technicians\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Reporting LIS reduction from three systems to one\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">LIMS transmits data directly to Tableau\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Enables more sophisticated queries and data analysis for quality metrics reporting and troubleshooting\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">N\/A\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Automated calculation for reagent addition in FISH\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> Saves time<br \/><b>2.<\/b> Eliminates arithmetic errors<br \/><b>3.<\/b> Automates recording of probe(s) used, lot numbers, expiration dates\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Time-savings, measurements in progress\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Case tracking (FISH laboratory)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<p><b>1.<\/b> TAT tracking automated<br \/><b>2.<\/b> Rush samples or samples approaching TAT limit more easily sorted and found<br \/><b>3.<\/b> Facilitates case assignment to technologists\n<\/p>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1.<\/b> Time-savings, measurements in progress\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>The Molecular Pathology Section, Pathology & Laboratory Medicine Institute, Cleveland Clinic performs high-complexity clinical laboratory testing in support of the practice of genomic medicine. A revitalization and modernization program, begun in 2016, established the need for improvements in laboratory data management. Organization of clinical laboratory testing workflows in the twenty-first century is best matched to modern software and information management tools, not tools from the previous century (i.e., paper, Excel, flash drives). Education was pivotal in accelerating the project toward success. Educating all members in this team-based approach in respective domains led to the acknowledgment that both software development and molecular pathology (with inherent regulation) were of equal importance in the LIMS development process. Education, not unlike the build process itself, was accomplished iteratively and continually throughout the project. The more that subject matter experts from all disciplines understood each other, the better the team was able to optimize and improve each build iteration and, subsequently, execute the shared process successfully. The importance of partnership between the laboratory and software engineering teams was a lesson well learned.\n<\/p><p>Modeling clinical laboratory test workflows digitally and integrating a LIMS into the clinical hardware and software architectures of the laboratory required a significant amount of customized software engineering. Most commercial LIMS are touted as configurable. Principles and practices from the domains of computer science and software engineering were required to produce a maintainable and scalable LIMS implementation, alongside a greater set of laboratory software services and applications. Laboratories often do not have the resources in-house to integrate such a solution into their existing system(s). Software and process engineers were required to build effective customized test-workflow models <i>in silico<\/i> that automated processes and managed the inherent workflow data. Their role also included installing and successfully integrating the LIMS application alongside other supporting software that existed in the clinical informatics architecture. By employing a team-based collaborative approach between the clinical laboratory and software engineers, the existing software system was significantly upgraded, the use of paper and electronic spreadsheets was reduced (with the eventual goal of the complete elimination of paper), and efficiency was increased, putting the laboratory in a better position to scale up throughput and manage complex data.\n<\/p><p>The results reporting environment is complex; here we show one of the benefits of the LIMS implementation. The Pathology & Laboratory Medicine Institute (composed of two departments: anatomical pathology and laboratory medicine) uses Sunquest Laboratory to output test results. CoPathPlus is used to report anatomic pathology results and additional associated testing of tissue, cytology, and bone marrow specimens (i.e., special stains, FISH, cytogenetics, PCR, and NGS testing). Clarity LIMS streamlined reporting so that all molecular pathology tests are now reported back to Sunquest Laboratory and posted as a discrete item in the patient's EHR in Epic for the specific test. Tests that must be reported as part of an anatomic pathology report are sent back to CoPathPlus from Sunquest Laboratory so that clinicians may view a comprehensive report on that specimen.\n<\/p><p>Formulating an effective software development framework was important, considering the challenges in generating and operating customized clinical laboratory software. Such software must address testing intricacies and diverse molecular technologies within a complex clinical laboratory architecture. Rigorous building methods and techniques were needed to ensure build quality and maintenance sustainability.\n<\/p><p>Scrum best practices are valuable in the modernization of clinical laboratory information management workflows via custom software development. Scrum best practices are demonstrated to be extensible, scalable, and cost-effective. It is crucial that any given Scrum format be lightweight, with clearly defined roles and responsibilities of the participants; be comprehensively simple; and assume room for improvement.\n<\/p><p>Notably, a laboratory science framework for molecular biology research, termed LabScrum, has gained support in research-oriented molecular biology laboratories. LabScrum emulates the principles of Scrum software development. The writers of LabScrum illustrated three critical principles of the Scrum framework's utility in research laboratories.<sup id=\"rdp-ebb-cite_ref-:1_9-0\" class=\"reference\"><a href=\"#cite_note-:1-9\">[9]<\/a><\/sup> These principles are valid for building customized information management software in the setting of clinical laboratory testing.\n<\/p><p>The adoption of some form of Scrum in developing customized laboratory software should focus on three essential components: transparency, inspection, and adaptation. LabScrum proponents have argued that a management framework based on empiricism is highly consistent with the scientific method.<sup id=\"rdp-ebb-cite_ref-:1_9-1\" class=\"reference\"><a href=\"#cite_note-:1-9\">[9]<\/a><\/sup> Anecdotally, research scientists rigorously apply empiricism and the scientific method for results, or product, but often do not think empirically about tasks, techniques, or processes. Generating process visibility and analysis utilizing a framework for ongoing improvement can improve the quality of the science (i.e., more rigorous science), the quantity of the science (i.e., more productive science), and the quality of life of scientists (i.e., more sustainable science). In effect, to run a modern clinical laboratory necessitates having a laboratory function to interact with the processes of configuring or generating customized software, because, by definition, this software does not yet exist or, more accurately, must be customized for use in every clinical laboratory.\n<\/p>\n<h3><span id=\"rdp-ebb-Limitations,_lessons_learned,_and_future_work\"><\/span><span class=\"mw-headline\" id=\"Limitations.2C_lessons_learned.2C_and_future_work\">Limitations, lessons learned, and future work<\/span><\/h3>\n<p>The inability of the LIMS implementation to store unique patients in their own table with a one-to-many relationship between the patients table and the specimens table in the database is a limitation of the existing system. The system is maintained via IT department personnel, two full-time laboratorian, and one part-time laboratorian.\n<\/p><p>An important lesson learned in executing the LIMS project was the concept of a minimally viable product (MVP). Early in the project, the laboratory team was excited about the flexibility and customizability of the chosen LIMS product. In understanding what was possible and what was needed to elevate the laboratory's capabilities, overreaching and unrealistic goals were imagined. The team grew too ambitious, frustration accompanied scope creep, and project velocity decreased. Once it became clear that an MVP was, by definition, good enough, goals became simultaneously more modest and attainable. Thus the project's progress toward full execution accelerated over the last approximately 12 months of a 30-month effort from late 2017 to early 2020. \n<\/p><p>With LIMS launch, experience using the LIMS, and newly acquired local skills and knowledge, the laboratory team looks forward to independently adding more functionality via new customizations.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>We thank Gordon Meyer, Justin Chant, Emily Wong, Jeremy Snell, Danny Hopkins, Mark Swinkels, Mark Luszniak, and the rest of the Semaphore team for their technical expertise; Wendy Nedlik for organizational management expertise, Hillard Meade for project management expertise; James Fenske for software implementation assistance; Michael Reese for financial analysis; Eric D. Hsi, MD, for leadership; and Jacqueline Urankar and Susan Brennan for excellent administrative support.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>Supported by the Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>E.T., S.A., W.E.R., and C.M. are full-time employees of Semaphore Solutions, the vendor retained by Cleveland Clinic in the development and launch of the LIMS described in this article.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kang, Wenjun; Kadri, Sabah; Puranik, Rutika; Wurst, Michelle N.; Patil, Sushant A.; Mujacic, Ibro; Benhamed, Sonia; Niu, Nifang <i>et al.<\/i> (1 July 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29698836\" target=\"_blank\">\"System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management\"<\/a>. <i>The Journal of molecular diagnostics: JMD<\/i> <b>20<\/b> (4): 522\u2013532. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jmoldx.2018.03.008\" target=\"_blank\">10.1016\/j.jmoldx.2018.03.008<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1943-7811\" target=\"_blank\">1943-7811<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/6039793\/\" target=\"_blank\">6039793<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29698836\" target=\"_blank\">29698836<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29698836\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/29698836<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=System+for+Informatics+in+the+Molecular+Pathology+Laboratory%3A+An+Open-Source+End-to-End+Solution+for+Next-Generation+Sequencing+Clinical+Data+Management&rft.jtitle=The+Journal+of+molecular+diagnostics%3A+JMD&rft.aulast=Kang&rft.aufirst=Wenjun&rft.au=Kang%2C%26%2332%3BWenjun&rft.au=Kadri%2C%26%2332%3BSabah&rft.au=Puranik%2C%26%2332%3BRutika&rft.au=Wurst%2C%26%2332%3BMichelle+N.&rft.au=Patil%2C%26%2332%3BSushant+A.&rft.au=Mujacic%2C%26%2332%3BIbro&rft.au=Benhamed%2C%26%2332%3BSonia&rft.au=Niu%2C%26%2332%3BNifang&rft.au=Zhen%2C%26%2332%3BChao+Jie&rft.date=1+July+2018&rft.volume=20&rft.issue=4&rft.pages=522%E2%80%93532&rft_id=info:doi\/10.1016%2Fj.jmoldx.2018.03.008&rft.issn=1943-7811&rft_id=info:pmc\/6039793&rft_id=info:pmid\/29698836&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F29698836&rfr_id=info:sid\/en.wikipedia.org:Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-2\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_2-0\">2.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_2-1\">2.1<\/a><\/sup> <sup><a href=\"#cite_ref-:0_2-2\">2.2<\/a><\/sup> <sup><a href=\"#cite_ref-:0_2-3\">2.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Myers, Charles; Swadley, Matthew; Carter, Alexis B. 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Retrieved 04 August 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=pallets+%2F+jinja&rft.atitle=GitHub&rft.aulast=Ronacher%2C+A.&rft.au=Ronacher%2C+A.&rft.date=18+May+2021&rft_id=https%3A%2F%2Fgithub.com%2Fpallets%2Fjinja&rfr_id=info:sid\/en.wikipedia.org:Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sinard, John H.; Gershkovich, Peter (2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23372985\" target=\"_blank\">\"Custom software development for use in a clinical laboratory\"<\/a>. <i>Journal of Pathology Informatics<\/i> <b>3<\/b>: 44\u201353. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2153-3539.104906\" target=\"_blank\">10.4103\/2153-3539.104906<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/3551490\/\" target=\"_blank\">3551490<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23372985\" target=\"_blank\">23372985<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23372985\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/23372985<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Custom+software+development+for+use+in+a+clinical+laboratory&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Sinard&rft.aufirst=John+H.&rft.au=Sinard%2C%26%2332%3BJohn+H.&rft.au=Gershkovich%2C%26%2332%3BPeter&rft.date=2012&rft.volume=3&rft.pages=44%E2%80%9353&rft_id=info:doi\/10.4103%2F2153-3539.104906&rft.issn=2153-3539&rft_id=info:pmc\/3551490&rft_id=info:pmid\/23372985&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23372985&rfr_id=info:sid\/en.wikipedia.org:Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_9-0\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_9-1\">9.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">May, L.; Runyon, T. (25 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.cutter.com\/article\/labscrum-case-study-agility-academic-research-labs-504061\" target=\"_blank\">\"LabScrum: A Case Study for Agility in Academic Research Labs\"<\/a>. <i>Cutter<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.cutter.com\/article\/labscrum-case-study-agility-academic-research-labs-504061\" target=\"_blank\">https:\/\/www.cutter.com\/article\/labscrum-case-study-agility-academic-research-labs-504061<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=LabScrum%3A+A+Case+Study+for+Agility+in+Academic+Research+Labs&rft.atitle=Cutter&rft.aulast=May%2C+L.%3B+Runyon%2C+T.&rft.au=May%2C+L.%3B+Runyon%2C+T.&rft.date=25+June+2019&rft_id=https%3A%2F%2Fwww.cutter.com%2Farticle%2Flabscrum-case-study-agility-academic-research-labs-504061&rfr_id=info:sid\/en.wikipedia.org:Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with minor changes to presentation, grammar, and punctuation. In some cases, important information was missing from the references, and that information was added. Everything else remains true to the original article, per the \"NoDerivatives\" portion of the distribution license.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628174910\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.210 seconds\nReal time usage: 0.434 seconds\nPreprocessor visited node count: 10813\/1000000\nPost\u2010expand include size: 92211\/2097152 bytes\nTemplate argument size: 30391\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 22512\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 168.389 1 -total\n 75.89% 127.797 1 Template:Reflist\n 52.83% 88.952 9 Template:Citation\/core\n 42.67% 71.855 6 Template:Cite_journal\n 16.85% 28.372 3 Template:Cite_web\n 16.22% 27.313 1 Template:Infobox_journal_article\n 13.53% 22.789 1 Template:Infobox\n 9.37% 15.783 9 Template:Date\n 8.57% 14.423 20 Template:Citation\/identifier\n 7.01% 11.802 80 Template:Infobox\/row\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13223-0!canonical and timestamp 20220628174909 and revision id 47447. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations\">https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","215d8425e45c087c83287d3b78268e65_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/0\/0d\/Fig1_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/6e\/Fig2_Tomlinson_JofMolDiag2022_S1525-1578-22.jpg"],"215d8425e45c087c83287d3b78268e65_timestamp":1656439825,"ef9487ab4d88db8c29a49a38ec04aec1_type":"article","ef9487ab4d88db8c29a49a38ec04aec1_title":"DigiPatICS: Digital pathology transformation of the Catalan Health Institute network of eight hospitals - Planning, implementation, and preliminary results (Temprana-Salvado et al. 2022)","ef9487ab4d88db8c29a49a38ec04aec1_url":"https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results","ef9487ab4d88db8c29a49a38ec04aec1_plaintext":"\n\nJournal:DigiPatICS: Digital pathology transformation of the Catalan Health Institute network of eight hospitals - Planning, implementation, and preliminary resultsFrom LIMSWikiJump to navigationJump to searchFull article title\n \nDigiPatICS: Digital pathology transformation of the Catalan Health Institute network of eight hospitals - Planning, implementation, and preliminary resultsJournal\n \nDiagnosticsAuthor(s)\n \nTemprana-Salvado, Jordi; L\u00f3pez-Garc\u00eda, Pablo; Vives, Josep C.; de Haro, Llu\u00eds; Ballesta, Eudald; Abusleme, Matias R.; Arrufat, Miquel; Marques, Ferran; Casas, Josep R.; Gallego, Carlos; Pons, Laura; Mate, Jos\u00e9 L.; Fern\u00e1ndez, Pedro L.; L\u00f3pez-Bonet, Eugeni; Bosch, Ramon; Mart\u00ednez, Salom\u00e9; Ram\u00f3n y Cajal, Santiago; Matias-Guiu, XavierAuthor affiliation(s)\n \nInstitut Catal\u00e0 de la Salut, Centre de Telecomunicacions i Tecnologies de la Informaci\u00f3, Vall d\u2019Hebron University Hospital, TIC Salut Social, Technical University of Catalonia, Germans Trias i Pujol University Hospital, Doctor Josep Trueta Hospital of Girona, Verge de la Cinta Hospital of Tortosa, Joan XXIII University Hospital of Tarragona, Arnau de Vilanova University Hospital, Bellvitge University HospitalPrimary contact\n \nEmail: jtemprana at vhebron dot netEditors\n \nEloy, CatarinaYear published\n \n2022Volume and issue\n \n12(4)Article #\n \n852DOI\n \n10.3390\/diagnostics12040852ISSN\n \n2075-4418Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2075-4418\/12\/4\/852\/htmlDownload\n \nhttps:\/\/www.mdpi.com\/2075-4418\/12\/4\/852\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Materials and methods \n\n3.1 Planning, scope, and tender process \n3.2 Scanners and technology for obtaining whole slide images (WSIs) \n3.3 Macroscopic imaging \n3.4 WSI viewing: Hardware \n3.5 WSI viewing: Software \n3.6 ETPAT: Our laboratory information system (LIS) \n3.7 Network needs, local area network (LAN), and wide area network (WAN) \n3.8 On-premises data processing centers (DPCs) \n3.9 SIMDCAT and DICOM \n3.10 AI and the Polytechnic University of Catalonia\u2013BarcelonaTech (UPC) \n\n\n4 Results \n\n4.1 Laboratory workflow, traceability, and barcode generation \n4.2 Scanning \n4.3 Monitors \n4.4 Teaching, telepathology, and networking \n\n\n5 Discussion \n6 Conclusions \n7 Acknowledgements \n\n7.1 Author contributions \n7.2 Funding \n7.3 Data availability statement \n7.4 Conflict of interest \n\n\n8 References \n9 Notes \n\n\n\nAbstract \nComplete digital pathology transformation for primary histopathological diagnosis is a challenging yet rewarding endeavor. Its advantages are clear with more efficient workflows, but there are many technical and functional difficulties to be faced. The Catalan Health Institute (Institut Catal\u00e0 de la Salut or ICS) has started its DigiPatICS project, aiming to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of eight hospitals, over 168 pathologists, and over one million slides each year. We describe the bidding process and the careful planning that was required, followed by swift implementation in stages. The purpose of the DigiPatICS project is to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in the pathological anatomy departments of the ICS through process improvement, digital pathology, and artificial intelligence (AI) tools.\nKeywords: digital pathology, computational pathology, artificial intelligence, deep learning, implementation, workflow, primary diagnosis, LIS, telepathology, network\n\nIntroduction \nThe Catalan Health Institute (Institut Catal\u00e0 de la Salut or ICS) is the largest provider for the Catalan Health Service, the insurer of universal health coverage in Catalonia. It is the company with the most employees in Catalonia and the largest public company in Spain, with almost 39,000 professionals who provide services to almost six million people throughout the territory.[1] The ICS manages 283 primary care teams, three large high-tech tertiary hospitals (Vall d\u2019Hebron, Bellvitge, and Germans Trias), four regional reference hospitals (Arnau de Vilanova in Lleida, Joan XXIII in Tarragona, Josep Trueta in Girona, and Verge de la Cinta in Tortosa), and a regional hospital (Viladecans) (Figure 1). The ICS accounts for seven percent of the Catalonian government budget, accounting for over 40 million primary visits and over 100,000 surgical interventions yearly.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 1. Map of Catalonia and the eight ICS hospitals.\n\n\n\nSome laboratories are beginning to successfully deploy digital pathology solutions for routine diagnosis, which we believe will be a growing trend in the next few years.[2][3][4][5][6][7][8][9][10] In Catalonia, the DigiPatICS project plans to accomplish a complete digital pathology transformation of primary histopathological diagnosis for over 168 pathologists. Many groups have reported equivalency between digital pathology and conventional pathology.[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]\nWith the DigiPatICS project, we aim to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in anatomical pathology departments of the ICS through digital pathology and artificial intelligence (AI) tools.[28] With digital pathology, we aim for a network of eight hospitals to work as one in terms of case sharing and teaching, putting all our patients on equal footing. This transversal digital transformation will have an impact on the care of patients treated by all medical and surgical specialists.\nFirst, we created a network between ICS centers. This helped us increase the reproducibility and quality of diagnoses, as well as offered greater equity and safety to patients. In turn, this network approach facilitated remote diagnosis, case sharing, sub-specialization, and teaching for pathologists. In addition, we aimed for better working conditions, impacting the optimization of workflows, productivity, and, finally, turnaround times. We also intended to improve ergonomics and postural health, as well as to facilitate morphometric tools and the quantification of diagnostic and prognostic biomarkers to involve the optimization of time and a higher quality in diagnosis.\nFrom a more technical point of view, the aim was to achieve a central digital repository of images on the network, thereby reducing the burden of slide file management and integrating medical imaging with SIMDCAT, a digital medical imaging system used in Catalonia. It was also intended as a subproject to establish bidirectional communications with other locations, such as operating rooms.\nThe project included the development of AI tools with machine learning (ML) and deep learning, taking advantage of the availability of whole slide images (WSIs) that were obtained after digitization. The objectives were to recognize tissue patterns, select tumor areas, and quantify them, among others. Hopefully, this use of AI tools will contribute to improving the quality of diagnosis and the efficiency of processes.\n\nMaterials and methods \nDigiPatICS was created as a European Regional Development Fund (ERDF) project, with European funds for the optimization of anatomopathological diagnosis in a network of public ICS hospitals in Catalonia through digitalization and AI tools.\nSubsequently, a market consultation was carried out, and, finally, it was tendered with the file code CSE\/CC00\/1101202869\/20\/AMUP.[29]\n\n Planning, scope, and tender process \nA definition of needs was first carried out. We firmly believe meticulous planning is essential, taking into account all functional and technological requisites. Failing to detail such requirements can end in the failure of a digitization project, resulting in expensive scanners installed in pathology laboratories that are barely used. It is also important to highlight that going digital is not about acquiring pathology scanners; we focused our project on the purchase of a service with a shared risk with the bidder to achieve our objectives. Since this transformation was meant to be a one-way street with no possibility of going back to microscopes, all planning needed to include sufficient contingencies to avoid any kind of downtime for pathologists, as well as to ensure they benefit from the potential added value.\nThe purpose of the DigiPatICS project was to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in pathological anatomy departments of the ICS using digital pathology and AI tools.\nIn defining the scope, several questions arose:\n\nDo we want to save the whole slide images (WSIs) forever? Who will store them?\nIs our laboratory information system (LIS) ready?\nDo we want to (or have to) address pre-analytics?\nDo we want to address dark-field microscopy (e.g., direct fluorescence, FISH)?\nDo we want to digitize the macroscopic images?\nDo we need to update the hospital network?\nDo we need to update our pathologists\u2019 workstations?\nDo we want to share cases with the outside world?\nIs teaching important?\nDo we want AI algorithms?\nDo we want to do telepathology?\nWhat do we do with cytology?\nDo we have money for everything?\nThose concerns and how they were resolved will be addressed shortly, but we can already answer some of these. We did want to store all the WSIs forever and to use that repository to train our own AI algorithms, which is clearly one of the great advantages of such a transformation. We also believed that this project must be an integral transformation, including routine histopathology, fluorescence, research, and macroscopic images. Tools for teaching and teleconsultation should be included, which meant having the option to share images outside our hospitals\u2019 secured LAN. We realized that our LIS, preanalytics, network, and pathologist workstations all needed substantial upgrades to be able to undertake such a transformation.[9]\nWhat about cytology? Digitizing cytology, even if feasible[30][31][32][33], has some particular concerns, including scanning times being much longer than in histology (due to the need for more resolution, larger scan area, zero tolerance of out-of-focus areas, and Z-stacking). That means needing to install more scanners to be able to take on the same activity, and it impacts storage needs. Dark-field scanning (FISH) has similar issues, but there was a significant difference in the volume of slides to scan. Cytology involves a large number of samples to digitize in our hospitals (over 400,000 each year), which is not affordable currently in this project due to budgetary constraints. (In other words, the activity addressed in our project included all bright-field, routine histopathology, histochemistry, immunohistochemistry, direct immunofluorescence, ISH, and FISH slides. Cytology was scanned on an as-needed basis.)\nIn Table 1, we summarize the total number of slides generated during 2019 at our eight hospitals, broken down by type. To that number of over one million slides, an expected growth in activity of 10% to 15% must be added each year. In addition, some resources were reserved for research and non-strictly routine samples and were not accounted for in these numbers.\n\n\n\n\n\n\n\nTable 1. Number of slides in 2019.\n\n\nSlide type\n\n# of that slide type\n\n\nRoutine histopathology\n\n814,573\n\n\nImmunohistochemistry\n\n186,453\n\n\nHistochemistry\n\n64,209\n\n\nDirect immunofluorescence\n\n12,392\n\n\nFISH\n\n2,695\n\n\nCISH\n\n1,983\n\n\nTotal\n\n1,082,305\n\n\n\nRegarding the amount of personnel involved, DigiPatICS provided service to 107 pathologists, seven biologists, 40 residents, and 14 observers, adding up to a total of 168 professionals working with digital diagnosis.\nIn the tender process, all relevant aspects were taken into account for bidder evaluation, as shown in the following list:\n\n\u25aa Automatic evaluation criteria (51 points)\n\u25cb Economic valuation (40 points)\n\u25aa Evaluation of the financial offer (30 points)\n\u25aa Evaluation of the maintenance offer (10 points)<\/dd>\n\u25cb Automatic technical evaluation (11 points)\n\u25aa Quality management system. Certification of processes and algorithms (3 points)\n\u25aa Process consulting (1 point)\n\u25aa Image management platform adaptations (3 points)\n\u25aa Storage for research slides (1 point)\n\u25aa Short-term \u201chot\u201d storage (3 points)<\/dd><\/dd>\n\u25aa Criteria subject to judgment value (49 points)\n\u25cb Scanners: deployment and image quality (17 points)\n\u25cb Diagnostic viewer (8 points)\n\u25cbImage management platform (4 points)\n\u25cb Training module (2 points)\n\u25cb Built-in tools and algorithms (3 points)\n\u25cb Architecture and monitoring (1 point)\n\u25cb Definitive storage in SIMDCAT (4 points)\n\u25cb Integration of case information in a unified model (2 points)\n\u25cb Server infrastructure requirements and DPCs. Coherence, management model, virtualization (2 points)\n\u25cb Workstations (2 points)\n\u25cb Artificial intelligence (3 points)\n\u25cb Implementation and additional improvements (1 point)<\/dd>\nHowever, some aspects were considered very difficult to assess by evaluating their technical characteristics alone, and that is why three technical tests were defined for the scanner, viewer, and image management platform. For the scanner test, a large sample of glass slides from the eight hospitals was collected and fed to all the scanners offered by the three bidders for a week at 24 hours a day. In the fastest scanner, over 10,000 glass slides were digitized. Real scanning speeds, jamming, incidents, etc. were recorded to ensure the reliability of the equipment (Figure 2).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 2. Testing room for Test 1, showing the Palex 3DHISTECH team and equipment (PANNORAMIC SCAN II, PANNORAMIC 300 Flash DX, and PANNORAMIC 1000 Flash DX).\n\n\n\nIn the second and third tests, we brought together a group of pathologists from all the involved hospitals, along with IT experts, and they assessed the functionalities of the viewing software and the image management platform, as well as the image quality offered by the scanners using images scanned from ICS samples during the first technical test (Figure 3).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 3. Testing room for Test 2 and 3, showing from left to right, Miquel Arrufat (ICS), Ramon Bosch (ICS), Pablo L\u00f3pez-Garc\u00eda (ICS), Josep Maria Argimon (ICS), and Tam\u00e1s Reg\u00e9nyi (3DHISTECH) with the Palex 3DHISTECH equipment (LG 32HL512D 8MP Diagnostic Monitor, Logitech MX Vertical Ergonomic Wireless Mouse, and 3DHISTECH SlideDriver).\n\n\n\nThe contract file was definitively awarded by the decision of the Managing Director of the Catalan Health Institute (ICS) to the Palex Medical, S.A. 3DHISTECH Digital Pathology solution. This solution stood out for the proposal in the following main aspects:\n\nScanners: Technical requirements, deployment requirements, and technical service requirements\nImage management platform: Diagnostic viewer, learning platform, and quantification modules\nArchitecture: SIMDCAT interaction (DICOM), unified image management model (for all slide types), infrastructure management, and coherence model\n Scanners and technology for obtaining whole slide images (WSIs) \nTwenty-four scanners were installed and integrated into the workflow of the eight hospitals. Different scanner models were deployed according to the needs of each institution. In Table 2, we summarize the number of each scanner type and the capabilities.\n\n\n\n\n\n\n\nTable 2. Scanner deployment and capabilities summary. HT: high-throughput capability; DS: double-width slide capability; FL: fluorescent scanning capability; IN: immersion scanning capability; Z: Z-stack scanning capability; S: slide capacity; N: number of deployed scanners; \u2713: Capabilities available in each scanner.\n\n\nModel\n\nHT\n\nDS\n\nFL\n\nIN\n\nZ\n\nS\n\nN\n\n\nPANNORAMIC 1000 Flash DX\n\n\u2713\n\n\u2713\n\n\n\n\u2713\n\n\u2713\n\n1,000\n\n11\n\n\nPANNORAMIC 300 Flash DX\n\n\u2713\n\n\n\n\u2713\n\n\n\n\u2713\n\n300\n\n7\n\n\nPANNORAMIC SCAN II\n\n\n\n\n\n\u2713\n\n\n\n\u2713\n\n150\n\n5\n\n\nPANNORAMIC MIDI\n\n\n\n\n\n\u2713\n\n\n\n\u2713\n\n12\n\n1\n\n\nTotal\n\n\n\n\n\n\n\n\n\n\n\n\n\n24\n\n\n\nThe PANNORAMIC 1000 Flash DX (3DHISTECH Ltd., Budapest, Hungary) (P1000) is a large (154 \u00d7 100 \u00d7 91 cm) and heavy (270 kg) scanner, but it offers the largest slide capacity on the market at 1,000 slides (using Leica slide racks, slide loading capacity could be further increased to 1,200). It is the fastest whole-slide scanner on the market, at up to 100 slides per hour and 2,000 slides per day (at 40\u00d7 resolution, 0.25 \u03bcm\/pixel, single layer). The P1000 uses Sakura slide racks, which seamlessly integrated with our laboratory workflow and allowed for priority slide handling and scanning in arbitrary order because it is flexible and automatic. It is also being used for double-width slides. Regarding image quality, it is able to scan at 0.25 \u03bcm\/pixel, which is the 40\u00d7 resolution equivalent (industry standard), and also at 0.12 \u03bcm\/pixel, which is roughly the 80\u00d7 resolution equivalent. Multilayer (Z-stack) and extended focus scanning are available, as well as automatic water immersion.[34][35] Furthermore, thanks to its AI-based software control, it is able to automatically rescan suboptimal slides, adding multilayer scanning if required. The P1000 are used for all bright-field and double-width slide related imaging.\nThe PANNORAMIC 300 Flash DX (3DHISTECH Ltd., Budapest, Hungary) (P300) is a fast bright-field and fluorescence scanner capable of high throughputs as a standalone machine in smaller institutions or serving as backup for P1000s in larger hospitals. It has the capacity for 300 slides, and its use is mainly for fluorescence, scanning FISH, and direct immunofluorescence.[36]\nBoth the PANNORAMIC SCAN II and the PANNORAMIC MIDI (3DHISTECH Ltd., Budapest, Hungary), with slide capacities of 150 and 12 slides, respectively, are mainly focused on fluorescence imaging but are still able to scan bright-field images, even though they are slower than their high-throughput counterparts.[37]\n\nMacroscopic imaging \nRegarding macroscopic imaging, 13 MacroPATH QX systems (Milestone Medical, Sorisole, Italy) were installed to obtain and incorporate gross imaging into the workflow. All the images were stored on the DigiPatICS servers and were fully integrated and available at the pathologist workstations for making diagnoses.\n\nWSI viewing: Hardware \nTo be able to view WSIs, 183 new workstations were installed (Table 3) for pathologists, residents, biologists, observers, and meeting rooms. Each pathologist workstation consisted of two 32-inch 4K UHD (3840 \u00d7 2160 pixel) diagnostic medical-grade FDA-approved monitors (LG 32HL512D) (Figure 4) that could be used indistinctly in flexible ways. Normal intended use is for a pathologist to have an LIS with all laboratory data, clinical data, and reporting available on one monitor, while on the other, a microscopic image is displayed. However, both monitors could be used for microscopic images, or both could be used for reporting, clinical data, bibliography, or other tasks. Biologist workstations were the same as those of the pathologists. Residents and observers shared the same workstations; however, they only consisted of one LG 32HL512D medical-grade monitor due to space constraints (the dual-monitor setup required over 150 cm of desk surface).\n\n\n\n\n\n\n\nTable 3. Workstation and monitor deployment. N: number of equipment.\n\n\nEquipment\n\nN\n\n\nWorkstations\n\n183\n\n\n32\u2033 8MP Medical Monitor LG 32HL512D\n\n286\n\n\n55\u2033 4K UHD Monitor 55UH5F-B\n\n6\n\n\n4K UHD DICOM ProBeam LG Projector\n\n7\n\n\n\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 4. A pathologist in his office with a resident diagnosing with two LG 32HL512D 8MP diagnostic monitors.\n\n\n\nThirteen additional workstations with six 55-inch 4K UHD monitors and seven 4K UHD DICOM ProBeam LG projectors were installed in small and medium meeting rooms for teaching and clinical sessions as a replacement for multi-head microscopes (Figure 5).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 5. Residents diagnosing using a 55-inch 4K UHD monitor (55UH5F-B).\n\n\n\nEach workstation was comprised of an Intel Core i5-9600K processor (Intel Corporation, Santa Clara, CA, USA), 16 Gb RAM, 512 Gb SSD, and an RTX 2060 graphics card (Nvidia Corporation, Santa Clara, CA, USA). All workstations were the same for easier maintenance, compatibility, and interchangeability of workplaces. Each workstation also contained a Logitech BRIO 4K UHD webcam (Logitech International, Lausanne, Switzerland) and a Jabra Evolve 40 headset with a microphone (GN Group, Ballerup, Denmark). Both the webcam and microphone aimed to facilitate networking among pathologists from the same hospital, from different hospitals within the ICS, or even with professionals outside our network.\nFurthermore, each workstation contained a Logitech MX Vertical Ergonomic Wireless Mouse (Logitech International, Lausanne, Switzerland), since vertical mice seem to put less strain on the wrist and demonstrate better ratings than conventional mice.[38] Each pathologist could also choose between two other ergonomic devices: a Kensington Expert Mouse Wireless Trackball (Kensington Computer Products Group, Redwood Shores, CA, USA) and a SlideDriver (3DHISTECH Ltd., Budapest, Hungary) (Figure 6). All devices were supported by our viewing software. The SlideDriver offers microscope-like navigation on digital slides for those who prefer a traditional method. Most of our pathologists and residents selected the SlideDriver as their input device (80% approximately).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 6. Ergonomic devices: (a) Logitech MX Vertical Ergonomic Wireless Mouse; (b) Kensington Expert Mouse Wireless Trackball; (c) SlideDriver.\n\n\n\nWSI viewing: Software \nThe diagnostic viewer used for all digital images was ClinicalViewer (3DHISTECH Ltd., Budapest, Hungary). It uses streaming technology to avoid downloading WSIs for diagnosis. It is capable of opening bright-field, fluorescence, double-slide, Z-stack, and macroscopic photography, etc. It also includes many positively valued features, such as the possibility of viewing and navigating up to nine automatically synchronized images at once. It also has IVD support and quantification algorithms, as well as some more standard tools, such as free rotation, free zoom, annotation, measuring, and object counting tools (Figure 7).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 7. ClinicalViewer: (a) slide with navigation panel; and (b) three auto-aligned slides.\n\n\n\nThe software also had a telepathology option available and a module to create training courses. Possessing all the WSI viewing needs, including fluorescence, integrated into one software system (one viewer) facilitated pathologist ergonomics and also enabled simplifying the technological model with fewer integrations required.\nThe software also had a telepathology option available and a module to create training courses. Possessing all the WSI viewing needs, including fluorescence, integrated into one software system (one viewer) facilitated pathologist ergonomics and also enabled simplifying the technological model with fewer integrations required.\n\n ETPAT: Our laboratory information system (LIS) \nThe evolution of information systems in the last 10 years has been meteoric. It has changed the paradigms for accessing and possessing the necessary information at each point of contact a patient has with a health system.\nAt the Catalan Health Institute (ICS), and within the ARGOS project, we have spent 15 years directing information towards users and clinical care, and we have progressively moved from the initial free texts to structured information. The ARGOS project started in 2006. It is a project to integrate in a transversal and transparent way all the information systems involved in clinical assistance to the citizens of the Catalan Health Institute and its eight hospitals, including the hospital information system, nursing, pharmacy, clinical analysis laboratory, pathology laboratory, and critical care units. Currently, ARGOS is the priority information system in Catalonia and is present in 23 hospitals of the Catalan public health network.\nThe SALUT4D project began in 2020 and is the evolution of clinical workstations within the ARGOS project. Its objective is to provide the necessary information at each moment of care to different professionals. It is based on four dimensions seeking to present the necessary data at each point of care:\n\nWhere am I? Scope of work, including emergencies, hospitalization, ambulatory consultation, operating room, etc.\nWho am I? Role, including nurse, surgeon, internist, psychologist, etc.\nWhom do I attend? A patient with hypertension, diabetes, bronchitis, etc.\nHow do I attend to it? With a computer, tablet, smartphone, etc.\nThe system presents the information that a professional needs clearly and orderly. The system is based on a clinical dictionary with more than 40,000 variables stored in a MongoDB-type database called the Global Variables Repository (RGV). This repository contains data from all sources, including laboratory, pathological anatomy, radiology, vital sign monitors, pharmacy, etc.\nTo construct this platform, created and designed for and by the ICS, HTML5 technology, SAP ISH (Information System Hospital), and SAP ISHMed (SAP SE, Walldorf, Germany) were used. The system connects directly with the Shared Clinical History of Catalonia (HC3) and provides access to information on all public hospitals and all primary care facilities in a fully integrated manner.\nThe workflow methodology was based on requirements submitted by over three hundred health professionals who continuously provided their contributions. Through AGILE methodologies, the new clinical workstation was progressively built. The new station is already in operation at the eight ICS hospitals and will gradually come into operation in 23 sections of the ARGOS system throughout 2022.\nIn order to incorporate the peculiarities of the new, fully digital workflow, a new LIS for our pathology laboratories named ETPAT was developed. It was deemed necessary to develop and improve pathologist workstations to provide them with tools that allow the integration of information from all sources and electronic records available. ETPAT has a fully integrative approach to all processes occurring in our pathology labs, from electronic requests from clinicians to pathology reports, with full traceability of all steps involved at the laboratory. Moreover, it enables the optimization of paper management as much as possible. This software was based on HTML5 and was prepared for 32-inch 4K UHD monitors, taking advantage of the hardware on hand (Figure 8).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 8. ETPAT screenshot (our proprietary LIS).\n\n\n\nOne of the most relevant aspects was the unification of workflow for all ICS laboratories, which should be able to work seamlessly as a network, or even as one big institution. The catalogs of techniques and sample types were also more coherent. All traceability data was integrated and convenient, and we were able to collect information on who carried out each phase of the diagnostic process to allow the correct attribution of costs and activities. This new LIS is clearly ready for the digital workflow of macroscopic and microscopic images and was fully integrated with the image management platform. In addition, the management of second opinions and case consultations was incorporated.\n\n Network needs, local area network (LAN), and wide area network (WAN) \nThe main source for generating information by volume of data was the scanners (in the order of around two petabytes yearly), which were located across the different centers included in the scope of the project. The systems were connected to a 10 Gbps network between the scanners and the local storage data processing center (DPC). The same criteria applied to the AI platform.\nThe network requirements for the DigiPatICS project were high, since access to the images needed to be instantaneous, as it was on a microscope. Images were accessed via streaming, but a large bandwidth was still required, making it necessary to adapt cabling and infrastructure, as well as switches, routers, and other telecommunications equipment. Each workstation required a 300 Mbps connection to the DPC to be able to stream the WSIs, but to ensure performance, the connection was established at 1 Gbps. MacroPATHs required a 100 Mbps connection.\nAdjustments were made to the WAN infrastructure to ensure that communications between the central repository and the centers were capable, on one hand, of transferring daily information to the central DPC and, on the other hand, of allowing consultation between hospitals and their corresponding DPCs. This WAN needed to support an approximate flow of six terabytes each night for the DigiPatICS project activity alone. To achieve these goals, both the Department of Health and Catsalut public institutions recognized this need and facilitated the creation of a dedicated network to support the data traffic requirements mentioned and response times for data recovery.\n\n On-premises data processing centers (DPCs) \nThe project proposal was to provide a good user experience to all users of the image management platform, as well as to facilitate their work, optimize performance times, and reduce the time invested in obtaining a correct diagnosis. That is why we considered infrastructure to be a fundamental technological pillar in this project that needed to be sized based on performance, scalability, and reliability criteria without excessively oversizing the system or implementing complex architectures that would create greater difficulties in maintenance. For the project, the deployment of its own infrastructure was carried out, but at the same time, it was integrated transversally across the health ecosystem.\nA common structure was used at all centers that only changed in terms of local storage dimensioning, adapting to the number of slides estimated per center. In this way, we made infrastructure maintenance easier. All the DPCs were provided with the energy and cooling requirements necessary for correct operation of the various systems, as well as redundant systems in terms of communications, servers, storage, and a secondary DPC in case of disaster recovery.\nThe system at each center was designed to have a high-availability configuration, meaning, in the event of a disaster in one of the elements of the system, it would be capable of continuing to offer service with minimum downtime, or even without interruption, depending on the source of the problem.\nThe high-availability elements implemented were:\n\na host server cluster under VMware vSphere in an active-passive configuration;\ndisk storage configured in RAID; and\nmirrored disk arrays with asynchronous replication.\nThe various redundant elements of the high-availability scenario were located in a DPC or complementary technical room that was not the main DPC in order to minimize the impact of any possible disaster on the main DPC. AI equipment was excluded from this high-availability policy.\nAt each center, a virtualization infrastructure was deployed, consisting of a set of two identical servers under a VMware vSphere infrastructure. This allowed the system to have the capacity to maintain service quality in an event where it was necessary to activate a contingency scenario (disaster recovery) in a matter of a few minutes. These servers were HPE ProLiant DL325 models dimensioned with AMD EPYC processors that offered the necessary computing capacity for all DICOM image integration, storage management, and processing operations that were carried out continuously. They also served as a virtualization platform for the controller structure of the AI cluster.\nAs for storage, MSA 1050 cabinets were chosen and presented to the host servers through iSCSI controllers. These storage cabinets contained a battery of SSD disks intended exclusively for virtual machine operating system disks. For medical image storage, a pool of rotational HDD disks was deployed. This decision was made based on the following factors:\n\nOnce the medical image was generated, it was not modified (writing on the disc only one time).\nAccess was completed in blocks through streaming (reduced reading rate).\nEach center had its own local storage (limited number of simultaneous writes).\nFor all these reasons, the increase in cost of deploying SSD technology for image storage was not justified for the required performance.\nhe same storage technology was used in all the centers, including the central DPC, with only capacity varying as a factor of the number of digitized images estimated per center. The total storage capacity between the eight hospitals was approximately 500 TB, which allowed short-term storage of up to 75 days for images.\nThe deployed server and storage infrastructure had the activation of the HPE IRS service, which automatically opened a ticket to the manufacturer in the event of a hardware component failure, guaranteeing proper functioning of the infrastructure. The entire server infrastructure was backed by a backup policy based on Veeam Backup that was integrated into existing control panels in each center in order to facilitate maintenance tasks.\nWithin the scope of this project, integration with SIMDCAT was included for the publication of images as a form of definitive storage. Publishing to SIMDCAT was asynchronous under a queue management system that published the images as soon as they became ready. As the publication to SIMDCAT was continuous, the need to make a backup copy of all the scanned images outside the same disk array cluster was not considered, delegating the backup function to the same SIMDCAT. If the need arose to retrieve one or more images, a small application was implemented that allowed downloading these images from SIMDCAT and placing them back in local storage. Only in the event of a major disaster would the procedure be the same as indicated above; however, there may be a minimal number of scanned images that would not have had the opportunity to be published in SIMDCAT due to the asynchronous nature of the publication process. In such a case, the images would be rescanned.\n\nSIMDCAT and DICOM \nSIMDCAT is the Digital Medical Image System of Catalonia. It is currently the unified system used by the network of entities called SISCAT (Comprehensive Health System of the Public Utility of Catalonia) to preserve digital medical images and provide services and digital resources based on the same software architecture using cloud services and to make information accessible from various electronic medical records. The system is used by approximately 450 Catalan health centers and by all SISCAT professionals to securely collect and share digital medical images generated by the centers. SIMDCAT was the definitive repository of this project in which the images and associated data were stored. SIMDCAT was set up in 2018 to provide the public health system with a secure and technologically advanced environment in which to store and share digital medical image services.\nThe project to develop in SIMDCAT a specific environment for anatomical pathology medical images presented multiple benefits for agents of the Catalan health system. Professionals in this specialty were provided with a network work environment based on cloud technology, and the anatomopathological diagnosis process was optimized so that medical images were immediately and safely available to professionals. As for patients, the quality of care was improved and their safety was increased.\nFinally, the sustainability of resources and costs of health information systems was promoted by providing a common and shared system for all providers.\nSIMDCAT\u2019s cloud-based technology is focused on the use of DICOM as a standard in the storage and distribution of medical objects. The capacity of standard DICOM beyond radiology has been demonstrated in recent years, where picture archiving and communication system (PACS) image storage systems have evolved into the VNA (Vendor Neutral Archive); SIMDCAT constitutes a VNA that allows the management of medical objects using the DICOM standard as a reference framework. In the case of pathology, the DICOM 145 extension is adopted; this extension facilitates the storage and distribution of medical objects independent of the device that generates the information. SIMDCAT adopts DICOM 145 natively, incorporating the pyramidal treatment of images, thus facilitating navigation through an image. SIMDCAT also adopts the DICOM 122 extension that reflects the representative data model of pathology.\nSIMDCAT manages the information in a private cloud model with a high-redundancy system to guarantee the availability of the information. Saving the information in different storage systems using data object technology, this model allows growth according to the needs of the system, optimizing available resources in addition to freeing hospitals from the custody and distribution of information.\n\n AI and the Polytechnic University of Catalonia\u2013BarcelonaTech (UPC) \nIt is now recognized that AI represents a turning point for society that is at least as significant as the Industrial Revolution. The ICS aims to be an autonomous and primary player in the creation of AI algorithms to avoid dependence on a commercial solution. Therefore, we wished to set up an AI-based platform tailored to the needs of the ICS. This platform was developed with free software and needed to be modeled to accommodate other AI projects in addition to DigiPatICS.\nCurrently, the ICS has signed a collaboration agreement with the Image Processing Group (GPI) of the Polytechnic University of Catalonia\u2013BarcelonaTECH (UPC) for the development of AI tools and platforms within the healthcare field, specifically in the field of medical imaging. The group belongs to the Intelligent Data Science and Artificial Intelligence Research Center (IDEAI), which is a hub created at the UPC in 2017 for the development of AI. GPI has extensive experience in image processing and the development of AI algorithms, with a long history in the healthcare field.\nGPI develops computer vision and deep learning (DL) tools to tackle WSI analysis tasks in DigiPatICS for stains, such as H&E, HER2, KI67, RE, and RP, as well as other immunohistochemical stains. DL technology that relies on instance and semantic segmentation architectures has the potential to provide high-quality results when properly trained. GPI has also introduced strategies, such as:\nDataset annotation: As the training database was limited in the first stage, a more classical computer vision strategy relying on morphological algorithms and machine learning (ML) tools produced proposals easier to validate by annotators and generated the ground truth needed to avoid limiting the performances of DL approaches.\nIntegration of AI algorithms: Integration into specialist workflow was facilitated by combining the systematic processing of a large number of WSIs with on-demand assessment by pathologists for improving the systematic results or for obtaining specific quantifications. First, nightly batch processing and inference on the WSIs yielded raw results, such as segmentation confidences and classification probabilities, as well as potential segmentation masks. From there, the results were integrated into 3DHISTECH ClinicalViewer using a specific plug-in and offered to the pathologists upon request when examining the slides. Then the pathologists could select or deselect regions in the WSI to visualize and quantify the results or to fine-tune inference results (classification and segmentation) using sliders. Finally, pathologists could also select specific areas for further online analysis on inference servers to be performed during the session with the viewer at their workstations.\nPathologists in the analysis loop: The integration of AI algorithms allowed not only flexible interaction for online and on-demand analysis, but also for recovering information about pathologists by selecting specific regions of interest and tuning inference results for reports. This information represents invaluable data and comments to further improve the annotated datasets.\nTraining in the ICS development servers: A specific committee formed by AI specialists and clinicians periodically reviewed the comments and data produced by pathologists using the viewer. This committee decided on the feedback, data, and set strategies for incremental training and improvement of the DL network architecture involved with continuously improving the inference results. Ultimately, former strategies facilitated the usage of AI tools in the daily work of pathologists, as well as productivity.\nAs mentioned, all images were stored in a central repository, SIMDCAT, where they were available for AI training after dissociation. AI training was performed in this central repository, where a large number of whole slide images were readily at hand. GPI researchers did not have direct access to sensitive clinical data, and datasets and whole slide images always remained within the ICS infrastructure. In fact, it should be noted that the entire circuit in production moved through an isolated dedicated network in an intranet environment, and the training environment was in a separate VLAN and intranet infrastructure. Once the inference algorithms were trained, they were run on-premises at each hospital DPC. In no case was the information transferred to external DPCs.\n\nResults \nThe digital pathology transformation envisioned in the DigiPatICS project involved great changes in most of the steps of workflow in our pathology laboratories. As mentioned above, all the processes were integrated in our ETPAT LIS.\n\n Laboratory workflow, traceability, and barcode generation \nAll incoming samples, biopsies, cytologies, autopsies, and even molecular requests are accompanied by an e-request generated in our electronic health record (EHR) system by the clinicians who input all the necessary clinical data.\nAt the time of registration, the request receives an identification number that is labeled with a Data Matrix-type barcode. Each sample container is also labeled with a unique Data Matrix-type barcode. The barcode structure is as follows, maintaining logical hierarchy, as seen in Figure 9. The case or request barcode includes the institution, the year, the sample type, and the case number (i.e., VH22B051337, for Vall d\u2019Hebron, year 2022, biopsy number 51,337). When labeling a container, the container ID is appended (i.e., VH22B051337A for container A). When a cassette is required, a Data Matrix-type barcode is also printed with the number of the paraffin block appended (i.e., VH22B051337A014 for block 14). For glass slides, whether they come from paraffin block sections or are cytologies, another number is appended, representing the slide number (i.e., VH22B051337A014001 for histological section 1). The full ID is printed and appears in a Data Matrix-type barcode in each slide.\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 9. Barcode anatomy.\n\n\n\nMost of our laboratory equipment, including scanners, is able to read these barcodes and is integrated with our LIS, providing automatic checkpoints for many steps of processing. The first checkpoint is when the sample is received with the labeling of the containers, as described previously. It is a manual step completed by technicians, but in the new LIS, the process was simplified so it was closer to optimal. The next step, grossing, was also improved: MacroPATHs were installed inside the pathology fume hoods, and computers with the LIS were placed next to them. Pathologists, residents, or technicians could print the cassettes, capture gross examination pictures, and dictate or type the macroscopic description in a convenient and fully digital way. Pictures of cassette contents are obtained and are available for verification in the next laboratory steps. After filling a cassette with tissue, the barcode is scanned for the first checkpoint of the paraffin block. The next checkpoint is when the cassette enters the tissue processor, and a technician reads the barcodes using a handheld device. Unfortunately, this step remained manual because our tissue processors could not read barcodes. We hope this will change in the future.\nEach embedding station had a computer with a barcode reader within reach. A technician read the barcode of the paraffin block, and the LIS displayed the tissue type and the confection notes (if present) and provided access to macroscopic images for verification, while, in fact, creating another checkpoint.\nThe next checkpoint is clearly when sectioning. Every microtome station had a barcode reader, a slide label printer, and a computer with the LIS. When scanning the paraffin block, the LIS displayed the tissue type and other information on that block, such as how many and which slides must be obtained from it. At the same time, it printed the slide labels automatically, which include the Data Matrix barcode described previously. This automation reduced the human error of manual workflow.[3] \nAt this point, the automatic part started. In most hospitals, Sakura Tissue-Tek Prisma Plus and Tissue-Tek Film (Sakura Finetek Europe B.V., Alphen aan den Rijn, The Netherlands) were used. After sectioning, a technician loaded the slides in the Sakura racks. Then, the racks were stained, cover-slipped with film, dried, and scanned using P1000s. Routine slides did not have to be treated individually until archiving because all the equipment used the same racks. In terms of traceability, an automatic checkpoint was recorded by Sakura Tissue-Tek Film, which was integrated with our LIS, and the final checkpoint was notified by a 3DHISTECH P1000 when the slide was scanned.\nUsing the same Sakura racks for all equipment enabled us to optimize technician slide handling time and reduce errors. Immunohistochemistry and histochemistry used the same Tissue-Tek Film, so checkpoints stayed the same. In the case of double slides, the steps needed to be conducted manually, but their volume was negligible compared to routine histology, where workflow optimization was key.\nIn some hospitals, other automatic stainers were used, such as VENTANA HE 600 (Roche, Basel, Switzerland). Integration was possible, but an extra step of transferring the slides from HE 600 trays to the scanner rack was needed.\nSubprocesses, such as slide allocation and delivery to pathologists, did not exist anymore, since the digital workflow did not require such manual steps.\nRegarding the destruction of containers, a new system was implemented. A tablet with the LIS, along with a handheld Data Matrix barcode reader, was used to scan the containers. If the containers were ready for elimination, a confirmation message appeared, and a checkpoint was created.\nThe whole workflow was designed for optimization and security. We aimed to reduce the time technicians spent on worthless tasks, allowing them to focus on what was important and increase their satisfaction in the workplace. Also, the checkpoints enabled a better awareness of sample status by all personnel and an obvious increase in safety.\nIt is also worth mentioning that the transformation was carried out simultaneously as a radical change with all the pathologists in the same center starting digital work at the same time. The alternative of making a gradual change implied many more difficulties by having to maintain two circuits (old and new) in the same laboratory. This measure was taken considering the possible reluctance and skepticism of the staff, which would be lessened if they could quickly see an optimization of circuits despite initial incidents. No benefits of a gradual approach were seen by the authors if all the infrastructure was in place.\nRegarding validation of WSIs for use in primary diagnosis, the digital pathology solution provided all necessary legal certifications, but it still was tested and validated previously by many pathologists using all types of preparations. The solution was also tested in the scanner and viewer technical tests during the bidding process. When the pathologists started working with digital slides, all of them could compare digital slides with glass slides until their grade of confidence was enough. No specific period of time or amount of resources was dedicated for this purpose; it was a matter of obtaining enough comfort for the pathologists in their routine workflow. A continuous validation of tissue detection was performed in every single case, since the pathologists had available the captured image of the slide next to the slide overview, as seen in Figure 7a, and were thus certain there was no tissue missing on the WSI.\nFurthermore, all the pathology departments involved in DigiPatICS were certified or accredited for ISO 9001 or ISO 15189. Because the ISO 15189 standard confirms technical competence of the laboratory and ensures reliability of test results, a continuous validation strategy was recommended following CAP recommendations.[39][40]\nThe initial reticence on the part of a couple pathologists could not be reversed despite several talks and explanations to try to make them partners in the transforming project. However, these reluctances completely disappeared after a few days of working in the digital flow without the need for any external intervention. The advantages of the new technology were obvious and sufficient on their own.\n\nScanning \nBeing able to scan slides and obtain WSIs are perhaps the obvious concerns of any digital pathology project, but, as mentioned, these are not the only relevant points. For example, it was essential that the scanners did not stop due to jamming, so the glass slides needed to be optimal. This implied possessing a decent glass or film coverslip; either could work as long as the quality of the histological slide was good. Labels also needed to fit perfectly within the boundaries of the glass slide. Anything that protruded could cause jamming. Slides needed to be fully dried, and under no circumstance could be dripping glue.[20]\nFurthermore, we considered crucial for the workflow the presence of automatic scanning with two objectives and, therefore, two resolutions, 40\u00d7 (0.25 \u03bcm\/pixel) and 80\u00d7 (0.12 \u03bcm\/pixel), to cover all possible needs. The scanners used different scanning profiles (40\u00d7 or 80\u00d7, Z-stack, etc.) depending on the sample and the stain type indicated by our LIS (ETPAT). The process was fully automatic. It was also possible to select profiles manually or tweak some settings, but manual parameterization was not used for high-throughput routine scanning. Routine scanner loading needed to be as easy, fast, and straightforward as possible for the laboratory technicians. In order to have the automatic profile feature in addition to automatic tissue detection obtained by an AI algorithm in the scanner control software, it was very important to scan slides at a suitable resolution.\nThe second concern regarding scanners was their deployment. Correct dimensioning is essential to address daily routine activity. Individual scanning speed or capacity is very important, but less relevant than the deployment of equipment meeting the needs of the center. In the event of a breakdown or maintenance, the remaining equipment must be able to compensate. Scanner deployment must also take into account the expected growth of activity (in our case, 10 to 15% annually). Scanners must not create bottlenecks in the workflow, and going fully digital cannot involve a delay in turnaround time. In our daily routine, scanning occurred right after the slides were dried, and the first WSIs were available during the morning. The scanners were continuously loaded until the end of the technician shift for each institution (in some cases 16:00, and 21:00 in others), and the scanners were intended to finish scanning overnight, around 2:00 to 3:00 a.m. in our institutions producing more slides, thus having time until 8:00 a.m. to accommodate this expected increase in activity before the pathologists started diagnosing. This workflow guaranteed no delay in turnaround time, even after adding steps to the conventional system, by completing slide production and digitation of all slides within the same day. The remaining advantages of digital pathology should optimize our routines and reduce diagnostic and reporting times.\nAnother aspect considered was where to physically locate the scanners. The location needed to be convenient for technicians within their workflow so that the new steps were not disruptive. Scanners were located near a stainer or cover-slipper, or next to a glass slide archive whenever possible.\nFluorescence workflow was taken into account to try to keep the slides cool and to preserve them from light.\n\nMonitors \nThe need for a high-quality monitor is indisputable, although recommendations for ideal screen size and resolution have changed over time. Currently, a size between 24 and 32 inches with a high resolution is considered necessary, and the trend is probably upwards. A larger monitor, such as the ones we used, with a smaller pixel size allows for a greater field of vision, avoiding displacement through digital preparation. However, this means that objects appear smaller when the original maximum magnification is reached and that it requires more bandwidth to stream the image.[41][42][43]\nIt is also important to take into account color fidelity (the panel can be calibrated), lighting (no backlight bleed), contrast, pixel size, pixel density, brightness, color space (sRGB, Adobe RGB), color depth, etc. However, a good monitor is not going to make up for poor digital preparation. A high-quality monitor is important to guarantee image fidelity and ergonomics, as well as to avoid visual fatigue for the user (Figure 10).\n\r\n\n\n\n\n\n\n\n\n\n\nFigure 10. Fluorescence seen in a totally integrated fashion on two 32-inch LG 32HL512D 8MP diagnostic monitors.\n\n\n\n Teaching, telepathology, and networking \nMany of the planned advantages of this project, such as networking between ICS hospitals, having a teaching platform, and being able to teleconsult cases with external pathologists, although not available right now, were binding in the contract and will be implemented in the following months.[44] The system will have an on-demand function to publish studies to an internet environment with previously anonymized data to allow the sharing of images.\n\nDiscussion \nThe DigiPatICS project, as a transformation of the Catalan Health Institute Network of eight hospitals, represented an important technological, organizational, and functional challenge. We incorporated digital pathology and AI in pathology departments, with an organizational change that modified work dynamics, as seen in the previous paragraphs. This change responded to current and future challenges, with the aim of improving quality, efficiency, effectiveness, equity, speed, systematization, and reproducibility of diagnoses. These improvements affected other disciplines and increased patient safety, with the following benefits: \n\nimprovement of diagnostic conditions by incorporating the digitalization of preparations, with maximum guarantees of traceability while also minimizing material losses and identification errors; and\nimprovement of workflow, productivity, and turnaround times.\nMoreover, there was also improvement in working conditions in terms of ergonomics. The viewers also provided tools for morphometry and quantification of diagnostic and prognostic biomarkers and facilitated the digital access of preparations from previous patient examinations without interrupting the diagnostic process.[4][7]\nIn the near future, we will enable access to images for decision making between pathology departments and other facilities (operating rooms, interventional examination rooms, transplantation, or clinical committees) using bidirectional communication. Also, the images will be available for clinical sessions, tumor boards, and pre- and postgraduate teaching. Being able to store pathology images digitally also reduces the workload for management of histological preparation files. Ergonomics, workflow improvement, and convenience of access to historical slides also encourage research.\nSuccessfully exchanging WSIs and AI algorithms between institutions had the following implications: \n\nWe improved the reproducibility of diagnoses, both in terms of interpretation and in the way they are reflected in medical reports, ensuring system-wide equity and fairness.\nWe encouraged an optimal exchange of information between hospitals, establishing second-opinion strategies according to clinical practice guidelines that immediately benefitted patients.\nAs such, we also encouraged the movement of patients between hospitals in a coordinated way, avoiding the physical movement of biological material, with fewer delays and courier costs and ensuring preservation.\nWe aimed to make more efficient use of the existing critical mass in terms of prevalent, complex, infrequent, and difficult diseases and guaranteeing equity among hospitals, regardless of size and geographical location, with the end-goal of organizing references for pathologies and territories.\nFrom a technological standpoint, innovation also occurred. We stored all images using DICOM standards in SIMDCAT, a unified system used by the SISCAT network of entities to preserve digital medical images, provide digital services and resources based on the same software architecture, and make digital medical images accessible. This repository can be used independently by different viewers and is also independent of the scanning system. The transformation of the laboratory information system and all IT infrastructure is key in this type of project.\nIn addition, from the technological point of view, we aimed to achieve an improvement in algorithms for the quantification of immunohistochemical biomarkers and for the assessment of in situ hybridization. In the future, we hope to develop AI algorithms with ML and DL in order to recognize patterns and segment tumor areas. We need to look for tools that help pathologists do their jobs, with AI algorithms developed by our researchers. We produced an image repository large enough for this aim. AI optimizes the reproducibility of diagnoses. The boom in AI will involve significant changes in the way pathologists work in the coming years.\nAll things considered, it is important to seek a digital pathology system and, therefore, a manufacturer and a distributor that adapt to the real needs of each particular case. In the DigiPatICS project, we looked for a complete holistic solution for our pathology departments. As shown, it was very difficult to compare products according to data sheets exclusively, and it was laborious to define a digital pathology project for all technical and functional implications.\nThe growing enthusiasm for digital pathology and the new possibilities AI offers indicate an emerging revolution in pathology that will change our way of working. However, for broad adoption, an integrative approach of digital pathology across clinicians, pathologists, LISs, viewers, hardware, research, and teaching is imperative. Digital pathology must simplify our workflows and not add complexity. Vast repositories of diagnosed images will allow us to make great strides in this direction. With our solution meeting these needs, we hope to inspire other pathologists and to provide useful guidance for their successful digital transformations.\n\nConclusions \nThe DigiPatICS project aimed to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of eight hospitals, incorporating 168 pathologists and over one million slides each year. After careful planning, implementation was carried out simultaneously for all the pathologists in each institution. A digital pathology system needed to be integrated with all health information systems, including electronic medical records. Teleconsultation, teaching platforms, fluorescence, and cytology were taken into account. The digital transformation of a pathology department represented a technological, organizational, and functional challenge. It provided an effective and safe diagnostic tool with clear benefits for diagnosis quality and patient safety.\n\nAcknowledgements \nThe authors thank over 250 people who were directly involved in making the DigiPatICS project a reality, including pathology laboratory teams, administration teams, artificial intelligence teams, network and IT teams, the SIMDCAT integration team, technical support, infrastructure teams, programmers, and logistics teams.\n\nAuthor contributions \nConceptualization, P.L.-G. and J.T.-S.; methodology, P.L.-G., J.T.-S., L.d.H. and E.B.; writing\u2014original draft preparation, J.T.-S.; writing\u2014review and editing, P.L.-G., J.T.-S., L.d.H., E.B., M.R.A., J.C.V., F.M., J.R.C., C.G. and X.M.-G.; supervision, L.d.H., E.B., M.A., J.C.V., M.R.A., E.L.-B., P.L.F., J.L.M., L.P., R.B., S.M., S.R.y.C. and X.M.-G.; project administration, L.d.H., E.B. and M.A.; funding acquisition, L.d.H., M.A., S.R.y.C. and X.M.-G. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis project was funded by European Regional Development Funds, Programa operatiu FEDER de Catalunya 2014\u20132020 and SA18-014623 DIGIPATICS. UPC activity in this project was partially supported by PID2020-116907RB-I00 and funded by MCIN\/AEI\/10.13039\/501100011033.\n\nData availability statement \nAll data generated or analyzed during this study are included in the article.\n\nConflict of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 \"El ICS\". Generalitat de Catalunya, Institut Catal\u00e0 de la Salut. http:\/\/ics.gencat.cat\/es\/lics\/ . Retrieved 25 December 2021 .   \n \n\n\u2191 Sch\u00fcffler, Peter J; Geneslaw, Luke; Yarlagadda, D Vijay K; Hanna, Matthew G; Samboy, Jennifer; Stamelos, Evangelos; Vanderbilt, Chad; Philip, John et al. 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Retrieved 25 December 2021 .   \n \n\n\u2191 Alcaraz Mateos, Eduardo; Caballero-Alem\u00e1n, Fuensanta; Albarrac\u00edn-Ferrer, Mariano; C\u00e1rceles-Moreno, Francisco; Hern\u00e1ndez-G\u00f3mez, Rub\u00e9n; Hern\u00e1ndez-Kakauridze, Sergio; Hern\u00e1ndez-Sabater, Laura; Jim\u00e9nez-Zafra, Ignacio et al. (2 December 2016). \"Research on Devices for Handling Whole Slide Images on Pathology Workstations. An Ergonomic Outlook\" (in en). Diagnostic Pathology: Vol 2 No 1 (2016): 2016. doi:10.17629\/WWW.DIAGNOSTICPATHOLOGY.EU-2016-2:232. http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/232 .   \n \n\n\u2191 Pantanowitz, Liron; Sinard, John H.; Henricks, Walter H.; Fatheree, Lisa A.; Carter, Alexis B.; Contis, Lydia; Beckwith, Bruce A.; Evans, Andrew J. et al. (1 December 2013). \"Validating Whole Slide Imaging for Diagnostic Purposes in Pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center\" (in en). Archives of Pathology & Laboratory Medicine 137 (12): 1710\u20131722. doi:10.5858\/arpa.2013-0093-CP. ISSN 0003-9985. PMC PMC7240346. PMID 23634907. http:\/\/www.archivesofpathology.org\/doi\/abs\/10.5858\/arpa.2013-0093-CP .   \n \n\n\u2191 Williams, Bethany Jill; Knowles, Chloe; Treanor, Darren (1 October 2019). \"Maintaining quality diagnosis with digital pathology: a practical guide to ISO 15189 accreditation\" (in en). Journal of Clinical Pathology 72 (10): 663\u2013668. doi:10.1136\/jclinpath-2019-205944. ISSN 0021-9746. https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-205944 .   \n \n\n\u2191 Rojo, Marcial Garc\u00eda; Bueno, Gloria (28 October 2015). \"Analysis of the impact of high-resolution monitors in digital pathology\". Journal of Pathology Informatics 6: 57. ISSN 2229-5089. PMC 4639949. PMID 26605122. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4639949\/ .   \n \n\n\u2191 Marchessoux, Cedric; Nave Dufour, A.; Espig, K.; Monaco, S.; Palekar, A.; Pantanowitz, L. (16 June 2016). \"Comparison Display Resolution On User Impact For Digital Pathology\" (in en). Diagnostic Pathology: Vol 1 No 8 (2016): 13. European Congress on Digital Pathology. doi:10.17629\/WWW.DIAGNOSTICPATHOLOGY.EU-2016-8:168. http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/168 .   \n \n\n\u2191 Randell, Rebecca; Ambepitiya, Thilina; Mello-Thoms, Claudia; Ruddle, Roy A.; Brettle, David; Thomas, Rhys G.; Treanor, Darren (1 February 2015). \"Effect of Display Resolution on Time to Diagnosis with Virtual Pathology Slides in a Systematic Search Task\" (in en). Journal of Digital Imaging 28 (1): 68\u201376. doi:10.1007\/s10278-014-9726-8. ISSN 0897-1889. PMC PMC4305057. PMID 25128321. http:\/\/link.springer.com\/10.1007\/s10278-014-9726-8 .   \n \n\n\u2191 Wilbur, David C.; Madi, Kalil; Colvin, Robert B.; Duncan, Lyn M.; Faquin, William C.; Ferry, Judith A.; Frosch, Matthew P.; Houser, Stuart L. et al. (1 December 2009). \"Whole-Slide Imaging Digital Pathology as a Platform for Teleconsultation: A Pilot Study Using Paired Subspecialist Correlations\" (in en). Archives of Pathology & Laboratory Medicine 133 (12): 1949\u20131953. doi:10.5858\/133.12.1949. ISSN 1543-2165. https:\/\/meridian.allenpress.com\/aplm\/article\/133\/12\/1949\/460648\/Whole-Slide-Imaging-Digital-Pathology-as-a .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation, though grammar and word usage was substantially updated for improved readability. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\">https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results<\/a>\nCategories: LIMSwiki journal articles (added in 2022)LIMSwiki journal articles (all)LIMSwiki journal articles on health informaticsLIMSwiki journal articles on pathology informaticsNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inRequest accountNavigationMain pageRecent changesRandom pageHelp about MediaWikiSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPermanent linkPage informationSponsors \r\n\n\t\r\n\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\n\t\r\n\n\t\n \n\t\n\t\n\t\r\n\n\t\r\n\n \n\t\n\t\r\n\n\t\r\n\n\t\n\t\n\t\r\n\n\t\n\t\n\t\n\t\r\n\n\t\n\t\n\t\r\n\n\t\r\n\n\t\r\n\n\t\r\nPrint\/exportCreate a bookDownload as PDFDownload as PDFDownload as Plain textPrintable version This page was last edited on 12 April 2022, at 16:21.Content is available under a Creative Commons Attribution-ShareAlike 4.0 International License unless otherwise noted.This page has been accessed 399 times.Privacy policyAbout LIMSWikiDisclaimers\n\n\n\n","ef9487ab4d88db8c29a49a38ec04aec1_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-206 ns-subject page-Journal_DigiPatICS_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning_implementation_and_preliminary_results rootpage-Journal_DigiPatICS_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning_implementation_and_preliminary_results skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:DigiPatICS: Digital pathology transformation of the Catalan Health Institute network of eight hospitals - Planning, implementation, and preliminary results<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Complete <a href=\"https:\/\/www.limswiki.org\/index.php\/Digital_pathology\" title=\"Digital pathology\" class=\"wiki-link\" data-key=\"d028733eb07372f6516e9a711a44e641\">digital pathology<\/a> transformation for primary <a href=\"https:\/\/www.limswiki.org\/index.php\/Histopathology\" title=\"Histopathology\" class=\"wiki-link\" data-key=\"1250dd919ba7b6079a53d9b17e5bc666\">histopathological<\/a> diagnosis is a challenging yet rewarding endeavor. Its advantages are clear with more efficient <a href=\"https:\/\/www.limswiki.org\/index.php\/Workflow\" title=\"Workflow\" class=\"wiki-link\" data-key=\"92bd8748272e20d891008dcb8243e8a8\">workflows<\/a>, but there are many technical and functional difficulties to be faced. The Catalan Health Institute (Institut Catal\u00e0 de la Salut or ICS) has started its DigiPatICS project, aiming to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of eight <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospitals<\/a>, over 168 <a href=\"https:\/\/www.limswiki.org\/index.php\/Pathology\" title=\"Pathology\" class=\"wiki-link\" data-key=\"5d8e2230b55d8760dcb729fc7dcd3dc1\">pathologists<\/a>, and over one million slides each year. We describe the bidding process and the careful planning that was required, followed by swift implementation in stages. The purpose of the DigiPatICS project is to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in the pathological anatomy departments of the ICS through process improvement, digital pathology, and <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI) tools.\n<\/p><p><b>Keywords<\/b>: digital pathology, computational pathology, artificial intelligence, deep learning, implementation, workflow, primary diagnosis, LIS, telepathology, network\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>The Catalan Health Institute (Institut Catal\u00e0 de la Salut or ICS) is the largest provider for the Catalan Health Service, the insurer of universal health coverage in Catalonia. It is the company with the most employees in Catalonia and the largest public company in Spain, with almost 39,000 professionals who provide services to almost six million people throughout the territory.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup> The ICS manages 283 primary care teams, three large high-tech tertiary <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital\" title=\"Hospital\" class=\"wiki-link\" data-key=\"b8f070c66d8123fe91063594befebdff\">hospitals<\/a> (Vall d\u2019Hebron, Bellvitge, and Germans Trias), four regional reference hospitals (Arnau de Vilanova in Lleida, Joan XXIII in Tarragona, Josep Trueta in Girona, and Verge de la Cinta in Tortosa), and a regional hospital (Viladecans) (Figure 1). The ICS accounts for seven percent of the Catalonian government budget, accounting for over 40 million primary visits and over 100,000 surgical interventions yearly.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig1_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"1ab0dd376e1be871aeb9cad53d7f947c\"><img alt=\"Fig1 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/db\/Fig1_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 1.<\/b> Map of Catalonia and the eight ICS hospitals.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Some <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"c57fc5aac9e4abf31dccae81df664c33\">laboratories<\/a> are beginning to successfully deploy <a href=\"https:\/\/www.limswiki.org\/index.php\/Digital_pathology\" title=\"Digital pathology\" class=\"wiki-link\" data-key=\"d028733eb07372f6516e9a711a44e641\">digital pathology<\/a> solutions for routine diagnosis, which we believe will be a growing trend in the next few years.<sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:0_3-0\" class=\"reference\"><a href=\"#cite_note-:0-3\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:1_4-0\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-6\" class=\"reference\"><a href=\"#cite_note-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:2_7-0\" class=\"reference\"><a href=\"#cite_note-:2-7\">[7]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-8\" class=\"reference\"><a href=\"#cite_note-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_9-0\" class=\"reference\"><a href=\"#cite_note-:3-9\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup> In Catalonia, the DigiPatICS project plans to accomplish a complete digital pathology transformation of primary <a href=\"https:\/\/www.limswiki.org\/index.php\/Histopathology\" title=\"Histopathology\" class=\"wiki-link\" data-key=\"1250dd919ba7b6079a53d9b17e5bc666\">histopathological<\/a> diagnosis for over 168 <a href=\"https:\/\/www.limswiki.org\/index.php\/Pathology\" title=\"Pathology\" class=\"wiki-link\" data-key=\"5d8e2230b55d8760dcb729fc7dcd3dc1\">pathologists<\/a>. Many groups have reported equivalency between digital pathology and conventional pathology.<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-19\" class=\"reference\"><a href=\"#cite_note-19\">[19]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_20-0\" class=\"reference\"><a href=\"#cite_note-:4-20\">[20]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[25]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup>\n<\/p><p>With the DigiPatICS project, we aim to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in <a href=\"https:\/\/www.limswiki.org\/index.php\/Anatomical_pathology\" title=\"Anatomical pathology\" class=\"wiki-link\" data-key=\"5668db6faf37e8c1432a1d7953f30cb7\">anatomical pathology<\/a> departments of the ICS through digital pathology and <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" title=\"Artificial intelligence\" class=\"wiki-link\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI) tools.<sup id=\"rdp-ebb-cite_ref-28\" class=\"reference\"><a href=\"#cite_note-28\">[28]<\/a><\/sup> With digital pathology, we aim for a network of eight hospitals to work as one in terms of case sharing and teaching, putting all our patients on equal footing. This transversal digital transformation will have an impact on the care of patients treated by all medical and surgical specialists.\n<\/p><p>First, we created a network between ICS centers. This helped us increase the reproducibility and quality of diagnoses, as well as offered greater equity and safety to patients. In turn, this network approach facilitated remote diagnosis, case sharing, sub-specialization, and teaching for pathologists. In addition, we aimed for better working conditions, impacting the optimization of workflows, productivity, and, finally, turnaround times. We also intended to improve ergonomics and postural health, as well as to facilitate morphometric tools and the quantification of diagnostic and prognostic biomarkers to involve the optimization of time and a higher quality in diagnosis.\n<\/p><p>From a more technical point of view, the aim was to achieve a central digital repository of images on the network, thereby reducing the burden of slide file management and integrating medical imaging with SIMDCAT, a digital medical imaging system used in Catalonia. It was also intended as a subproject to establish bidirectional communications with other locations, such as operating rooms.\n<\/p><p>The project included the development of AI tools with <a href=\"https:\/\/www.limswiki.org\/index.php\/Machine_learning\" title=\"Machine learning\" class=\"wiki-link\" data-key=\"79aab39cfa124c958cd1dbcab3dde122\">machine learning<\/a> (ML) and deep learning, taking advantage of the availability of whole slide images (WSIs) that were obtained after digitization. The objectives were to recognize tissue patterns, select tumor areas, and quantify them, among others. Hopefully, this use of AI tools will contribute to improving the quality of diagnosis and the efficiency of processes.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<p>DigiPatICS was created as a European Regional Development Fund (ERDF) project, with European funds for the optimization of anatomopathological diagnosis in a network of public ICS hospitals in Catalonia through digitalization and AI tools.\n<\/p><p>Subsequently, a market consultation was carried out, and, finally, it was tendered with the file code CSE\/CC00\/1101202869\/20\/AMUP.<sup id=\"rdp-ebb-cite_ref-29\" class=\"reference\"><a href=\"#cite_note-29\">[29]<\/a><\/sup>\n<\/p>\n<h3><span id=\"rdp-ebb-Planning,_scope,_and_tender_process\"><\/span><span class=\"mw-headline\" id=\"Planning.2C_scope.2C_and_tender_process\">Planning, scope, and tender process<\/span><\/h3>\n<p>A definition of needs was first carried out. We firmly believe meticulous planning is essential, taking into account all functional and technological requisites. Failing to detail such requirements can end in the failure of a digitization project, resulting in expensive scanners installed in pathology laboratories that are barely used. It is also important to highlight that going digital is not about acquiring pathology scanners; we focused our project on the purchase of a service with a shared risk with the bidder to achieve our objectives. Since this transformation was meant to be a one-way street with no possibility of going back to microscopes, all planning needed to include sufficient contingencies to avoid any kind of downtime for pathologists, as well as to ensure they benefit from the potential added value.\n<\/p><p>The purpose of the DigiPatICS project was to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in pathological anatomy departments of the ICS using digital pathology and AI tools.\n<\/p><p>In defining the scope, several questions arose:\n<\/p>\n<ul><li>Do we want to save the whole slide images (WSIs) forever? Who will store them?<\/li>\n<li>Is our <a href=\"https:\/\/www.limswiki.org\/index.php\/Laboratory_information_system\" title=\"Laboratory information system\" class=\"wiki-link\" data-key=\"37add65b4d1c678b382a7d4817a9cf64\">laboratory information system<\/a> (LIS) ready?<\/li>\n<li>Do we want to (or have to) address pre-analytics?<\/li>\n<li>Do we want to address dark-field microscopy (e.g., direct fluorescence, FISH)?<\/li>\n<li>Do we want to digitize the macroscopic images?<\/li>\n<li>Do we need to update the hospital network?<\/li>\n<li>Do we need to update our pathologists\u2019 workstations?<\/li>\n<li>Do we want to share cases with the outside world?<\/li>\n<li>Is teaching important?<\/li>\n<li>Do we want AI algorithms?<\/li>\n<li>Do we want to do telepathology?<\/li>\n<li>What do we do with <a href=\"https:\/\/www.limswiki.org\/index.php\/Cytopathology\" title=\"Cytopathology\" class=\"wiki-link\" data-key=\"41f4b2bf17f761e12a531040231d8c1e\">cytology<\/a>?<\/li>\n<li>Do we have money for everything?<\/li><\/ul>\n<p>Those concerns and how they were resolved will be addressed shortly, but we can already answer some of these. We did want to store all the WSIs forever and to use that repository to train our own AI algorithms, which is clearly one of the great advantages of such a transformation. We also believed that this project must be an integral transformation, including routine histopathology, fluorescence, research, and macroscopic images. Tools for teaching and <a href=\"https:\/\/www.limswiki.org\/index.php\/Telemedicine\" title=\"Telemedicine\" class=\"wiki-link\" data-key=\"d2cc9ab69dbfb679bcee20472b08fe93\">teleconsultation<\/a> should be included, which meant having the option to share images outside our hospitals\u2019 secured LAN. We realized that our LIS, preanalytics, network, and pathologist workstations all needed substantial upgrades to be able to undertake such a transformation.<sup id=\"rdp-ebb-cite_ref-:3_9-1\" class=\"reference\"><a href=\"#cite_note-:3-9\">[9]<\/a><\/sup>\n<\/p><p>What about cytology? Digitizing cytology, even if feasible<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup>, has some particular concerns, including scanning times being much longer than in histology (due to the need for more resolution, larger scan area, zero tolerance of out-of-focus areas, and Z-stacking). That means needing to install more scanners to be able to take on the same activity, and it impacts storage needs. Dark-field scanning (FISH) has similar issues, but there was a significant difference in the volume of slides to scan. Cytology involves a large number of <a href=\"https:\/\/www.limswiki.org\/index.php\/Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"7f8cd41a077a88d02370c02a3ba3d9d6\">samples<\/a> to digitize in our hospitals (over 400,000 each year), which is not affordable currently in this project due to budgetary constraints. (In other words, the activity addressed in our project included all bright-field, routine histopathology, histochemistry, immunohistochemistry, direct immunofluorescence, ISH, and FISH slides. Cytology was scanned on an as-needed basis.)\n<\/p><p>In Table 1, we summarize the total number of slides generated during 2019 at our eight hospitals, broken down by type. To that number of over one million slides, an expected growth in activity of 10% to 15% must be added each year. In addition, some resources were reserved for research and non-strictly routine samples and were not accounted for in these numbers.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Number of slides in 2019.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Slide type\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\"># of that slide type\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Routine histopathology\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">814,573\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Immunohistochemistry\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">186,453\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Histochemistry\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">64,209\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Direct immunofluorescence\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12,392\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">FISH\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2,695\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CISH\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1,983\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Total<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>1,082,305<\/b>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Regarding the amount of personnel involved, DigiPatICS provided service to 107 pathologists, seven biologists, 40 residents, and 14 observers, adding up to a total of 168 professionals working with digital diagnosis.\n<\/p><p>In the tender process, all relevant aspects were taken into account for bidder evaluation, as shown in the following list:\n<\/p>\n<dl><dd>\u25aa Automatic evaluation criteria (<i>51 points<\/i>)\n<dl><dd>\u25cb Economic valuation (<i>40 points<\/i>)\n<dl><dd>\u25aa Evaluation of the financial offer (<i>30 points<\/i>)<\/dd>\n<dd>\u25aa Evaluation of the maintenance offer (<i>10 points<\/i>)<\/dd><\/dl><\/dd>\n<dd>\u25cb Automatic technical evaluation (<i>11 points<\/i>)\n<dl><dd>\u25aa Quality management system. Certification of processes and algorithms (<i>3 points<\/i>)<\/dd>\n<dd>\u25aa Process consulting (<i>1 point<\/i>)<\/dd>\n<dd>\u25aa Image management platform adaptations (<i>3 points<\/i>)<\/dd>\n<dd>\u25aa Storage for research slides (<i>1 point<\/i>)<\/dd>\n<dd>\u25aa Short-term \u201chot\u201d storage (<i>3 points<\/i>)<\/dd><\/dl><\/dd><\/dl><\/dd>\n<dd>\u25aa Criteria subject to judgment value (<i>49 points<\/i>)\n<dl><dd>\u25cb Scanners: deployment and image quality (<i>17 points<\/i>)<\/dd>\n<dd>\u25cb Diagnostic viewer (<i>8 points<\/i>)<\/dd>\n<dd>\u25cbImage management platform (<i>4 points<\/i>)<\/dd>\n<dd>\u25cb Training module (<i>2 points<\/i>)<\/dd>\n<dd>\u25cb Built-in tools and algorithms (<i>3 points<\/i>)<\/dd>\n<dd>\u25cb Architecture and monitoring (<i>1 point<\/i>)<\/dd>\n<dd>\u25cb Definitive storage in SIMDCAT (<i>4 points<\/i>)<\/dd>\n<dd>\u25cb Integration of case information in a unified model (<i>2 points<\/i>)<\/dd>\n<dd>\u25cb Server infrastructure requirements and DPCs. Coherence, management model, virtualization (<i>2 points<\/i>)<\/dd>\n<dd>\u25cb Workstations (<i>2 points<\/i>)<\/dd>\n<dd>\u25cb Artificial intelligence (<i>3 points<\/i>)<\/dd>\n<dd>\u25cb Implementation and additional improvements (<i>1 point<\/i>)<\/dd><\/dl><\/dd><\/dl>\n<p>However, some aspects were considered very difficult to assess by evaluating their technical characteristics alone, and that is why three technical tests were defined for the scanner, viewer, and image management platform. For the scanner test, a large sample of glass slides from the eight hospitals was collected and fed to all the scanners offered by the three bidders for a week at 24 hours a day. In the fastest scanner, over 10,000 glass slides were digitized. Real scanning speeds, jamming, incidents, etc. were recorded to ensure the reliability of the equipment (Figure 2).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig2_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"bebc22d72df5b375ade75e70dce202f7\"><img alt=\"Fig2 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/24\/Fig2_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 2.<\/b> Testing room for Test 1, showing the Palex 3DHISTECH team and equipment (PANNORAMIC SCAN II, PANNORAMIC 300 Flash DX, and PANNORAMIC 1000 Flash DX).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>In the second and third tests, we brought together a group of pathologists from all the involved hospitals, along with IT experts, and they assessed the functionalities of the viewing software and the image management platform, as well as the image quality offered by the scanners using images scanned from ICS samples during the first technical test (Figure 3).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig3_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"c3a637f0ce8514c8b116a16d381e5d48\"><img alt=\"Fig3 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/5\/55\/Fig3_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 3.<\/b> Testing room for Test 2 and 3, showing from left to right, Miquel Arrufat (ICS), Ramon Bosch (ICS), Pablo L\u00f3pez-Garc\u00eda (ICS), Josep Maria Argimon (ICS), and Tam\u00e1s Reg\u00e9nyi (3DHISTECH) with the Palex 3DHISTECH equipment (LG 32HL512D 8MP Diagnostic Monitor, Logitech MX Vertical Ergonomic Wireless Mouse, and 3DHISTECH SlideDriver).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The contract file was definitively awarded by the decision of the Managing Director of the Catalan Health Institute (ICS) to the Palex Medical, S.A. 3DHISTECH Digital Pathology solution. This solution stood out for the proposal in the following main aspects:\n<\/p>\n<ul><li>Scanners: Technical requirements, deployment requirements, and technical service requirements<\/li>\n<li>Image management platform: Diagnostic viewer, learning platform, and quantification modules<\/li>\n<li>Architecture: SIMDCAT interaction (<a href=\"https:\/\/www.limswiki.org\/index.php\/DICOM\" title=\"DICOM\" class=\"wiki-link\" data-key=\"f0c7c747895286ff8785b6ed4dbc7ec0\">DICOM<\/a>), unified image management model (for all slide types), infrastructure management, and coherence model<\/li><\/ul>\n<h3><span id=\"rdp-ebb-Scanners_and_technology_for_obtaining_whole_slide_images_(WSIs)\"><\/span><span class=\"mw-headline\" id=\"Scanners_and_technology_for_obtaining_whole_slide_images_.28WSIs.29\">Scanners and technology for obtaining whole slide images (WSIs)<\/span><\/h3>\n<p>Twenty-four scanners were installed and integrated into the workflow of the eight hospitals. Different scanner models were deployed according to the needs of each institution. In Table 2, we summarize the number of each scanner type and the capabilities.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Scanner deployment and capabilities summary. HT: high-throughput capability; DS: double-width slide capability; FL: fluorescent scanning capability; IN: immersion scanning capability; Z: Z-stack scanning capability; S: slide capacity; N: number of deployed scanners; \u2713: Capabilities available in each scanner.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Model\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">HT\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">DS\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">FL\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">IN\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Z\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">S\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">N\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PANNORAMIC 1000 Flash DX\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1,000\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PANNORAMIC 300 Flash DX\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">300\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PANNORAMIC SCAN II\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">150\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">PANNORAMIC MIDI\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u2713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Total<\/b>\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>24<\/b>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The PANNORAMIC 1000 Flash DX (3DHISTECH Ltd., Budapest, Hungary) (P1000) is a large (154 \u00d7 100 \u00d7 91 cm) and heavy (270 kg) scanner, but it offers the largest slide capacity on the market at 1,000 slides (using Leica slide racks, slide loading capacity could be further increased to 1,200). It is the fastest whole-slide scanner on the market, at up to 100 slides per hour and 2,000 slides per day (at 40\u00d7 resolution, 0.25 \u03bcm\/pixel, single layer). The P1000 uses Sakura slide racks, which seamlessly integrated with our laboratory workflow and allowed for priority slide handling and scanning in arbitrary order because it is flexible and automatic. It is also being used for double-width slides. Regarding image quality, it is able to scan at 0.25 \u03bcm\/pixel, which is the 40\u00d7 resolution equivalent (industry standard), and also at 0.12 \u03bcm\/pixel, which is roughly the 80\u00d7 resolution equivalent. Multilayer (Z-stack) and extended focus scanning are available, as well as automatic water immersion.<sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[34]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup> Furthermore, thanks to its AI-based software control, it is able to automatically rescan suboptimal slides, adding multilayer scanning if required. The P1000 are used for all bright-field and double-width slide related imaging.\n<\/p><p>The PANNORAMIC 300 Flash DX (3DHISTECH Ltd., Budapest, Hungary) (P300) is a fast bright-field and fluorescence scanner capable of high throughputs as a standalone machine in smaller institutions or serving as backup for P1000s in larger hospitals. It has the capacity for 300 slides, and its use is mainly for fluorescence, scanning FISH, and direct immunofluorescence.<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup>\n<\/p><p>Both the PANNORAMIC SCAN II and the PANNORAMIC MIDI (3DHISTECH Ltd., Budapest, Hungary), with slide capacities of 150 and 12 slides, respectively, are mainly focused on fluorescence imaging but are still able to scan bright-field images, even though they are slower than their high-throughput counterparts.<sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Macroscopic_imaging\">Macroscopic imaging<\/span><\/h3>\n<p>Regarding macroscopic imaging, 13 MacroPATH QX systems (Milestone Medical, Sorisole, Italy) were installed to obtain and incorporate gross imaging into the workflow. All the images were stored on the DigiPatICS servers and were fully integrated and available at the pathologist workstations for making diagnoses.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"WSI_viewing:_Hardware\">WSI viewing: Hardware<\/span><\/h3>\n<p>To be able to view WSIs, 183 new workstations were installed (Table 3) for pathologists, residents, biologists, observers, and meeting rooms. Each pathologist workstation consisted of two 32-inch 4K UHD (3840 \u00d7 2160 pixel) diagnostic medical-grade FDA-approved monitors (LG 32HL512D) (Figure 4) that could be used indistinctly in flexible ways. Normal intended use is for a pathologist to have an LIS with all laboratory data, clinical data, and reporting available on one monitor, while on the other, a microscopic image is displayed. However, both monitors could be used for microscopic images, or both could be used for reporting, clinical data, bibliography, or other tasks. Biologist workstations were the same as those of the pathologists. Residents and observers shared the same workstations; however, they only consisted of one LG 32HL512D medical-grade monitor due to space constraints (the dual-monitor setup required over 150 cm of desk surface).\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"2\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> Workstation and monitor deployment. N: number of equipment.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Equipment\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">N\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Workstations\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">183\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">32\u2033 8MP Medical Monitor LG 32HL512D\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">286\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">55\u2033 4K UHD Monitor 55UH5F-B\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4K UHD DICOM ProBeam LG Projector\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig4_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"44bc9179c9d55722eefe5fb5effe027e\"><img alt=\"Fig4 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/64\/Fig4_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 4.<\/b> A pathologist in his office with a resident diagnosing with two LG 32HL512D 8MP diagnostic monitors.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Thirteen additional workstations with six 55-inch 4K UHD monitors and seven 4K UHD DICOM ProBeam LG projectors were installed in small and medium meeting rooms for teaching and clinical sessions as a replacement for multi-head microscopes (Figure 5).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig5_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"0fec06a952b861e40d0555b4bcf84af1\"><img alt=\"Fig5 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/e9\/Fig5_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 5.<\/b> Residents diagnosing using a 55-inch 4K UHD monitor (55UH5F-B).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Each workstation was comprised of an Intel Core i5-9600K processor (Intel Corporation, Santa Clara, CA, USA), 16 Gb RAM, 512 Gb SSD, and an RTX 2060 graphics card (Nvidia Corporation, Santa Clara, CA, USA). All workstations were the same for easier maintenance, compatibility, and interchangeability of workplaces. Each workstation also contained a Logitech BRIO 4K UHD webcam (Logitech International, Lausanne, Switzerland) and a Jabra Evolve 40 headset with a microphone (GN Group, Ballerup, Denmark). Both the webcam and microphone aimed to facilitate networking among pathologists from the same hospital, from different hospitals within the ICS, or even with professionals outside our network.\n<\/p><p>Furthermore, each workstation contained a Logitech MX Vertical Ergonomic Wireless Mouse (Logitech International, Lausanne, Switzerland), since vertical mice seem to put less strain on the wrist and demonstrate better ratings than conventional mice.<sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup> Each pathologist could also choose between two other ergonomic devices: a Kensington Expert Mouse Wireless Trackball (Kensington Computer Products Group, Redwood Shores, CA, USA) and a SlideDriver (3DHISTECH Ltd., Budapest, Hungary) (Figure 6). All devices were supported by our viewing software. The SlideDriver offers microscope-like navigation on digital slides for those who prefer a traditional method. Most of our pathologists and residents selected the SlideDriver as their input device (80% approximately).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig6_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"e36ced5a4bf60be5ccdcac1c7d5725ee\"><img alt=\"Fig6 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a3\/Fig6_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 6.<\/b> Ergonomic devices: (<b>a<\/b>) Logitech MX Vertical Ergonomic Wireless Mouse; (<b>b<\/b>) Kensington Expert Mouse Wireless Trackball; (<b>c<\/b>) SlideDriver.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"WSI_viewing:_Software\">WSI viewing: Software<\/span><\/h3>\n<p>The diagnostic viewer used for all digital images was ClinicalViewer (3DHISTECH Ltd., Budapest, Hungary). It uses streaming technology to avoid downloading WSIs for diagnosis. It is capable of opening bright-field, fluorescence, double-slide, Z-stack, and macroscopic photography, etc. It also includes many positively valued features, such as the possibility of viewing and navigating up to nine automatically synchronized images at once. It also has IVD support and quantification algorithms, as well as some more standard tools, such as free rotation, free zoom, annotation, measuring, and object counting tools (Figure 7).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig7_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"2d8bb34e26dc373f00a6972d8654bc32\"><img alt=\"Fig7 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/92\/Fig7_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 7.<\/b> ClinicalViewer: (<b>a<\/b>) slide with navigation panel; and (<b>b<\/b>) three auto-aligned slides.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The software also had a telepathology option available and a module to create training courses. Possessing all the WSI viewing needs, including fluorescence, integrated into one software system (one viewer) facilitated pathologist ergonomics and also enabled simplifying the technological model with fewer integrations required.\n<\/p><p>The software also had a telepathology option available and a module to create training courses. Possessing all the WSI viewing needs, including fluorescence, integrated into one software system (one viewer) facilitated pathologist ergonomics and also enabled simplifying the technological model with fewer integrations required.\n<\/p>\n<h3><span id=\"rdp-ebb-ETPAT:_Our_laboratory_information_system_(LIS)\"><\/span><span class=\"mw-headline\" id=\"ETPAT:_Our_laboratory_information_system_.28LIS.29\">ETPAT: Our laboratory information system (LIS)<\/span><\/h3>\n<p>The evolution of information systems in the last 10 years has been meteoric. It has changed the paradigms for accessing and possessing the necessary information at each point of contact a patient has with a health system.\n<\/p><p>At the Catalan Health Institute (ICS), and within the ARGOS project, we have spent 15 years directing information towards users and clinical care, and we have progressively moved from the initial free texts to structured information. The ARGOS project started in 2006. It is a project to integrate in a transversal and transparent way all the information systems involved in clinical assistance to the citizens of the Catalan Health Institute and its eight hospitals, including the <a href=\"https:\/\/www.limswiki.org\/index.php\/Hospital_information_system\" title=\"Hospital information system\" class=\"wiki-link\" data-key=\"d8385de7b1f39a39d793f8ce349b448d\">hospital information system<\/a>, nursing, pharmacy, clinical analysis laboratory, pathology laboratory, and critical care units. Currently, ARGOS is the priority information system in Catalonia and is present in 23 hospitals of the Catalan public health network.\n<\/p><p>The SALUT4D project began in 2020 and is the evolution of clinical workstations within the ARGOS project. Its objective is to provide the necessary information at each moment of care to different professionals. It is based on four dimensions seeking to present the necessary data at each point of care:\n<\/p>\n<ol><li>Where am I? Scope of work, including emergencies, hospitalization, ambulatory consultation, operating room, etc.<\/li>\n<li>Who am I? Role, including nurse, surgeon, internist, psychologist, etc.<\/li>\n<li>Whom do I attend? A patient with hypertension, diabetes, bronchitis, etc.<\/li>\n<li>How do I attend to it? With a computer, tablet, smartphone, etc.<\/li><\/ol>\n<p>The system presents the information that a professional needs clearly and orderly. The system is based on a clinical dictionary with more than 40,000 variables stored in a MongoDB-type database called the Global Variables Repository (RGV). This repository contains data from all sources, including laboratory, pathological anatomy, radiology, vital sign monitors, pharmacy, etc.\n<\/p><p>To construct this platform, created and designed for and by the ICS, HTML5 technology, SAP ISH (Information System Hospital), and SAP ISHMed (SAP SE, Walldorf, Germany) were used. The system connects directly with the Shared Clinical History of Catalonia (HC3) and provides access to information on all public hospitals and all primary care facilities in a fully integrated manner.\n<\/p><p>The workflow methodology was based on requirements submitted by over three hundred health professionals who continuously provided their contributions. Through AGILE methodologies, the new clinical workstation was progressively built. The new station is already in operation at the eight ICS hospitals and will gradually come into operation in 23 sections of the ARGOS system throughout 2022.\n<\/p><p>In order to incorporate the peculiarities of the new, fully digital workflow, a new LIS for our pathology laboratories named ETPAT was developed. It was deemed necessary to develop and improve pathologist workstations to provide them with tools that allow the integration of information from all sources and electronic records available. ETPAT has a fully integrative approach to all processes occurring in our pathology labs, from electronic requests from clinicians to pathology reports, with full traceability of all steps involved at the laboratory. Moreover, it enables the optimization of paper management as much as possible. This software was based on HTML5 and was prepared for 32-inch 4K UHD monitors, taking advantage of the hardware on hand (Figure 8).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig8_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"8e2f780c93510f6e6b12a98a76cd277b\"><img alt=\"Fig8 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1a\/Fig8_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 8.<\/b> ETPAT screenshot (our proprietary LIS).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>One of the most relevant aspects was the unification of workflow for all ICS laboratories, which should be able to work seamlessly as a network, or even as one big institution. The catalogs of techniques and sample types were also more coherent. All traceability data was integrated and convenient, and we were able to collect information on who carried out each phase of the diagnostic process to allow the correct attribution of costs and activities. This new LIS is clearly ready for the digital workflow of macroscopic and microscopic images and was fully integrated with the image management platform. In addition, the management of second opinions and case consultations was incorporated.\n<\/p>\n<h3><span id=\"rdp-ebb-Network_needs,_local_area_network_(LAN),_and_wide_area_network_(WAN)\"><\/span><span class=\"mw-headline\" id=\"Network_needs.2C_local_area_network_.28LAN.29.2C_and_wide_area_network_.28WAN.29\">Network needs, local area network (LAN), and wide area network (WAN)<\/span><\/h3>\n<p>The main source for generating information by volume of data was the scanners (in the order of around two petabytes yearly), which were located across the different centers included in the scope of the project. The systems were connected to a 10 Gbps network between the scanners and the local storage data processing center (DPC). The same criteria applied to the AI platform.\n<\/p><p>The network requirements for the DigiPatICS project were high, since access to the images needed to be instantaneous, as it was on a microscope. Images were accessed via streaming, but a large bandwidth was still required, making it necessary to adapt cabling and infrastructure, as well as switches, routers, and other telecommunications equipment. Each workstation required a 300 Mbps connection to the DPC to be able to stream the WSIs, but to ensure performance, the connection was established at 1 Gbps. MacroPATHs required a 100 Mbps connection.\n<\/p><p>Adjustments were made to the WAN infrastructure to ensure that communications between the central repository and the centers were capable, on one hand, of transferring daily information to the central DPC and, on the other hand, of allowing consultation between hospitals and their corresponding DPCs. This WAN needed to support an approximate flow of six terabytes each night for the DigiPatICS project activity alone. To achieve these goals, both the Department of Health and Catsalut public institutions recognized this need and facilitated the creation of a dedicated network to support the data traffic requirements mentioned and response times for data recovery.\n<\/p>\n<h3><span id=\"rdp-ebb-On-premises_data_processing_centers_(DPCs)\"><\/span><span class=\"mw-headline\" id=\"On-premises_data_processing_centers_.28DPCs.29\">On-premises data processing centers (DPCs)<\/span><\/h3>\n<p>The project proposal was to provide a good user experience to all users of the image management platform, as well as to facilitate their work, optimize performance times, and reduce the time invested in obtaining a correct diagnosis. That is why we considered infrastructure to be a fundamental technological pillar in this project that needed to be sized based on performance, scalability, and reliability criteria without excessively oversizing the system or implementing complex architectures that would create greater difficulties in maintenance. For the project, the deployment of its own infrastructure was carried out, but at the same time, it was integrated transversally across the health ecosystem.\n<\/p><p>A common structure was used at all centers that only changed in terms of local storage dimensioning, adapting to the number of slides estimated per center. In this way, we made infrastructure maintenance easier. All the DPCs were provided with the energy and cooling requirements necessary for correct operation of the various systems, as well as redundant systems in terms of communications, servers, storage, and a secondary DPC in case of disaster recovery.\n<\/p><p>The system at each center was designed to have a high-availability configuration, meaning, in the event of a disaster in one of the elements of the system, it would be capable of continuing to offer service with minimum downtime, or even without interruption, depending on the source of the problem.\n<\/p><p>The high-availability elements implemented were:\n<\/p>\n<ul><li>a host server cluster under VMware vSphere in an active-passive configuration;<\/li>\n<li>disk storage configured in RAID; and<\/li>\n<li>mirrored disk arrays with asynchronous replication.<\/li><\/ul>\n<p>The various redundant elements of the high-availability scenario were located in a DPC or complementary technical room that was not the main DPC in order to minimize the impact of any possible disaster on the main DPC. AI equipment was excluded from this high-availability policy.\n<\/p><p>At each center, a virtualization infrastructure was deployed, consisting of a set of two identical servers under a VMware vSphere infrastructure. This allowed the system to have the capacity to maintain service quality in an event where it was necessary to activate a contingency scenario (disaster recovery) in a matter of a few minutes. These servers were HPE ProLiant DL325 models dimensioned with AMD EPYC processors that offered the necessary computing capacity for all DICOM image integration, storage management, and processing operations that were carried out continuously. They also served as a virtualization platform for the controller structure of the AI cluster.\n<\/p><p>As for storage, MSA 1050 cabinets were chosen and presented to the host servers through iSCSI controllers. These storage cabinets contained a battery of SSD disks intended exclusively for virtual machine operating system disks. For medical image storage, a pool of rotational HDD disks was deployed. This decision was made based on the following factors:\n<\/p>\n<ul><li>Once the medical image was generated, it was not modified (writing on the disc only one time).<\/li>\n<li>Access was completed in blocks through streaming (reduced reading rate).<\/li>\n<li>Each center had its own local storage (limited number of simultaneous writes).<\/li><\/ul>\n<p>For all these reasons, the increase in cost of deploying SSD technology for image storage was not justified for the required performance.\n<\/p><p>he same storage technology was used in all the centers, including the central DPC, with only capacity varying as a factor of the number of digitized images estimated per center. The total storage capacity between the eight hospitals was approximately 500 TB, which allowed short-term storage of up to 75 days for images.\n<\/p><p>The deployed server and storage infrastructure had the activation of the HPE IRS service, which automatically opened a ticket to the manufacturer in the event of a hardware component failure, guaranteeing proper functioning of the infrastructure. The entire server infrastructure was backed by a backup policy based on Veeam Backup that was integrated into existing control panels in each center in order to facilitate maintenance tasks.\n<\/p><p>Within the scope of this project, integration with SIMDCAT was included for the publication of images as a form of definitive storage. Publishing to SIMDCAT was asynchronous under a queue management system that published the images as soon as they became ready. As the publication to SIMDCAT was continuous, the need to make a backup copy of all the scanned images outside the same disk array cluster was not considered, delegating the backup function to the same SIMDCAT. If the need arose to retrieve one or more images, a small application was implemented that allowed downloading these images from SIMDCAT and placing them back in local storage. Only in the event of a major disaster would the procedure be the same as indicated above; however, there may be a minimal number of scanned images that would not have had the opportunity to be published in SIMDCAT due to the asynchronous nature of the publication process. In such a case, the images would be rescanned.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"SIMDCAT_and_DICOM\">SIMDCAT and DICOM<\/span><\/h3>\n<p>SIMDCAT is the Digital Medical Image System of Catalonia. It is currently the unified system used by the network of entities called SISCAT (Comprehensive Health System of the Public Utility of Catalonia) to preserve digital medical images and provide services and digital resources based on the same software architecture using cloud services and to make information accessible from various electronic medical records. The system is used by approximately 450 Catalan health centers and by all SISCAT professionals to securely collect and share digital medical images generated by the centers. SIMDCAT was the definitive repository of this project in which the images and associated data were stored. SIMDCAT was set up in 2018 to provide the public health system with a secure and technologically advanced environment in which to store and share digital medical image services.\n<\/p><p>The project to develop in SIMDCAT a specific environment for anatomical pathology medical images presented multiple benefits for agents of the Catalan health system. Professionals in this specialty were provided with a network work environment based on <a href=\"https:\/\/www.limswiki.org\/index.php\/Cloud_computing\" title=\"Cloud computing\" class=\"wiki-link\" data-key=\"fcfe5882eaa018d920cedb88398b604f\">cloud technology<\/a>, and the anatomopathological diagnosis process was optimized so that medical images were immediately and safely available to professionals. As for patients, the quality of care was improved and their safety was increased.\n<\/p><p>Finally, the sustainability of resources and costs of health information systems was promoted by providing a common and shared system for all providers.\n<\/p><p>SIMDCAT\u2019s cloud-based technology is focused on the use of DICOM as a standard in the storage and distribution of medical objects. The capacity of standard DICOM beyond radiology has been demonstrated in recent years, where <a href=\"https:\/\/www.limswiki.org\/index.php\/Picture_archiving_and_communication_system\" title=\"Picture archiving and communication system\" class=\"wiki-link\" data-key=\"523b73ff51fa83663dc0b1d59e6d0f05\">picture archiving and communication system<\/a> (PACS) image storage systems have evolved into the VNA (Vendor Neutral Archive); SIMDCAT constitutes a VNA that allows the management of medical objects using the DICOM standard as a reference framework. In the case of pathology, the DICOM 145 extension is adopted; this extension facilitates the storage and distribution of medical objects independent of the device that generates the information. SIMDCAT adopts DICOM 145 natively, incorporating the pyramidal treatment of images, thus facilitating navigation through an image. SIMDCAT also adopts the DICOM 122 extension that reflects the representative data model of pathology.\n<\/p><p>SIMDCAT manages the information in a private cloud model with a high-redundancy system to guarantee the availability of the information. Saving the information in different storage systems using data object technology, this model allows growth according to the needs of the system, optimizing available resources in addition to freeing hospitals from the custody and distribution of information.\n<\/p>\n<h3><span id=\"rdp-ebb-AI_and_the_Polytechnic_University_of_Catalonia\u2013BarcelonaTech_(UPC)\"><\/span><span class=\"mw-headline\" id=\"AI_and_the_Polytechnic_University_of_Catalonia.E2.80.93BarcelonaTech_.28UPC.29\">AI and the Polytechnic University of Catalonia\u2013BarcelonaTech (UPC)<\/span><\/h3>\n<p>It is now recognized that AI represents a turning point for society that is at least as significant as the Industrial Revolution. The ICS aims to be an autonomous and primary player in the creation of AI algorithms to avoid dependence on a commercial solution. Therefore, we wished to set up an AI-based platform tailored to the needs of the ICS. This platform was developed with free software and needed to be modeled to accommodate other AI projects in addition to DigiPatICS.\n<\/p><p>Currently, the ICS has signed a collaboration agreement with the <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/imatge.upc.edu\/web\/\" target=\"_blank\">Image Processing Group<\/a> (GPI) of the Polytechnic University of Catalonia\u2013BarcelonaTECH (UPC) for the development of AI tools and platforms within the healthcare field, specifically in the field of medical imaging. The group belongs to the Intelligent Data Science and Artificial Intelligence Research Center (IDEAI), which is a hub created at the UPC in 2017 for the development of AI. GPI has extensive experience in image processing and the development of AI algorithms, with a long history in the healthcare field.\n<\/p><p>GPI develops computer vision and deep learning (DL) tools to tackle WSI analysis tasks in DigiPatICS for stains, such as H&E, HER2, KI67, RE, and RP, as well as other immunohistochemical stains. DL technology that relies on instance and semantic segmentation architectures has the potential to provide high-quality results when properly trained. GPI has also introduced strategies, such as:\n<\/p><p><b>Dataset annotation<\/b>: As the training database was limited in the first stage, a more classical computer vision strategy relying on morphological algorithms and machine learning (ML) tools produced proposals easier to validate by annotators and generated the ground truth needed to avoid limiting the performances of DL approaches.\n<\/p><p><b>Integration of AI algorithms<\/b>: Integration into specialist workflow was facilitated by combining the systematic processing of a large number of WSIs with on-demand assessment by pathologists for improving the systematic results or for obtaining specific quantifications. First, nightly batch processing and inference on the WSIs yielded raw results, such as segmentation confidences and classification probabilities, as well as potential segmentation masks. From there, the results were integrated into 3DHISTECH ClinicalViewer using a specific plug-in and offered to the pathologists upon request when examining the slides. Then the pathologists could select or deselect regions in the WSI to visualize and quantify the results or to fine-tune inference results (classification and segmentation) using sliders. Finally, pathologists could also select specific areas for further online analysis on inference servers to be performed during the session with the viewer at their workstations.\n<\/p><p><b>Pathologists in the analysis loop<\/b>: The integration of AI algorithms allowed not only flexible interaction for online and on-demand analysis, but also for recovering information about pathologists by selecting specific regions of interest and tuning inference results for reports. This information represents invaluable data and comments to further improve the annotated datasets.\n<\/p><p><b>Training in the ICS development servers<\/b>: A specific committee formed by AI specialists and clinicians periodically reviewed the comments and data produced by pathologists using the viewer. This committee decided on the feedback, data, and set strategies for incremental training and improvement of the DL network architecture involved with continuously improving the inference results. Ultimately, former strategies facilitated the usage of AI tools in the daily work of pathologists, as well as productivity.\n<\/p><p>As mentioned, all images were stored in a central repository, SIMDCAT, where they were available for AI training after dissociation. AI training was performed in this central repository, where a large number of whole slide images were readily at hand. GPI researchers did not have direct access to sensitive clinical data, and datasets and whole slide images always remained within the ICS infrastructure. In fact, it should be noted that the entire circuit in production moved through an isolated dedicated network in an intranet environment, and the training environment was in a separate VLAN and intranet infrastructure. Once the inference algorithms were trained, they were run on-premises at each hospital DPC. In no case was the information transferred to external DPCs.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results\">Results<\/span><\/h2>\n<p>The digital pathology transformation envisioned in the DigiPatICS project involved great changes in most of the steps of workflow in our pathology laboratories. As mentioned above, all the processes were integrated in our ETPAT LIS.\n<\/p>\n<h3><span id=\"rdp-ebb-Laboratory_workflow,_traceability,_and_barcode_generation\"><\/span><span class=\"mw-headline\" id=\"Laboratory_workflow.2C_traceability.2C_and_barcode_generation\">Laboratory workflow, traceability, and barcode generation<\/span><\/h3>\n<p>All incoming samples, biopsies, cytologies, autopsies, and even molecular requests are accompanied by an e-request generated in our <a href=\"https:\/\/www.limswiki.org\/index.php\/Electronic_health_record\" title=\"Electronic health record\" class=\"wiki-link\" data-key=\"f2e31a73217185bb01389404c1fd5255\">electronic health record<\/a> (EHR) system by the clinicians who input all the necessary clinical data.\n<\/p><p>At the time of registration, the request receives an identification number that is labeled with a Data Matrix-type barcode. Each sample container is also labeled with a unique Data Matrix-type barcode. The barcode structure is as follows, maintaining logical hierarchy, as seen in Figure 9. The case or request barcode includes the institution, the year, the sample type, and the case number (i.e., VH22B051337, for Vall d\u2019Hebron, year 2022, biopsy number 51,337). When labeling a container, the container ID is appended (i.e., VH22B051337A for container A). When a cassette is required, a Data Matrix-type barcode is also printed with the number of the paraffin block appended (i.e., VH22B051337A014 for block 14). For glass slides, whether they come from paraffin block sections or are cytologies, another number is appended, representing the slide number (i.e., VH22B051337A014001 for histological section 1). The full ID is printed and appears in a Data Matrix-type barcode in each slide.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig9_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"399adb56ed9e2ff5d12b365f49cffcee\"><img alt=\"Fig9 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a2\/Fig9_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 9.<\/b> Barcode anatomy.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Most of our laboratory equipment, including scanners, is able to read these barcodes and is integrated with our LIS, providing automatic checkpoints for many steps of processing. The first checkpoint is when the sample is received with the labeling of the containers, as described previously. It is a manual step completed by technicians, but in the new LIS, the process was simplified so it was closer to optimal. The next step, grossing, was also improved: MacroPATHs were installed inside the pathology fume hoods, and computers with the LIS were placed next to them. Pathologists, residents, or technicians could print the cassettes, capture gross examination pictures, and dictate or type the macroscopic description in a convenient and fully digital way. Pictures of cassette contents are obtained and are available for verification in the next laboratory steps. After filling a cassette with tissue, the barcode is scanned for the first checkpoint of the paraffin block. The next checkpoint is when the cassette enters the tissue processor, and a technician reads the barcodes using a handheld device. Unfortunately, this step remained manual because our tissue processors could not read barcodes. We hope this will change in the future.\n<\/p><p>Each embedding station had a computer with a barcode reader within reach. A technician read the barcode of the paraffin block, and the LIS displayed the tissue type and the confection notes (if present) and provided access to macroscopic images for verification, while, in fact, creating another checkpoint.\n<\/p><p>The next checkpoint is clearly when sectioning. Every microtome station had a barcode reader, a slide label printer, and a computer with the LIS. When scanning the paraffin block, the LIS displayed the tissue type and other information on that block, such as how many and which slides must be obtained from it. At the same time, it printed the slide labels automatically, which include the Data Matrix barcode described previously. This automation reduced the human error of manual workflow.<sup id=\"rdp-ebb-cite_ref-:0_3-1\" class=\"reference\"><a href=\"#cite_note-:0-3\">[3]<\/a><\/sup> \n<\/p><p>At this point, the automatic part started. In most hospitals, Sakura Tissue-Tek Prisma Plus and Tissue-Tek Film (Sakura Finetek Europe B.V., Alphen aan den Rijn, The Netherlands) were used. After sectioning, a technician loaded the slides in the Sakura racks. Then, the racks were stained, cover-slipped with film, dried, and scanned using P1000s. Routine slides did not have to be treated individually until archiving because all the equipment used the same racks. In terms of traceability, an automatic checkpoint was recorded by Sakura Tissue-Tek Film, which was integrated with our LIS, and the final checkpoint was notified by a 3DHISTECH P1000 when the slide was scanned.\n<\/p><p>Using the same Sakura racks for all equipment enabled us to optimize technician slide handling time and reduce errors. Immunohistochemistry and histochemistry used the same Tissue-Tek Film, so checkpoints stayed the same. In the case of double slides, the steps needed to be conducted manually, but their volume was negligible compared to routine histology, where workflow optimization was key.\n<\/p><p>In some hospitals, other automatic stainers were used, such as VENTANA HE 600 (Roche, Basel, Switzerland). Integration was possible, but an extra step of transferring the slides from HE 600 trays to the scanner rack was needed.\n<\/p><p>Subprocesses, such as slide allocation and delivery to pathologists, did not exist anymore, since the digital workflow did not require such manual steps.\n<\/p><p>Regarding the destruction of containers, a new system was implemented. A tablet with the LIS, along with a handheld Data Matrix barcode reader, was used to scan the containers. If the containers were ready for elimination, a confirmation message appeared, and a checkpoint was created.\n<\/p><p>The whole workflow was designed for optimization and security. We aimed to reduce the time technicians spent on worthless tasks, allowing them to focus on what was important and increase their satisfaction in the workplace. Also, the checkpoints enabled a better awareness of sample status by all personnel and an obvious increase in safety.\n<\/p><p>It is also worth mentioning that the transformation was carried out simultaneously as a radical change with all the pathologists in the same center starting digital work at the same time. The alternative of making a gradual change implied many more difficulties by having to maintain two circuits (old and new) in the same laboratory. This measure was taken considering the possible reluctance and skepticism of the staff, which would be lessened if they could quickly see an optimization of circuits despite initial incidents. No benefits of a gradual approach were seen by the authors if all the infrastructure was in place.\n<\/p><p>Regarding validation of WSIs for use in primary diagnosis, the digital pathology solution provided all necessary legal certifications, but it still was tested and validated previously by many pathologists using all types of preparations. The solution was also tested in the scanner and viewer technical tests during the bidding process. When the pathologists started working with digital slides, all of them could compare digital slides with glass slides until their grade of confidence was enough. No specific period of time or amount of resources was dedicated for this purpose; it was a matter of obtaining enough comfort for the pathologists in their routine workflow. A continuous validation of tissue detection was performed in every single case, since the pathologists had available the captured image of the slide next to the slide overview, as seen in Figure 7a, and were thus certain there was no tissue missing on the WSI.\n<\/p><p>Furthermore, all the pathology departments involved in DigiPatICS were certified or accredited for <a href=\"https:\/\/www.limswiki.org\/index.php\/ISO_9000\" title=\"ISO 9000\" class=\"wiki-link\" data-key=\"53ace2d12e80a7d890ce881bc6fe244a\">ISO 9001<\/a> or <a href=\"https:\/\/www.limswiki.org\/index.php\/ISO_15189\" title=\"ISO 15189\" class=\"wiki-link\" data-key=\"e7867fe884a6e63d87c5a1bff5c28bc2\">ISO 15189<\/a>. Because the ISO 15189 standard confirms technical competence of the laboratory and ensures reliability of test results, a continuous validation strategy was recommended following CAP recommendations.<sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup>\n<\/p><p>The initial reticence on the part of a couple pathologists could not be reversed despite several talks and explanations to try to make them partners in the transforming project. However, these reluctances completely disappeared after a few days of working in the digital flow without the need for any external intervention. The advantages of the new technology were obvious and sufficient on their own.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Scanning\">Scanning<\/span><\/h3>\n<p>Being able to scan slides and obtain WSIs are perhaps the obvious concerns of any digital pathology project, but, as mentioned, these are not the only relevant points. For example, it was essential that the scanners did not stop due to jamming, so the glass slides needed to be optimal. This implied possessing a decent glass or film coverslip; either could work as long as the quality of the histological slide was good. Labels also needed to fit perfectly within the boundaries of the glass slide. Anything that protruded could cause jamming. Slides needed to be fully dried, and under no circumstance could be dripping glue.<sup id=\"rdp-ebb-cite_ref-:4_20-1\" class=\"reference\"><a href=\"#cite_note-:4-20\">[20]<\/a><\/sup>\n<\/p><p>Furthermore, we considered crucial for the workflow the presence of automatic scanning with two objectives and, therefore, two resolutions, 40\u00d7 (0.25 \u03bcm\/pixel) and 80\u00d7 (0.12 \u03bcm\/pixel), to cover all possible needs. The scanners used different scanning profiles (40\u00d7 or 80\u00d7, Z-stack, etc.) depending on the sample and the stain type indicated by our LIS (ETPAT). The process was fully automatic. It was also possible to select profiles manually or tweak some settings, but manual parameterization was not used for high-throughput routine scanning. Routine scanner loading needed to be as easy, fast, and straightforward as possible for the laboratory technicians. In order to have the automatic profile feature in addition to automatic tissue detection obtained by an AI algorithm in the scanner control software, it was very important to scan slides at a suitable resolution.\n<\/p><p>The second concern regarding scanners was their deployment. Correct dimensioning is essential to address daily routine activity. Individual scanning speed or capacity is very important, but less relevant than the deployment of equipment meeting the needs of the center. In the event of a breakdown or maintenance, the remaining equipment must be able to compensate. Scanner deployment must also take into account the expected growth of activity (in our case, 10 to 15% annually). Scanners must not create bottlenecks in the workflow, and going fully digital cannot involve a delay in turnaround time. In our daily routine, scanning occurred right after the slides were dried, and the first WSIs were available during the morning. The scanners were continuously loaded until the end of the technician shift for each institution (in some cases 16:00, and 21:00 in others), and the scanners were intended to finish scanning overnight, around 2:00 to 3:00 a.m. in our institutions producing more slides, thus having time until 8:00 a.m. to accommodate this expected increase in activity before the pathologists started diagnosing. This workflow guaranteed no delay in turnaround time, even after adding steps to the conventional system, by completing slide production and digitation of all slides within the same day. The remaining advantages of digital pathology should optimize our routines and reduce diagnostic and reporting times.\n<\/p><p>Another aspect considered was where to physically locate the scanners. The location needed to be convenient for technicians within their workflow so that the new steps were not disruptive. Scanners were located near a stainer or cover-slipper, or next to a glass slide archive whenever possible.\n<\/p><p>Fluorescence workflow was taken into account to try to keep the slides cool and to preserve them from light.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Monitors\">Monitors<\/span><\/h3>\n<p>The need for a high-quality monitor is indisputable, although recommendations for ideal screen size and resolution have changed over time. Currently, a size between 24 and 32 inches with a high resolution is considered necessary, and the trend is probably upwards. A larger monitor, such as the ones we used, with a smaller pixel size allows for a greater field of vision, avoiding displacement through digital preparation. However, this means that objects appear smaller when the original maximum magnification is reached and that it requires more bandwidth to stream the image.<sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[41]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-43\" class=\"reference\"><a href=\"#cite_note-43\">[43]<\/a><\/sup>\n<\/p><p>It is also important to take into account color fidelity (the panel can be calibrated), lighting (no backlight bleed), contrast, pixel size, pixel density, brightness, color space (sRGB, Adobe RGB), color depth, etc. However, a good monitor is not going to make up for poor digital preparation. A high-quality monitor is important to guarantee image fidelity and ergonomics, as well as to avoid visual fatigue for the user (Figure 10).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.limswiki.org\/index.php\/File:Fig10_Temprana-Salvado_Diagnostics22_12-4.png\" class=\"image wiki-link\" data-key=\"61ec64b56f45564e75fba72ddecd72b9\"><img alt=\"Fig10 Temprana-Salvado Diagnostics22 12-4.png\" src=\"https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/85\/Fig10_Temprana-Salvado_Diagnostics22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Figure 10.<\/b> Fluorescence seen in a totally integrated fashion on two 32-inch LG 32HL512D 8MP diagnostic monitors.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span id=\"rdp-ebb-Teaching,_telepathology,_and_networking\"><\/span><span class=\"mw-headline\" id=\"Teaching.2C_telepathology.2C_and_networking\">Teaching, telepathology, and networking<\/span><\/h3>\n<p>Many of the planned advantages of this project, such as networking between ICS hospitals, having a teaching platform, and being able to teleconsult cases with external pathologists, although not available right now, were binding in the contract and will be implemented in the following months.<sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup> The system will have an on-demand function to publish studies to an internet environment with previously anonymized data to allow the sharing of images.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Discussion\">Discussion<\/span><\/h2>\n<p>The DigiPatICS project, as a transformation of the Catalan Health Institute Network of eight hospitals, represented an important technological, organizational, and functional challenge. We incorporated digital pathology and AI in pathology departments, with an organizational change that modified work dynamics, as seen in the previous paragraphs. This change responded to current and future challenges, with the aim of improving quality, efficiency, effectiveness, equity, speed, systematization, and reproducibility of diagnoses. These improvements affected other disciplines and increased patient safety, with the following benefits: \n<\/p>\n<ul><li>improvement of diagnostic conditions by incorporating the digitalization of preparations, with maximum guarantees of traceability while also minimizing material losses and identification errors; and<\/li>\n<li>improvement of workflow, productivity, and turnaround times.<\/li><\/ul>\n<p>Moreover, there was also improvement in working conditions in terms of ergonomics. The viewers also provided tools for morphometry and quantification of diagnostic and prognostic biomarkers and facilitated the digital access of preparations from previous patient examinations without interrupting the diagnostic process.<sup id=\"rdp-ebb-cite_ref-:1_4-1\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:2_7-1\" class=\"reference\"><a href=\"#cite_note-:2-7\">[7]<\/a><\/sup>\n<\/p><p>In the near future, we will enable access to images for decision making between pathology departments and other facilities (operating rooms, interventional examination rooms, transplantation, or clinical committees) using bidirectional communication. Also, the images will be available for clinical sessions, tumor boards, and pre- and postgraduate teaching. Being able to store pathology images digitally also reduces the workload for management of histological preparation files. Ergonomics, workflow improvement, and convenience of access to historical slides also encourage research.\n<\/p><p>Successfully exchanging WSIs and AI algorithms between institutions had the following implications: \n<\/p>\n<ul><li>We improved the reproducibility of diagnoses, both in terms of interpretation and in the way they are reflected in medical reports, ensuring system-wide equity and fairness.<\/li>\n<li>We encouraged an optimal exchange of information between hospitals, establishing second-opinion strategies according to clinical practice guidelines that immediately benefitted patients.<\/li>\n<li>As such, we also encouraged the movement of patients between hospitals in a coordinated way, avoiding the physical movement of biological material, with fewer delays and courier costs and ensuring preservation.<\/li>\n<li>We aimed to make more efficient use of the existing critical mass in terms of prevalent, complex, infrequent, and difficult diseases and guaranteeing equity among hospitals, regardless of size and geographical location, with the end-goal of organizing references for pathologies and territories.<\/li><\/ul>\n<p>From a technological standpoint, innovation also occurred. We stored all images using DICOM standards in SIMDCAT, a unified system used by the SISCAT network of entities to preserve digital medical images, provide digital services and resources based on the same software architecture, and make digital medical images accessible. This repository can be used independently by different viewers and is also independent of the scanning system. The transformation of the laboratory information system and all IT infrastructure is key in this type of project.\n<\/p><p>In addition, from the technological point of view, we aimed to achieve an improvement in algorithms for the quantification of immunohistochemical biomarkers and for the assessment of <i>in situ<\/i> hybridization. In the future, we hope to develop AI algorithms with ML and DL in order to recognize patterns and segment tumor areas. We need to look for tools that help pathologists do their jobs, with AI algorithms developed by our researchers. We produced an image repository large enough for this aim. AI optimizes the reproducibility of diagnoses. The boom in AI will involve significant changes in the way pathologists work in the coming years.\n<\/p><p>All things considered, it is important to seek a digital pathology system and, therefore, a manufacturer and a distributor that adapt to the real needs of each particular case. In the DigiPatICS project, we looked for a complete holistic solution for our pathology departments. As shown, it was very difficult to compare products according to data sheets exclusively, and it was laborious to define a digital pathology project for all technical and functional implications.\n<\/p><p>The growing enthusiasm for digital pathology and the new possibilities AI offers indicate an emerging revolution in pathology that will change our way of working. However, for broad adoption, an integrative approach of digital pathology across clinicians, pathologists, LISs, viewers, hardware, research, and teaching is imperative. Digital pathology must simplify our workflows and not add complexity. Vast repositories of diagnosed images will allow us to make great strides in this direction. With our solution meeting these needs, we hope to inspire other pathologists and to provide useful guidance for their successful digital transformations.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>The DigiPatICS project aimed to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of eight hospitals, incorporating 168 pathologists and over one million slides each year. After careful planning, implementation was carried out simultaneously for all the pathologists in each institution. A digital pathology system needed to be integrated with all health information systems, including electronic medical records. Teleconsultation, teaching platforms, fluorescence, and cytology were taken into account. The digital transformation of a pathology department represented a technological, organizational, and functional challenge. It provided an effective and safe diagnostic tool with clear benefits for diagnosis quality and patient safety.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The authors thank over 250 people who were directly involved in making the DigiPatICS project a reality, including pathology laboratory teams, administration teams, artificial intelligence teams, network and IT teams, the SIMDCAT integration team, technical support, infrastructure teams, programmers, and logistics teams.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Conceptualization, P.L.-G. and J.T.-S.; methodology, P.L.-G., J.T.-S., L.d.H. and E.B.; writing\u2014original draft preparation, J.T.-S.; writing\u2014review and editing, P.L.-G., J.T.-S., L.d.H., E.B., M.R.A., J.C.V., F.M., J.R.C., C.G. and X.M.-G.; supervision, L.d.H., E.B., M.A., J.C.V., M.R.A., E.L.-B., P.L.F., J.L.M., L.P., R.B., S.M., S.R.y.C. and X.M.-G.; project administration, L.d.H., E.B. and M.A.; funding acquisition, L.d.H., M.A., S.R.y.C. and X.M.-G. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This project was funded by European Regional Development Funds, Programa operatiu FEDER de Catalunya 2014\u20132020 and SA18-014623 DIGIPATICS. UPC activity in this project was partially supported by PID2020-116907RB-I00 and funded by MCIN\/AEI\/10.13039\/501100011033.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_availability_statement\">Data availability statement<\/span><\/h3>\n<p>All data generated or analyzed during this study are included in the article.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/ics.gencat.cat\/es\/lics\/\" target=\"_blank\">\"El ICS\"<\/a>. Generalitat de Catalunya, Institut Catal\u00e0 de la Salut<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/ics.gencat.cat\/es\/lics\/\" target=\"_blank\">http:\/\/ics.gencat.cat\/es\/lics\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=El+ICS&rft.atitle=&rft.pub=Generalitat+de+Catalunya%2C+Institut+Catal%C3%A0+de+la+Salut&rft_id=http%3A%2F%2Fics.gencat.cat%2Fes%2Flics%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-2\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-2\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sch\u00fcffler, Peter J; Geneslaw, Luke; Yarlagadda, D Vijay K; Hanna, Matthew G; Samboy, Jennifer; Stamelos, Evangelos; Vanderbilt, Chad; Philip, John <i>et al.<\/i> (13 August 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jamia\/article\/28\/9\/1874\/6321440\" target=\"_blank\">\"Integrated digital pathology at scale: A solution for clinical diagnostics and cancer research at a large academic medical center\"<\/a> (in en). <i>Journal of the American Medical Informatics Association<\/i> <b>28<\/b> (9): 1874\u20131884. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fjamia%2Focab085\" target=\"_blank\">10.1093\/jamia\/ocab085<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1527-974X\" target=\"_blank\">1527-974X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8344580\/\" target=\"_blank\">PMC8344580<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34260720\" target=\"_blank\">34260720<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jamia\/article\/28\/9\/1874\/6321440\" target=\"_blank\">https:\/\/academic.oup.com\/jamia\/article\/28\/9\/1874\/6321440<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Integrated+digital+pathology+at+scale%3A+A+solution+for+clinical+diagnostics+and+cancer+research+at+a+large+academic+medical+center&rft.jtitle=Journal+of+the+American+Medical+Informatics+Association&rft.aulast=Sch%C3%BCffler&rft.aufirst=Peter+J&rft.au=Sch%C3%BCffler%2C%26%2332%3BPeter+J&rft.au=Geneslaw%2C%26%2332%3BLuke&rft.au=Yarlagadda%2C%26%2332%3BD+Vijay+K&rft.au=Hanna%2C%26%2332%3BMatthew+G&rft.au=Samboy%2C%26%2332%3BJennifer&rft.au=Stamelos%2C%26%2332%3BEvangelos&rft.au=Vanderbilt%2C%26%2332%3BChad&rft.au=Philip%2C%26%2332%3BJohn&rft.au=Jean%2C%26%2332%3BMarc-Henri&rft.date=13+August+2021&rft.volume=28&rft.issue=9&rft.pages=1874%E2%80%931884&rft_id=info:doi\/10.1093%2Fjamia%2Focab085&rft.issn=1527-974X&rft_id=info:pmc\/PMC8344580&rft_id=info:pmid\/34260720&rft_id=https%3A%2F%2Facademic.oup.com%2Fjamia%2Farticle%2F28%2F9%2F1874%2F6321440&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-3\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_3-0\">3.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_3-1\">3.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Fraggetta, Filippo; Caputo, Alessandro; Guglielmino, Rosa; Pellegrino, Maria Giovanna; Runza, Giampaolo; L'Imperio, Vincenzo (16 October 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1916\" target=\"_blank\">\"A Survival Guide for the Rapid Transition to a Fully Digital Workflow: The \u201cCaltagirone Example\u201d\"<\/a> (in en). <i>Diagnostics<\/i> <b>11<\/b> (10): 1916. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fdiagnostics11101916\" target=\"_blank\">10.3390\/diagnostics11101916<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2075-4418\" target=\"_blank\">2075-4418<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8534326\/\" target=\"_blank\">PMC8534326<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34679614\" target=\"_blank\">34679614<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1916\" target=\"_blank\">https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1916<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Survival+Guide+for+the+Rapid+Transition+to+a+Fully+Digital+Workflow%3A+The+%E2%80%9CCaltagirone+Example%E2%80%9D&rft.jtitle=Diagnostics&rft.aulast=Fraggetta&rft.aufirst=Filippo&rft.au=Fraggetta%2C%26%2332%3BFilippo&rft.au=Caputo%2C%26%2332%3BAlessandro&rft.au=Guglielmino%2C%26%2332%3BRosa&rft.au=Pellegrino%2C%26%2332%3BMaria+Giovanna&rft.au=Runza%2C%26%2332%3BGiampaolo&rft.au=L%27Imperio%2C%26%2332%3BVincenzo&rft.date=16+October+2021&rft.volume=11&rft.issue=10&rft.pages=1916&rft_id=info:doi\/10.3390%2Fdiagnostics11101916&rft.issn=2075-4418&rft_id=info:pmc\/PMC8534326&rft_id=info:pmid\/34679614&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2075-4418%2F11%2F10%2F1916&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-4\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_4-0\">4.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-1\">4.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Eloy, Catarina; Vale, Jo\u00e3o; Curado, M\u00f3nica; Pol\u00f3nia, Ant\u00f3nio; Campelos, Sofia; Caramelo, Ana; Sousa, Rui; Sobrinho-Sim\u00f5es, Manuel (15 November 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2111\" target=\"_blank\">\"Digital Pathology Workflow Implementation at IPATIMUP\"<\/a> (in en). <i>Diagnostics<\/i> <b>11<\/b> (11): 2111. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fdiagnostics11112111\" target=\"_blank\">10.3390\/diagnostics11112111<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2075-4418\" target=\"_blank\">2075-4418<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8620597\/\" target=\"_blank\">PMC8620597<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34829458\" target=\"_blank\">34829458<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2111\" target=\"_blank\">https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2111<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+Pathology+Workflow+Implementation+at+IPATIMUP&rft.jtitle=Diagnostics&rft.aulast=Eloy&rft.aufirst=Catarina&rft.au=Eloy%2C%26%2332%3BCatarina&rft.au=Vale%2C%26%2332%3BJo%C3%A3o&rft.au=Curado%2C%26%2332%3BM%C3%B3nica&rft.au=Pol%C3%B3nia%2C%26%2332%3BAnt%C3%B3nio&rft.au=Campelos%2C%26%2332%3BSofia&rft.au=Caramelo%2C%26%2332%3BAna&rft.au=Sousa%2C%26%2332%3BRui&rft.au=Sobrinho-Sim%C3%B5es%2C%26%2332%3BManuel&rft.date=15+November+2021&rft.volume=11&rft.issue=11&rft.pages=2111&rft_id=info:doi\/10.3390%2Fdiagnostics11112111&rft.issn=2075-4418&rft_id=info:pmc\/PMC8620597&rft_id=info:pmid\/34829458&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2075-4418%2F11%2F11%2F2111&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-5\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-5\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Retamero, Juan Antonio; Aneiros-Fernandez, Jose; del Moral, Raimundo G. (1 February 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/144\/2\/221\/433661\/Complete-Digital-Pathology-for-Routine\" target=\"_blank\">\"Complete Digital Pathology for Routine Histopathology Diagnosis in a Multicenter Hospital Network\"<\/a> (in en). <i>Archives of Pathology & Laboratory Medicine<\/i> <b>144<\/b> (2): 221\u2013228. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2018-0541-OA\" target=\"_blank\">10.5858\/arpa.2018-0541-OA<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-9985\" target=\"_blank\">0003-9985<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/144\/2\/221\/433661\/Complete-Digital-Pathology-for-Routine\" target=\"_blank\">http:\/\/meridian.allenpress.com\/aplm\/article\/144\/2\/221\/433661\/Complete-Digital-Pathology-for-Routine<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Complete+Digital+Pathology+for+Routine+Histopathology+Diagnosis+in+a+Multicenter+Hospital+Network&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Retamero&rft.aufirst=Juan+Antonio&rft.au=Retamero%2C%26%2332%3BJuan+Antonio&rft.au=Aneiros-Fernandez%2C%26%2332%3BJose&rft.au=del+Moral%2C%26%2332%3BRaimundo+G.&rft.date=1+February+2020&rft.volume=144&rft.issue=2&rft.pages=221%E2%80%93228&rft_id=info:doi\/10.5858%2Farpa.2018-0541-OA&rft.issn=0003-9985&rft_id=http%3A%2F%2Fmeridian.allenpress.com%2Faplm%2Farticle%2F144%2F2%2F221%2F433661%2FComplete-Digital-Pathology-for-Routine&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-6\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-6\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hanna, Matthew G; Pantanowitz, Liron; Evans, Andrew J (1 July 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2015-202914\" target=\"_blank\">\"Overview of contemporary guidelines in digital pathology: what is available in 2015 and what still needs to be addressed?\"<\/a> (in en). <i>Journal of Clinical Pathology<\/i> <b>68<\/b> (7): 499\u2013505. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjclinpath-2015-202914\" target=\"_blank\">10.1136\/jclinpath-2015-202914<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0021-9746\" target=\"_blank\">0021-9746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2015-202914\" target=\"_blank\">http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2015-202914<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Overview+of+contemporary+guidelines+in+digital+pathology%3A+what+is+available+in+2015+and+what+still+needs+to+be+addressed%3F&rft.jtitle=Journal+of+Clinical+Pathology&rft.aulast=Hanna&rft.aufirst=Matthew+G&rft.au=Hanna%2C%26%2332%3BMatthew+G&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Evans%2C%26%2332%3BAndrew+J&rft.date=1+July+2015&rft.volume=68&rft.issue=7&rft.pages=499%E2%80%93505&rft_id=info:doi\/10.1136%2Fjclinpath-2015-202914&rft.issn=0021-9746&rft_id=http%3A%2F%2Fjcp.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fjclinpath-2015-202914&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_7-0\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_7-1\">7.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Eloy, Catarina; Bychkov, Andrey; Pantanowitz, Liron; Fraggetta, Filippo; Bui, MarilynM; Fukuoka, Junya; Zerbe, Norman; Hassell, Lewis <i>et al.<\/i> (2021). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2021\/12\/1\/51\/332680\" target=\"_blank\">\"DPA\u2013ESDIP\u2013JSDP task force for worldwide adoption of digital pathology\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>12<\/b> (1): 51. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2Fjpi.jpi_65_21\" target=\"_blank\">10.4103\/jpi.jpi_65_21<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8721866\/\" target=\"_blank\">PMC8721866<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/35070480\" target=\"_blank\">35070480<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2021\/12\/1\/51\/332680\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2021\/12\/1\/51\/332680<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DPA%E2%80%93ESDIP%E2%80%93JSDP+task+force+for+worldwide+adoption+of+digital+pathology&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Eloy&rft.aufirst=Catarina&rft.au=Eloy%2C%26%2332%3BCatarina&rft.au=Bychkov%2C%26%2332%3BAndrey&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Fraggetta%2C%26%2332%3BFilippo&rft.au=Bui%2C%26%2332%3BMarilynM&rft.au=Fukuoka%2C%26%2332%3BJunya&rft.au=Zerbe%2C%26%2332%3BNorman&rft.au=Hassell%2C%26%2332%3BLewis&rft.au=Parwani%2C%26%2332%3BAnil&rft.date=2021&rft.volume=12&rft.issue=1&rft.pages=51&rft_id=info:doi\/10.4103%2Fjpi.jpi_65_21&rft.issn=2153-3539&rft_id=info:pmc\/PMC8721866&rft_id=info:pmid\/35070480&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2021%2F12%2F1%2F51%2F332680&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-8\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-8\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Fraggetta, Filippo; L\u2019Imperio, Vincenzo; Ameisen, David; Carvalho, Rita; Leh, Sabine; Kiehl, Tim-Rasmus; Serbanescu, Mircea; Racoceanu, Daniel <i>et al.<\/i> (22 November 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2167\" target=\"_blank\">\"Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)\"<\/a> (in en). <i>Diagnostics<\/i> <b>11<\/b> (11): 2167. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fdiagnostics11112167\" target=\"_blank\">10.3390\/diagnostics11112167<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2075-4418\" target=\"_blank\">2075-4418<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8623219\/\" target=\"_blank\">PMC8623219<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34829514\" target=\"_blank\">34829514<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2167\" target=\"_blank\">https:\/\/www.mdpi.com\/2075-4418\/11\/11\/2167<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Best+Practice+Recommendations+for+the+Implementation+of+a+Digital+Pathology+Workflow+in+the+Anatomic+Pathology+Laboratory+by+the+European+Society+of+Digital+and+Integrative+Pathology+%28ESDIP%29&rft.jtitle=Diagnostics&rft.aulast=Fraggetta&rft.aufirst=Filippo&rft.au=Fraggetta%2C%26%2332%3BFilippo&rft.au=L%E2%80%99Imperio%2C%26%2332%3BVincenzo&rft.au=Ameisen%2C%26%2332%3BDavid&rft.au=Carvalho%2C%26%2332%3BRita&rft.au=Leh%2C%26%2332%3BSabine&rft.au=Kiehl%2C%26%2332%3BTim-Rasmus&rft.au=Serbanescu%2C%26%2332%3BMircea&rft.au=Racoceanu%2C%26%2332%3BDaniel&rft.au=Della+Mea%2C%26%2332%3BVincenzo&rft.date=22+November+2021&rft.volume=11&rft.issue=11&rft.pages=2167&rft_id=info:doi\/10.3390%2Fdiagnostics11112167&rft.issn=2075-4418&rft_id=info:pmc\/PMC8623219&rft_id=info:pmid\/34829514&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2075-4418%2F11%2F11%2F2167&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_9-0\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_9-1\">9.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chong, Thomas; Palma-Diaz, MFernando; Fisher, Craig; Gui, Dorina; Ostrzega, NoraL; Sempa, Geoffrey; Sisk, AnthonyE; Valasek, Mark <i>et al.<\/i> (2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/31\/268078\" target=\"_blank\">\"The California Telepathology Service: UCLA's experience in deploying a regional digital pathology subspecialty consultation network\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>10<\/b> (1): 31. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2Fjpi.jpi_22_19\" target=\"_blank\">10.4103\/jpi.jpi_22_19<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6788184\/\" target=\"_blank\">PMC6788184<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31620310\" target=\"_blank\">31620310<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/31\/268078\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/31\/268078<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+California+Telepathology+Service%3A+UCLA%27s+experience+in+deploying+a+regional+digital+pathology+subspecialty+consultation+network&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Chong&rft.aufirst=Thomas&rft.au=Chong%2C%26%2332%3BThomas&rft.au=Palma-Diaz%2C%26%2332%3BMFernando&rft.au=Fisher%2C%26%2332%3BCraig&rft.au=Gui%2C%26%2332%3BDorina&rft.au=Ostrzega%2C%26%2332%3BNoraL&rft.au=Sempa%2C%26%2332%3BGeoffrey&rft.au=Sisk%2C%26%2332%3BAnthonyE&rft.au=Valasek%2C%26%2332%3BMark&rft.au=Wang%2C%26%2332%3BBeverlyY&rft.date=2019&rft.volume=10&rft.issue=1&rft.pages=31&rft_id=info:doi\/10.4103%2Fjpi.jpi_22_19&rft.issn=2153-3539&rft_id=info:pmc\/PMC6788184&rft_id=info:pmid\/31620310&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2019%2F10%2F1%2F31%2F268078&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Williams, Bethany Jill; Treanor, Darren (1 July 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-206319\" target=\"_blank\">\"Practical guide to training and validation for primary diagnosis with digital pathology\"<\/a> (in en). <i>Journal of Clinical Pathology<\/i> <b>73<\/b> (7): 418\u2013422. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjclinpath-2019-206319\" target=\"_blank\">10.1136\/jclinpath-2019-206319<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0021-9746\" target=\"_blank\">0021-9746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-206319\" target=\"_blank\">http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-206319<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Practical+guide+to+training+and+validation+for+primary+diagnosis+with+digital+pathology&rft.jtitle=Journal+of+Clinical+Pathology&rft.aulast=Williams&rft.aufirst=Bethany+Jill&rft.au=Williams%2C%26%2332%3BBethany+Jill&rft.au=Treanor%2C%26%2332%3BDarren&rft.date=1+July+2020&rft.volume=73&rft.issue=7&rft.pages=418%E2%80%93422&rft_id=info:doi\/10.1136%2Fjclinpath-2019-206319&rft.issn=0021-9746&rft_id=http%3A%2F%2Fjcp.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fjclinpath-2019-206319&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mukhopadhyay, Sanjay; Feldman, Michael D.; Abels, Esther; Ashfaq, Raheela; Beltaifa, Senda; Cacciabeve, Nicolas G.; Cathro, Helen P.; Cheng, Liang <i>et al.<\/i> (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/journals.lww.com\/00000478-201801000-00006\" target=\"_blank\">\"Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)\"<\/a> (in en). <i>American Journal of Surgical Pathology<\/i> <b>42<\/b> (1): 39\u201352. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1097%2FPAS.0000000000000948\" target=\"_blank\">10.1097\/PAS.0000000000000948<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0147-5185\" target=\"_blank\">0147-5185<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5737464\/\" target=\"_blank\">PMC5737464<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28961557\" target=\"_blank\">28961557<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/journals.lww.com\/00000478-201801000-00006\" target=\"_blank\">https:\/\/journals.lww.com\/00000478-201801000-00006<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole+Slide+Imaging+Versus+Microscopy+for+Primary+Diagnosis+in+Surgical+Pathology%3A+A+Multicenter+Blinded+Randomized+Noninferiority+Study+of+1992+Cases+%28Pivotal+Study%29&rft.jtitle=American+Journal+of+Surgical+Pathology&rft.aulast=Mukhopadhyay&rft.aufirst=Sanjay&rft.au=Mukhopadhyay%2C%26%2332%3BSanjay&rft.au=Feldman%2C%26%2332%3BMichael+D.&rft.au=Abels%2C%26%2332%3BEsther&rft.au=Ashfaq%2C%26%2332%3BRaheela&rft.au=Beltaifa%2C%26%2332%3BSenda&rft.au=Cacciabeve%2C%26%2332%3BNicolas+G.&rft.au=Cathro%2C%26%2332%3BHelen+P.&rft.au=Cheng%2C%26%2332%3BLiang&rft.au=Cooper%2C%26%2332%3BKumarasen&rft.date=1+January+2018&rft.volume=42&rft.issue=1&rft.pages=39%E2%80%9352&rft_id=info:doi\/10.1097%2FPAS.0000000000000948&rft.issn=0147-5185&rft_id=info:pmc\/PMC5737464&rft_id=info:pmid\/28961557&rft_id=https%3A%2F%2Fjournals.lww.com%2F00000478-201801000-00006&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Borowsky, Alexander D.; Glassy, Eric F.; Wallace, William Dean; Kallichanda, Nathash S.; Behling, Cynthia A.; Miller, Dylan V.; Oswal, Hemlata N.; Feddersen, Richard M. <i>et al.<\/i> (1 October 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/144\/10\/1245\/427502\/Digital-Whole-Slide-Imaging-Compared-With-Light\" target=\"_blank\">\"Digital Whole Slide Imaging Compared With Light Microscopy for Primary Diagnosis in Surgical Pathology\"<\/a> (in en). <i>Archives of Pathology & Laboratory Medicine<\/i> <b>144<\/b> (10): 1245\u20131253. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2019-0569-OA\" target=\"_blank\">10.5858\/arpa.2019-0569-OA<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1543-2165\" target=\"_blank\">1543-2165<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/144\/10\/1245\/427502\/Digital-Whole-Slide-Imaging-Compared-With-Light\" target=\"_blank\">http:\/\/meridian.allenpress.com\/aplm\/article\/144\/10\/1245\/427502\/Digital-Whole-Slide-Imaging-Compared-With-Light<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+Whole+Slide+Imaging+Compared+With+Light+Microscopy+for+Primary+Diagnosis+in+Surgical+Pathology&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Borowsky&rft.aufirst=Alexander+D.&rft.au=Borowsky%2C%26%2332%3BAlexander+D.&rft.au=Glassy%2C%26%2332%3BEric+F.&rft.au=Wallace%2C%26%2332%3BWilliam+Dean&rft.au=Kallichanda%2C%26%2332%3BNathash+S.&rft.au=Behling%2C%26%2332%3BCynthia+A.&rft.au=Miller%2C%26%2332%3BDylan+V.&rft.au=Oswal%2C%26%2332%3BHemlata+N.&rft.au=Feddersen%2C%26%2332%3BRichard+M.&rft.au=Bakhtar%2C%26%2332%3BOmid+R.&rft.date=1+October+2020&rft.volume=144&rft.issue=10&rft.pages=1245%E2%80%931253&rft_id=info:doi\/10.5858%2Farpa.2019-0569-OA&rft.issn=1543-2165&rft_id=http%3A%2F%2Fmeridian.allenpress.com%2Faplm%2Farticle%2F144%2F10%2F1245%2F427502%2FDigital-Whole-Slide-Imaging-Compared-With-Light&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Montezuma, Diana; Monteiro, Ana; Fraga, Jo\u00e3o; Ribeiro, Liliana; Gon\u00e7alves, Sofia; Tavares, Andr\u00e9; Monteiro, Jo\u00e3o; Macedo-Pinto, Isabel (18 February 2022). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/2075-4418\/12\/2\/529\" target=\"_blank\">\"Digital Pathology Implementation in Private Practice: Specific Challenges and Opportunities\"<\/a> (in en). <i>Diagnostics<\/i> <b>12<\/b> (2): 529. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fdiagnostics12020529\" target=\"_blank\">10.3390\/diagnostics12020529<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2075-4418\" target=\"_blank\">2075-4418<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8871027\/\" target=\"_blank\">PMC8871027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/35204617\" target=\"_blank\">35204617<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/2075-4418\/12\/2\/529\" target=\"_blank\">https:\/\/www.mdpi.com\/2075-4418\/12\/2\/529<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+Pathology+Implementation+in+Private+Practice%3A+Specific+Challenges+and+Opportunities&rft.jtitle=Diagnostics&rft.aulast=Montezuma&rft.aufirst=Diana&rft.au=Montezuma%2C%26%2332%3BDiana&rft.au=Monteiro%2C%26%2332%3BAna&rft.au=Fraga%2C%26%2332%3BJo%C3%A3o&rft.au=Ribeiro%2C%26%2332%3BLiliana&rft.au=Gon%C3%A7alves%2C%26%2332%3BSofia&rft.au=Tavares%2C%26%2332%3BAndr%C3%A9&rft.au=Monteiro%2C%26%2332%3BJo%C3%A3o&rft.au=Macedo-Pinto%2C%26%2332%3BIsabel&rft.date=18+February+2022&rft.volume=12&rft.issue=2&rft.pages=529&rft_id=info:doi\/10.3390%2Fdiagnostics12020529&rft.issn=2075-4418&rft_id=info:pmc\/PMC8871027&rft_id=info:pmid\/35204617&rft_id=https%3A%2F%2Fwww.mdpi.com%2F2075-4418%2F12%2F2%2F529&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Girolami, Ilaria; Pantanowitz, Liron; Marletta, Stefano; Brunelli, Matteo; Mescoli, Claudia; Parisi, Alice; Barresi, Valeria; Parwani, Anil <i>et al.<\/i> (1 January 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22195\" target=\"_blank\">\"Diagnostic concordance between whole slide imaging and conventional light microscopy in cytopathology: A systematic review\"<\/a> (in en). <i>Cancer Cytopathology<\/i> <b>128<\/b> (1): 17\u201328. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fcncy.22195\" target=\"_blank\">10.1002\/cncy.22195<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1934-662X\" target=\"_blank\">1934-662X<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22195\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22195<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Diagnostic+concordance+between+whole+slide+imaging+and+conventional+light+microscopy+in+cytopathology%3A+A+systematic+review&rft.jtitle=Cancer+Cytopathology&rft.aulast=Girolami&rft.aufirst=Ilaria&rft.au=Girolami%2C%26%2332%3BIlaria&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Marletta%2C%26%2332%3BStefano&rft.au=Brunelli%2C%26%2332%3BMatteo&rft.au=Mescoli%2C%26%2332%3BClaudia&rft.au=Parisi%2C%26%2332%3BAlice&rft.au=Barresi%2C%26%2332%3BValeria&rft.au=Parwani%2C%26%2332%3BAnil&rft.au=Neil%2C%26%2332%3BDesley&rft.date=1+January+2020&rft.volume=128&rft.issue=1&rft.pages=17%E2%80%9328&rft_id=info:doi\/10.1002%2Fcncy.22195&rft.issn=1934-662X&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fcncy.22195&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Goacher, Edward; Randell, Rebecca; Williams, Bethany; Treanor, Darren (1 January 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/141\/1\/151\/65950\/The-Diagnostic-Concordance-of-Whole-Slide-Imaging\" target=\"_blank\">\"The Diagnostic Concordance of Whole Slide Imaging and Light Microscopy: A Systematic Review\"<\/a> (in en). <i>Archives of Pathology & Laboratory Medicine<\/i> <b>141<\/b> (1): 151\u2013161. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2016-0025-RA\" target=\"_blank\">10.5858\/arpa.2016-0025-RA<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-9985\" target=\"_blank\">0003-9985<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/meridian.allenpress.com\/aplm\/article\/141\/1\/151\/65950\/The-Diagnostic-Concordance-of-Whole-Slide-Imaging\" target=\"_blank\">http:\/\/meridian.allenpress.com\/aplm\/article\/141\/1\/151\/65950\/The-Diagnostic-Concordance-of-Whole-Slide-Imaging<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Diagnostic+Concordance+of+Whole+Slide+Imaging+and+Light+Microscopy%3A+A+Systematic+Review&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Goacher&rft.aufirst=Edward&rft.au=Goacher%2C%26%2332%3BEdward&rft.au=Randell%2C%26%2332%3BRebecca&rft.au=Williams%2C%26%2332%3BBethany&rft.au=Treanor%2C%26%2332%3BDarren&rft.date=1+January+2017&rft.volume=141&rft.issue=1&rft.pages=151%E2%80%93161&rft_id=info:doi\/10.5858%2Farpa.2016-0025-RA&rft.issn=0003-9985&rft_id=http%3A%2F%2Fmeridian.allenpress.com%2Faplm%2Farticle%2F141%2F1%2F151%2F65950%2FThe-Diagnostic-Concordance-of-Whole-Slide-Imaging&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-16\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Houghton, Joseph P; Ervine, Aaron J; Kenny, Sarah L; Kelly, Paul J; Napier, Seamus S; McCluggage, W Glenn; Walsh, Maureen Y; Hamilton, Peter W (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2014-202491\" target=\"_blank\">\"Concordance between digital pathology and light microscopy in general surgical pathology: a pilot study of 100 cases\"<\/a> (in en). <i>Journal of Clinical Pathology<\/i> <b>67<\/b> (12): 1052\u20131055. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjclinpath-2014-202491\" target=\"_blank\">10.1136\/jclinpath-2014-202491<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0021-9746\" target=\"_blank\">0021-9746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2014-202491\" target=\"_blank\">http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2014-202491<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Concordance+between+digital+pathology+and+light+microscopy+in+general+surgical+pathology%3A+a+pilot+study+of+100+cases&rft.jtitle=Journal+of+Clinical+Pathology&rft.aulast=Houghton&rft.aufirst=Joseph+P&rft.au=Houghton%2C%26%2332%3BJoseph+P&rft.au=Ervine%2C%26%2332%3BAaron+J&rft.au=Kenny%2C%26%2332%3BSarah+L&rft.au=Kelly%2C%26%2332%3BPaul+J&rft.au=Napier%2C%26%2332%3BSeamus+S&rft.au=McCluggage%2C%26%2332%3BW+Glenn&rft.au=Walsh%2C%26%2332%3BMaureen+Y&rft.au=Hamilton%2C%26%2332%3BPeter+W&rft.date=1+December+2014&rft.volume=67&rft.issue=12&rft.pages=1052%E2%80%931055&rft_id=info:doi\/10.1136%2Fjclinpath-2014-202491&rft.issn=0021-9746&rft_id=http%3A%2F%2Fjcp.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fjclinpath-2014-202491&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Elmore, JoannG; Longton, GaryM; Pepe, MargaretS; Carney, PatriciaA; Nelson, HeidiD; Allison, KimberlyH; Geller, BertaM; Onega, Tracy <i>et al.<\/i> (2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2017\/8\/1\/12\/201920\" target=\"_blank\">\"A randomized study comparing digital imaging to traditional glass slide microscopy for breast biopsy and cancer diagnosis\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>8<\/b> (1): 12. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2153-3539.201920\" target=\"_blank\">10.4103\/2153-3539.201920<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5364740\/\" target=\"_blank\">PMC5364740<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28382226\" target=\"_blank\">28382226<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2017\/8\/1\/12\/201920\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2017\/8\/1\/12\/201920<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+randomized+study+comparing+digital+imaging+to+traditional+glass+slide+microscopy+for+breast+biopsy+and+cancer+diagnosis&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Elmore&rft.aufirst=JoannG&rft.au=Elmore%2C%26%2332%3BJoannG&rft.au=Longton%2C%26%2332%3BGaryM&rft.au=Pepe%2C%26%2332%3BMargaretS&rft.au=Carney%2C%26%2332%3BPatriciaA&rft.au=Nelson%2C%26%2332%3BHeidiD&rft.au=Allison%2C%26%2332%3BKimberlyH&rft.au=Geller%2C%26%2332%3BBertaM&rft.au=Onega%2C%26%2332%3BTracy&rft.au=Tosteson%2C%26%2332%3BAnnaN.+A&rft.date=2017&rft.volume=8&rft.issue=1&rft.pages=12&rft_id=info:doi\/10.4103%2F2153-3539.201920&rft.issn=2153-3539&rft_id=info:pmc\/PMC5364740&rft_id=info:pmid\/28382226&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2017%2F8%2F1%2F12%2F201920&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tabata, Kazuhiro; Mori, Ichiro; Sasaki, Takeshi; Itoh, Tomoo; Shiraishi, Taizo; Yoshimi, Naoki; Maeda, Ichiro; Harada, Oi <i>et al.<\/i> (1 November 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.12590\" target=\"_blank\">\"Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes: Validating whole-slide imaging in Japan\"<\/a> (in en). <i>Pathology International<\/i> <b>67<\/b> (11): 547\u2013554. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fpin.12590\" target=\"_blank\">10.1111\/pin.12590<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.12590\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.12590<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole-slide+imaging+at+primary+pathological+diagnosis%3A+Validation+of+whole-slide+imaging-based+primary+pathological+diagnosis+at+twelve+Japanese+academic+institutes%3A+Validating+whole-slide+imaging+in+Japan&rft.jtitle=Pathology+International&rft.aulast=Tabata&rft.aufirst=Kazuhiro&rft.au=Tabata%2C%26%2332%3BKazuhiro&rft.au=Mori%2C%26%2332%3BIchiro&rft.au=Sasaki%2C%26%2332%3BTakeshi&rft.au=Itoh%2C%26%2332%3BTomoo&rft.au=Shiraishi%2C%26%2332%3BTaizo&rft.au=Yoshimi%2C%26%2332%3BNaoki&rft.au=Maeda%2C%26%2332%3BIchiro&rft.au=Harada%2C%26%2332%3BOi&rft.au=Taniyama%2C%26%2332%3BKiyomi&rft.date=1+November+2017&rft.volume=67&rft.issue=11&rft.pages=547%E2%80%93554&rft_id=info:doi\/10.1111%2Fpin.12590&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fpin.12590&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-19\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-19\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Williams, Bethany Jill; Bottoms, David; Treanor, Darren (1 December 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2017-204644\" target=\"_blank\">\"Future-proofing pathology: the case for clinical adoption of digital pathology\"<\/a> (in en). <i>Journal of Clinical Pathology<\/i> <b>70<\/b> (12): 1010\u20131018. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjclinpath-2017-204644\" target=\"_blank\">10.1136\/jclinpath-2017-204644<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0021-9746\" target=\"_blank\">0021-9746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2017-204644\" target=\"_blank\">http:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2017-204644<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Future-proofing+pathology%3A+the+case+for+clinical+adoption+of+digital+pathology&rft.jtitle=Journal+of+Clinical+Pathology&rft.aulast=Williams&rft.aufirst=Bethany+Jill&rft.au=Williams%2C%26%2332%3BBethany+Jill&rft.au=Bottoms%2C%26%2332%3BDavid&rft.au=Treanor%2C%26%2332%3BDarren&rft.date=1+December+2017&rft.volume=70&rft.issue=12&rft.pages=1010%E2%80%931018&rft_id=info:doi\/10.1136%2Fjclinpath-2017-204644&rft.issn=0021-9746&rft_id=http%3A%2F%2Fjcp.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fjclinpath-2017-204644&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-20\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_20-0\">20.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_20-1\">20.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Garc\u00eda-Rojo, Marcial; De Mena, David; Muriel-Cueto, Pedro; Atienza-Cuevas, Lidia; Dom\u00ednguez-G\u00f3mez, Manuel; Bueno, Gloria (2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/2\/250754\" target=\"_blank\">\"New European union regulations related to whole slide image scanners and image analysis software\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>10<\/b> (1): 2. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2Fjpi.jpi_33_18\" target=\"_blank\">10.4103\/jpi.jpi_33_18<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6369630\/\" target=\"_blank\">PMC6369630<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30783546\" target=\"_blank\">30783546<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/2\/250754\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/2\/250754<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=New+European+union+regulations+related+to+whole+slide+image+scanners+and+image+analysis+software&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Garc%C3%ADa-Rojo&rft.aufirst=Marcial&rft.au=Garc%C3%ADa-Rojo%2C%26%2332%3BMarcial&rft.au=De+Mena%2C%26%2332%3BDavid&rft.au=Muriel-Cueto%2C%26%2332%3BPedro&rft.au=Atienza-Cuevas%2C%26%2332%3BLidia&rft.au=Dom%C3%ADnguez-G%C3%B3mez%2C%26%2332%3BManuel&rft.au=Bueno%2C%26%2332%3BGloria&rft.date=2019&rft.volume=10&rft.issue=1&rft.pages=2&rft_id=info:doi\/10.4103%2Fjpi.jpi_33_18&rft.issn=2153-3539&rft_id=info:pmc\/PMC6369630&rft_id=info:pmid\/30783546&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2019%2F10%2F1%2F2%2F250754&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pantanowitz, Liron; Sharma, Ashish; Carter, AlexisB; Kurc, Tahsin; Sussman, Alan; Saltz, Joel (2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2018\/9\/1\/40\/245903\" target=\"_blank\">\"Twenty years of digital pathology: An overview of the road travelled, what is on the horizon, and the emergence of vendor-neutral archives\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>9<\/b> (1): 40. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2Fjpi.jpi_69_18\" target=\"_blank\">10.4103\/jpi.jpi_69_18<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6289005\/\" target=\"_blank\">PMC6289005<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30607307\" target=\"_blank\">30607307<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2018\/9\/1\/40\/245903\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2018\/9\/1\/40\/245903<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Twenty+years+of+digital+pathology%3A+An+overview+of+the+road+travelled%2C+what+is+on+the+horizon%2C+and+the+emergence+of+vendor-neutral+archives&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Pantanowitz&rft.aufirst=Liron&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Sharma%2C%26%2332%3BAshish&rft.au=Carter%2C%26%2332%3BAlexisB&rft.au=Kurc%2C%26%2332%3BTahsin&rft.au=Sussman%2C%26%2332%3BAlan&rft.au=Saltz%2C%26%2332%3BJoel&rft.date=2018&rft.volume=9&rft.issue=1&rft.pages=40&rft_id=info:doi\/10.4103%2Fjpi.jpi_69_18&rft.issn=2153-3539&rft_id=info:pmc\/PMC6289005&rft_id=info:pmid\/30607307&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2018%2F9%2F1%2F40%2F245903&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ho, Jonhan; Kuzmishin, JohnA; Montalto, MichaelC; Pantanowitz, Liron; Parwani, AnilV; Stratman, Curtis; Ahlers, StefanM; Aridor, Orly <i>et al.<\/i> (2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2014\/5\/1\/33\/139714\" target=\"_blank\">\"Can digital pathology result in cost savings? A financial projection for digital pathology implementation at a large integrated health care organization\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>5<\/b> (1): 33. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2153-3539.139714\" target=\"_blank\">10.4103\/2153-3539.139714<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4168664\/\" target=\"_blank\">PMC4168664<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25250191\" target=\"_blank\">25250191<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2014\/5\/1\/33\/139714\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2014\/5\/1\/33\/139714<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Can+digital+pathology+result+in+cost+savings%3F+A+financial+projection+for+digital+pathology+implementation+at+a+large+integrated+health+care+organization&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Ho&rft.aufirst=Jonhan&rft.au=Ho%2C%26%2332%3BJonhan&rft.au=Kuzmishin%2C%26%2332%3BJohnA&rft.au=Montalto%2C%26%2332%3BMichaelC&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Parwani%2C%26%2332%3BAnilV&rft.au=Stratman%2C%26%2332%3BCurtis&rft.au=Ahlers%2C%26%2332%3BStefanM&rft.au=Aridor%2C%26%2332%3BOrly&rft.au=Fine%2C%26%2332%3BJeffreyL&rft.date=2014&rft.volume=5&rft.issue=1&rft.pages=33&rft_id=info:doi\/10.4103%2F2153-3539.139714&rft.issn=2153-3539&rft_id=info:pmc\/PMC4168664&rft_id=info:pmid\/25250191&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2014%2F5%2F1%2F33%2F139714&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Aeffner, Famke; Zarella, MarkD; Buchbinder, Nathan; Bui, MarilynM; Goodman, MatthewR; Hartman, DouglasJ; Lujan, GiovanniM; Molani, MariamA <i>et al.<\/i> (2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/9\/253721\" target=\"_blank\">\"Introduction to digital image analysis in whole-slide imaging: A white paper from the digital pathology association\"<\/a> (in en). <i>Journal of Pathology Informatics<\/i> <b>10<\/b> (1): 9. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2Fjpi.jpi_82_18\" target=\"_blank\">10.4103\/jpi.jpi_82_18<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2153-3539\" target=\"_blank\">2153-3539<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6437786\/\" target=\"_blank\">PMC6437786<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30984469\" target=\"_blank\">30984469<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/9\/253721\" target=\"_blank\">http:\/\/www.jpathinformatics.org\/text.asp?2019\/10\/1\/9\/253721<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Introduction+to+digital+image+analysis+in+whole-slide+imaging%3A+A+white+paper+from+the+digital+pathology+association&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Aeffner&rft.aufirst=Famke&rft.au=Aeffner%2C%26%2332%3BFamke&rft.au=Zarella%2C%26%2332%3BMarkD&rft.au=Buchbinder%2C%26%2332%3BNathan&rft.au=Bui%2C%26%2332%3BMarilynM&rft.au=Goodman%2C%26%2332%3BMatthewR&rft.au=Hartman%2C%26%2332%3BDouglasJ&rft.au=Lujan%2C%26%2332%3BGiovanniM&rft.au=Molani%2C%26%2332%3BMariamA&rft.au=Parwani%2C%26%2332%3BAnilV&rft.date=2019&rft.volume=10&rft.issue=1&rft.pages=9&rft_id=info:doi\/10.4103%2Fjpi.jpi_82_18&rft.issn=2153-3539&rft_id=info:pmc\/PMC6437786&rft_id=info:pmid\/30984469&rft_id=http%3A%2F%2Fwww.jpathinformatics.org%2Ftext.asp%3F2019%2F10%2F1%2F9%2F253721&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Abels, Esther; Pantanowitz, Liron; Aeffner, Famke; Zarella, Mark D; Laak, Jeroen; Bui, Marilyn M; Vemuri, Venkata NP; Parwani, Anil V <i>et al.<\/i> (1 November 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/path.5331\" target=\"_blank\">\"Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association\"<\/a> (in en). <i>The Journal of Pathology<\/i> <b>249<\/b> (3): 286\u2013294. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fpath.5331\" target=\"_blank\">10.1002\/path.5331<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0022-3417\" target=\"_blank\">0022-3417<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6852275\/\" target=\"_blank\">PMC6852275<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31355445\" target=\"_blank\">31355445<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/path.5331\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/path.5331<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Computational+pathology+definitions%2C+best+practices%2C+and+recommendations+for+regulatory+guidance%3A+a+white+paper+from+the+Digital+Pathology+Association&rft.jtitle=The+Journal+of+Pathology&rft.aulast=Abels&rft.aufirst=Esther&rft.au=Abels%2C%26%2332%3BEsther&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Aeffner%2C%26%2332%3BFamke&rft.au=Zarella%2C%26%2332%3BMark+D&rft.au=Laak%2C%26%2332%3BJeroen&rft.au=Bui%2C%26%2332%3BMarilyn+M&rft.au=Vemuri%2C%26%2332%3BVenkata+NP&rft.au=Parwani%2C%26%2332%3BAnil+V&rft.au=Gibbs%2C%26%2332%3BJeff&rft.date=1+November+2019&rft.volume=249&rft.issue=3&rft.pages=286%E2%80%93294&rft_id=info:doi\/10.1002%2Fpath.5331&rft.issn=0022-3417&rft_id=info:pmc\/PMC6852275&rft_id=info:pmid\/31355445&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fpath.5331&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ara\u00fajo, Anna Lu\u00edza Damaceno; Arboleda, Lady Paola Aristiz\u00e1bal; Palmier, Natalia Rangel; Fons\u00eaca, J\u00e9ssica Montenegro; de Pauli Paglioni, Mariana; Gomes-Silva, Wagner; Ribeiro, Ana Carolina Prado; Brand\u00e3o, Tha\u00eds Bianca <i>et al.<\/i> (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00428-018-02519-z\" target=\"_blank\">\"The performance of digital microscopy for primary diagnosis in human pathology: a systematic review\"<\/a> (in en). <i>Virchows Archiv<\/i> <b>474<\/b> (3): 269\u2013287. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00428-018-02519-z\" target=\"_blank\">10.1007\/s00428-018-02519-z<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0945-6317\" target=\"_blank\">0945-6317<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00428-018-02519-z\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00428-018-02519-z<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+performance+of+digital+microscopy+for+primary+diagnosis+in+human+pathology%3A+a+systematic+review&rft.jtitle=Virchows+Archiv&rft.aulast=Ara%C3%BAjo&rft.aufirst=Anna+Lu%C3%ADza+Damaceno&rft.au=Ara%C3%BAjo%2C%26%2332%3BAnna+Lu%C3%ADza+Damaceno&rft.au=Arboleda%2C%26%2332%3BLady+Paola+Aristiz%C3%A1bal&rft.au=Palmier%2C%26%2332%3BNatalia+Rangel&rft.au=Fons%C3%AAca%2C%26%2332%3BJ%C3%A9ssica+Montenegro&rft.au=de+Pauli+Paglioni%2C%26%2332%3BMariana&rft.au=Gomes-Silva%2C%26%2332%3BWagner&rft.au=Ribeiro%2C%26%2332%3BAna+Carolina+Prado&rft.au=Brand%C3%A3o%2C%26%2332%3BTha%C3%ADs+Bianca&rft.au=Simonato%2C%26%2332%3BLuciana+Estevam&rft.date=1+March+2019&rft.volume=474&rft.issue=3&rft.pages=269%E2%80%93287&rft_id=info:doi\/10.1007%2Fs00428-018-02519-z&rft.issn=0945-6317&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00428-018-02519-z&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-26\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hanna, Matthew G.; Reuter, Victor E.; Ardon, Orly; Kim, David; Sirintrapun, Sahussapont Joseph; Sch\u00fcffler, Peter J.; Busam, Klaus J.; Sauter, Jennifer L. <i>et al.<\/i> (1 November 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41379-020-0601-5\" target=\"_blank\">\"Validation of a digital pathology system including remote review during the COVID-19 pandemic\"<\/a> (in en). <i>Modern Pathology<\/i> <b>33<\/b> (11): 2115\u20132127. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41379-020-0601-5\" target=\"_blank\">10.1038\/s41379-020-0601-5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0893-3952\" target=\"_blank\">0893-3952<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7306935\/\" target=\"_blank\">PMC7306935<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32572154\" target=\"_blank\">32572154<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41379-020-0601-5\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41379-020-0601-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Validation+of+a+digital+pathology+system+including+remote+review+during+the+COVID-19+pandemic&rft.jtitle=Modern+Pathology&rft.aulast=Hanna&rft.aufirst=Matthew+G.&rft.au=Hanna%2C%26%2332%3BMatthew+G.&rft.au=Reuter%2C%26%2332%3BVictor+E.&rft.au=Ardon%2C%26%2332%3BOrly&rft.au=Kim%2C%26%2332%3BDavid&rft.au=Sirintrapun%2C%26%2332%3BSahussapont+Joseph&rft.au=Sch%C3%BCffler%2C%26%2332%3BPeter+J.&rft.au=Busam%2C%26%2332%3BKlaus+J.&rft.au=Sauter%2C%26%2332%3BJennifer+L.&rft.au=Brogi%2C%26%2332%3BEdi&rft.date=1+November+2020&rft.volume=33&rft.issue=11&rft.pages=2115%E2%80%932127&rft_id=info:doi\/10.1038%2Fs41379-020-0601-5&rft.issn=0893-3952&rft_id=info:pmc\/PMC7306935&rft_id=info:pmid\/32572154&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41379-020-0601-5&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alassiri, Ali; Almutrafi, Amna; Alsufiani, Fahd; Al Nehkilan, Atheer; Al Salim, Alaa; Musleh, Hesham; Aziz, Mohammad; Khalbuss, Walid (1 January 2020). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.annsaudimed.net\/doi\/10.5144\/0256-4947.2020.36\" target=\"_blank\">\"Whole slide imaging compared with light microscopy for primary diagnosis in surgical neuropathology: a validation study\"<\/a> (in en). <i>Annals of Saudi Medicine<\/i> <b>40<\/b> (1): 36\u201341. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5144%2F0256-4947.2020.36\" target=\"_blank\">10.5144\/0256-4947.2020.36<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0256-4947\" target=\"_blank\">0256-4947<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7012027\/\" target=\"_blank\">PMC7012027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32026707\" target=\"_blank\">32026707<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.annsaudimed.net\/doi\/10.5144\/0256-4947.2020.36\" target=\"_blank\">http:\/\/www.annsaudimed.net\/doi\/10.5144\/0256-4947.2020.36<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole+slide+imaging+compared+with+light+microscopy+for+primary+diagnosis+in+surgical+neuropathology%3A+a+validation+study&rft.jtitle=Annals+of+Saudi+Medicine&rft.aulast=Alassiri&rft.aufirst=Ali&rft.au=Alassiri%2C%26%2332%3BAli&rft.au=Almutrafi%2C%26%2332%3BAmna&rft.au=Alsufiani%2C%26%2332%3BFahd&rft.au=Al+Nehkilan%2C%26%2332%3BAtheer&rft.au=Al+Salim%2C%26%2332%3BAlaa&rft.au=Musleh%2C%26%2332%3BHesham&rft.au=Aziz%2C%26%2332%3BMohammad&rft.au=Khalbuss%2C%26%2332%3BWalid&rft.date=1+January+2020&rft.volume=40&rft.issue=1&rft.pages=36%E2%80%9341&rft_id=info:doi\/10.5144%2F0256-4947.2020.36&rft.issn=0256-4947&rft_id=info:pmc\/PMC7012027&rft_id=info:pmid\/32026707&rft_id=http%3A%2F%2Fwww.annsaudimed.net%2Fdoi%2F10.5144%2F0256-4947.2020.36&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-28\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-28\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rojo, Marcial Garc\u00eda (1 October 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1699885519300789\" target=\"_blank\">\"Inteligencia artificial en Anatom\u00eda Patol\u00f3gica\"<\/a> (in es). <i>Revista Espa\u00f1ola de Patolog\u00eda<\/i> <b>52<\/b> (4): 205\u2013207. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.patol.2019.09.001\" target=\"_blank\">10.1016\/j.patol.2019.09.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1699885519300789\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1699885519300789<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Inteligencia+artificial+en+Anatom%C3%ADa+Patol%C3%B3gica&rft.jtitle=Revista+Espa%C3%B1ola+de+Patolog%C3%ADa&rft.aulast=Rojo&rft.aufirst=Marcial+Garc%C3%ADa&rft.au=Rojo%2C%26%2332%3BMarcial+Garc%C3%ADa&rft.date=1+October+2019&rft.volume=52&rft.issue=4&rft.pages=205%E2%80%93207&rft_id=info:doi\/10.1016%2Fj.patol.2019.09.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1699885519300789&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-29\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Institut Catal\u00e0 de la Salut (ICS) (6 July 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/contractaciopublica.gencat.cat\/ecofin_pscp\/AppJava\/es_ES\/notice.pscp?mode=full&idDoc=63997703&reqCode=viewCn\" target=\"_blank\">\"Servei de digitalitzaci\u00f3 de proves diagn\u00f2stiques als hospitals de l'ICS\"<\/a>. <i>Contrataci\u00f3n P\u00fablica<\/i>. Generalitat de Catalu\u00f1a<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/contractaciopublica.gencat.cat\/ecofin_pscp\/AppJava\/es_ES\/notice.pscp?mode=full&idDoc=63997703&reqCode=viewCn\" target=\"_blank\">https:\/\/contractaciopublica.gencat.cat\/ecofin_pscp\/AppJava\/es_ES\/notice.pscp?mode=full&idDoc=63997703&reqCode=viewCn<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Servei+de+digitalitzaci%C3%B3+de+proves+diagn%C3%B2stiques+als+hospitals+de+l%27ICS&rft.atitle=Contrataci%C3%B3n+P%C3%BAblica&rft.aulast=Institut+Catal%C3%A0+de+la+Salut+%28ICS%29&rft.au=Institut+Catal%C3%A0+de+la+Salut+%28ICS%29&rft.date=6+July+2020&rft.pub=Generalitat+de+Catalu%C3%B1a&rft_id=https%3A%2F%2Fcontractaciopublica.gencat.cat%2Fecofin_pscp%2FAppJava%2Fes_ES%2Fnotice.pscp%3Fmode%3Dfull%26idDoc%3D63997703%26reqCode%3DviewCn&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Capitanio, A.; Dina, R. E.; Treanor, D. (1 August 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12554\" target=\"_blank\">\"Digital cytology: A short review of technical and methodological approaches and applications\"<\/a> (in en). <i>Cytopathology<\/i> <b>29<\/b> (4): 317\u2013325. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fcyt.12554\" target=\"_blank\">10.1111\/cyt.12554<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12554\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12554<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+cytology%3A+A+short+review+of+technical+and+methodological+approaches+and+applications&rft.jtitle=Cytopathology&rft.aulast=Capitanio&rft.aufirst=A.&rft.au=Capitanio%2C%26%2332%3BA.&rft.au=Dina%2C%26%2332%3BR.+E.&rft.au=Treanor%2C%26%2332%3BD.&rft.date=1+August+2018&rft.volume=29&rft.issue=4&rft.pages=317%E2%80%93325&rft_id=info:doi\/10.1111%2Fcyt.12554&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fcyt.12554&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pantanowitz, L.; Parwani, A. V.; Khalbuss, W. E. (1 April 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2303.2011.00852.x\" target=\"_blank\">\"Digital imaging for cytopathology: are we there yet?: Editorial\"<\/a> (in en). <i>Cytopathology<\/i> <b>22<\/b> (2): 73\u201374. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1365-2303.2011.00852.x\" target=\"_blank\">10.1111\/j.1365-2303.2011.00852.x<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2303.2011.00852.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2303.2011.00852.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+imaging+for+cytopathology%3A+are+we+there+yet%3F%3A+Editorial&rft.jtitle=Cytopathology&rft.aulast=Pantanowitz&rft.aufirst=L.&rft.au=Pantanowitz%2C%26%2332%3BL.&rft.au=Parwani%2C%26%2332%3BA.+V.&rft.au=Khalbuss%2C%26%2332%3BW.+E.&rft.date=1+April+2011&rft.volume=22&rft.issue=2&rft.pages=73%E2%80%9374&rft_id=info:doi\/10.1111%2Fj.1365-2303.2011.00852.x&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1365-2303.2011.00852.x&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-32\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Van Es, Simone L.; White, Vanessa; Ross, Jennifer; Greaves, Janelle; Gay, Stephanie; Holzhauser, Derek; Badrick, Tony (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12664\" target=\"_blank\">\"Digital cytopathology: A constant evolution (Comments on Capitanio et al. Digital cytology: A short review of technical and methodological approaches and applications)\"<\/a> (in en). <i>Cytopathology<\/i> <b>30<\/b> (2): 262\u2013263. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fcyt.12664\" target=\"_blank\">10.1111\/cyt.12664<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0956-5507\" target=\"_blank\">0956-5507<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12664\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12664<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+cytopathology%3A+A+constant+evolution+%28Comments+on+Capitanio+et+al.+Digital+cytology%3A+A+short+review+of+technical+and+methodological+approaches+and+applications%29&rft.jtitle=Cytopathology&rft.aulast=Van+Es&rft.aufirst=Simone+L.&rft.au=Van+Es%2C%26%2332%3BSimone+L.&rft.au=White%2C%26%2332%3BVanessa&rft.au=Ross%2C%26%2332%3BJennifer&rft.au=Greaves%2C%26%2332%3BJanelle&rft.au=Gay%2C%26%2332%3BStephanie&rft.au=Holzhauser%2C%26%2332%3BDerek&rft.au=Badrick%2C%26%2332%3BTony&rft.date=1+March+2019&rft.volume=30&rft.issue=2&rft.pages=262%E2%80%93263&rft_id=info:doi\/10.1111%2Fcyt.12664&rft.issn=0956-5507&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fcyt.12664&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-33\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-33\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Eccher, Albino; Girolami, Ilaria (1 September 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12806\" target=\"_blank\">\"Current state of whole slide imaging use in cytopathology: Pros and pitfalls\"<\/a> (in en). <i>Cytopathology<\/i> <b>31<\/b> (5): 372\u2013378. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fcyt.12806\" target=\"_blank\">10.1111\/cyt.12806<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0956-5507\" target=\"_blank\">0956-5507<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12806\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12806<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Current+state+of+whole+slide+imaging+use+in+cytopathology%3A+Pros+and+pitfalls&rft.jtitle=Cytopathology&rft.aulast=Eccher&rft.aufirst=Albino&rft.au=Eccher%2C%26%2332%3BAlbino&rft.au=Girolami%2C%26%2332%3BIlaria&rft.date=1+September+2020&rft.volume=31&rft.issue=5&rft.pages=372%E2%80%93378&rft_id=info:doi\/10.1111%2Fcyt.12806&rft.issn=0956-5507&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fcyt.12806&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-34\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">3DHISTECH (September 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.3dhistech.com\/wp-content\/uploads\/2021\/09\/p1000-rx-brochure-v7-final.pdf\" target=\"_blank\">\"Pannoramic 100 RX\"<\/a> (PDF). 3DHISTECH Ltd.<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.3dhistech.com\/wp-content\/uploads\/2021\/09\/p1000-rx-brochure-v7-final.pdf\" target=\"_blank\">https:\/\/www.3dhistech.com\/wp-content\/uploads\/2021\/09\/p1000-rx-brochure-v7-final.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Pannoramic+100+RX&rft.atitle=&rft.aulast=3DHISTECH&rft.au=3DHISTECH&rft.date=September+2021&rft.pub=3DHISTECH+Ltd.&rft_id=https%3A%2F%2Fwww.3dhistech.com%2Fwp-content%2Fuploads%2F2021%2F09%2Fp1000-rx-brochure-v7-final.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">3DHISTECH. <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-1000\/\" target=\"_blank\">\"Pannoramic 1000\"<\/a>. 3DHISTECH Ltd.<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-1000\/\" target=\"_blank\">https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-1000\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Pannoramic+1000&rft.atitle=&rft.aulast=3DHISTECH&rft.au=3DHISTECH&rft.pub=3DHISTECH+Ltd.&rft_id=https%3A%2F%2Fwww.3dhistech.com%2Fresearch%2Fpannoramic-digital-slide-scanners%2Fpannoramic-1000%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">3DHISTECH. <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-250-flash-iii\/\" target=\"_blank\">\"Pannoramic 250 Flash III\"<\/a>. 3DHISTECH Ltd.<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-250-flash-iii\/\" target=\"_blank\">https:\/\/www.3dhistech.com\/research\/pannoramic-digital-slide-scanners\/pannoramic-250-flash-iii\/<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Pannoramic+250+Flash+III&rft.atitle=&rft.aulast=3DHISTECH&rft.au=3DHISTECH&rft.pub=3DHISTECH+Ltd.&rft_id=https%3A%2F%2Fwww.3dhistech.com%2Fresearch%2Fpannoramic-digital-slide-scanners%2Fpannoramic-250-flash-iii%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">3DHISTECH (June 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.3dhistech.com\/wp-content\/uploads\/2020\/06\/br-sc-102019-1.pdf\" target=\"_blank\">\"Pannoramic Slide Scanners\"<\/a> (PDF). 3DHISTECH Ltd.<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.3dhistech.com\/wp-content\/uploads\/2020\/06\/br-sc-102019-1.pdf\" target=\"_blank\">https:\/\/www.3dhistech.com\/wp-content\/uploads\/2020\/06\/br-sc-102019-1.pdf<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 25 December 2021<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Pannoramic+Slide+Scanners&rft.atitle=&rft.aulast=3DHISTECH&rft.au=3DHISTECH&rft.date=June+2020&rft.pub=3DHISTECH+Ltd.&rft_id=https%3A%2F%2Fwww.3dhistech.com%2Fwp-content%2Fuploads%2F2020%2F06%2Fbr-sc-102019-1.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Alcaraz Mateos, Eduardo; Caballero-Alem\u00e1n, Fuensanta; Albarrac\u00edn-Ferrer, Mariano; C\u00e1rceles-Moreno, Francisco; Hern\u00e1ndez-G\u00f3mez, Rub\u00e9n; Hern\u00e1ndez-Kakauridze, Sergio; Hern\u00e1ndez-Sabater, Laura; Jim\u00e9nez-Zafra, Ignacio <i>et al.<\/i> (2 December 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/232\" target=\"_blank\">\"Research on Devices for Handling Whole Slide Images on Pathology Workstations. An Ergonomic Outlook\"<\/a> (in en). <i>Diagnostic Pathology<\/i>: Vol 2 No 1 (2016): 2016. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17629%2FWWW.DIAGNOSTICPATHOLOGY.EU-2016-2%3A232\" target=\"_blank\">10.17629\/WWW.DIAGNOSTICPATHOLOGY.EU-2016-2:232<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/232\" target=\"_blank\">http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/232<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Research+on+Devices+for+Handling+Whole+Slide+Images+on+Pathology+Workstations.+An+Ergonomic+Outlook&rft.jtitle=Diagnostic+Pathology&rft.aulast=Alcaraz+Mateos&rft.aufirst=Eduardo&rft.au=Alcaraz+Mateos%2C%26%2332%3BEduardo&rft.au=Caballero-Alem%C3%A1n%2C%26%2332%3BFuensanta&rft.au=Albarrac%C3%ADn-Ferrer%2C%26%2332%3BMariano&rft.au=C%C3%A1rceles-Moreno%2C%26%2332%3BFrancisco&rft.au=Hern%C3%A1ndez-G%C3%B3mez%2C%26%2332%3BRub%C3%A9n&rft.au=Hern%C3%A1ndez-Kakauridze%2C%26%2332%3BSergio&rft.au=Hern%C3%A1ndez-Sabater%2C%26%2332%3BLaura&rft.au=Jim%C3%A9nez-Zafra%2C%26%2332%3BIgnacio&rft.au=L%C3%B3pez-Alacid%2C%26%2332%3BAlberto&rft.date=2+December+2016&rft.pages=Vol+2+No+1+%282016%29%3A+2016&rft_id=info:doi\/10.17629%2FWWW.DIAGNOSTICPATHOLOGY.EU-2016-2%3A232&rft_id=http%3A%2F%2Fwww.diagnosticpathology.eu%2Fcontent%2Findex.php%2Fdpath%2Farticle%2Fview%2F232&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pantanowitz, Liron; Sinard, John H.; Henricks, Walter H.; Fatheree, Lisa A.; Carter, Alexis B.; Contis, Lydia; Beckwith, Bruce A.; Evans, Andrew J. <i>et al.<\/i> (1 December 2013). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.archivesofpathology.org\/doi\/abs\/10.5858\/arpa.2013-0093-CP\" target=\"_blank\">\"Validating Whole Slide Imaging for Diagnostic Purposes in Pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center\"<\/a> (in en). <i>Archives of Pathology & Laboratory Medicine<\/i> <b>137<\/b> (12): 1710\u20131722. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2Farpa.2013-0093-CP\" target=\"_blank\">10.5858\/arpa.2013-0093-CP<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-9985\" target=\"_blank\">0003-9985<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7240346\/\" target=\"_blank\">PMC7240346<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23634907\" target=\"_blank\">23634907<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.archivesofpathology.org\/doi\/abs\/10.5858\/arpa.2013-0093-CP\" target=\"_blank\">http:\/\/www.archivesofpathology.org\/doi\/abs\/10.5858\/arpa.2013-0093-CP<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Validating+Whole+Slide+Imaging+for+Diagnostic+Purposes+in+Pathology%3A+Guideline+from+the+College+of+American+Pathologists+Pathology+and+Laboratory+Quality+Center&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Pantanowitz&rft.aufirst=Liron&rft.au=Pantanowitz%2C%26%2332%3BLiron&rft.au=Sinard%2C%26%2332%3BJohn+H.&rft.au=Henricks%2C%26%2332%3BWalter+H.&rft.au=Fatheree%2C%26%2332%3BLisa+A.&rft.au=Carter%2C%26%2332%3BAlexis+B.&rft.au=Contis%2C%26%2332%3BLydia&rft.au=Beckwith%2C%26%2332%3BBruce+A.&rft.au=Evans%2C%26%2332%3BAndrew+J.&rft.au=Lal%2C%26%2332%3BAvtar&rft.date=1+December+2013&rft.volume=137&rft.issue=12&rft.pages=1710%E2%80%931722&rft_id=info:doi\/10.5858%2Farpa.2013-0093-CP&rft.issn=0003-9985&rft_id=info:pmc\/PMC7240346&rft_id=info:pmid\/23634907&rft_id=http%3A%2F%2Fwww.archivesofpathology.org%2Fdoi%2Fabs%2F10.5858%2Farpa.2013-0093-CP&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Williams, Bethany Jill; Knowles, Chloe; Treanor, Darren (1 October 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-205944\" target=\"_blank\">\"Maintaining quality diagnosis with digital pathology: a practical guide to ISO 15189 accreditation\"<\/a> (in en). <i>Journal of Clinical Pathology<\/i> <b>72<\/b> (10): 663\u2013668. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1136%2Fjclinpath-2019-205944\" target=\"_blank\">10.1136\/jclinpath-2019-205944<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0021-9746\" target=\"_blank\">0021-9746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-205944\" target=\"_blank\">https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2019-205944<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Maintaining+quality+diagnosis+with+digital+pathology%3A+a+practical+guide+to+ISO+15189+accreditation&rft.jtitle=Journal+of+Clinical+Pathology&rft.aulast=Williams&rft.aufirst=Bethany+Jill&rft.au=Williams%2C%26%2332%3BBethany+Jill&rft.au=Knowles%2C%26%2332%3BChloe&rft.au=Treanor%2C%26%2332%3BDarren&rft.date=1+October+2019&rft.volume=72&rft.issue=10&rft.pages=663%E2%80%93668&rft_id=info:doi\/10.1136%2Fjclinpath-2019-205944&rft.issn=0021-9746&rft_id=https%3A%2F%2Fjcp.bmj.com%2Flookup%2Fdoi%2F10.1136%2Fjclinpath-2019-205944&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rojo, Marcial Garc\u00eda; Bueno, Gloria (28 October 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4639949\/\" target=\"_blank\">\"Analysis of the impact of high-resolution monitors in digital pathology\"<\/a>. <i>Journal of Pathology Informatics<\/i> <b>6<\/b>: 57. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2229-5089\" target=\"_blank\">2229-5089<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/4639949\/\" target=\"_blank\">4639949<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26605122\" target=\"_blank\">26605122<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4639949\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4639949\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+the+impact+of+high-resolution+monitors+in+digital+pathology&rft.jtitle=Journal+of+Pathology+Informatics&rft.aulast=Rojo&rft.aufirst=Marcial+Garc%C3%ADa&rft.au=Rojo%2C%26%2332%3BMarcial+Garc%C3%ADa&rft.au=Bueno%2C%26%2332%3BGloria&rft.date=28+October+2015&rft.volume=6&rft.pages=57&rft.issn=2229-5089&rft_id=info:pmc\/4639949&rft_id=info:pmid\/26605122&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4639949%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Marchessoux, Cedric; Nave Dufour, A.; Espig, K.; Monaco, S.; Palekar, A.; Pantanowitz, L. (16 June 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/168\" target=\"_blank\">\"Comparison Display Resolution On User Impact For Digital Pathology\"<\/a> (in en). <i>Diagnostic Pathology<\/i>: Vol 1 No 8 (2016): 13. European Congress on Digital Pathology. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.17629%2FWWW.DIAGNOSTICPATHOLOGY.EU-2016-8%3A168\" target=\"_blank\">10.17629\/WWW.DIAGNOSTICPATHOLOGY.EU-2016-8:168<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/168\" target=\"_blank\">http:\/\/www.diagnosticpathology.eu\/content\/index.php\/dpath\/article\/view\/168<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comparison+Display+Resolution+On+User+Impact+For+Digital+Pathology&rft.jtitle=Diagnostic+Pathology&rft.aulast=Marchessoux&rft.aufirst=Cedric&rft.au=Marchessoux%2C%26%2332%3BCedric&rft.au=Nave+Dufour%2C%26%2332%3BA.&rft.au=Espig%2C%26%2332%3BK.&rft.au=Monaco%2C%26%2332%3BS.&rft.au=Palekar%2C%26%2332%3BA.&rft.au=Pantanowitz%2C%26%2332%3BL.&rft.date=16+June+2016&rft.pages=Vol+1+No+8+%282016%29%3A+13.+European+Congress+on+Digital+Pathology&rft_id=info:doi\/10.17629%2FWWW.DIAGNOSTICPATHOLOGY.EU-2016-8%3A168&rft_id=http%3A%2F%2Fwww.diagnosticpathology.eu%2Fcontent%2Findex.php%2Fdpath%2Farticle%2Fview%2F168&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-43\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-43\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Randell, Rebecca; Ambepitiya, Thilina; Mello-Thoms, Claudia; Ruddle, Roy A.; Brettle, David; Thomas, Rhys G.; Treanor, Darren (1 February 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10278-014-9726-8\" target=\"_blank\">\"Effect of Display Resolution on Time to Diagnosis with Virtual Pathology Slides in a Systematic Search Task\"<\/a> (in en). <i>Journal of Digital Imaging<\/i> <b>28<\/b> (1): 68\u201376. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10278-014-9726-8\" target=\"_blank\">10.1007\/s10278-014-9726-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0897-1889\" target=\"_blank\">0897-1889<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4305057\/\" target=\"_blank\">PMC4305057<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25128321\" target=\"_blank\">25128321<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10278-014-9726-8\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10278-014-9726-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effect+of+Display+Resolution+on+Time+to+Diagnosis+with+Virtual+Pathology+Slides+in+a+Systematic+Search+Task&rft.jtitle=Journal+of+Digital+Imaging&rft.aulast=Randell&rft.aufirst=Rebecca&rft.au=Randell%2C%26%2332%3BRebecca&rft.au=Ambepitiya%2C%26%2332%3BThilina&rft.au=Mello-Thoms%2C%26%2332%3BClaudia&rft.au=Ruddle%2C%26%2332%3BRoy+A.&rft.au=Brettle%2C%26%2332%3BDavid&rft.au=Thomas%2C%26%2332%3BRhys+G.&rft.au=Treanor%2C%26%2332%3BDarren&rft.date=1+February+2015&rft.volume=28&rft.issue=1&rft.pages=68%E2%80%9376&rft_id=info:doi\/10.1007%2Fs10278-014-9726-8&rft.issn=0897-1889&rft_id=info:pmc\/PMC4305057&rft_id=info:pmid\/25128321&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10278-014-9726-8&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wilbur, David C.; Madi, Kalil; Colvin, Robert B.; Duncan, Lyn M.; Faquin, William C.; Ferry, Judith A.; Frosch, Matthew P.; Houser, Stuart L. <i>et al.<\/i> (1 December 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/meridian.allenpress.com\/aplm\/article\/133\/12\/1949\/460648\/Whole-Slide-Imaging-Digital-Pathology-as-a\" target=\"_blank\">\"Whole-Slide Imaging Digital Pathology as a Platform for Teleconsultation: A Pilot Study Using Paired Subspecialist Correlations\"<\/a> (in en). <i>Archives of Pathology & Laboratory Medicine<\/i> <b>133<\/b> (12): 1949\u20131953. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5858%2F133.12.1949\" target=\"_blank\">10.5858\/133.12.1949<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1543-2165\" target=\"_blank\">1543-2165<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/meridian.allenpress.com\/aplm\/article\/133\/12\/1949\/460648\/Whole-Slide-Imaging-Digital-Pathology-as-a\" target=\"_blank\">https:\/\/meridian.allenpress.com\/aplm\/article\/133\/12\/1949\/460648\/Whole-Slide-Imaging-Digital-Pathology-as-a<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole-Slide+Imaging+Digital+Pathology+as+a+Platform+for+Teleconsultation%3A+A+Pilot+Study+Using+Paired+Subspecialist+Correlations&rft.jtitle=Archives+of+Pathology+%26+Laboratory+Medicine&rft.aulast=Wilbur&rft.aufirst=David+C.&rft.au=Wilbur%2C%26%2332%3BDavid+C.&rft.au=Madi%2C%26%2332%3BKalil&rft.au=Colvin%2C%26%2332%3BRobert+B.&rft.au=Duncan%2C%26%2332%3BLyn+M.&rft.au=Faquin%2C%26%2332%3BWilliam+C.&rft.au=Ferry%2C%26%2332%3BJudith+A.&rft.au=Frosch%2C%26%2332%3BMatthew+P.&rft.au=Houser%2C%26%2332%3BStuart+L.&rft.au=Kradin%2C%26%2332%3BRichard+L.&rft.date=1+December+2009&rft.volume=133&rft.issue=12&rft.pages=1949%E2%80%931953&rft_id=info:doi\/10.5858%2F133.12.1949&rft.issn=1543-2165&rft_id=https%3A%2F%2Fmeridian.allenpress.com%2Faplm%2Farticle%2F133%2F12%2F1949%2F460648%2FWhole-Slide-Imaging-Digital-Pathology-as-a&rfr_id=info:sid\/en.wikipedia.org:Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation, though grammar and word usage was substantially updated for improved readability. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628174755\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.598 seconds\nReal time usage: 1.929 seconds\nPreprocessor visited node count: 48670\/1000000\nPost\u2010expand include size: 487553\/2097152 bytes\nTemplate argument size: 141968\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 125560\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 553.215 1 -total\n 90.77% 502.176 1 Template:Reflist\n 59.15% 327.243 44 Template:Citation\/core\n 55.55% 307.325 38 Template:Cite_journal\n 9.08% 50.231 41 Template:Date\n 7.77% 42.973 107 Template:Citation\/identifier\n 7.20% 39.805 6 Template:Cite_web\n 5.05% 27.955 1 Template:Infobox_journal_article\n 4.22% 23.373 1 Template:Infobox\n 2.51% 13.893 214 Template:Hide_in_print\n-->\n\n<!-- Saved in parser cache with key limswiki:pcache:idhash:13212-0!canonical and timestamp 20220628174753 and revision id 47431. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results\">https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n\n\n\n<\/body>","ef9487ab4d88db8c29a49a38ec04aec1_images":["https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/d\/db\/Fig1_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/2\/24\/Fig2_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/5\/55\/Fig3_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/6\/64\/Fig4_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/e\/e9\/Fig5_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a3\/Fig6_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/9\/92\/Fig7_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/1\/1a\/Fig8_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/a\/a2\/Fig9_Temprana-Salvado_Diagnostics22_12-4.png","https:\/\/s3.limswiki.org\/www.limswiki.org\/images\/8\/85\/Fig10_Temprana-Salvado_Diagnostics22_12-4.png"],"ef9487ab4d88db8c29a49a38ec04aec1_timestamp":1656439824,"e54c0b7e681c5437811a012a24acebea_type":"article","e54c0b7e681c5437811a012a24acebea_title":"Potential of NIRS technology for the determination of cannabinoid content in industrial hemp (Cannabis sativa L.) (Jar\u00e9n et al. 2022)","e54c0b7e681c5437811a012a24acebea_url":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)","e54c0b7e681c5437811a012a24acebea_plaintext":"\n\nJournal:Potential of NIRS technology for the determination of cannabinoid content in industrial hemp (Cannabis sativa L.)From CannaQAWikiJump to navigationJump to searchFull article title\n \nPotential of NIRS technology for the determination of cannabinoid content in industrial hemp (Cannabis sativa L.)Journal\n \nAgronomyAuthor(s)\n \nJar\u00e9n, Carmen; Zambrana, Paula C.; P\u00e9rez-Roncal, Claudia; L\u00f3pez-Maestresalas, Ainara; \u00c1brego, Andr\u00e9s; Arazuri, SilviaAuthor affiliation(s)\n \nUniversidad P\u00fablica de Navarra, Genscore Navarra S.L.Primary contact\n \nEmail: cjaren at unavarra dot esYear published\n \n2022Volume and issue\n \n12(4)Article #\n \n938DOI\n \n10.3390\/agronomy12040938ISSN\n \n2073-4395Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2073-4395\/12\/4\/938\/htmDownload\n \nhttps:\/\/www.mdpi.com\/2073-4395\/12\/4\/938\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Materials and methods \n\n3.1 Vegetal material \n3.2 Spectra acquisition \n3.3 Reference measurements: HPLC \n3.4 Multivariate data analysis \n\n\n4 Results and discussions \n\n4.1 HPLC results \n4.2 Spectral data \n4.3 Interpretation of spectra \n4.4 PLS model for total THC \n4.5 PLS model for total CBD \n\n\n5 Conclusions \n6 Acknowledgements \n\n6.1 Author contributions \n6.2 Funding \n6.3 Conflicts of interest \n\n\n7 References \n8 Notes \n\n\n\nAbstract \nIndustrial hemp (Cannabis sativa L.) is a plant native to Asia and is considered to be a primary source of food, textile fiber, and medicines. It is characterized by containing minimal concentrations of \u03949-tetrahydrocannabinol (THC), which is the main psychoactive chemical component, and cannabidiol (CBD), a non-psychoactive substance. In most European countries, the maximum concentration legally allowed for cultivation is 0.2% of THC, and it is currently under debate whether to increase this level to 0.3%. Moreover, in many countries its production is being regulated and legalized, increasing the need for a rapid analysis method. \nThe present work evaluated the cannabinoid content in hemp using near-infrared spectroscopy (NIRS) technology in combination with chemometric techniques. For this, several samples of the Kompolti variety were analyzed. Samples were dried and ground, and the content of total THC (%) and total CBD (%) was determined by high-performance liquid chromatography (HPLC) with a diode array detector for reference measurements, and then the spectra were collected by NIRS. Principal component analysis and partial least square regression models were developed. Good coefficients of determination of cross-validation of 0.77 for THC and CBD, and a ratio of prediction to deviation >2 for total THC and CBD, were achieved. The results obtained show that NIRS technology has potential for the quantitative determination of cannabinoids. Therefore, this analytical method would allow a simpler, more robust, precise, and sustainable estimation than the current HPLC approach.\nKeywords: CBD, THC, near infrared spectroscopy, quantification, HPLC, chemometrics\n\nIntroduction \nThe non-psychotropic species Cannabis sativa L., referred to as industrial hemp[1], is characterized by containing minimal concentrations of \u03949-tetrahydrocannabinol (THC), the main psychoactive chemical component, and cannabidiol (CBD), a non-psychoactive substance that is often present in amounts similar to those of THC.[1][2] Hemp is mainly used for food or textile purposes and, in addition, offers great medicinal potential. Although the regulations of different countries vary according to the definition of the maximum accepted THC limit, industrial-hemp-producing countries require that the varieties used contain THC concentrations lower than 1%. In most European countries, the current upper legal limit for cultivation is 0.2% of THC and the ratio of CBD to THC should be greater than one. Currently, the maximum concentration legally permitted for cultivation is under debate in the European Union.[3]\nIt is important to note that the flower is the part of hemp with the highest significant content of cannabinoids.[4] These, when heated, spontaneously decarboxylate to the \u201cneutral\u201d cannabinoids THC and CBD. This heat-labile characteristic of acidic cannabinoids (e.g., tetrahydrocannabinolic acid [THCA] and cannabidiolic acid [CBDA]) highlights the importance of using a low-temperature, non-destructive method to achieve a precise quantification of these molecules.[5] Moreover, for all stakeholders in the cannabis supply chain, a precise and trustworthy identification of these cannabinoids would be of great economic importance.[4]\nTraditionally, cannabinoid content has been determined by high-performance liquid chromatography (HPLC) and gas chromatography (GC). HPLC provides a full cannabinoid profile, but it has several associated disadvantages, including sample destruction, complex instrumentation, involvement of hazardous chemicals, and longer sample preparation times, which limit its application on-site, where a fast and non-destructive process is preferable.[4] Similarly, GC is another preferred method for the determination of these compounds. However, it is a slow and expensive technique, requiring a tedious sample preparation stage that involves the extraction of the active ingredients through the use of organic solvents, whose subsequent residues must be managed with a considerable increase in cost and time.[6]\nThese limitations have led to a search for faster and easier-to-use alternatives to HPLC and GC.[4] Therefore, it is important to develop a simple, fast, and sustainable method for the quantification of cannabinoids. In recent years, spectroscopic methods have emerged as techniques that are used on a wide range of biological samples without the need for extraction.[7] One such technique is near-infrared spectroscopy (NIRS), which is a fast, cost-effective, versatile, robust, and sustainable technique. In addition, it allows both quantitative and qualitative determinations of the main parameters, such as proteins, fats, humidity, ashes, starch, or sugar, of the raw materials related to the quality of agricultural products.[6] In recent years, the interest in NIRS applied to hemp has gained importance due to the moisture, volatile substances, and chemical compounds in herbal products absorbed in the NIR region. In general, NIRS combined with chemometrics has great potential in the analysis of natural plant products.[8]\nIt should be taken into account that the cannabis flower is heterogeneous in nature, which presents a series of problems and drawbacks. It is a complex matrix, made up of a great variety of types of plant tissues and more than 500 different naturally produced chemicals. Moreover, it is a material that can vary widely between plants of the same crop, in an individual plant, and even within the same sample.[9] Consequently, no two parts of the cannabis flower are alike, and their cannabinoid content is likely to vary widely. In this scenario, NIRS technology is an adequate alternative for the analysis of heterogeneous vegetal samples and may therefore overcome the inherent heterogeneity of the cannabis plant.[4]\nNIRS has been applied to discriminate between cannabis \u201cdrug type\u201d (chemotype I) and \u201cfiber type\u201d (chemotype II)[10], for the discrimination of leaves of Cannabis sativa L. and other plant species[11], and for the prediction of the growth stage of cannabis plants in the early stages of cultivation.[12]\nMarcel et al.[13] developed a prediction model of the chemical composition of the fiber and the central fraction of hemp (chemotype III) using NIRS combined with a partial least squares (PLS) regression analysis. Similarly, a procedure was developed for the identification and quantitative determination of synthetic cannabinoids in illicit herbal samples. The methodology was based on the measurement by Fourier-transform infrared spectroscopy of attenuated total reflectance (ATR-FTIR).[14]\nMoreover, the total content of THC and CBD in the cannabis flower has been determined by Fourier-transform near-infrared spectroscopy (FT\u2013NIR).[4] Similarly, S\u00e1nchez-Carnerero et al.[6] studied the prediction of cannabinoid content using NIRS. They used both FT-NIR and NIR spectrophotometers for their analysis and compared the results obtained with the two techniques. Similar results were obtained using both instruments, thus confirming that there is enough information in the spectral region of the NIR for the prediction of cannabinoids.\nMore recently, Duchateau et al.[15] created two classification methods according to the European laws about the discrimination of the legal limits of Cannabis spp. using NIR. Valinger et al.[7] described the development of artificial neural network (ANN) models for the prediction of the physical and chemical properties of industrial hemp extracts, based on the combination of ultraviolet-visible near-infrared (UV-VIS-NIR) spectra. For this, two different extraction methods were prepared (solid\u2013liquid extraction and microwave-assisted extraction). The results showed that reliable ANN models can be developed to describe the physical and chemical characteristics, without the need for pre-processing of the spectra. In a recent study, Risoluti et al.[16], using a MicroNIR spectrometer, developed a test for cannabinoid determination in commercial hemp flours spiked with THC, CBD, and cannabigerol (CBG).\nTherefore, the aim of this study was to evaluate the functionality of NIRS for the quantification of the main cannabinoids present in hemp samples. In addition, a study of the NIR spectra was carried out to identify the peaks.\n\nMaterials and methods \nVegetal material \nThirty-five hemp samples were obtained in collaboration with Genscore Navarra S.L. The specimens obtained were of the Kompolti variety, which is among the varieties authorized for the cultivation of industrial hemp in Spain.[17]\nThe plant material was weighed on a AB104 Mettler-Toledo analytical balance and dried in an oven at 60 \u00b0C for 24 hours, until a humidity between 8% and 13% was achieved, as recommended by regulation (EU) 2017\/1155.[18]\nStems and seeds of more than 2 mm were removed from the dry samples and, with the help of a mortar, they were crushed until obtaining a semi-fine powder, in such a way that it could pass through a 1 mm mesh sieve. The samples were stored, without crushing them, in a dark place at a temperature below 25 \u00b0C.[18][19]\n\nSpectra acquisition \nSpectra were collected using an Acousto-Optic Tunable Filter (AOTF) NIR and Indium Gallium Arsenide (InGaAs) detector, called a Luminar 5030 Miniature \"Hand-held,\" in the reflectance mode and equipped with Snap32! software (Brimrose Corporation of America, Sparks, MD, USA). A spectral range of 1200\u20132200 nm was used to obtain the spectra, with a sampling interval of 2 nm, and scanning speed of 60 ms. Each spectrum recorded by the instrument was the average of 50 scans.\nIn this study, 3 g of each of the 35 hemp powder samples was weighed and placed on the rotating cell of the AOTF-NIR spectrophotometer. As the sample rotates, the spectrum is measured so that different parts of the sample are scanned from above and inhomogeneities averaged. For each individual sample, three reflectance spectra were acquired by contacting the probe with the sample.\n\nReference measurements: HPLC \nAfter acquisition of the NIRS data, the same hemp samples were removed from the Petri dishes and sent to a certified laboratory, ANANDA ANALYTICS LAB S.L., where an HPLC with diode array detector (HPLC-DAD) method was used for the determination of total THC and total CBD cannabinoids. The extraction was performed by ultrasound with subsequent methanol-chloroform decarboxylation. The mobile phase was acetonitrile (water [8:2 v\/v], isocratic, stop time 8 minutes) according to Recommended methods for the identification and analysis of cannabis and cannabis products by the United Nations Office on Drugs and Crime.[19] Regarding the result, for a qualitative identification, the retention time and the DAD spectrum of the cannabinoid must match. The calculation for the quantitative results was carried out at the wavelengths of 220 and 240 nm.\nThe results were received after 10 days and, then, these reference chromatographic data were correlated with the spectral information to generate the NIR models for total THC and CBD prediction. Thirty-two of 35 samples were analyzed by HPLC-DAD, with three fungus-infected hemp plants being identified and excluded.\n\nMultivariate data analysis \nData analysis was performed using the specific software The Unscrambler X v.10.4 (Camo Software AS, Oslo, Norway). First, principal component analysis (PCA) was performed with the full set of samples. PCA was applied to explore the spectral variability of the population[20], which also allows elimination of outliers that can have a negative effect on modeling.[21]\nDuring the pre-model building phase, data pre-processing was carried out to eliminate the non-informative effects of light scattering or system noise. For the development of the models, in addition to working with the raw data, different data pretreatments were applied: spectra normalization, standard normal variate (SNV), standard normal variate and detrend (SNV-DT), multiplicative scatter correction (MSC), and first derivative. These are described as such:\n\nRaw data: The absolute reflectance was obtained from the radiation measurements of the 35 samples, with three repetitions each.\nSpectra normalization: Raw NIR spectra are often mathematically processed prior to development of the calibration model; such treatments include normalization, which is performed to minimize unwanted sources of data variation prior to calibration and to improve spectral characteristics.[22] Mean normalization was performed in this study, which is the most classical approach. In this normalization, each sample of the dataset (each row of the data matrix) is divided by its average.\nSNV: To eliminate interferences due to path length effects, SNV consists of subtracting the mean value of the spectrum from each reflectance value at each wavelength and dividing it by the standard deviation.[23]\nSNV-DT: This method was developed by Barnes et al.[24] to eliminate multiplicative scattering interferences and particle size, and to take into account the variation in the baseline change and curvilinearity in diffuse reflectance spectra. Detrend consists of fitting a second-order polynomial to the spectrum corrected by SNV, which is subtracted to eliminate the dispersion effect that is dependent on each wavelength.[25]\nMSC: This is another preprocessing technique that corrects the displacements between samples due to the particles of the samples.[26] MSC is undertaken by using a reference spectrum and correcting the different spectra to it so that the baseline and the amplification effects are at the same average level in all spectra.[27] The basic concept of MSC is to remove non-linearities in the data caused by scattering from particulates in the samples.[28]\nFirst derivative: The first derivative of the spectra, based on the Savitzky\u2013Golay algorithm, is used to increase the spectral resolution and interpret the spectra.[29] One smoothing point was applied to the right and another to the left, and a polynomial of order two was used to smooth and eliminate random noise from the NIR spectra. Vasques et al.[30] confirmed that the Savitzky\u2013Golay derivatives were among the best methods for preprocessing the spectra. Similarly, Ertlen et al.[31] reported that by using derivatives, more convenient information can be taken from NIR spectra.\nAfter data pretreatments, a PLS regression analysis was applied to the dataset to build a model capable of predicting the content of cannabinoids, both for total THC and total CBD, in the hemp samples, and to be able to assess the effectiveness of NIR spectroscopy. For the validation of the model, cross-validation (CV) was used in order to calculate the relationships between spectral and chemical properties. Williams et al.[32] recommend CV for the evaluation of any calibration model based on small sets of samples below 100 units.\nThe performance of the calibration models was evaluated using the root mean square error of the calibration (RMSEC), the root mean square error of cross-validation (RMSECV), the coefficient of determination of calibration (R2c), the coefficient of determination of cross-validation (R2cv), and the ratio of prediction to deviation (RPD). The number of latent variables (LV) was used to prevent overfitting.\n\nResults and discussions \nHPLC results \nFor each of the samples analyzed, an individualized report was received with the sample identification data, the characteristics of the analysis methods used, and the results obtained from the HPLC-DAD analysis. The results provided by the reference laboratory, expressed as a percentage, included data for humidity, THC total, CBD total, and 12 other cannabinoids that were not the subject of this study. Thirty-two samples of 35 were analyzed by HPLC-DAD because three hemp plants infected with fungi were identified. The mean, the maximum, the minimum, and the standard deviation of the reference results can be seen in Table 1.\n\n\n\n\n\n\n\nTable 1. HPLC-DAD analysis results\n\n\nSamples\n\nHumidity (%)\n\nTHC total (%)\n\nCBD total (%)\n\n\nMin\n\nMax\n\nMean\n\nSD\n\nMin\n\nMax\n\nMean\n\nSD\n\nMin\n\nMax\n\nMean\n\nSD\n\n\n32\n\n9.02\n\n12.34\n\n10.65\n\n3.16\n\n0.057\n\n0.161\n\n0.103\n\n0.028\n\n2.178\n\n5.342\n\n3.367\n\n0.892\n\n\n\nRegarding the percentage of humidity, all samples presented values between 9.02% and 12.34%. These values are between the ranges established in the delegated regulation[18], which indicates a humidity of 8\u201313% in the preparation of cannabis samples. All selected samples had a THC value detected between 0.057% and 0.161%. Concerning CBD, which is currently the compound of greatest interest, the results in Table 1 show a maximum value of 5.342% and a minimum value of 2.178%, which indicates the high concentration of CBD in the samples, a characteristic of industrial cannabis.[19]\n\nSpectral data \nIn Figure 1, the spectra of the hemp sample set are shown, which correspond to the spectra collected in the Luminar 5030 AOTF-NIR spectrophotometer, where the typical reflectance bands of hemp appear in the NIR region from 1200 to 2200 nm.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 Raw spectra of the complete set of hemp samples.\n\n\n\nPrincipal component analysis (PCA) was applied to explore the spectral variability of the population, where no atypical samples were identified. This indicates that the dataset was uniformly distributed and covered as much spectral variation as possible (Figure 2). Then, PLS analysis was applied to the dataset. The results for each PLS model, for total THC and total CBD, with each pretreatment applied, including the number of samples used, were compared based on the values obtained for RMSEC, RMSECV, R2c, R2cv, LV, SD, and RPD.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 Score plot of PC1 versus PC2 from the PCA model.\n\n\n\nInterpretation of spectra \nFigure 3 shows the reflectance spectra of the samples after applying the first derivative based on the Savitzky\u2013Golay algorithm. The typical absorption bands of plant material appear in the NIR region derived from the superpositions corresponding mainly to overtones and to the combination of vibration modes that involve chemical bonds of the types C-H, O-H, and N-H.[8] In NIR reflectance spectra, the absorption bands of the molecules that make up the sample are described as valleys rather than peaks, since the absorbance equals Log (1\/Reflectance). The hemp spectra obtained in this study show the characteristic bands around 1210, 1450, 1736, 1762, 1820, 1940, 2060, and 2090 nm that are characteristic of proteins, lipids, water, and other compounds present in hemp in the main absorptions (of OH, NH, CH, and other bonds).\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 3 Main absorption bands of the spectra pretreated with the Savitzky\u2013Golay first derivative.\n\n\n\nThe 1450 and 1940 nm bands that appear in the spectra correspond to the first overtone and to the -OH group combination bands, mainly due to the presence of water. Although the samples were oven dried at 60 \u00b0C, they were left with a humidity between 8 and 13%, which may be responsible of these absorption bands. Bands associated with lipids were found around 1210 nm (second overtone of stretching vibrations) and 1762 nm (first overtone of stretching vibrations) of functional groups -CH and -CH2 corresponding to aliphatic hydrocarbons. Bands around 2060 nm have been associated with protein absorption, which are related to NH secondary combination bands of amides in proteins, for peptide groups, and those around 1820 and 2090 nm correspond to associated bands of cellulose and polymeric structure, which are related to the fiber content of hemp.[33][34] In addition, the reflectance band found at 1736 nm corresponds to the aromatic hydrocarbons of the terpenes, of the functional group C-H.[33][34][35] This band is more evident in samples that have a higher CBD content, because terpenes and cannabinoids share biosynthetic pathways, and because cannabinoids are terpene-phenolic compounds.[6] In general, the absorption bands obtained in the present study are similar to those reported by other similar studies on cannabinoids.[6]\n\nPLS model for total THC \nPLS analysis was applied to the dataset using the same number of samples for both calibration and CV predictive models. The results of each PLS model for total THC applied with each pretreatment include the number of samples used, RMSEC, RMSECV, R2c, R2cv, SD, and RPD.\nThe results for the R2cv of the predictive models were higher than 0.72, which indicates that the calibration models can be considered good.[20]\nSimilarly, the RPD was considered a good indicator of the predictive capacity. In the prediction of total THC content, RPD values > 2 were obtained, which indicates the goodness of the models. The higher the RPD value, the greater the ability of the calibration model to accurately predict the reference parameter values (Table 2).\n\n\n\n\n\n\n\nTable 2. Calibration and validation statistics to predict total THC content\n\n\nPretreatment\n\nNc\n\nRMSEC\n\nRMSECV\n\nR2c\n\nR2cv\n\nLV\n\nRPD\n\n\nRaw data\n\n91\n\n0.010\n\n0.014\n\n0.87\n\n0.77\n\n7\n\n2.04\n\n\nStandardization\n\n94\n\n0.011\n\n0.014\n\n0.85\n\n0.75\n\n7\n\n2.04\n\n\nSNV\n\n94\n\n0.010\n\n0.014\n\n0.87\n\n0.76\n\n7\n\n2.04\n\n\nSNV-DT\n\n94\n\n0.011\n\n0.014\n\n0.84\n\n0.72\n\n6\n\n2.04\n\n\nMSC\n\n94\n\n0.010\n\n0.014\n\n0.86\n\n0.76\n\n7\n\n2.04\n\n\nFirst derivative\n\n94\n\n0.010\n\n0.014\n\n0.86\n\n0.75\n\n7\n\n2.04\n\n\n\nSome authors have established five levels of prediction accuracy based on the RPD. Saeys et al.[36] indicated that models with RPD values below 1.5 should not be used for prediction; an RPD value between 1.5 and 2.0 should only be used to distinguish between high and low values; and a value between 2.0 and 2.5 can be used to make approximate quantitative predictions. Values between 2.5 and 3.0 and above 3.0 can be used for good and excellent predictions, respectively.\nFor total THC (%), the best model was selected according to the highest values of R2cv and RPD, and the lowest values of RMSECV. The results without applying any data pretreatment technique presented higher values of R2c of 0.87, R2cv of 0.77, and an RPD > 2, which indicates that approximate quantitative predictions are possible. The lower RMSECV values of 0.014 were also taken into account.\nFigure 4 represents the result of the PLS model without applying any data pretreatment technique, for the quantification of total THC. The graph shows measured values (X-axis) versus predicted values (Y-axis) for total THC from the cross-validation dataset showing analogous results. The proximity between the calibration line and the cross-validation line can be observed with slopes very close to the unit, which provides an idea of the quality of the model obtained.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 4 PLS model for total THC without pretreatment (numbers above [blue]: calibration; numbers below [red]: cross-validation).\n\n\n\nIn general, the results showed that the developed models had the ability to make approximate predictions of total THC content, with high R2 and RPD, and low RMSE. Furthermore, the difference between RMSEC and RMSECV was low in all models developed. Therefore, for the determination of total THC, the prediction model obtained without applying any data pretreatment technique presented the best results, taking seven latent variables. For the rest of the calibration models carried out applying different combinations of data pretreatments, similar results were obtained with minimal differences.\n\nPLS model for total CBD \nThe results for the R2cv of the predictive models were higher than 0.73, which indicates that the calibration models can be considered good, except for the first derivative model, which has an R2cv value of 0.68. The latter would allow adequate discrimination between samples having high, medium, and low total CBD content.[20]\nThe standard deviation of CBD content was equal to 0.892, considering only the samples used for each calibration model, and 0.871 for the first derivative model. In general, the results obtained for the RPD were around 2, which indicates the possibility for approximate quantitative predictions (Table 3).\n\n\n\n\n\n\n\nTable 3. Calibration and validation statistics for predicting total CBD content\n\n\nPretreatment\n\nNc\n\nRMSEC\n\nRMSECV\n\nR2c\n\nR2cv\n\nLV\n\nRPD\n\n\nRaw data\n\n103\n\n0.333\n\n0.431\n\n0.86\n\n0.77\n\n7\n\n2.07\n\n\nStandardization\n\n103\n\n0.361\n\n0.459\n\n0.83\n\n0.74\n\n7\n\n1.94\n\n\nSNV\n\n103\n\n0.357\n\n0.464\n\n0.84\n\n0.73\n\n7\n\n1.92\n\n\nSNV-DT\n\n103\n\n0.358\n\n0.459\n\n0.84\n\n0.74\n\n6\n\n1.94\n\n\nMSC\n\n103\n\n0.359\n\n0.465\n\n0.84\n\n0.73\n\n7\n\n1.91\n\n\nFirst derivative\n\n98\n\n0.389\n\n0.494\n\n0.79\n\n0.68\n\n3\n\n1.76\n\n\n\nThe best model to predict CBD content was also obtained without applying any data pretreatment technique. A high R2c value of 0.86, R2cv of 0.77, and an RPD > 2 were achieved, indicating the predictive capacity of the model. The lower RMSECV values of 0.431 were also considered.\nFigure 5 represents the result of the PLS model without applying any data pretreatment technique, for the quantification of total CBD.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 5 PLS model for total CBD without pretreatment (numbers above [blue]: calibration; numbers below [red]: cross-validation).\n\n\n\nMoreover, as with the prediction of THC, all developed models showed an excellent performance in predicting total CBD content, with high R2 and RPD, and low RMSE, which demonstrates the potential of NIRS for cannabinoid content estimation.\nFurthermore, the difference between RMSEC and RMSECV was low in all models developed. Therefore, for the determination of the total CBD, the prediction model obtained without applying any data pre-treatment technique presented the best results, taking seven latent variables. Comparable results were obtained for the rest of the calibration models carried out applying different combinations of data pretreatments.\nInterest in the determination of the cannabinoid content of Cannabis sativa has increased in recent years, as indicated by the various studies published in this field. As in this study, other authors have achieved good results for the prediction of THC and CBD by NIRS without any data pretreatment. For example, S\u00e1nchez-Carnerero et al.[6] obtained an R2cv of 0.99 for CBD and an R2cv of 0.99 for THC with an FT-NIR instrument. However, using a NIR Systems 6500 scanning monochromator for CBD prediction, a SNV-DT pretreatment was applied, and resulted in an R2cv of 0.99 and a MSC for THC with an R2cv 0.98 and an RPD of 3.07.\nIn a more recent study, Deidda et al.[37] explored the feasibility of using NIRS for the quantitative analysis of THC. For this study, two handheld NIR spectrophotometers were used and compared, a low-cost device (NIR-S-G1) and a mid-cost device (MicroNIR onsite W 1700). Both entire inflorescence and resin samples were analyzed, and the reference method used was UHPLC coupled to UV detection. A preliminary study was conducted on 26 entire inflorescences that were then ground and sieved in order to evaluate the impact of sample homogeneity on the THC content predictions. Researchers obtained a THC concentration far wider than in our study, ranging from 0.92 to 22.21%. RPD values between 1 and 4.54 were obtained for the different physical forms of samples using both devices. In general, the MicroNIR spectrophotometer outperformed NIR-S-G1. Moreover, 45 resin samples were analyzed with both devices, obtaining an RPD value of 2.26 with the MicroNIR and 1.51 with NIR-S-G1. Therefore, authors concluded that the mid-cost system was the best-suited spectrophotometer for their application.\nIn another study carried out by Chen et al.[38], a different approach was adopted in which the authors explored the potential of NIRS for the in situ determination of CBD in hemp oil. For their study, 20 hemp oil samples with different concentrations of CBD and CBDA (determined by HPLC) were analyzed by a Bruker MATRIX-F FT-NIR spectrometer covering the 4000 to 12,000 cm\u22121 range. Super partial least-squares regression (sPLSR) and a self-optimizing support vector elastic net (SOSVEN) were applied to predict the concentrations of CBD, achieving promising results with a coefficient of determination for the validation set >0.98 and an RMSEV of 6.4 \u00b1 0.1 mg\/mL.\nIn addition, as mentioned in the introduction, spectroscopic techniques have been used to differentiate fiber-type from drug-type Cannabis sativa L.[39] In that study, ATR-FTIR in the 5000\u2013400 cm\u22121 region was used to assess 36 samples of C. sativa inflorescences; eight were drug-type, 14 fiber-type, and another set of 14 were cannabis samples having a low THC concentration. PLS models were developed to predict the content of seven neutral and acidic cannabinoids (THC, THCA, CBD, CBDA, CBG, cannabigerolic acid [CBGA], and cannabinol [CBN]). Authors achieved very good results, with an R2cv higher than 0.99 for each cannabinoid and RMSECV values ranging from 0.020 to 0.163.\nMoreover, mid-infrared (MIR) spectroscopy has been explored for the prediction of THC and CBD content in C. sativa. For example, Geskovski et al.[40] used an ATR-FTIR spectrometer, in the 1700 to 400 cm\u22121 range, to quantify the content of THC and CBD in 45 flowers and 34 cannabis extracts. PLS models were developed for both types of sample, obtaining good results with R2p and RMSEP values of 0.99% and 2.32% for THC, and 0.99% and 1.33% for CBD, respectively, for the flower samples, and R2p and RMSEP values of 0.95% and 3.79% for THC, and 0.99% and 1.44% for CBD, in the cannabis extract samples, respectively.\nIn the current study, we present a feasible and low-cost method for THC and CBD content determination in C. sativa samples using NIRS. Promising results were obtained for both cannabinoids, indicating the potential of NIR technology as a predictive tool.\n\nConclusions \nThe functionality of NIRS for the quantification of THC and CBD as principal cannabinoids in hemp, along with their related spectral peaks, was evaluated in this study. According to the latter, the region of the NIR spectrum analyzed presents characteristic absorption bands around 1210, 1450, 1736, 1762, 1820, 1940, 2060, and 2090 nm that are typical of proteins, lipids, water, and other compounds present in hemp (from OH, NH, CH, and other bonds). In addition, the band at 1736 nm, related to aromatic hydrocarbons of the terpenes, was associated with the CBD content, since cannabinoids are terpene-phenolic compounds.\nMoreover, predictive models of the cannabinoid content in hemp were obtained combining NIR spectroscopy and chemometric analysis. The best results for the prediction of both THC and CBD were obtained using the raw data, providing a simpler form of analysis. For the THC, the best PLS model achieved a determination coefficient of cross-validation of 0.77 and an RPD value > 2, which indicates its predictive capacity. For the CBD, the best PLS model achieved a coefficient of 0.77 and an RPD value > 2, also indicating the goodness of the prediction model.\nAlthough the number of samples in this study was limited due to the high cost of HPLC, it allowed us to demonstrate the potential of NIRS for the determination of the main cannabinoid content in samples of the Kompolti variety. Due to the goodness of the models and the results obtained, this study may be extended to include a larger number of samples or other varieties of industrial hemp with a wider concentration of THC.\nThe results obtained here demonstrate that NIR spectroscopy offers speed and simplicity unmatched by other traditional techniques. Accordingly, it was tested as an alternative to conventional HPLC analysis for the evaluation of cannabinoid content with promising results.\n\nAcknowledgements \nThe authors would like to thank Genscore Navarra S.L. for access to the plant material samples used in this study.\n\nAuthor contributions \nConceptualization, C.J., A.\u00c1. and S.A.; Data curation, S.A., A.L.-M. and C.J.; Formal analysis, S.A., C.P.-R., A.L.-M. and P.C.Z.; Funding acquisition, C.J. and A.\u00c1.; Investigation, C.P.-R., A.L.-M., C.J., P.C.Z. and S.A.; Methodology, P.C.Z., C.J., C.P.-R., A.L.-M. and S.A.; Project administration, A.\u00c1. and S.A.; Resources, C.J., A.\u00c1. and S.A.; Software, S.A.; Supervision, C.P.-R., A.L.-M., C.J. and S.A.; Validation, P.C.Z., C.P.-R., A.L.-M. and C.J.; Visualization, C.P.-R. and A.L.-M.; Writing\u2014original draft, P.C.Z., C.J. and A.L.-M.; Writing\u2014review and editing, P.C.Z., C.P.-R., A.L.-M., C.J., A.\u00c1. and S.A. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis research received no external funding. Open access co-funding provided by Institute for Sustainability & Food Chain Innovation (IS-FOOD).\n\nConflicts of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 1.0 1.1 Iversen, Leslie L. (2019). The science of marijuana (3rd Edition ed.). New York: Oxford University Press. ISBN 978-0-19-084684-8.   \n \n\n\u2191 Russo, Ethan B (1 August 2011). \"Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects\" (in en). British Journal of Pharmacology 163 (7): 1344\u20131364. doi:10.1111\/j.1476-5381.2011.01238.x. PMC PMC3165946. PMID 21749363. https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01238.x .   \n \n\n\u2191 HempToday (23 October 2020). \"El Parlamento Europeo aprueba el aumento del l\u00edmite de THC de la UE al 0,3%\". 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Talanta 167: 344\u2013351. doi:10.1016\/j.talanta.2017.02.026. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914017302400 .   \n \n\n\u2191 Duchateau, C\u00e9line; Kauffmann, Jean\u2010Michel; Canfyn, Micha\u00ebl; St\u00e9vigny, Caroline; De Braekeleer, Kris; Deconinck, Eric (1 September 2020). \"Discrimination of legal and illegal Cannabis spp. according to European legislation using near infrared spectroscopy and chemometrics\" (in en). Drug Testing and Analysis 12 (9): 1309\u20131319. doi:10.1002\/dta.2865. ISSN 1942-7603. https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dta.2865 .   \n \n\n\u2191 Risoluti, Roberta; Gullifa, Giuseppina; Battistini, Alfredo; Materazzi, Stefano (1 May 2020). \"Monitoring of cannabinoids in hemp flours by MicroNIR\/Chemometrics\" (in en). Talanta 211: 120672. doi:10.1016\/j.talanta.2019.120672. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914019313050 .   \n \n\n\u2191 Ministerio de Agricultura, Pesca y Alimentaci\u00f3n (12 November 1999). \"Real Decreto 1729\/1999, de 12 de noviembre, por el que se establecen las normas para la solicitud y concesi\u00f3n de las ayudas al lino textil y al c\u00e1\u00f1amo\". Agencia Estatal Bolet\u00edn Oficial del Estado. Gobierno de Espa\u00f1a. https:\/\/www.boe.es\/eli\/es\/rd\/1999\/11\/12\/1729 .   \n \n\n\u2191 18.0 18.1 18.2 \"Commission Delegated Regulation (EU) 2017\/1155 of 15 February 2017 amending Delegated Regulation (EU) No 639\/2014 as regards the control measures relating to the cultivation of hemp, certain provisions on the greening payment, the payment for young farmers in control of a legal person, the calculation of the per unit amount in the framework of voluntary coupled support, the fractions of payment entitlements and certain notification requirements relating to the single area payment scheme and the voluntary coupled support, and amending Annex X to Regulation (EU) No 1307\/2013 of the European Parliament and of the Council\". EUR-Lex. European Union. 15 February 2017. http:\/\/data.europa.eu\/eli\/reg_del\/2017\/1155\/oj .   \n \n\n\u2191 19.0 19.1 19.2 United Nations Office on Drugs and Crime (March 2022). \"Recommended Methods for the Identification and Analysis of Cannabis and Cannabis Products\". United Nations. https:\/\/www.unodc.org\/unodc\/en\/scientists\/recommended-methods-for-the-identification-and-analysis-of-cannabis-and-cannabis-products.html .   \n \n\n\u2191 20.0 20.1 20.2 Shenk, J.S.; Westerhaus, M.O. (1996). \"Calibration the ISI way\". In Davies, Anthony M. C.; International Conference on Near Infrared Spectroscopy. Near infrared spectroscopy: the future waves ; the proceedings of the 7th International Conference on Near Infrared Spectroscopy, Montr\u00e9al, Canada, 6 - 11 August 1995. Chichester: NIR Publ. pp. 198\u2013202. ISBN 978-0-9528666-0-2. OCLC 636222940. https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/636222940 .   \n \n\n\u2191 Nicola\u00ef, Bart M.; Beullens, Katrien; Bobelyn, Els; Peirs, Ann; Saeys, Wouter; Theron, Karen I.; Lammertyn, Jeroen (1 November 2007). \"Nondestructive measurement of fruit and vegetable quality by means of NIR spectroscopy: A review\" (in en). Postharvest Biology and Technology 46 (2): 99\u2013118. doi:10.1016\/j.postharvbio.2007.06.024. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925521407002293 .   \n \n\n\u2191 European Medicines Agency (6 May 2014). \"Guideline on the use of near-infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations\". European Union. https:\/\/www.ema.europa.eu\/en\/use-near-infrared-spectroscopy-nirs-pharmaceutical-industry-data-requirements-new-submissions .   \n \n\n\u2191 Zeaiter, M.; Roger, J.-M.; Bellon-Maurel, V. (1 May 2005). \"Robustness of models developed by multivariate calibration. Part II: The influence of pre-processing methods\" (in en). TrAC Trends in Analytical Chemistry 24 (5): 437\u2013445. doi:10.1016\/j.trac.2004.11.023. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993605000580 .   \n \n\n\u2191 Barnes, R. J.; Dhanoa, M. S.; Lister, Susan J. (1 July 1989). \"Standard Normal Variate Transformation and De-Trending of Near-Infrared Diffuse Reflectance Spectra\" (in en). Applied Spectroscopy 43 (5): 772\u2013777. doi:10.1366\/0003702894202201. ISSN 0003-7028. http:\/\/journals.sagepub.com\/doi\/10.1366\/0003702894202201 .   \n \n\n\u2191 Buddenbaum, Henning; Steffens, Markus (2012). \"The Effects of Spectral Pretreatments on Chemometric Analyses of Soil Profiles Using Laboratory Imaging Spectroscopy\" (in en). Applied and Environmental Soil Science 2012: 1\u201312. doi:10.1155\/2012\/274903. ISSN 1687-7667. http:\/\/www.hindawi.com\/journals\/aess\/2012\/274903\/ .   \n \n\n\u2191 Datt, B. (1 January 1999). \"Visible\/near infrared reflectance and chlorophyll content in Eucalyptus leaves\" (in en). International Journal of Remote Sensing 20 (14): 2741\u20132759. doi:10.1080\/014311699211778. ISSN 0143-1161. https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/014311699211778 .   \n \n\n\u2191 Martens, Harald; Stark, Edward (1 January 1991). \"Extended multiplicative signal correction and spectral interference subtraction: New preprocessing methods for near infrared spectroscopy\" (in en). Journal of Pharmaceutical and Biomedical Analysis 9 (8): 625\u2013635. doi:10.1016\/0731-7085(91)80188-F. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/073170859180188F .   \n \n\n\u2191 Rinnan, \u00c5smund; Berg, Frans van den; Engelsen, S\u00f8ren Balling (1 November 2009). \"Review of the most common pre-processing techniques for near-infrared spectra\" (in en). TrAC Trends in Analytical Chemistry 28 (10): 1201\u20131222. doi:10.1016\/j.trac.2009.07.007. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993609001629 .   \n \n\n\u2191 Jamshidi, Bahareh; Minaei, Saeid; Mohajerani, Ezzedin; Ghassemian, Hassan (1 July 2012). \"Reflectance Vis\/NIR spectroscopy for nondestructive taste characterization of Valencia oranges\" (in en). Computers and Electronics in Agriculture 85: 64\u201369. doi:10.1016\/j.compag.2012.03.008. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169912000828 .   \n \n\n\u2191 Vasques, G.M.; Grunwald, S.; Sickman, J.O. (1 July 2008). \"Comparison of multivariate methods for inferential modeling of soil carbon using visible\/near-infrared spectra\" (in en). Geoderma 146 (1-2): 14\u201325. doi:10.1016\/j.geoderma.2008.04.007. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016706108000980 .   \n \n\n\u2191 Ertlen, D.; Schwartz, D.; Trautmann, M.; Webster, R.; Brunet, D. (1 April 2010). \"Discriminating between organic matter in soil from grass and forest by near-infrared spectroscopy\" (in en). European Journal of Soil Science 61 (2): 207\u2013216. doi:10.1111\/j.1365-2389.2009.01219.x. https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2389.2009.01219.x .   \n \n\n\u2191 Williams, Phil; Dardenne, Pierre; Flinn, Peter (1 April 2017). \"Tutorial: Items to be included in a report on a near infrared spectroscopy project\" (in en). Journal of Near Infrared Spectroscopy 25 (2): 85\u201390. doi:10.1177\/0967033517702395. ISSN 0967-0335. http:\/\/journals.sagepub.com\/doi\/10.1177\/0967033517702395 .   \n \n\n\u2191 33.0 33.1 Williams, Phil; Norris, K. H.; American Association of Cereal Chemists, eds. (2001). Near-infrared technology: in the agricultural and food industries (2nd ed ed.). St. Paul, Minn: American Association of Cereal Chemists. ISBN 978-1-891127-24-3.   \n \n\n\u2191 34.0 34.1 Workman, Jerry; Weyer, Lois (2012) (in English). Practical guide and spectral atlas for interpretive near-infrared spectroscopy. Boca Raton: CRC Press. ISBN 978-1-4398-7526-1. OCLC 939973422. http:\/\/www.crcnetbase.com\/isbn\/9781439875261 .   \n \n\n\u2191 Williams, Phil; Antoniszyn, John; Manley, Marena (2019) (in English). Near infrared technology: getting the best out of light. ISBN 978-1-928480-30-3. OCLC 1128180884. https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1128180884 .   \n \n\n\u2191 Saeys, W.; Mouazen, A.M.; Ramon, H. (1 August 2005). \"Potential for Onsite and Online Analysis of Pig Manure using Visible and Near Infrared Reflectance Spectroscopy\" (in en). Biosystems Engineering 91 (4): 393\u2013402. doi:10.1016\/j.biosystemseng.2005.05.001. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1537511005000838 .   \n \n\n\u2191 Deidda, Riccardo; Coppey, Florentin; Damergi, Dhouha; Schelling, C\u00e9dric; Co\u00efc, Laureen; Veuthey, Jean-Luc; Sacr\u00e9, Pierre-Yves; De Bleye, Charlotte et al. (1 August 2021). \"New perspective for the in-field analysis of cannabis samples using handheld near-infrared spectroscopy: A case study focusing on the determination of \u03949-tetrahydrocannabinol\" (in en). Journal of Pharmaceutical and Biomedical Analysis 202: 114150. doi:10.1016\/j.jpba.2021.114150. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521002612 .   \n \n\n\u2191 Chen, Zewei; de Boves Harrington, Peter; Griffin, Veronica; Griffin, Todd (26 November 2021). \"In Situ Determination of Cannabidiol in Hemp Oil by Near-Infrared Spectroscopy\" (in en). Journal of Natural Products 84 (11): 2851\u20132857. doi:10.1021\/acs.jnatprod.1c00557. ISSN 0163-3864. https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00557 .   \n \n\n\u2191 Cirrincione, Marco; Saladini, Bruno; Brighenti, Virginia; Salamone, Stefano; Mandrioli, Roberto; Pollastro, Federica; Pellati, Federica; Protti, Michele et al. (1 September 2021). \"Discriminating different Cannabis sativa L. chemotypes using attenuated total reflectance - infrared (ATR-FTIR) spectroscopy: A proof of concept\" (in en). Journal of Pharmaceutical and Biomedical Analysis 204: 114270. doi:10.1016\/j.jpba.2021.114270. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521003812 .   \n \n\n\u2191 Geskovski, Nikola; Stefkov, Gjose; Gigopulu, Olga; Stefov, Stefan; Huck, Christian W.; Makreski, Petre (1 April 2021). \"Mid-infrared spectroscopy as process analytical technology tool for estimation of THC and CBD content in Cannabis flowers and extracts\" (in en). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 251: 119422. doi:10.1016\/j.saa.2020.119422. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142520314013 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)<\/a>\nCategories: CannaQAwiki journal articles (added in 2022)CannaQAwiki journal articles (all)CannaQAwiki journal articles on cannabis cannabinoidsCannaQAwiki journal articles on cannabis testingNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inNavigationMain pageList of articlesRandom pageRecent changesHelpSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPrintable versionPermanent linkPage information This page was last edited on 11 May 2022, at 17:43.Content is available under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License unless otherwise noted.Privacy policyAbout CannaQAWikiDisclaimers\n","e54c0b7e681c5437811a012a24acebea_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-170 ns-subject page-Journal_Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_Cannabis_sativa_L rootpage-Journal_Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_Cannabis_sativa_L skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Potential of NIRS technology for the determination of cannabinoid content in industrial hemp (<i>Cannabis sativa<\/i> L.)<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>Industrial <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Hemp\" title=\"Hemp\" class=\"wiki-link\" data-key=\"c23e30b6cf1df54f1dc338492c9f9da2\">hemp<\/a> (<i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\">Cannabis sativa<\/a><\/i> L.) is a plant native to Asia and is considered to be a primary source of food, textile fiber, and medicines. It is characterized by containing minimal concentrations of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinol\" title=\"Tetrahydrocannabinol\" class=\"wiki-link\" data-key=\"15f3b3e338baeb54c04c715818759ec9\">\u0394<sup>9<\/sup>-tetrahydrocannabinol<\/a> (THC), which is the main <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Psychoactive_drug\" title=\"Psychoactive drug\" class=\"wiki-link\" data-key=\"abba12c7100bf1c8457208da20b4234b\">psychoactive chemical<\/a> component, and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiol\" title=\"Cannabidiol\" class=\"wiki-link\" data-key=\"bbfcdd40d5eda5d20d1d5ab368c922a0\">cannabidiol<\/a> (CBD), a non-psychoactive substance. In most European countries, the maximum concentration legally allowed for cultivation is 0.2% of THC, and it is currently under debate whether to increase this level to 0.3%. Moreover, in many countries its production is being regulated and legalized, increasing the need for a rapid analysis method. \n<\/p><p>The present work evaluated the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">cannabinoid<\/a> content in hemp using <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Near-infrared_spectroscopy\" title=\"Near-infrared spectroscopy\" class=\"wiki-link\" data-key=\"14e10c9378a8697e87e36208c4f057de\">near-infrared spectroscopy<\/a> (NIRS) technology in combination with <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chemometrics\" title=\"Chemometrics\" class=\"wiki-link\" data-key=\"b2d14e445af0e6bd6ab5534a017591cc\">chemometric techniques<\/a>. For this, several <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"2d7596b7c3616db8f56af698be478d3d\">samples<\/a> of the Kompolti variety were analyzed. Samples were dried and ground, and the content of total THC (%) and total CBD (%) was determined by <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=High-performance_liquid_chromatography\" title=\"High-performance liquid chromatography\" class=\"wiki-link\" data-key=\"4c5d83ffa9785383c3eb0be7ea78dd2b\">high-performance liquid chromatography<\/a> (HPLC) with a <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chromatography_detector\" title=\"Chromatography detector\" class=\"wiki-link\" data-key=\"7787a159a1c7c0a3b2cc28bbc3189587\">diode array detector<\/a> for reference measurements, and then the spectra were collected by NIRS. Principal component analysis and partial least square regression models were developed. Good coefficients of determination of cross-validation of 0.77 for THC and CBD, and a ratio of prediction to deviation >2 for total THC and CBD, were achieved. The results obtained show that NIRS technology has potential for the quantitative determination of cannabinoids. Therefore, this analytical method would allow a simpler, more robust, precise, and sustainable estimation than the current HPLC approach.\n<\/p><p><b>Keywords<\/b>: CBD, THC, near infrared spectroscopy, quantification, HPLC, chemometrics\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p>The non-psychotropic species <i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\">Cannabis sativa<\/a><\/i> L., referred to as industrial <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Hemp\" title=\"Hemp\" class=\"wiki-link\" data-key=\"c23e30b6cf1df54f1dc338492c9f9da2\">hemp<\/a><sup id=\"rdp-ebb-cite_ref-:0_1-0\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup>, is characterized by containing minimal concentrations of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinol\" title=\"Tetrahydrocannabinol\" class=\"wiki-link\" data-key=\"15f3b3e338baeb54c04c715818759ec9\">\u0394<sup>9<\/sup>-tetrahydrocannabinol<\/a> (THC), the main <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Psychoactive_drug\" title=\"Psychoactive drug\" class=\"wiki-link\" data-key=\"abba12c7100bf1c8457208da20b4234b\">psychoactive chemical<\/a> component, and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiol\" title=\"Cannabidiol\" class=\"wiki-link\" data-key=\"bbfcdd40d5eda5d20d1d5ab368c922a0\">cannabidiol<\/a> (CBD), a non-psychoactive substance that is often present in amounts similar to those of THC.<sup id=\"rdp-ebb-cite_ref-:0_1-1\" class=\"reference\"><a href=\"#cite_note-:0-1\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-2\" class=\"reference\"><a href=\"#cite_note-2\">[2]<\/a><\/sup> Hemp is mainly used for food or textile purposes and, in addition, offers great <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_(drug)\" title=\"Cannabis (drug)\" class=\"wiki-link\" data-key=\"6500790ffdd84957d4b055c47e48efca\">medicinal<\/a> potential. Although the regulations of different countries vary according to the definition of the maximum accepted THC limit, industrial-hemp-producing countries require that the varieties used contain THC concentrations lower than 1%. In most European countries, the current upper legal limit for cultivation is 0.2% of THC and the ratio of CBD to THC should be greater than one. Currently, the maximum concentration legally permitted for <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_cultivation\" title=\"Cannabis cultivation\" class=\"wiki-link\" data-key=\"2a93fc4d018f9aaacd8e9024a56eaa13\">cultivation<\/a> is under debate in the European Union.<sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup>\n<\/p><p>It is important to note that the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Inflorescence\" title=\"Inflorescence\" class=\"wiki-link\" data-key=\"d8122354225ee6a932a086ca8a1b999f\">flower<\/a> is the part of hemp with the highest significant content of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">cannabinoids<\/a>.<sup id=\"rdp-ebb-cite_ref-:1_4-0\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> These, when heated, spontaneously <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Decarboxylation\" title=\"Decarboxylation\" class=\"wiki-link\" data-key=\"d193a62772bddc5385f7d9c5e8543446\">decarboxylate<\/a> to the \u201cneutral\u201d cannabinoids THC and CBD. This heat-labile characteristic of acidic cannabinoids (e.g., <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinolic_acid\" title=\"Tetrahydrocannabinolic acid\" class=\"wiki-link\" data-key=\"a047dcf0f7a85c57e1d2d308b56e5e4a\">tetrahydrocannabinolic acid<\/a> [THCA] and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiolic_acid\" title=\"Cannabidiolic acid\" class=\"wiki-link\" data-key=\"772927eeed478eff799c410179be18a1\">cannabidiolic acid<\/a> [CBDA]) highlights the importance of using a low-temperature, non-destructive method to achieve a precise quantification of these molecules.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup> Moreover, for all stakeholders in the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis\" title=\"Cannabis\" class=\"wiki-link\" data-key=\"a70b76268930d795518ff1f98d7e500d\">cannabis<\/a> supply chain, a precise and trustworthy identification of these cannabinoids would be of great economic importance.<sup id=\"rdp-ebb-cite_ref-:1_4-1\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup>\n<\/p><p>Traditionally, cannabinoid content has been determined by <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=High-performance_liquid_chromatography\" title=\"High-performance liquid chromatography\" class=\"wiki-link\" data-key=\"4c5d83ffa9785383c3eb0be7ea78dd2b\">high-performance liquid chromatography<\/a> (HPLC) and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Gas_chromatography\" title=\"Gas chromatography\" class=\"wiki-link\" data-key=\"5094f035cb8bead5003deb9181e398b8\">gas chromatography<\/a> (GC). HPLC provides a full cannabinoid profile, but it has several associated disadvantages, including <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"2d7596b7c3616db8f56af698be478d3d\">sample<\/a> destruction, complex instrumentation, involvement of hazardous chemicals, and longer sample preparation times, which limit its application on-site, where a fast and non-destructive process is preferable.<sup id=\"rdp-ebb-cite_ref-:1_4-2\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> Similarly, GC is another preferred method for the determination of these compounds. However, it is a slow and expensive technique, requiring a tedious sample preparation stage that involves the extraction of the active ingredients through the use of organic <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Solvent\" title=\"Solvent\" class=\"wiki-link\" data-key=\"978fd0f359891b1cb3927105fa01e23f\">solvents<\/a>, whose subsequent <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Contamination\" title=\"Contamination\" class=\"wiki-link\" data-key=\"0663203ff7531a97a6d414b3ecc2c94d\">residues<\/a> must be managed with a considerable increase in cost and time.<sup id=\"rdp-ebb-cite_ref-:2_6-0\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup>\n<\/p><p>These limitations have led to a search for faster and easier-to-use alternatives to HPLC and GC.<sup id=\"rdp-ebb-cite_ref-:1_4-3\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> Therefore, it is important to develop a simple, fast, and sustainable method for the quantification of cannabinoids. In recent years, <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Spectroscopy\" title=\"Spectroscopy\" class=\"wiki-link\" data-key=\"428e22273ecbb259c2e0215537151584\">spectroscopic<\/a> methods have emerged as techniques that are used on a wide range of biological samples without the need for extraction.<sup id=\"rdp-ebb-cite_ref-:3_7-0\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup> One such technique is <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Near-infrared_spectroscopy\" title=\"Near-infrared spectroscopy\" class=\"wiki-link\" data-key=\"14e10c9378a8697e87e36208c4f057de\">near-infrared spectroscopy<\/a> (NIRS), which is a fast, cost-effective, versatile, robust, and sustainable technique. In addition, it allows both quantitative and qualitative determinations of the main parameters, such as proteins, fats, humidity, ashes, starch, or sugar, of the raw materials related to the quality of agricultural products.<sup id=\"rdp-ebb-cite_ref-:2_6-1\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> In recent years, the interest in NIRS applied to hemp has gained importance due to the moisture, volatile substances, and chemical compounds in herbal products absorbed in the NIR region. In general, NIRS combined with <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chemometrics\" title=\"Chemometrics\" class=\"wiki-link\" data-key=\"b2d14e445af0e6bd6ab5534a017591cc\">chemometrics<\/a> has great potential in the analysis of natural plant products.<sup id=\"rdp-ebb-cite_ref-:4_8-0\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup>\n<\/p><p>It should be taken into account that the cannabis flower is heterogeneous in nature, which presents a series of problems and drawbacks. It is a complex matrix, made up of a great variety of types of plant tissues and more than 500 different naturally produced chemicals. Moreover, it is a material that can vary widely between plants of the same crop, in an individual plant, and even within the same sample.<sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup> Consequently, no two parts of the cannabis flower are alike, and their cannabinoid content is likely to vary widely. In this scenario, NIRS technology is an adequate alternative for the analysis of heterogeneous vegetal samples and may therefore overcome the inherent heterogeneity of the cannabis plant.<sup id=\"rdp-ebb-cite_ref-:1_4-4\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup>\n<\/p><p>NIRS has been applied to discriminate between cannabis \u201cdrug type\u201d (<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chemotype\" title=\"Chemotype\" class=\"wiki-link\" data-key=\"2cee49cb83af61d36357ce99efa5ab72\">chemotype<\/a> I) and \u201cfiber type\u201d (chemotype II)<sup id=\"rdp-ebb-cite_ref-10\" class=\"reference\"><a href=\"#cite_note-10\">[10]<\/a><\/sup>, for the discrimination of leaves of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\"><i>Cannabis sativa<\/i><\/a> L. and other plant species<sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup>, and for the prediction of the growth stage of cannabis plants in the early stages of cultivation.<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup>\n<\/p><p>Marcel <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup> developed a prediction model of the chemical composition of the fiber and the central fraction of hemp (chemotype III) using NIRS combined with a partial least squares (PLS) regression analysis. Similarly, a procedure was developed for the identification and quantitative determination of synthetic cannabinoids in illicit herbal samples. The methodology was based on the measurement by <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Fourier-transform_infrared_spectroscopy\" title=\"Fourier-transform infrared spectroscopy\" class=\"wiki-link\" data-key=\"ed4db292d8cae0aec6becf614dfa9bff\">Fourier-transform infrared spectroscopy<\/a> of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Attenuated_total_reflectance\" title=\"Attenuated total reflectance\" class=\"wiki-link\" data-key=\"f08d8566935999f3db4964d4f167d03d\">attenuated total reflectance<\/a> (ATR-FTIR).<sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup>\n<\/p><p>Moreover, the total content of THC and CBD in the cannabis flower has been determined by <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Fourier-transform_infrared_spectroscopy#Near-infrared\" title=\"Fourier-transform infrared spectroscopy\" class=\"wiki-link\" data-key=\"1a72ff70672b574849970777d8063760\">Fourier-transform near-infrared spectroscopy<\/a> (FT\u2013NIR).<sup id=\"rdp-ebb-cite_ref-:1_4-5\" class=\"reference\"><a href=\"#cite_note-:1-4\">[4]<\/a><\/sup> Similarly, S\u00e1nchez-Carnerero <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:2_6-2\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> studied the prediction of cannabinoid content using NIRS. They used both FT-NIR and NIR <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Spectrophotometry\" title=\"Spectrophotometry\" class=\"wiki-link\" data-key=\"d3cee63e4f34b9fef1bd638cc1f5a66f\">spectrophotometers<\/a> for their analysis and compared the results obtained with the two techniques. Similar results were obtained using both instruments, thus confirming that there is enough information in the spectral region of the NIR for the prediction of cannabinoids.\n<\/p><p>More recently, Duchateau <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup> created two classification methods according to the European laws about the discrimination of the legal limits of <i>Cannabis<\/i> spp. using NIR. Valinger <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:3_7-1\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup> described the development of <a href=\"https:\/\/en.wikipedia.org\/wiki\/artificial_neural_network\" class=\"extiw wiki-link\" title=\"wikipedia:artificial neural network\" data-key=\"ddefcd0489da4a97376f7d723f975535\">artificial neural network<\/a> (ANN) models for the prediction of the physical and chemical properties of industrial hemp extracts, based on the combination of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Ultraviolet%E2%80%93visible_spectroscopy\" title=\"Ultraviolet\u2013visible spectroscopy\" class=\"wiki-link\" data-key=\"544f7ef37bc31936b5584244f6f6e635\">ultraviolet-visible<\/a> near-infrared (UV-VIS-NIR) spectra. For this, two different extraction methods were prepared (solid\u2013liquid extraction and microwave-assisted extraction). The results showed that reliable ANN models can be developed to describe the physical and chemical characteristics, without the need for pre-processing of the spectra. In a recent study, Risoluti <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-16\" class=\"reference\"><a href=\"#cite_note-16\">[16]<\/a><\/sup>, using a MicroNIR spectrometer, developed a test for cannabinoid determination in commercial hemp flours spiked with THC, CBD, and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerol\" title=\"Cannabigerol\" class=\"wiki-link\" data-key=\"6fc007b4c33a4c59a485b2c621035714\">cannabigerol<\/a> (CBG).\n<\/p><p>Therefore, the aim of this study was to evaluate the functionality of NIRS for the quantification of the main cannabinoids present in hemp samples. In addition, a study of the NIR spectra was carried out to identify the peaks.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Vegetal_material\">Vegetal material<\/span><\/h3>\n<p>Thirty-five hemp samples were obtained in collaboration with Genscore Navarra S.L. The specimens obtained were of the Kompolti variety, which is among the varieties authorized for the cultivation of industrial hemp in Spain.<sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup>\n<\/p><p>The plant material was weighed on a AB104 Mettler-Toledo analytical balance and dried in an oven at 60 \u00b0C for 24 hours, until a humidity between 8% and 13% was achieved, as recommended by regulation (EU) 2017\/1155.<sup id=\"rdp-ebb-cite_ref-:5_18-0\" class=\"reference\"><a href=\"#cite_note-:5-18\">[18]<\/a><\/sup>\n<\/p><p>Stems and seeds of more than 2 mm were removed from the dry samples and, with the help of a mortar, they were crushed until obtaining a semi-fine powder, in such a way that it could pass through a 1 mm mesh sieve. The samples were stored, without crushing them, in a dark place at a temperature below 25 \u00b0C.<sup id=\"rdp-ebb-cite_ref-:5_18-1\" class=\"reference\"><a href=\"#cite_note-:5-18\">[18]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_19-0\" class=\"reference\"><a href=\"#cite_note-:6-19\">[19]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Spectra_acquisition\">Spectra acquisition<\/span><\/h3>\n<p>Spectra were collected using an Acousto-Optic Tunable Filter (AOTF) NIR and Indium Gallium Arsenide (InGaAs) detector, called a Luminar 5030 Miniature \"Hand-held,\" in the reflectance mode and equipped with Snap32! software (Brimrose Corporation of America, Sparks, MD, USA). A spectral range of 1200\u20132200 nm was used to obtain the spectra, with a sampling interval of 2 nm, and scanning speed of 60 ms. Each spectrum recorded by the instrument was the average of 50 scans.\n<\/p><p>In this study, 3 g of each of the 35 hemp powder samples was weighed and placed on the rotating cell of the AOTF-NIR spectrophotometer. As the sample rotates, the spectrum is measured so that different parts of the sample are scanned from above and inhomogeneities averaged. For each individual sample, three reflectance spectra were acquired by contacting the probe with the sample.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Reference_measurements:_HPLC\">Reference measurements: HPLC<\/span><\/h3>\n<p>After acquisition of the NIRS data, the same hemp samples were removed from the Petri dishes and sent to a certified <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"ed14e6a67b4b14ad2c190c28455725f6\">laboratory<\/a>, ANANDA ANALYTICS LAB S.L., where an HPLC with <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chromatography_detector\" title=\"Chromatography detector\" class=\"wiki-link\" data-key=\"7787a159a1c7c0a3b2cc28bbc3189587\">diode array detector<\/a> (HPLC-DAD) method was used for the determination of total THC and total CBD cannabinoids. The extraction was performed by ultrasound with subsequent methanol-chloroform decarboxylation. The mobile phase was acetonitrile (water [8:2 v\/v], isocratic, stop time 8 minutes) according to <i>Recommended methods for the identification and analysis of cannabis and cannabis products<\/i> by the United Nations Office on Drugs and Crime.<sup id=\"rdp-ebb-cite_ref-:6_19-1\" class=\"reference\"><a href=\"#cite_note-:6-19\">[19]<\/a><\/sup> Regarding the result, for a qualitative identification, the retention time and the DAD spectrum of the cannabinoid must match. The calculation for the quantitative results was carried out at the wavelengths of 220 and 240 nm.\n<\/p><p>The results were received after 10 days and, then, these reference chromatographic data were correlated with the spectral information to generate the NIR models for total THC and CBD prediction. Thirty-two of 35 samples were analyzed by HPLC-DAD, with three fungus-infected hemp plants being identified and excluded.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Multivariate_data_analysis\">Multivariate data analysis<\/span><\/h3>\n<p>Data analysis was performed using the specific software The Unscrambler X v.10.4 (Camo Software AS, Oslo, Norway). First, principal component analysis (PCA) was performed with the full set of samples. PCA was applied to explore the spectral variability of the population<sup id=\"rdp-ebb-cite_ref-:7_20-0\" class=\"reference\"><a href=\"#cite_note-:7-20\">[20]<\/a><\/sup>, which also allows elimination of outliers that can have a negative effect on modeling.<sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup>\n<\/p><p>During the pre-model building phase, data pre-processing was carried out to eliminate the non-informative effects of light scattering or system noise. For the development of the models, in addition to working with the raw data, different data pretreatments were applied: spectra normalization, standard normal variate (SNV), standard normal variate and detrend (SNV-DT), multiplicative scatter correction (MSC), and first derivative. These are described as such:\n<\/p>\n<ul><li><b>Raw data<\/b>: The absolute reflectance was obtained from the radiation measurements of the 35 samples, with three repetitions each.<\/li>\n<li><b>Spectra normalization<\/b>: Raw NIR spectra are often mathematically processed prior to development of the calibration model; such treatments include normalization, which is performed to minimize unwanted sources of data variation prior to calibration and to improve spectral characteristics.<sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup> Mean normalization was performed in this study, which is the most classical approach. In this normalization, each sample of the dataset (each row of the data matrix) is divided by its average.<\/li>\n<li><b>SNV<\/b>: To eliminate interferences due to path length effects, SNV consists of subtracting the mean value of the spectrum from each reflectance value at each wavelength and dividing it by the standard deviation.<sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup><\/li>\n<li><b>SNV-DT<\/b>: This method was developed by Barnes <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup> to eliminate multiplicative scattering interferences and particle size, and to take into account the variation in the baseline change and curvilinearity in diffuse reflectance spectra. Detrend consists of fitting a second-order polynomial to the spectrum corrected by SNV, which is subtracted to eliminate the dispersion effect that is dependent on each wavelength.<sup id=\"rdp-ebb-cite_ref-25\" class=\"reference\"><a href=\"#cite_note-25\">[25]<\/a><\/sup><\/li>\n<li><b>MSC<\/b>: This is another preprocessing technique that corrects the displacements between samples due to the particles of the samples.<sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup> MSC is undertaken by using a reference spectrum and correcting the different spectra to it so that the baseline and the amplification effects are at the same average level in all spectra.<sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup> The basic concept of MSC is to remove non-linearities in the data caused by scattering from particulates in the samples.<sup id=\"rdp-ebb-cite_ref-28\" class=\"reference\"><a href=\"#cite_note-28\">[28]<\/a><\/sup><\/li>\n<li><b>First derivative<\/b>: The first derivative of the spectra, based on the Savitzky\u2013Golay algorithm, is used to increase the spectral resolution and interpret the spectra.<sup id=\"rdp-ebb-cite_ref-29\" class=\"reference\"><a href=\"#cite_note-29\">[29]<\/a><\/sup> One smoothing point was applied to the right and another to the left, and a polynomial of order two was used to smooth and eliminate random noise from the NIR spectra. Vasques <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup> confirmed that the Savitzky\u2013Golay derivatives were among the best methods for preprocessing the spectra. Similarly, Ertlen <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup> reported that by using derivatives, more convenient information can be taken from NIR spectra.<\/li><\/ul>\n<p>After data pretreatments, a PLS regression analysis was applied to the dataset to build a model capable of predicting the content of cannabinoids, both for total THC and total CBD, in the hemp samples, and to be able to assess the effectiveness of NIR spectroscopy. For the validation of the model, cross-validation (CV) was used in order to calculate the relationships between spectral and chemical properties. Williams <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-32\" class=\"reference\"><a href=\"#cite_note-32\">[32]<\/a><\/sup> recommend CV for the evaluation of any calibration model based on small sets of samples below 100 units.\n<\/p><p>The performance of the calibration models was evaluated using the root mean square error of the calibration (RMSEC), the root mean square error of cross-validation (RMSECV), the coefficient of determination of calibration (R<sup>2<\/sup>c), the coefficient of determination of cross-validation (R<sup>2<\/sup>cv), and the ratio of prediction to deviation (RPD). The number of latent variables (LV) was used to prevent overfitting.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussions\">Results and discussions<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"HPLC_results\">HPLC results<\/span><\/h3>\n<p>For each of the samples analyzed, an individualized report was received with the sample identification data, the characteristics of the analysis methods used, and the results obtained from the HPLC-DAD analysis. The results provided by the reference laboratory, expressed as a percentage, included data for humidity, THC total, CBD total, and 12 other cannabinoids that were not the subject of this study. Thirty-two samples of 35 were analyzed by HPLC-DAD because three hemp plants infected with fungi were identified. The mean, the maximum, the minimum, and the standard deviation of the reference results can be seen in Table 1.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"13\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> HPLC-DAD analysis results\n<\/td><\/tr>\n<tr>\n<th rowspan=\"2\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Samples\n<\/th>\n<th colspan=\"4\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Humidity (%)\n<\/th>\n<th colspan=\"4\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">THC total (%)\n<\/th>\n<th colspan=\"4\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">CBD total (%)\n<\/th><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Min\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Max\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mean\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">SD\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Min\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Max\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mean\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">SD\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Min\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Max\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mean\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">SD\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">32\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.02\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12.34\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10.65\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.16\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.057\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.161\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.028\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.178\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.342\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.367\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.892\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Regarding the percentage of humidity, all samples presented values between 9.02% and 12.34%. These values are between the ranges established in the delegated regulation<sup id=\"rdp-ebb-cite_ref-:5_18-2\" class=\"reference\"><a href=\"#cite_note-:5-18\">[18]<\/a><\/sup>, which indicates a humidity of 8\u201313% in the preparation of cannabis samples. All selected samples had a THC value detected between 0.057% and 0.161%. Concerning CBD, which is currently the compound of greatest interest, the results in Table 1 show a maximum value of 5.342% and a minimum value of 2.178%, which indicates the high concentration of CBD in the samples, a characteristic of industrial cannabis.<sup id=\"rdp-ebb-cite_ref-:6_19-2\" class=\"reference\"><a href=\"#cite_note-:6-19\">[19]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Spectral_data\">Spectral data<\/span><\/h3>\n<p>In Figure 1, the spectra of the hemp sample set are shown, which correspond to the spectra collected in the Luminar 5030 AOTF-NIR spectrophotometer, where the typical reflectance bands of hemp appear in the NIR region from 1200 to 2200 nm.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig1_Jar%C3%A9n_Agronomy22_12-4.png\" class=\"image wiki-link\" data-key=\"f483e1a31e46d2569125b71c129a6647\"><img alt=\"Fig1 Jar\u00e9n Agronomy22 12-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/0\/0f\/Fig1_Jar%C3%A9n_Agronomy22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> Raw spectra of the complete set of hemp samples.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Principal component analysis (PCA) was applied to explore the spectral variability of the population, where no atypical samples were identified. This indicates that the dataset was uniformly distributed and covered as much spectral variation as possible (Figure 2). Then, PLS analysis was applied to the dataset. The results for each PLS model, for total THC and total CBD, with each pretreatment applied, including the number of samples used, were compared based on the values obtained for RMSEC, RMSECV, R<sup>2<\/sup>c, R<sup>2<\/sup>cv, LV, SD, and RPD.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig2_Jar%C3%A9n_Agronomy22_12-4.png\" class=\"image wiki-link\" data-key=\"d119c69864ccb3eb593d5da4766f2d35\"><img alt=\"Fig2 Jar\u00e9n Agronomy22 12-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/d\/da\/Fig2_Jar%C3%A9n_Agronomy22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> Score plot of PC1 versus PC2 from the PCA model.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h3><span class=\"mw-headline\" id=\"Interpretation_of_spectra\">Interpretation of spectra<\/span><\/h3>\n<p>Figure 3 shows the reflectance spectra of the samples after applying the first derivative based on the Savitzky\u2013Golay algorithm. The typical absorption bands of plant material appear in the NIR region derived from the superpositions corresponding mainly to overtones and to the combination of vibration modes that involve chemical bonds of the types C-H, O-H, and N-H.<sup id=\"rdp-ebb-cite_ref-:4_8-1\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup> In NIR reflectance spectra, the absorption bands of the molecules that make up the sample are described as valleys rather than peaks, since the absorbance equals Log (1\/Reflectance). The hemp spectra obtained in this study show the characteristic bands around 1210, 1450, 1736, 1762, 1820, 1940, 2060, and 2090 nm that are characteristic of proteins, lipids, water, and other compounds present in hemp in the main absorptions (of OH, NH, CH, and other bonds).\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig3_Jar%C3%A9n_Agronomy22_12-4.png\" class=\"image wiki-link\" data-key=\"4319d2252d9a879463349c18f2210f08\"><img alt=\"Fig3 Jar\u00e9n Agronomy22 12-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/e\/e1\/Fig3_Jar%C3%A9n_Agronomy22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 3<\/b> Main absorption bands of the spectra pretreated with the Savitzky\u2013Golay first derivative.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The 1450 and 1940 nm bands that appear in the spectra correspond to the first overtone and to the -OH group combination bands, mainly due to the presence of water. Although the samples were oven dried at 60 \u00b0C, they were left with a humidity between 8 and 13%, which may be responsible of these absorption bands. Bands associated with lipids were found around 1210 nm (second overtone of stretching vibrations) and 1762 nm (first overtone of stretching vibrations) of functional groups -CH and -CH2 corresponding to aliphatic hydrocarbons. Bands around 2060 nm have been associated with protein absorption, which are related to NH secondary combination bands of amides in proteins, for peptide groups, and those around 1820 and 2090 nm correspond to associated bands of cellulose and polymeric structure, which are related to the fiber content of hemp.<sup id=\"rdp-ebb-cite_ref-:8_33-0\" class=\"reference\"><a href=\"#cite_note-:8-33\">[33]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:9_34-0\" class=\"reference\"><a href=\"#cite_note-:9-34\">[34]<\/a><\/sup> In addition, the reflectance band found at 1736 nm corresponds to the aromatic hydrocarbons of the terpenes, of the functional group C-H.<sup id=\"rdp-ebb-cite_ref-:8_33-1\" class=\"reference\"><a href=\"#cite_note-:8-33\">[33]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:9_34-1\" class=\"reference\"><a href=\"#cite_note-:9-34\">[34]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup> This band is more evident in samples that have a higher CBD content, because <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Terpene\" title=\"Terpene\" class=\"wiki-link\" data-key=\"6bcbb95d582c08073101e9c4cfc91931\">terpenes<\/a> and cannabinoids share biosynthetic pathways, and because cannabinoids are terpene-phenolic compounds.<sup id=\"rdp-ebb-cite_ref-:2_6-3\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> In general, the absorption bands obtained in the present study are similar to those reported by other similar studies on cannabinoids.<sup id=\"rdp-ebb-cite_ref-:2_6-4\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup>\n<\/p>\n<h3><span class=\"mw-headline\" id=\"PLS_model_for_total_THC\">PLS model for total THC<\/span><\/h3>\n<p>PLS analysis was applied to the dataset using the same number of samples for both calibration and CV predictive models. The results of each PLS model for total THC applied with each pretreatment include the number of samples used, RMSEC, RMSECV, R<sup>2<\/sup>c, R<sup>2<\/sup>cv, SD, and RPD.\n<\/p><p>The results for the R<sup>2<\/sup>cv of the predictive models were higher than 0.72, which indicates that the calibration models can be considered good.<sup id=\"rdp-ebb-cite_ref-:7_20-1\" class=\"reference\"><a href=\"#cite_note-:7-20\">[20]<\/a><\/sup>\n<\/p><p>Similarly, the RPD was considered a good indicator of the predictive capacity. In the prediction of total THC content, RPD values > 2 were obtained, which indicates the goodness of the models. The higher the RPD value, the greater the ability of the calibration model to accurately predict the reference parameter values (Table 2).\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Calibration and validation statistics to predict total THC content\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Pretreatment\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Nc\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RMSEC\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RMSECV\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">R<sup>2<\/sup>c\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">R<sup>2<\/sup>cv\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LV\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RPD\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Raw data\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">91\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.010\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.87\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.77\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Standardization\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.011\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.85\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.75\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SNV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.010\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.87\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.76\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SNV-DT\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.011\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.84\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.72\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MSC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.010\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.86\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.76\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">First derivative\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.010\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.014\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.86\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.75\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.04\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Some authors have established five levels of prediction accuracy based on the RPD. Saeys <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup> indicated that models with RPD values below 1.5 should not be used for prediction; an RPD value between 1.5 and 2.0 should only be used to distinguish between high and low values; and a value between 2.0 and 2.5 can be used to make approximate quantitative predictions. Values between 2.5 and 3.0 and above 3.0 can be used for good and excellent predictions, respectively.\n<\/p><p>For total THC (%), the best model was selected according to the highest values of R<sup>2<\/sup>cv and RPD, and the lowest values of RMSECV. The results without applying any data pretreatment technique presented higher values of R<sup>2<\/sup>c of 0.87, R<sup>2<\/sup>cv of 0.77, and an RPD > 2, which indicates that approximate quantitative predictions are possible. The lower RMSECV values of 0.014 were also taken into account.\n<\/p><p>Figure 4 represents the result of the PLS model without applying any data pretreatment technique, for the quantification of total THC. The graph shows measured values (X-axis) versus predicted values (Y-axis) for total THC from the cross-validation dataset showing analogous results. The proximity between the calibration line and the cross-validation line can be observed with slopes very close to the unit, which provides an idea of the quality of the model obtained.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig4_Jar%C3%A9n_Agronomy22_12-4.png\" class=\"image wiki-link\" data-key=\"488ed04bd83b4d19c61a344cd4cdbc4e\"><img alt=\"Fig4 Jar\u00e9n Agronomy22 12-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/7\/7c\/Fig4_Jar%C3%A9n_Agronomy22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 4<\/b> PLS model for total THC without pretreatment (numbers above [blue]: calibration; numbers below [red]: cross-validation).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>In general, the results showed that the developed models had the ability to make approximate predictions of total THC content, with high R<sup>2<\/sup> and RPD, and low RMSE. Furthermore, the difference between RMSEC and RMSECV was low in all models developed. Therefore, for the determination of total THC, the prediction model obtained without applying any data pretreatment technique presented the best results, taking seven latent variables. For the rest of the calibration models carried out applying different combinations of data pretreatments, similar results were obtained with minimal differences.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"PLS_model_for_total_CBD\">PLS model for total CBD<\/span><\/h3>\n<p>The results for the R<sup>2<\/sup>cv of the predictive models were higher than 0.73, which indicates that the calibration models can be considered good, except for the first derivative model, which has an R<sup>2<\/sup>cv value of 0.68. The latter would allow adequate discrimination between samples having high, medium, and low total CBD content.<sup id=\"rdp-ebb-cite_ref-:7_20-2\" class=\"reference\"><a href=\"#cite_note-:7-20\">[20]<\/a><\/sup>\n<\/p><p>The standard deviation of CBD content was equal to 0.892, considering only the samples used for each calibration model, and 0.871 for the first derivative model. In general, the results obtained for the RPD were around 2, which indicates the possibility for approximate quantitative predictions (Table 3).\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> Calibration and validation statistics for predicting total CBD content\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Pretreatment\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Nc\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RMSEC\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RMSECV\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">R<sup>2<\/sup>c\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">R<sup>2<\/sup>cv\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LV\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RPD\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Raw data\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.333\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.431\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.86\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.77\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.07\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Standardization\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.361\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.459\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.83\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.74\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.94\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SNV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.357\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.464\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.84\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.73\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.92\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">SNV-DT\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.358\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.459\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.84\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.74\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.94\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">MSC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.359\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.465\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.84\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.73\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.91\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">First derivative\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">98\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.389\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.494\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.79\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.68\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.76\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The best model to predict CBD content was also obtained without applying any data pretreatment technique. A high R<sup>2<\/sup>c value of 0.86, R<sup>2<\/sup>cv of 0.77, and an RPD > 2 were achieved, indicating the predictive capacity of the model. The lower RMSECV values of 0.431 were also considered.\n<\/p><p>Figure 5 represents the result of the PLS model without applying any data pretreatment technique, for the quantification of total CBD.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig5_Jar%C3%A9n_Agronomy22_12-4.png\" class=\"image wiki-link\" data-key=\"fc6b077e8444f7b389b540c2809a016d\"><img alt=\"Fig5 Jar\u00e9n Agronomy22 12-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/0\/0e\/Fig5_Jar%C3%A9n_Agronomy22_12-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 5<\/b> PLS model for total CBD without pretreatment (numbers above [blue]: calibration; numbers below [red]: cross-validation).<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Moreover, as with the prediction of THC, all developed models showed an excellent performance in predicting total CBD content, with high R<sup>2<\/sup> and RPD, and low RMSE, which demonstrates the potential of NIRS for cannabinoid content estimation.\n<\/p><p>Furthermore, the difference between RMSEC and RMSECV was low in all models developed. Therefore, for the determination of the total CBD, the prediction model obtained without applying any data pre-treatment technique presented the best results, taking seven latent variables. Comparable results were obtained for the rest of the calibration models carried out applying different combinations of data pretreatments.\n<\/p><p>Interest in the determination of the cannabinoid content of <i>Cannabis sativa<\/i> has increased in recent years, as indicated by the various studies published in this field. As in this study, other authors have achieved good results for the prediction of THC and CBD by NIRS without any data pretreatment. For example, S\u00e1nchez-Carnerero <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:2_6-5\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> obtained an R<sup>2<\/sup>cv of 0.99 for CBD and an R<sup>2<\/sup>cv of 0.99 for THC with an FT-NIR instrument. However, using a NIR Systems 6500 scanning monochromator for CBD prediction, a SNV-DT pretreatment was applied, and resulted in an R<sup>2<\/sup>cv of 0.99 and a MSC for THC with an R<sup>2<\/sup>cv 0.98 and an RPD of 3.07.\n<\/p><p>In a more recent study, Deidda <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup> explored the feasibility of using NIRS for the quantitative analysis of THC. For this study, two handheld NIR spectrophotometers were used and compared, a low-cost device (NIR-S-G1) and a mid-cost device (MicroNIR onsite W 1700). Both entire inflorescence and resin samples were analyzed, and the reference method used was UHPLC coupled to UV detection. A preliminary study was conducted on 26 entire inflorescences that were then ground and sieved in order to evaluate the impact of sample homogeneity on the THC content predictions. Researchers obtained a THC concentration far wider than in our study, ranging from 0.92 to 22.21%. RPD values between 1 and 4.54 were obtained for the different physical forms of samples using both devices. In general, the MicroNIR spectrophotometer outperformed NIR-S-G1. Moreover, 45 resin samples were analyzed with both devices, obtaining an RPD value of 2.26 with the MicroNIR and 1.51 with NIR-S-G1. Therefore, authors concluded that the mid-cost system was the best-suited spectrophotometer for their application.\n<\/p><p>In another study carried out by Chen <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup>, a different approach was adopted in which the authors explored the potential of NIRS for the <i>in situ<\/i> determination of CBD in hemp oil. For their study, 20 hemp oil samples with different concentrations of CBD and CBDA (determined by HPLC) were analyzed by a Bruker MATRIX-F FT-NIR spectrometer covering the 4000 to 12,000 cm<sup>\u22121<\/sup> range. Super partial least-squares regression (sPLSR) and a self-optimizing support vector elastic net (SOSVEN) were applied to predict the concentrations of CBD, achieving promising results with a coefficient of determination for the validation set >0.98 and an RMSEV of 6.4 \u00b1 0.1 mg\/mL.\n<\/p><p>In addition, as mentioned in the introduction, spectroscopic techniques have been used to differentiate fiber-type from drug-type <i>Cannabis sativa<\/i> L.<sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup> In that study, ATR-FTIR in the 5000\u2013400 cm<sup>\u22121<\/sup> region was used to assess 36 samples of <i>C. sativa<\/i> inflorescences; eight were drug-type, 14 fiber-type, and another set of 14 were cannabis samples having a low THC concentration. PLS models were developed to predict the content of seven neutral and acidic cannabinoids (THC, THCA, CBD, CBDA, CBG, <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerolic_acid\" title=\"Cannabigerolic acid\" class=\"wiki-link\" data-key=\"d0a5399af99137ebf5aa893d34531e49\">cannabigerolic acid<\/a> [CBGA], and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinol\" title=\"Cannabinol\" class=\"wiki-link\" data-key=\"651d2d238facf7e91a42dc755b1cdb88\">cannabinol<\/a> [CBN]). Authors achieved very good results, with an R<sup>2<\/sup>cv higher than 0.99 for each cannabinoid and RMSECV values ranging from 0.020 to 0.163.\n<\/p><p>Moreover, mid-infrared (MIR) spectroscopy has been explored for the prediction of THC and CBD content in <i>C. sativa<\/i>. For example, Geskovski <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup> used an ATR-FTIR spectrometer, in the 1700 to 400 cm<sup>\u22121<\/sup> range, to quantify the content of THC and CBD in 45 flowers and 34 cannabis extracts. PLS models were developed for both types of sample, obtaining good results with R<sup>2<\/sup>p and RMSEP values of 0.99% and 2.32% for THC, and 0.99% and 1.33% for CBD, respectively, for the flower samples, and R<sup>2<\/sup>p and RMSEP values of 0.95% and 3.79% for THC, and 0.99% and 1.44% for CBD, in the cannabis extract samples, respectively.\n<\/p><p>In the current study, we present a feasible and low-cost method for THC and CBD content determination in <i>C. sativa<\/i> samples using NIRS. Promising results were obtained for both cannabinoids, indicating the potential of NIR technology as a predictive tool.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>The functionality of NIRS for the quantification of THC and CBD as principal cannabinoids in hemp, along with their related spectral peaks, was evaluated in this study. According to the latter, the region of the NIR spectrum analyzed presents characteristic absorption bands around 1210, 1450, 1736, 1762, 1820, 1940, 2060, and 2090 nm that are typical of proteins, lipids, water, and other compounds present in hemp (from OH, NH, CH, and other bonds). In addition, the band at 1736 nm, related to aromatic hydrocarbons of the terpenes, was associated with the CBD content, since cannabinoids are terpene-phenolic compounds.\n<\/p><p>Moreover, predictive models of the cannabinoid content in hemp were obtained combining NIR spectroscopy and chemometric analysis. The best results for the prediction of both THC and CBD were obtained using the raw data, providing a simpler form of analysis. For the THC, the best PLS model achieved a determination coefficient of cross-validation of 0.77 and an RPD value > 2, which indicates its predictive capacity. For the CBD, the best PLS model achieved a coefficient of 0.77 and an RPD value > 2, also indicating the goodness of the prediction model.\n<\/p><p>Although the number of samples in this study was limited due to the high cost of HPLC, it allowed us to demonstrate the potential of NIRS for the determination of the main cannabinoid content in samples of the Kompolti variety. Due to the goodness of the models and the results obtained, this study may be extended to include a larger number of samples or other varieties of industrial hemp with a wider concentration of THC.\n<\/p><p>The results obtained here demonstrate that NIR spectroscopy offers speed and simplicity unmatched by other traditional techniques. Accordingly, it was tested as an alternative to conventional HPLC analysis for the evaluation of cannabinoid content with promising results.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>The authors would like to thank Genscore Navarra S.L. for access to the plant material samples used in this study.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Conceptualization, C.J., A.\u00c1. and S.A.; Data curation, S.A., A.L.-M. and C.J.; Formal analysis, S.A., C.P.-R., A.L.-M. and P.C.Z.; Funding acquisition, C.J. and A.\u00c1.; Investigation, C.P.-R., A.L.-M., C.J., P.C.Z. and S.A.; Methodology, P.C.Z., C.J., C.P.-R., A.L.-M. and S.A.; Project administration, A.\u00c1. and S.A.; Resources, C.J., A.\u00c1. and S.A.; Software, S.A.; Supervision, C.P.-R., A.L.-M., C.J. and S.A.; Validation, P.C.Z., C.P.-R., A.L.-M. and C.J.; Visualization, C.P.-R. and A.L.-M.; Writing\u2014original draft, P.C.Z., C.J. and A.L.-M.; Writing\u2014review and editing, P.C.Z., C.P.-R., A.L.-M., C.J., A.\u00c1. and S.A. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This research received no external funding. Open access co-funding provided by Institute for Sustainability & Food Chain Innovation (IS-FOOD).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-:0-1\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_1-0\">1.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_1-1\">1.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Iversen, Leslie L. (2019). <i>The science of marijuana<\/i> (3rd Edition ed.). New York: Oxford University Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-19-084684-8.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+science+of+marijuana&rft.aulast=Iversen&rft.aufirst=Leslie+L.&rft.au=Iversen%2C%26%2332%3BLeslie+L.&rft.date=2019&rft.edition=3rd+Edition&rft.place=New+York&rft.pub=Oxford+University+Press&rft.isbn=978-0-19-084684-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-2\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-2\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Russo, Ethan B (1 August 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01238.x\" target=\"_blank\">\"Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects\"<\/a> (in en). <i>British Journal of Pharmacology<\/i> <b>163<\/b> (7): 1344\u20131364. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1476-5381.2011.01238.x\" target=\"_blank\">10.1111\/j.1476-5381.2011.01238.x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3165946\" target=\"_blank\">PMC3165946<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21749363\" target=\"_blank\">21749363<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01238.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2011.01238.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Taming+THC%3A+potential+cannabis+synergy+and+phytocannabinoid-terpenoid+entourage+effects%3A+Phytocannabinoid-terpenoid+entourage+effects&rft.jtitle=British+Journal+of+Pharmacology&rft.aulast=Russo&rft.aufirst=Ethan+B&rft.au=Russo%2C%26%2332%3BEthan+B&rft.date=1+August+2011&rft.volume=163&rft.issue=7&rft.pages=1344%E2%80%931364&rft_id=info:doi\/10.1111%2Fj.1476-5381.2011.01238.x&rft_id=info:pmc\/PMC3165946&rft_id=info:pmid\/21749363&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1476-5381.2011.01238.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-3\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-3\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">HempToday (23 October 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/hemptoday.net\/es\/el-parlamento-europeo-aprueba-el-aumento-del-limite-de-thc-de-la-ue-al-03\/\" target=\"_blank\">\"El Parlamento Europeo aprueba el aumento del l\u00edmite de THC de la UE al 0,3%\"<\/a>. <i>Hemp Today En Espa\u00f1ol<\/i><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/hemptoday.net\/es\/el-parlamento-europeo-aprueba-el-aumento-del-limite-de-thc-de-la-ue-al-03\/\" target=\"_blank\">https:\/\/hemptoday.net\/es\/el-parlamento-europeo-aprueba-el-aumento-del-limite-de-thc-de-la-ue-al-03\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=El+Parlamento+Europeo+aprueba+el+aumento+del+l%C3%ADmite+de+THC+de+la+UE+al+0%2C3%25&rft.atitle=Hemp+Today+En+Espa%C3%B1ol&rft.aulast=HempToday&rft.au=HempToday&rft.date=23+October+2020&rft_id=https%3A%2F%2Fhemptoday.net%2Fes%2Fel-parlamento-europeo-aprueba-el-aumento-del-limite-de-thc-de-la-ue-al-03%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-4\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_4-0\">4.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-1\">4.1<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-2\">4.2<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-3\">4.3<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-4\">4.4<\/a><\/sup> <sup><a href=\"#cite_ref-:1_4-5\">4.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">Townsend, D.; Eustis, I.; Lewis, M. et al. (2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/resources.perkinelmer.com\/lab-solutions\/resources\/docs\/app_determination_of_thc_and_cbd_cannabisflower.pdf\" target=\"_blank\">\"The Determination of Total THC and CBD Content in Cannabis Flower by Fourier Transform Near Infrared Spectroscopy\"<\/a> (PDF). PerkinElmer<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/resources.perkinelmer.com\/lab-solutions\/resources\/docs\/app_determination_of_thc_and_cbd_cannabisflower.pdf\" target=\"_blank\">https:\/\/resources.perkinelmer.com\/lab-solutions\/resources\/docs\/app_determination_of_thc_and_cbd_cannabisflower.pdf<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=The+Determination+of+Total+THC+and+CBD+Content+in+Cannabis+Flower+by+Fourier+Transform+Near+Infrared+Spectroscopy&rft.atitle=&rft.aulast=Townsend%2C+D.%3B+Eustis%2C+I.%3B+Lewis%2C+M.+et+al.&rft.au=Townsend%2C+D.%3B+Eustis%2C+I.%3B+Lewis%2C+M.+et+al.&rft.date=2018&rft.pub=PerkinElmer&rft_id=https%3A%2F%2Fresources.perkinelmer.com%2Flab-solutions%2Fresources%2Fdocs%2Fapp_determination_of_thc_and_cbd_cannabisflower.pdf&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-5\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-5\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Brown, Alistair K.; Xia, Zhe; Bulloch, Patrique; Idowu, Ifeoluwa; Francisco, Olga; Stetefeld, Jorg; Stout, Jake; Zimmer, Jeff <i>et al.<\/i> (1 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003267019309833\" target=\"_blank\">\"Validated quantitative cannabis profiling for Canadian regulatory compliance - Cannabinoids, aflatoxins, and terpenes\"<\/a> (in en). <i>Analytica Chimica Acta<\/i> <b>1088<\/b>: 79\u201388. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.aca.2019.08.042\" target=\"_blank\">10.1016\/j.aca.2019.08.042<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003267019309833\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003267019309833<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Validated+quantitative+cannabis+profiling+for+Canadian+regulatory+compliance+-+Cannabinoids%2C+aflatoxins%2C+and+terpenes&rft.jtitle=Analytica+Chimica+Acta&rft.aulast=Brown&rft.aufirst=Alistair+K.&rft.au=Brown%2C%26%2332%3BAlistair+K.&rft.au=Xia%2C%26%2332%3BZhe&rft.au=Bulloch%2C%26%2332%3BPatrique&rft.au=Idowu%2C%26%2332%3BIfeoluwa&rft.au=Francisco%2C%26%2332%3BOlga&rft.au=Stetefeld%2C%26%2332%3BJorg&rft.au=Stout%2C%26%2332%3BJake&rft.au=Zimmer%2C%26%2332%3BJeff&rft.au=Marvin%2C%26%2332%3BChris&rft.date=1+December+2019&rft.volume=1088&rft.pages=79%E2%80%9388&rft_id=info:doi\/10.1016%2Fj.aca.2019.08.042&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0003267019309833&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_6-0\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-1\">6.1<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-2\">6.2<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-3\">6.3<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-4\">6.4<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-5\">6.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">S\u00e1nchez-Carnerero Callado, C.; N\u00fa\u00f1ez-S\u00e1nchez, N.; Casano, S.; Ferreiro-Vera, C. (1 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914018307938\" target=\"_blank\">\"The potential of near infrared spectroscopy to estimate the content of cannabinoids in Cannabis sativa L.: A comparative study\"<\/a> (in en). <i>Talanta<\/i> <b>190<\/b>: 147\u2013157. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.talanta.2018.07.085\" target=\"_blank\">10.1016\/j.talanta.2018.07.085<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914018307938\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914018307938<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+potential+of+near+infrared+spectroscopy+to+estimate+the+content+of+cannabinoids+in+Cannabis+sativa+L.%3A+A+comparative+study&rft.jtitle=Talanta&rft.aulast=S%C3%A1nchez-Carnerero+Callado&rft.aufirst=C.&rft.au=S%C3%A1nchez-Carnerero+Callado%2C%26%2332%3BC.&rft.au=N%C3%BA%C3%B1ez-S%C3%A1nchez%2C%26%2332%3BN.&rft.au=Casano%2C%26%2332%3BS.&rft.au=Ferreiro-Vera%2C%26%2332%3BC.&rft.date=1+December+2018&rft.volume=190&rft.pages=147%E2%80%93157&rft_id=info:doi\/10.1016%2Fj.talanta.2018.07.085&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0039914018307938&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_7-0\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-1\">7.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Valinger, Davor; Jurina, Tamara; \u0160ain, Adela; Mate\u0161i\u0107, Nikolina; Pani\u0107, Manuela; Benkovi\u0107, Maja; Gajdo\u0161 Kljusuri\u0107, Jasenka; Jurinjak Tu\u0161ek, Ana (1 May 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pca.2979\" target=\"_blank\">\"Development of ANN models based on combined UV\u2010vis\u2010NIR spectra for rapid quantification of physical and chemical properties of industrial hemp extracts\"<\/a> (in en). <i>Phytochemical Analysis<\/i> <b>32<\/b> (3): 326\u2013338. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fpca.2979\" target=\"_blank\">10.1002\/pca.2979<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0958-0344\" target=\"_blank\">0958-0344<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pca.2979\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pca.2979<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Development+of+ANN+models+based+on+combined+UV%E2%80%90vis%E2%80%90NIR+spectra+for+rapid+quantification+of+physical+and+chemical+properties+of+industrial+hemp+extracts&rft.jtitle=Phytochemical+Analysis&rft.aulast=Valinger&rft.aufirst=Davor&rft.au=Valinger%2C%26%2332%3BDavor&rft.au=Jurina%2C%26%2332%3BTamara&rft.au=%C5%A0ain%2C%26%2332%3BAdela&rft.au=Mate%C5%A1i%C4%87%2C%26%2332%3BNikolina&rft.au=Pani%C4%87%2C%26%2332%3BManuela&rft.au=Benkovi%C4%87%2C%26%2332%3BMaja&rft.au=Gajdo%C5%A1+Kljusuri%C4%87%2C%26%2332%3BJasenka&rft.au=Jurinjak+Tu%C5%A1ek%2C%26%2332%3BAna&rft.date=1+May+2021&rft.volume=32&rft.issue=3&rft.pages=326%E2%80%93338&rft_id=info:doi\/10.1002%2Fpca.2979&rft.issn=0958-0344&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fpca.2979&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_8-0\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_8-1\">8.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cozzolino, Daniel (1 June 2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0028-1112220\" target=\"_blank\">\"Near Infrared Spectroscopy in Natural Products Analysis\"<\/a> (in en). <i>Planta Medica<\/i> <b>75<\/b> (07): 746\u2013756. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1055%2Fs-0028-1112220\" target=\"_blank\">10.1055\/s-0028-1112220<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0943\" target=\"_blank\">0032-0943<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0028-1112220\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0028-1112220<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Near+Infrared+Spectroscopy+in+Natural+Products+Analysis&rft.jtitle=Planta+Medica&rft.aulast=Cozzolino&rft.aufirst=Daniel&rft.au=Cozzolino%2C%26%2332%3BDaniel&rft.date=1+June+2009&rft.volume=75&rft.issue=07&rft.pages=746%E2%80%93756&rft_id=info:doi\/10.1055%2Fs-0028-1112220&rft.issn=0032-0943&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.1055%2Fs-0028-1112220&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-9\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-9\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Warner, Marcus L.; Alford, Ilene; Lawrence, Diana M.; Kohl, Amber C.; Williams, Steven J.; Yeatman, Dustin T. (1 March 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468170916300868\" target=\"_blank\">\"Comparative analysis of freshly harvested cannabis plant weight and dried cannabis plant weight\"<\/a> (in en). <i>Forensic Chemistry<\/i> <b>3<\/b>: 52\u201357. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.forc.2017.02.001\" target=\"_blank\">10.1016\/j.forc.2017.02.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468170916300868\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468170916300868<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comparative+analysis+of+freshly+harvested+cannabis+plant+weight+and+dried+cannabis+plant+weight&rft.jtitle=Forensic+Chemistry&rft.aulast=Warner&rft.aufirst=Marcus+L.&rft.au=Warner%2C%26%2332%3BMarcus+L.&rft.au=Alford%2C%26%2332%3BIlene&rft.au=Lawrence%2C%26%2332%3BDiana+M.&rft.au=Kohl%2C%26%2332%3BAmber+C.&rft.au=Williams%2C%26%2332%3BSteven+J.&rft.au=Yeatman%2C%26%2332%3BDustin+T.&rft.date=1+March+2017&rft.volume=3&rft.pages=52%E2%80%9357&rft_id=info:doi\/10.1016%2Fj.forc.2017.02.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2468170916300868&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-10\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-10\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wilson, N; Heinrich, M (24 August 2006). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-2006-950060\" target=\"_blank\">\"The Use of Near Infrared Spectroscopy to discriminate between THC-rich and hemp forms of Cannabis\"<\/a> (in en). <i>Planta Medica<\/i> <b>72<\/b> (11): s\u20132006\u2013950060. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1055%2Fs-2006-950060\" target=\"_blank\">10.1055\/s-2006-950060<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0943\" target=\"_blank\">0032-0943<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-2006-950060\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-2006-950060<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Use+of+Near+Infrared+Spectroscopy+to+discriminate+between+THC-rich+and+hemp+forms+of+Cannabis&rft.jtitle=Planta+Medica&rft.aulast=Wilson&rft.aufirst=N&rft.au=Wilson%2C%26%2332%3BN&rft.au=Heinrich%2C%26%2332%3BM&rft.date=24+August+2006&rft.volume=72&rft.issue=11&rft.pages=s%E2%80%932006%E2%80%93950060&rft_id=info:doi\/10.1055%2Fs-2006-950060&rft.issn=0032-0943&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.1055%2Fs-2006-950060&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Daughtry, C.S.T.; Walthall, C.L. (1 May 1998). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0034425798000029\" target=\"_blank\">\"Spectral Discrimination of Cannabis sativa L. Leaves and Canopies\"<\/a> (in en). <i>Remote Sensing of Environment<\/i> <b>64<\/b> (2): 192\u2013201. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0034-4257%2898%2900002-9\" target=\"_blank\">10.1016\/S0034-4257(98)00002-9<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0034425798000029\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0034425798000029<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Spectral+Discrimination+of+Cannabis+sativa+L.+Leaves+and+Canopies&rft.jtitle=Remote+Sensing+of+Environment&rft.aulast=Daughtry&rft.aufirst=C.S.T.&rft.au=Daughtry%2C%26%2332%3BC.S.T.&rft.au=Walthall%2C%26%2332%3BC.L.&rft.date=1+May+1998&rft.volume=64&rft.issue=2&rft.pages=192%E2%80%93201&rft_id=info:doi\/10.1016%2FS0034-4257%2898%2900002-9&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0034425798000029&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Borille, Bruna Tassi; Marcelo, Marcelo Caetano Alexandre; Ortiz, Rafael Scorsatto; Mariotti, Kristiane de C\u00e1ssia; Ferr\u00e3o, Marco Fl\u00f4res; Limberger, Renata Pereira (1 February 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142516305583\" target=\"_blank\">\"Near infrared spectroscopy combined with chemometrics for growth stage classification of cannabis cultivated in a greenhouse from seized seeds\"<\/a> (in en). <i>Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy<\/i> <b>173<\/b>: 318\u2013323. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.saa.2016.09.040\" target=\"_blank\">10.1016\/j.saa.2016.09.040<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142516305583\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142516305583<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Near+infrared+spectroscopy+combined+with+chemometrics+for+growth+stage+classification+of+cannabis+cultivated+in+a+greenhouse+from+seized+seeds&rft.jtitle=Spectrochimica+Acta+Part+A%3A+Molecular+and+Biomolecular+Spectroscopy&rft.aulast=Borille&rft.aufirst=Bruna+Tassi&rft.au=Borille%2C%26%2332%3BBruna+Tassi&rft.au=Marcelo%2C%26%2332%3BMarcelo+Caetano+Alexandre&rft.au=Ortiz%2C%26%2332%3BRafael+Scorsatto&rft.au=Mariotti%2C%26%2332%3BKristiane+de+C%C3%A1ssia&rft.au=Ferr%C3%A3o%2C%26%2332%3BMarco+Fl%C3%B4res&rft.au=Limberger%2C%26%2332%3BRenata+Pereira&rft.date=1+February+2017&rft.volume=173&rft.pages=318%E2%80%93323&rft_id=info:doi\/10.1016%2Fj.saa.2016.09.040&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1386142516305583&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Toonen, Marcel A. J.; Maliepaard, Chris; Reijmers, Theo H.; van der Voet, Hilko; Mastebroek, H. Dick; van den Broeck, Hetty C.; Ebskamp, Michel J. M.; Kessler, Waltraud <i>et al.<\/i> (1 January 2004). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/link.springer.com\/10.1007\/s10681-004-4753-z\" target=\"_blank\">\"Predicting the chemical composition of fibre and core fraction of hemp (Cannabis sativa L.)\"<\/a> (in en). <i>Euphytica<\/i> <b>140<\/b> (1-2): 39\u201345. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10681-004-4753-z\" target=\"_blank\">10.1007\/s10681-004-4753-z<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0014-2336\" target=\"_blank\">0014-2336<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/link.springer.com\/10.1007\/s10681-004-4753-z\" target=\"_blank\">https:\/\/link.springer.com\/10.1007\/s10681-004-4753-z<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Predicting+the+chemical+composition+of+fibre+and+core+fraction+of+hemp+%28Cannabis+sativa+L.%29&rft.jtitle=Euphytica&rft.aulast=Toonen&rft.aufirst=Marcel+A.+J.&rft.au=Toonen%2C%26%2332%3BMarcel+A.+J.&rft.au=Maliepaard%2C%26%2332%3BChris&rft.au=Reijmers%2C%26%2332%3BTheo+H.&rft.au=van+der+Voet%2C%26%2332%3BHilko&rft.au=Mastebroek%2C%26%2332%3BH.+Dick&rft.au=van+den+Broeck%2C%26%2332%3BHetty+C.&rft.au=Ebskamp%2C%26%2332%3BMichel+J.+M.&rft.au=Kessler%2C%26%2332%3BWaltraud&rft.au=Kessler%2C%26%2332%3BRudolf+W.&rft.date=1+January+2004&rft.volume=140&rft.issue=1-2&rft.pages=39%E2%80%9345&rft_id=info:doi\/10.1007%2Fs10681-004-4753-z&rft.issn=0014-2336&rft_id=https%3A%2F%2Flink.springer.com%2F10.1007%2Fs10681-004-4753-z&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">de la Asunci\u00f3n-Nadal, Victor; Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel (1 May 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914017302400\" target=\"_blank\">\"Identification and determination of synthetic cannabinoids in herbal products by dry film attenuated total reflectance-infrared spectroscopy\"<\/a> (in en). <i>Talanta<\/i> <b>167<\/b>: 344\u2013351. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.talanta.2017.02.026\" target=\"_blank\">10.1016\/j.talanta.2017.02.026<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914017302400\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914017302400<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+and+determination+of+synthetic+cannabinoids+in+herbal+products+by+dry+film+attenuated+total+reflectance-infrared+spectroscopy&rft.jtitle=Talanta&rft.aulast=de+la+Asunci%C3%B3n-Nadal&rft.aufirst=Victor&rft.au=de+la+Asunci%C3%B3n-Nadal%2C%26%2332%3BVictor&rft.au=Armenta%2C%26%2332%3BSergio&rft.au=Garrigues%2C%26%2332%3BSalvador&rft.au=de+la+Guardia%2C%26%2332%3BMiguel&rft.date=1+May+2017&rft.volume=167&rft.pages=344%E2%80%93351&rft_id=info:doi\/10.1016%2Fj.talanta.2017.02.026&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0039914017302400&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Duchateau, C\u00e9line; Kauffmann, Jean\u2010Michel; Canfyn, Micha\u00ebl; St\u00e9vigny, Caroline; De Braekeleer, Kris; Deconinck, Eric (1 September 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dta.2865\" target=\"_blank\">\"Discrimination of legal and illegal Cannabis spp. according to European legislation using near infrared spectroscopy and chemometrics\"<\/a> (in en). <i>Drug Testing and Analysis<\/i> <b>12<\/b> (9): 1309\u20131319. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fdta.2865\" target=\"_blank\">10.1002\/dta.2865<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1942-7603\" target=\"_blank\">1942-7603<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dta.2865\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dta.2865<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Discrimination+of+legal+and+illegal+Cannabis+spp.+according+to+European+legislation+using+near+infrared+spectroscopy+and+chemometrics&rft.jtitle=Drug+Testing+and+Analysis&rft.aulast=Duchateau&rft.aufirst=C%C3%A9line&rft.au=Duchateau%2C%26%2332%3BC%C3%A9line&rft.au=Kauffmann%2C%26%2332%3BJean%E2%80%90Michel&rft.au=Canfyn%2C%26%2332%3BMicha%C3%ABl&rft.au=St%C3%A9vigny%2C%26%2332%3BCaroline&rft.au=De+Braekeleer%2C%26%2332%3BKris&rft.au=Deconinck%2C%26%2332%3BEric&rft.date=1+September+2020&rft.volume=12&rft.issue=9&rft.pages=1309%E2%80%931319&rft_id=info:doi\/10.1002%2Fdta.2865&rft.issn=1942-7603&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fdta.2865&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-16\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-16\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Risoluti, Roberta; Gullifa, Giuseppina; Battistini, Alfredo; Materazzi, Stefano (1 May 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914019313050\" target=\"_blank\">\"Monitoring of cannabinoids in hemp flours by MicroNIR\/Chemometrics\"<\/a> (in en). <i>Talanta<\/i> <b>211<\/b>: 120672. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.talanta.2019.120672\" target=\"_blank\">10.1016\/j.talanta.2019.120672<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914019313050\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0039914019313050<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Monitoring+of+cannabinoids+in+hemp+flours+by+MicroNIR%2FChemometrics&rft.jtitle=Talanta&rft.aulast=Risoluti&rft.aufirst=Roberta&rft.au=Risoluti%2C%26%2332%3BRoberta&rft.au=Gullifa%2C%26%2332%3BGiuseppina&rft.au=Battistini%2C%26%2332%3BAlfredo&rft.au=Materazzi%2C%26%2332%3BStefano&rft.date=1+May+2020&rft.volume=211&rft.pages=120672&rft_id=info:doi\/10.1016%2Fj.talanta.2019.120672&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0039914019313050&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Ministerio de Agricultura, Pesca y Alimentaci\u00f3n (12 November 1999). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.boe.es\/eli\/es\/rd\/1999\/11\/12\/1729\" target=\"_blank\">\"Real Decreto 1729\/1999, de 12 de noviembre, por el que se establecen las normas para la solicitud y concesi\u00f3n de las ayudas al lino textil y al c\u00e1\u00f1amo\"<\/a>. <i>Agencia Estatal Bolet\u00edn Oficial del Estado<\/i>. Gobierno de Espa\u00f1a<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.boe.es\/eli\/es\/rd\/1999\/11\/12\/1729\" target=\"_blank\">https:\/\/www.boe.es\/eli\/es\/rd\/1999\/11\/12\/1729<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Real+Decreto+1729%2F1999%2C+de+12+de+noviembre%2C+por+el+que+se+establecen+las+normas+para+la+solicitud+y+concesi%C3%B3n+de+las+ayudas+al+lino+textil+y+al+c%C3%A1%C3%B1amo&rft.atitle=Agencia+Estatal+Bolet%C3%ADn+Oficial+del+Estado&rft.aulast=Ministerio+de+Agricultura%2C+Pesca+y+Alimentaci%C3%B3n&rft.au=Ministerio+de+Agricultura%2C+Pesca+y+Alimentaci%C3%B3n&rft.date=12+November+1999&rft.pub=Gobierno+de+Espa%C3%B1a&rft_id=https%3A%2F%2Fwww.boe.es%2Feli%2Fes%2Frd%2F1999%2F11%2F12%2F1729&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-18\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_18-0\">18.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_18-1\">18.1<\/a><\/sup> <sup><a href=\"#cite_ref-:5_18-2\">18.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"http:\/\/data.europa.eu\/eli\/reg_del\/2017\/1155\/oj\" target=\"_blank\">\"Commission Delegated Regulation (EU) 2017\/1155 of 15 February 2017 amending Delegated Regulation (EU) No 639\/2014 as regards the control measures relating to the cultivation of hemp, certain provisions on the greening payment, the payment for young farmers in control of a legal person, the calculation of the per unit amount in the framework of voluntary coupled support, the fractions of payment entitlements and certain notification requirements relating to the single area payment scheme and the voluntary coupled support, and amending Annex X to Regulation (EU) No 1307\/2013 of the European Parliament and of the Council\"<\/a>. <i>EUR-Lex<\/i>. European Union. 15 February 2017<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/data.europa.eu\/eli\/reg_del\/2017\/1155\/oj\" target=\"_blank\">http:\/\/data.europa.eu\/eli\/reg_del\/2017\/1155\/oj<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Commission+Delegated+Regulation+%28EU%29+2017%2F1155+of+15+February+2017+amending+Delegated+Regulation+%28EU%29+No+639%2F2014+as+regards+the+control+measures+relating+to+the+cultivation+of+hemp%2C+certain+provisions+on+the+greening+payment%2C+the+payment+for+young+farmers+in+control+of+a+legal+person%2C+the+calculation+of+the+per+unit+amount+in+the+framework+of+voluntary+coupled+support%2C+the+fractions+of+payment+entitlements+and+certain+notification+requirements+relating+to+the+single+area+payment+scheme+and+the+voluntary+coupled+support%2C+and+amending+Annex+X+to+Regulation+%28EU%29+No+1307%2F2013+of+the+European+Parliament+and+of+the+Council&rft.atitle=EUR-Lex&rft.date=15+February+2017&rft.pub=European+Union&rft_id=http%3A%2F%2Fdata.europa.eu%2Feli%2Freg_del%2F2017%2F1155%2Foj&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-19\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_19-0\">19.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_19-1\">19.1<\/a><\/sup> <sup><a href=\"#cite_ref-:6_19-2\">19.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">United Nations Office on Drugs and Crime (March 2022). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.unodc.org\/unodc\/en\/scientists\/recommended-methods-for-the-identification-and-analysis-of-cannabis-and-cannabis-products.html\" target=\"_blank\">\"Recommended Methods for the Identification and Analysis of Cannabis and Cannabis Products\"<\/a>. United Nations<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.unodc.org\/unodc\/en\/scientists\/recommended-methods-for-the-identification-and-analysis-of-cannabis-and-cannabis-products.html\" target=\"_blank\">https:\/\/www.unodc.org\/unodc\/en\/scientists\/recommended-methods-for-the-identification-and-analysis-of-cannabis-and-cannabis-products.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Recommended+Methods+for+the+Identification+and+Analysis+of+Cannabis+and+Cannabis+Products&rft.atitle=&rft.aulast=United+Nations+Office+on+Drugs+and+Crime&rft.au=United+Nations+Office+on+Drugs+and+Crime&rft.date=March+2022&rft.pub=United+Nations&rft_id=https%3A%2F%2Fwww.unodc.org%2Funodc%2Fen%2Fscientists%2Frecommended-methods-for-the-identification-and-analysis-of-cannabis-and-cannabis-products.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-20\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_20-0\">20.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_20-1\">20.1<\/a><\/sup> <sup><a href=\"#cite_ref-:7_20-2\">20.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Shenk, J.S.; Westerhaus, M.O. (1996). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/636222940\" target=\"_blank\">\"Calibration the ISI way\"<\/a>. In Davies, Anthony M. C.; International Conference on Near Infrared Spectroscopy. <i>Near infrared spectroscopy: the future waves ; the proceedings of the 7th International Conference on Near Infrared Spectroscopy, Montr\u00e9al, Canada, 6 - 11 August 1995<\/i>. Chichester: NIR Publ. pp. 198\u2013202. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-9528666-0-2. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/636222940\" target=\"_blank\">636222940<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/636222940\" target=\"_blank\">https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/636222940<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Calibration+the+ISI+way&rft.atitle=Near+infrared+spectroscopy%3A+the+future+waves+%3B+the+proceedings+of+the+7th+International+Conference+on+Near+Infrared+Spectroscopy%2C+Montr%C3%A9al%2C+Canada%2C+6+-+11+August+1995&rft.aulast=Shenk%2C+J.S.%3B+Westerhaus%2C+M.O.&rft.au=Shenk%2C+J.S.%3B+Westerhaus%2C+M.O.&rft.date=1996&rft.pages=pp.%26nbsp%3B198%E2%80%93202&rft.place=Chichester&rft.pub=NIR+Publ&rft.isbn=978-0-9528666-0-2&rft_id=info:oclcnum\/636222940&rft_id=https%3A%2F%2Fwww.worldcat.org%2Ftitle%2Fmediawiki%2Foclc%2F636222940&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-21\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-21\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nicola\u00ef, Bart M.; Beullens, Katrien; Bobelyn, Els; Peirs, Ann; Saeys, Wouter; Theron, Karen I.; Lammertyn, Jeroen (1 November 2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925521407002293\" target=\"_blank\">\"Nondestructive measurement of fruit and vegetable quality by means of NIR spectroscopy: A review\"<\/a> (in en). <i>Postharvest Biology and Technology<\/i> <b>46<\/b> (2): 99\u2013118. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.postharvbio.2007.06.024\" target=\"_blank\">10.1016\/j.postharvbio.2007.06.024<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925521407002293\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925521407002293<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nondestructive+measurement+of+fruit+and+vegetable+quality+by+means+of+NIR+spectroscopy%3A+A+review&rft.jtitle=Postharvest+Biology+and+Technology&rft.aulast=Nicola%C3%AF&rft.aufirst=Bart+M.&rft.au=Nicola%C3%AF%2C%26%2332%3BBart+M.&rft.au=Beullens%2C%26%2332%3BKatrien&rft.au=Bobelyn%2C%26%2332%3BEls&rft.au=Peirs%2C%26%2332%3BAnn&rft.au=Saeys%2C%26%2332%3BWouter&rft.au=Theron%2C%26%2332%3BKaren+I.&rft.au=Lammertyn%2C%26%2332%3BJeroen&rft.date=1+November+2007&rft.volume=46&rft.issue=2&rft.pages=99%E2%80%93118&rft_id=info:doi\/10.1016%2Fj.postharvbio.2007.06.024&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0925521407002293&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">European Medicines Agency (6 May 2014). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ema.europa.eu\/en\/use-near-infrared-spectroscopy-nirs-pharmaceutical-industry-data-requirements-new-submissions\" target=\"_blank\">\"Guideline on the use of near-infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations\"<\/a>. European Union<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ema.europa.eu\/en\/use-near-infrared-spectroscopy-nirs-pharmaceutical-industry-data-requirements-new-submissions\" target=\"_blank\">https:\/\/www.ema.europa.eu\/en\/use-near-infrared-spectroscopy-nirs-pharmaceutical-industry-data-requirements-new-submissions<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Guideline+on+the+use+of+near-infrared+spectroscopy+by+the+pharmaceutical+industry+and+the+data+requirements+for+new+submissions+and+variations&rft.atitle=&rft.aulast=European+Medicines+Agency&rft.au=European+Medicines+Agency&rft.date=6+May+2014&rft.pub=European+Union&rft_id=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fuse-near-infrared-spectroscopy-nirs-pharmaceutical-industry-data-requirements-new-submissions&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zeaiter, M.; Roger, J.-M.; Bellon-Maurel, V. (1 May 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993605000580\" target=\"_blank\">\"Robustness of models developed by multivariate calibration. Part II: The influence of pre-processing methods\"<\/a> (in en). <i>TrAC Trends in Analytical Chemistry<\/i> <b>24<\/b> (5): 437\u2013445. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.trac.2004.11.023\" target=\"_blank\">10.1016\/j.trac.2004.11.023<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993605000580\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993605000580<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Robustness+of+models+developed+by+multivariate+calibration.+Part+II%3A+The+influence+of+pre-processing+methods&rft.jtitle=TrAC+Trends+in+Analytical+Chemistry&rft.aulast=Zeaiter&rft.aufirst=M.&rft.au=Zeaiter%2C%26%2332%3BM.&rft.au=Roger%2C%26%2332%3BJ.-M.&rft.au=Bellon-Maurel%2C%26%2332%3BV.&rft.date=1+May+2005&rft.volume=24&rft.issue=5&rft.pages=437%E2%80%93445&rft_id=info:doi\/10.1016%2Fj.trac.2004.11.023&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165993605000580&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Barnes, R. J.; Dhanoa, M. S.; Lister, Susan J. (1 July 1989). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1366\/0003702894202201\" target=\"_blank\">\"Standard Normal Variate Transformation and De-Trending of Near-Infrared Diffuse Reflectance Spectra\"<\/a> (in en). <i>Applied Spectroscopy<\/i> <b>43<\/b> (5): 772\u2013777. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1366%2F0003702894202201\" target=\"_blank\">10.1366\/0003702894202201<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-7028\" target=\"_blank\">0003-7028<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1366\/0003702894202201\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1366\/0003702894202201<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Standard+Normal+Variate+Transformation+and+De-Trending+of+Near-Infrared+Diffuse+Reflectance+Spectra&rft.jtitle=Applied+Spectroscopy&rft.aulast=Barnes&rft.aufirst=R.+J.&rft.au=Barnes%2C%26%2332%3BR.+J.&rft.au=Dhanoa%2C%26%2332%3BM.+S.&rft.au=Lister%2C%26%2332%3BSusan+J.&rft.date=1+July+1989&rft.volume=43&rft.issue=5&rft.pages=772%E2%80%93777&rft_id=info:doi\/10.1366%2F0003702894202201&rft.issn=0003-7028&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1366%2F0003702894202201&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-25\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-25\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Buddenbaum, Henning; Steffens, Markus (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.hindawi.com\/journals\/aess\/2012\/274903\/\" target=\"_blank\">\"The Effects of Spectral Pretreatments on Chemometric Analyses of Soil Profiles Using Laboratory Imaging Spectroscopy\"<\/a> (in en). <i>Applied and Environmental Soil Science<\/i> <b>2012<\/b>: 1\u201312. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1155%2F2012%2F274903\" target=\"_blank\">10.1155\/2012\/274903<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1687-7667\" target=\"_blank\">1687-7667<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.hindawi.com\/journals\/aess\/2012\/274903\/\" target=\"_blank\">http:\/\/www.hindawi.com\/journals\/aess\/2012\/274903\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Effects+of+Spectral+Pretreatments+on+Chemometric+Analyses+of+Soil+Profiles+Using+Laboratory+Imaging+Spectroscopy&rft.jtitle=Applied+and+Environmental+Soil+Science&rft.aulast=Buddenbaum&rft.aufirst=Henning&rft.au=Buddenbaum%2C%26%2332%3BHenning&rft.au=Steffens%2C%26%2332%3BMarkus&rft.date=2012&rft.volume=2012&rft.pages=1%E2%80%9312&rft_id=info:doi\/10.1155%2F2012%2F274903&rft.issn=1687-7667&rft_id=http%3A%2F%2Fwww.hindawi.com%2Fjournals%2Faess%2F2012%2F274903%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-26\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-26\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Datt, B. (1 January 1999). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/014311699211778\" target=\"_blank\">\"Visible\/near infrared reflectance and chlorophyll content in Eucalyptus leaves\"<\/a> (in en). <i>International Journal of Remote Sensing<\/i> <b>20<\/b> (14): 2741\u20132759. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F014311699211778\" target=\"_blank\">10.1080\/014311699211778<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0143-1161\" target=\"_blank\">0143-1161<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/014311699211778\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/014311699211778<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Visible%2Fnear+infrared+reflectance+and+chlorophyll+content+in+Eucalyptus+leaves&rft.jtitle=International+Journal+of+Remote+Sensing&rft.aulast=Datt&rft.aufirst=B.&rft.au=Datt%2C%26%2332%3BB.&rft.date=1+January+1999&rft.volume=20&rft.issue=14&rft.pages=2741%E2%80%932759&rft_id=info:doi\/10.1080%2F014311699211778&rft.issn=0143-1161&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F014311699211778&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-27\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-27\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Martens, Harald; Stark, Edward (1 January 1991). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/073170859180188F\" target=\"_blank\">\"Extended multiplicative signal correction and spectral interference subtraction: New preprocessing methods for near infrared spectroscopy\"<\/a> (in en). <i>Journal of Pharmaceutical and Biomedical Analysis<\/i> <b>9<\/b> (8): 625\u2013635. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2F0731-7085%2891%2980188-F\" target=\"_blank\">10.1016\/0731-7085(91)80188-F<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/073170859180188F\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/073170859180188F<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Extended+multiplicative+signal+correction+and+spectral+interference+subtraction%3A+New+preprocessing+methods+for+near+infrared+spectroscopy&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.aulast=Martens&rft.aufirst=Harald&rft.au=Martens%2C%26%2332%3BHarald&rft.au=Stark%2C%26%2332%3BEdward&rft.date=1+January+1991&rft.volume=9&rft.issue=8&rft.pages=625%E2%80%93635&rft_id=info:doi\/10.1016%2F0731-7085%2891%2980188-F&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F073170859180188F&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-28\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-28\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rinnan, \u00c5smund; Berg, Frans van den; Engelsen, S\u00f8ren Balling (1 November 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993609001629\" target=\"_blank\">\"Review of the most common pre-processing techniques for near-infrared spectra\"<\/a> (in en). <i>TrAC Trends in Analytical Chemistry<\/i> <b>28<\/b> (10): 1201\u20131222. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.trac.2009.07.007\" target=\"_blank\">10.1016\/j.trac.2009.07.007<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993609001629\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165993609001629<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Review+of+the+most+common+pre-processing+techniques+for+near-infrared+spectra&rft.jtitle=TrAC+Trends+in+Analytical+Chemistry&rft.aulast=Rinnan&rft.aufirst=%C3%85smund&rft.au=Rinnan%2C%26%2332%3B%C3%85smund&rft.au=Berg%2C%26%2332%3BFrans+van+den&rft.au=Engelsen%2C%26%2332%3BS%C3%B8ren+Balling&rft.date=1+November+2009&rft.volume=28&rft.issue=10&rft.pages=1201%E2%80%931222&rft_id=info:doi\/10.1016%2Fj.trac.2009.07.007&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165993609001629&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-29\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-29\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Jamshidi, Bahareh; Minaei, Saeid; Mohajerani, Ezzedin; Ghassemian, Hassan (1 July 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169912000828\" target=\"_blank\">\"Reflectance Vis\/NIR spectroscopy for nondestructive taste characterization of Valencia oranges\"<\/a> (in en). <i>Computers and Electronics in Agriculture<\/i> <b>85<\/b>: 64\u201369. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.compag.2012.03.008\" target=\"_blank\">10.1016\/j.compag.2012.03.008<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169912000828\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168169912000828<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Reflectance+Vis%2FNIR+spectroscopy+for+nondestructive+taste+characterization+of+Valencia+oranges&rft.jtitle=Computers+and+Electronics+in+Agriculture&rft.aulast=Jamshidi&rft.aufirst=Bahareh&rft.au=Jamshidi%2C%26%2332%3BBahareh&rft.au=Minaei%2C%26%2332%3BSaeid&rft.au=Mohajerani%2C%26%2332%3BEzzedin&rft.au=Ghassemian%2C%26%2332%3BHassan&rft.date=1+July+2012&rft.volume=85&rft.pages=64%E2%80%9369&rft_id=info:doi\/10.1016%2Fj.compag.2012.03.008&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168169912000828&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-30\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-30\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vasques, G.M.; Grunwald, S.; Sickman, J.O. (1 July 2008). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016706108000980\" target=\"_blank\">\"Comparison of multivariate methods for inferential modeling of soil carbon using visible\/near-infrared spectra\"<\/a> (in en). <i>Geoderma<\/i> <b>146<\/b> (1-2): 14\u201325. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.geoderma.2008.04.007\" target=\"_blank\">10.1016\/j.geoderma.2008.04.007<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016706108000980\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016706108000980<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comparison+of+multivariate+methods+for+inferential+modeling+of+soil+carbon+using+visible%2Fnear-infrared+spectra&rft.jtitle=Geoderma&rft.aulast=Vasques&rft.aufirst=G.M.&rft.au=Vasques%2C%26%2332%3BG.M.&rft.au=Grunwald%2C%26%2332%3BS.&rft.au=Sickman%2C%26%2332%3BJ.O.&rft.date=1+July+2008&rft.volume=146&rft.issue=1-2&rft.pages=14%E2%80%9325&rft_id=info:doi\/10.1016%2Fj.geoderma.2008.04.007&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0016706108000980&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-31\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-31\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ertlen, D.; Schwartz, D.; Trautmann, M.; Webster, R.; Brunet, D. (1 April 2010). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2389.2009.01219.x\" target=\"_blank\">\"Discriminating between organic matter in soil from grass and forest by near-infrared spectroscopy\"<\/a> (in en). <i>European Journal of Soil Science<\/i> <b>61<\/b> (2): 207\u2013216. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1365-2389.2009.01219.x\" target=\"_blank\">10.1111\/j.1365-2389.2009.01219.x<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2389.2009.01219.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2389.2009.01219.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Discriminating+between+organic+matter+in+soil+from+grass+and+forest+by+near-infrared+spectroscopy&rft.jtitle=European+Journal+of+Soil+Science&rft.aulast=Ertlen&rft.aufirst=D.&rft.au=Ertlen%2C%26%2332%3BD.&rft.au=Schwartz%2C%26%2332%3BD.&rft.au=Trautmann%2C%26%2332%3BM.&rft.au=Webster%2C%26%2332%3BR.&rft.au=Brunet%2C%26%2332%3BD.&rft.date=1+April+2010&rft.volume=61&rft.issue=2&rft.pages=207%E2%80%93216&rft_id=info:doi\/10.1111%2Fj.1365-2389.2009.01219.x&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1365-2389.2009.01219.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-32\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-32\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Williams, Phil; Dardenne, Pierre; Flinn, Peter (1 April 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0967033517702395\" target=\"_blank\">\"Tutorial: Items to be included in a report on a near infrared spectroscopy project\"<\/a> (in en). <i>Journal of Near Infrared Spectroscopy<\/i> <b>25<\/b> (2): 85\u201390. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1177%2F0967033517702395\" target=\"_blank\">10.1177\/0967033517702395<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0967-0335\" target=\"_blank\">0967-0335<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journals.sagepub.com\/doi\/10.1177\/0967033517702395\" target=\"_blank\">http:\/\/journals.sagepub.com\/doi\/10.1177\/0967033517702395<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Tutorial%3A+Items+to+be+included+in+a+report+on+a+near+infrared+spectroscopy+project&rft.jtitle=Journal+of+Near+Infrared+Spectroscopy&rft.aulast=Williams&rft.aufirst=Phil&rft.au=Williams%2C%26%2332%3BPhil&rft.au=Dardenne%2C%26%2332%3BPierre&rft.au=Flinn%2C%26%2332%3BPeter&rft.date=1+April+2017&rft.volume=25&rft.issue=2&rft.pages=85%E2%80%9390&rft_id=info:doi\/10.1177%2F0967033517702395&rft.issn=0967-0335&rft_id=http%3A%2F%2Fjournals.sagepub.com%2Fdoi%2F10.1177%2F0967033517702395&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-33\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_33-0\">33.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_33-1\">33.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Williams, Phil; Norris, K. H.; American Association of Cereal Chemists, eds. (2001). <i>Near-infrared technology: in the agricultural and food industries<\/i> (2nd ed ed.). St. Paul, Minn: American Association of Cereal Chemists. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-891127-24-3.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Near-infrared+technology%3A+in+the+agricultural+and+food+industries&rft.date=2001&rft.edition=2nd+ed&rft.place=St.+Paul%2C+Minn&rft.pub=American+Association+of+Cereal+Chemists&rft.isbn=978-1-891127-24-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-34\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_34-0\">34.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_34-1\">34.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation book\">Workman, Jerry; Weyer, Lois (2012) (in English). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.crcnetbase.com\/isbn\/9781439875261\" target=\"_blank\"><i>Practical guide and spectral atlas for interpretive near-infrared spectroscopy<\/i><\/a>. Boca Raton: CRC Press. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-4398-7526-1. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/939973422\" target=\"_blank\">939973422<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.crcnetbase.com\/isbn\/9781439875261\" target=\"_blank\">http:\/\/www.crcnetbase.com\/isbn\/9781439875261<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Practical+guide+and+spectral+atlas+for+interpretive+near-infrared+spectroscopy&rft.aulast=Workman&rft.aufirst=Jerry&rft.au=Workman%2C%26%2332%3BJerry&rft.au=Weyer%2C%26%2332%3BLois&rft.date=2012&rft.place=Boca+Raton&rft.pub=CRC+Press&rft.isbn=978-1-4398-7526-1&rft_id=info:oclcnum\/939973422&rft_id=http%3A%2F%2Fwww.crcnetbase.com%2Fisbn%2F9781439875261&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Williams, Phil; Antoniszyn, John; Manley, Marena (2019) (in English). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1128180884\" target=\"_blank\"><i>Near infrared technology: getting the best out of light<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-1-928480-30-3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/1128180884\" target=\"_blank\">1128180884<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1128180884\" target=\"_blank\">https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/1128180884<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Near+infrared+technology%3A+getting+the+best+out+of+light&rft.aulast=Williams&rft.aufirst=Phil&rft.au=Williams%2C%26%2332%3BPhil&rft.au=Antoniszyn%2C%26%2332%3BJohn&rft.au=Manley%2C%26%2332%3BMarena&rft.date=2019&rft.isbn=978-1-928480-30-3&rft_id=info:oclcnum\/1128180884&rft_id=https%3A%2F%2Fwww.worldcat.org%2Ftitle%2Fmediawiki%2Foclc%2F1128180884&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Saeys, W.; Mouazen, A.M.; Ramon, H. (1 August 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1537511005000838\" target=\"_blank\">\"Potential for Onsite and Online Analysis of Pig Manure using Visible and Near Infrared Reflectance Spectroscopy\"<\/a> (in en). <i>Biosystems Engineering<\/i> <b>91<\/b> (4): 393\u2013402. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.biosystemseng.2005.05.001\" target=\"_blank\">10.1016\/j.biosystemseng.2005.05.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1537511005000838\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1537511005000838<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Potential+for+Onsite+and+Online+Analysis+of+Pig+Manure+using+Visible+and+Near+Infrared+Reflectance+Spectroscopy&rft.jtitle=Biosystems+Engineering&rft.aulast=Saeys&rft.aufirst=W.&rft.au=Saeys%2C%26%2332%3BW.&rft.au=Mouazen%2C%26%2332%3BA.M.&rft.au=Ramon%2C%26%2332%3BH.&rft.date=1+August+2005&rft.volume=91&rft.issue=4&rft.pages=393%E2%80%93402&rft_id=info:doi\/10.1016%2Fj.biosystemseng.2005.05.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1537511005000838&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Deidda, Riccardo; Coppey, Florentin; Damergi, Dhouha; Schelling, C\u00e9dric; Co\u00efc, Laureen; Veuthey, Jean-Luc; Sacr\u00e9, Pierre-Yves; De Bleye, Charlotte <i>et al.<\/i> (1 August 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521002612\" target=\"_blank\">\"New perspective for the in-field analysis of cannabis samples using handheld near-infrared spectroscopy: A case study focusing on the determination of \u03949-tetrahydrocannabinol\"<\/a> (in en). <i>Journal of Pharmaceutical and Biomedical Analysis<\/i> <b>202<\/b>: 114150. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jpba.2021.114150\" target=\"_blank\">10.1016\/j.jpba.2021.114150<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521002612\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521002612<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=New+perspective+for+the+in-field+analysis+of+cannabis+samples+using+handheld+near-infrared+spectroscopy%3A+A+case+study+focusing+on+the+determination+of+%CE%949-tetrahydrocannabinol&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.aulast=Deidda&rft.aufirst=Riccardo&rft.au=Deidda%2C%26%2332%3BRiccardo&rft.au=Coppey%2C%26%2332%3BFlorentin&rft.au=Damergi%2C%26%2332%3BDhouha&rft.au=Schelling%2C%26%2332%3BC%C3%A9dric&rft.au=Co%C3%AFc%2C%26%2332%3BLaureen&rft.au=Veuthey%2C%26%2332%3BJean-Luc&rft.au=Sacr%C3%A9%2C%26%2332%3BPierre-Yves&rft.au=De+Bleye%2C%26%2332%3BCharlotte&rft.au=Hubert%2C%26%2332%3BPhilippe&rft.date=1+August+2021&rft.volume=202&rft.pages=114150&rft_id=info:doi\/10.1016%2Fj.jpba.2021.114150&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0731708521002612&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chen, Zewei; de Boves Harrington, Peter; Griffin, Veronica; Griffin, Todd (26 November 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00557\" target=\"_blank\">\"In Situ Determination of Cannabidiol in Hemp Oil by Near-Infrared Spectroscopy\"<\/a> (in en). <i>Journal of Natural Products<\/i> <b>84<\/b> (11): 2851\u20132857. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1021%2Facs.jnatprod.1c00557\" target=\"_blank\">10.1021\/acs.jnatprod.1c00557<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0163-3864\" target=\"_blank\">0163-3864<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00557\" target=\"_blank\">https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00557<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=In+Situ+Determination+of+Cannabidiol+in+Hemp+Oil+by+Near-Infrared+Spectroscopy&rft.jtitle=Journal+of+Natural+Products&rft.aulast=Chen&rft.aufirst=Zewei&rft.au=Chen%2C%26%2332%3BZewei&rft.au=de+Boves+Harrington%2C%26%2332%3BPeter&rft.au=Griffin%2C%26%2332%3BVeronica&rft.au=Griffin%2C%26%2332%3BTodd&rft.date=26+November+2021&rft.volume=84&rft.issue=11&rft.pages=2851%E2%80%932857&rft_id=info:doi\/10.1021%2Facs.jnatprod.1c00557&rft.issn=0163-3864&rft_id=https%3A%2F%2Fpubs.acs.org%2Fdoi%2F10.1021%2Facs.jnatprod.1c00557&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cirrincione, Marco; Saladini, Bruno; Brighenti, Virginia; Salamone, Stefano; Mandrioli, Roberto; Pollastro, Federica; Pellati, Federica; Protti, Michele <i>et al.<\/i> (1 September 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521003812\" target=\"_blank\">\"Discriminating different Cannabis sativa L. chemotypes using attenuated total reflectance - infrared (ATR-FTIR) spectroscopy: A proof of concept\"<\/a> (in en). <i>Journal of Pharmaceutical and Biomedical Analysis<\/i> <b>204<\/b>: 114270. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jpba.2021.114270\" target=\"_blank\">10.1016\/j.jpba.2021.114270<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521003812\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708521003812<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Discriminating+different+Cannabis+sativa+L.+chemotypes+using+attenuated+total+reflectance+-+infrared+%28ATR-FTIR%29+spectroscopy%3A+A+proof+of+concept&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.aulast=Cirrincione&rft.aufirst=Marco&rft.au=Cirrincione%2C%26%2332%3BMarco&rft.au=Saladini%2C%26%2332%3BBruno&rft.au=Brighenti%2C%26%2332%3BVirginia&rft.au=Salamone%2C%26%2332%3BStefano&rft.au=Mandrioli%2C%26%2332%3BRoberto&rft.au=Pollastro%2C%26%2332%3BFederica&rft.au=Pellati%2C%26%2332%3BFederica&rft.au=Protti%2C%26%2332%3BMichele&rft.au=Mercolini%2C%26%2332%3BLaura&rft.date=1+September+2021&rft.volume=204&rft.pages=114270&rft_id=info:doi\/10.1016%2Fj.jpba.2021.114270&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0731708521003812&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Geskovski, Nikola; Stefkov, Gjose; Gigopulu, Olga; Stefov, Stefan; Huck, Christian W.; Makreski, Petre (1 April 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142520314013\" target=\"_blank\">\"Mid-infrared spectroscopy as process analytical technology tool for estimation of THC and CBD content in Cannabis flowers and extracts\"<\/a> (in en). <i>Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy<\/i> <b>251<\/b>: 119422. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.saa.2020.119422\" target=\"_blank\">10.1016\/j.saa.2020.119422<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142520314013\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1386142520314013<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mid-infrared+spectroscopy+as+process+analytical+technology+tool+for+estimation+of+THC+and+CBD+content+in+Cannabis+flowers+and+extracts&rft.jtitle=Spectrochimica+Acta+Part+A%3A+Molecular+and+Biomolecular+Spectroscopy&rft.aulast=Geskovski&rft.aufirst=Nikola&rft.au=Geskovski%2C%26%2332%3BNikola&rft.au=Stefkov%2C%26%2332%3BGjose&rft.au=Gigopulu%2C%26%2332%3BOlga&rft.au=Stefov%2C%26%2332%3BStefan&rft.au=Huck%2C%26%2332%3BChristian+W.&rft.au=Makreski%2C%26%2332%3BPetre&rft.date=1+April+2021&rft.volume=251&rft.pages=119422&rft_id=info:doi\/10.1016%2Fj.saa.2020.119422&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1386142520314013&rfr_id=info:sid\/en.wikipedia.org:Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220627224346\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.448 seconds\nReal time usage: 0.588 seconds\nPreprocessor visited node count: 39377\/1000000\nPost\u2010expand include size: 341911\/2097152 bytes\nTemplate argument size: 115099\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 94774\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 456.626 1 -total\n 88.20% 402.743 1 Template:Reflist\n 61.88% 282.540 40 Template:Citation\/core\n 46.88% 214.066 29 Template:Cite_journal\n 12.36% 56.417 5 Template:Cite_book\n 12.22% 55.803 39 Template:Date\n 7.33% 33.452 6 Template:Cite_web\n 5.65% 25.818 49 Template:Citation\/identifier\n 5.40% 24.678 1 Template:Infobox_journal_article\n 4.63% 21.148 1 Template:Infobox\n-->\n\n<!-- Saved in parser cache with key cannaqa_wiki:pcache:idhash:5666-0!canonical and timestamp 20220627224345 and revision id 17479. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n<\/body>","e54c0b7e681c5437811a012a24acebea_images":["https:\/\/www.cannaqa.wiki\/images\/0\/0f\/Fig1_Jar%C3%A9n_Agronomy22_12-4.png","https:\/\/www.cannaqa.wiki\/images\/d\/da\/Fig2_Jar%C3%A9n_Agronomy22_12-4.png","https:\/\/www.cannaqa.wiki\/images\/e\/e1\/Fig3_Jar%C3%A9n_Agronomy22_12-4.png","https:\/\/www.cannaqa.wiki\/images\/7\/7c\/Fig4_Jar%C3%A9n_Agronomy22_12-4.png","https:\/\/www.cannaqa.wiki\/images\/0\/0e\/Fig5_Jar%C3%A9n_Agronomy22_12-4.png"],"e54c0b7e681c5437811a012a24acebea_timestamp":1656439824,"4e539c9ca5c42af2a2ca977a314b2e2f_type":"article","4e539c9ca5c42af2a2ca977a314b2e2f_title":"Cannabis sativa research trends, challenges, and new-age perspectives (Hussain et al. 2021)","4e539c9ca5c42af2a2ca977a314b2e2f_url":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives","4e539c9ca5c42af2a2ca977a314b2e2f_plaintext":"\n\nJournal:Cannabis sativa research trends, challenges, and new-age perspectivesFrom CannaQAWikiJump to navigationJump to searchFull article title\n \nCannabis sativa research trends, challenges, and new-age perspectivesJournal\n \niScienceAuthor(s)\n \nHussain, Tajammul; Jeena, Ganga; Pitakbut, Thanet; Vasilev, Nikolay; Kayser, OliverAuthor affiliation(s)\n \nTU Dortmund UniversityPrimary contact\n \nEmail: Tajammul dot hussain at tu-dortmund dot deYear published\n \n2021Volume and issue\n \n24(12)Article #\n \n103391DOI\n \n10.1016\/j.isci.2021.103391ISSN\n \n2589-0042Distribution license\n \nCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalWebsite\n \nhttps:\/\/www.sciencedirect.com\/science\/article\/pii\/S2589004221013626Download\n \nhttps:\/\/www.sciencedirect.com\/science\/article\/pii\/S2589004221013626\/pdfft (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Methods \n4 Trends of cannabis research from 1783 to 2021 \n5 Cannabis sativa L. physiology and legal status \n6 Trichomes and cannabinoid biosynthesis \n7 Developments in cannabis genomics \n8 Developments in cannabis transcriptomics \n9 Patents for Cannabis sativa L. \n10 Cannabis in COVID-19 \n11 Conclusion and future prospective \n12 Supplemental information \n13 Acknowledgements \n\n13.1 Author contributions \n13.2 Conflict of interest \n\n\n14 References \n15 Notes \n\n\n\nAbstract \nBackground: Cannabis sativa L. is one of the oldest known medicinal plants, cultivated for at least 10,000 years for several agricultural and industrial applications. However, the plant became controversial owing to some psychoactive components that have adverse effects on human health. \nMethods: In this review, we analyze the trends in cannabis research for the past two centuries. We discuss the historical transitions of cannabis from the category of \"herbal medicine\" to an illicit drug and back to a medicinal product post-legalization. In addition, we address the new-age application of immuno-suppressive and anti-inflammatory cannabis extracts for the treatment of COVID-19 inflammation. We further address the influence of the legal aspects of cannabis cultivation for medicinal, pharmaceutical, and biotechnological research. Finally, we review the up-to-date cannabis-related genomic resources and advanced technologies for their potential application in genomic-based cannabis improvement. \nResults: Overall, this review discusses the diverse aspects of cannabis research developments, ranging from traditional use as herbal medicine to the latest potential in COVID-19, legal practices with updated patent status, and current state of the art genetic and genomic tools reshaping cannabis biotechnology in the modern agriculture and pharmaceutical industries.\nConclusions: Remarkable growth in genomic data, combined with fast-paced development of artificial intelligence (AI)-based data analysis tools have made it possible to explore the Cannabis plant at the genetic and molecular levels. In the future, the combination of these genetic technologies will make it possible to obtain enhanced expression rates, which will lead to enhanced cannabinoid yields in an economically feasible manner. Pharmacological research, coupled with rapidly evolving genome-based biotechnology, will further facilitate exploring the Cannabis plant for its tremendous potential in drug discovery.\nKeywords: cannabis, cannabis research, plant biology, plant genetics, genomics\n\nIntroduction \nCannabis sativa L. is one of the earliest known cultivated plants since agricultural farming started around 10,000 years ago.[1] It is a multi-purpose crop plant with diverse agricultural and industrial applications, ranging from the production of paper, wood, and fiber, to its actual and potential use in the medicinal and pharmaceutical industries. The first-ever report to reveal the prospects of C. sativa L. as a medicinal plant was published in 1843 and described the use of plant extracts to treat patients suffering from tetanus, hydrophobia, and cholera.[2] However, the first chemical constituent identified was oxy-cannabis, in 1869.[3] Cannabinoids were being isolated as early as 1896, followed by a variety of full identifications like:\n\ncannabidiol (CBD) in 1940[4],\ntetrahydrocannabinol (THC) in 1964[5][6],\ncannabigerol (CBG) in 1964[5], and\ncannabichromene (CBC) in 1966.[7]\nIdentification of THC later led to an understanding of the endocannabinoid system, followed by the discovery of the first cannabinoid receptor (CB1) in 1988.[8][9] The CB1 receptor acts as a homeostatic regulator of neurotransmitters for pain relief mechanisms, but the same mode of action was responsible for the intoxicating effects from excessive cannabinoids use. This greater understanding of the mode of action of the CB1 receptor raised concerns about the adverse effects of cannabis use. Consequently, the plant was removed from the \"medicinal\" category and re-categorized exclusively to the category of \"illicit drug.\"\nCultivation and use of the Cannabis plant for recreational, medical, and industrial use were strictly banned, which severely limited the scientific research in the field. Owing to strict legal regulations, the plant remained unexplored for its incredible potential in drug discovery for an extended period until it was legalized for medical use first in California and later in many countries around the globe. Extensive research followed legalization in order to explore the chemodiversity of cannabinoids for potential clinical value. In total, more than one thousand compounds have been identified, including 278 cannabinoids, 174 terpenes, 221 terpenoids, 19 flavonoids, 63 flavonoid glycosides, 46 polyphenols, and 92 steroids\u2014have been identified.[10][11][12] Nearly 278 of these compounds are cannabinoids and classified as phytocannabinoids plant-based) to distinguish them from endocannabinoids (non-plant). Cannabimimetic drugs binding to CB1 receptors in the endocannabinoid system can also be found in algae, bryophytes, and monilophytes.[13][14] The major cannabinoids in cannabis include THC, CBD, and CBC, as well as their precursors CBG and cannabinol (CBN).[15] To date, 10 CBN-type, 17 CBG-type, 8 CBD-type, and 18 THC-type cannabinoids have been isolated.[5] Cannabigerolic acid (CBGA), a CBG-type cannabinoid, is the central precursor for the biosynthesis of psychoactive THC, non-psychoactive CBD, and CBC.[10][11][12]\nCannabinoid biosynthesis in plants occurs in specialized biosynthetic organs called glandular trichomes[16] on female flowers and leaves. Several studies use metabolic profiling of trichomes to demonstrate variation in trichome size, density, and relative concentration of cannabinoids.[16][17] However, the genetic mechanisms underlying the developmental changes in trichomes and consecutive cannabinoid content are still unknown. Apart from natural and chemical biosynthesis methods[18], heterologous biosynthesis of cannabinoids has also been reported.[19] However, the considerable amount of side products is still one of the major bottlenecks in cannabinoid production.[19][20]\nThis review highlights the latest research developments and challenges in Cannabis plant sciences, as well as the role of trichomes as biosynthetic sites, with a special focus on plant biology. Additionally, we discuss the existing legal practices with patent information for C. sativa L. We also discuss the new potential use of cannabinoids for COVID-19 treatment. Finally, we address the available genomic and transcriptomic resources and discuss their potential toward the genetic improvement of cannabis. Overall, we provide the first in-depth review of diverse aspects of C. sativa L. from traditional medicinal use to genomics insights and research perspective to broad industrial applications.\n\nMethods \nCannabis-related publications were searched in four major scientific literature and citation databases of biomedical and life sciences journals: EMBL-EBI's Europe PMC (Data S1, Supplemental information), Elsevier's Scopus (Data S2, Supplemental information), National Library of Medicine's PubMed Central (Data S3, Supplemental information), and Clarivate's Web of Science. The search criteria\u2014\u201ccannabis OR marijuana OR hemp OR cannabinoids OR cannabidiol OR cannabinol\u201d\u2014were used to examine available research articles. Some 80,979 (EuropePMC), 64,637 (Scopus), 43,182 (Web of Science), and 28,759 (PubMed Central) cannabis-related research articles were found. \nThe sheer difference in the number of articles could be attributed to the years for which the cannabis records are present in the databases. Europe PMC currently holds cannabis records dating back 239 years, with the oldest publication dating to 1783, whereas Scopus has data for 194 years (dating back to 1828), PubMed Central 182 years (dating back to 1840), and Web of Science 77 years (since 1945) (Figure 1A). Despite cannabis records only going back 77 years, the Web of Science record count exceeds PubMed Central's, owing to a data acquisition policy similar to Scopus, wherein all the cited references for a publication are pulled and listed in the database. \nAnother major reason for the different records in the archives could be owing to the source repositories and partner journals. Although PubMed Central has only 6.9 million articles from over 10,656 journals (as of April 2021), Scopus has more than 77.8 million records from nearly 23,500 journals, and Web of Science comprises over 171 million records, including journals, books, and proceedings. However, Europe PMC acquires data from multiple bibliographic repositories such as PubMed, MEDLINE, PubMed Central, AGRICOLA, and Chinese Biological Abstracts (CBA) (Figure 1D). It includes more than 45.6 million documents, including articles, books, preprints, patents, conference papers, and microPublications.\nCannabis citation metadata was publicly available for bulk download from Europe PMC (6,586 journals), Scopus (8647 journals), and PubMed Central (3864 journals) (Figure 1B). Among the various article identifiers used such as DOI, PMCID, and PMID, the DOI was found for 85.62% of records at Europe PMC, 85.44% of records at Scopus, and 91.9% of records at PubMed Central. Since DOI was the only common identifier, it was used for the comparison of three datasets (Figure 1C). Cannabis records in Europe PMC comprised nearly 76.73% of PubMed Central and 49.75% of Scopus data (Figure 1C). Hence, metadata from Europe PMC was selected for downstream bibliometric analysis. The majority of cannabis-related records in Europe PMC were from MEDLINE (94.94%), followed by 4.29% from PubMed Central, with only 0.75% from Agricola and 0.02% from CBA (Figure 1D). The distribution of source databases indicates the most explored field in cannabis research for the last 239 years.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 Cannabis research trend. (A) Timeline of cannabis records. Timeline and years from the earliest to the latest cannabis records in the literature databases of life science and biomedical journals are depicted with a color coded radial bar for Europe PMC (green), Scopus (blue), Pubmed Central (gray), and Web of Science (lilac). The publication year of the first available cannabis-related document in each database is marked by a vertical line at top of corresponding bar. The number of years from the oldest available article to the most recent publication in 2021 are indicated at the base of each bar. (B) Cannabis documents in the literature archives. The bar plot shows number of documents in the selected databases, with Y axis divided into two sections to show the journals (upper section) and articles (lower section). (C) Common citations in databases. Europe PMC, Scopus and Pubmed Central records were compared using DOI identifiers, and the number of shared and unique documents between three sets are shown as a Venn plot. The size of the circle corresponds to the number of articles with a DOI in each database. (D) Cannabis literature source in Europe PMC. Color-coded pie chart depicts the source repositories of cannabis articles in Europe PMC. The contribution (percentage of articles) from Medline (MED), AGRICOLA (AGR), PubMed Central (PMC) and Chinese Biological Abstracts (CBA) are shown by orange, gray, turquoise, and cyan color, respectively. (E) Cannabis research trends. The overall pattern of cannabis research from 1783 to 2021 is depicted by the trend line (log scaled), with each dot representing the number of articles (Y axis) per year (X axis). The research periods are categorized as Zero (1783\u20131840), I (1840\u20131937), II (1937\u20131996), and III (1996\u20132021), and they are separated by vertical dotted lines. The three major achievements\u2014(I) discovery of cannabinoids, ii) cannabinoid receptors, and iii) endocannabinoids\u2014that pushed the interest in cannabis are marked in pink color. The number of articles in 2021 are still growing and therefore depicted as a hollow enlarged dot. (F) Cannabis research subjects. A bubble plot depicts the most and least explored scientific subject areas, with size corresponding to the number of articles (Y axis) and journals (Y axis) in each category. A major proportion of cannabis research was related to medical and medicinal sciences, followed by pharmacology and pharmaceuticals, neurosciences and psychology, biochemistry and biotechnology, genetics and genomic sciences, agriculture and plant biology, and bioinformatics.\n\n\n\nTrends of cannabis research from 1783 to 2021 \nC. sativa L. originated in central Asia and later spread to Europe during its cultivation, with diverse applications. Archaeological evidence of early medical use was found in fossil records dating back to 315\u2013392 A.D.[21] Researchers largely have a consensus that the plant has at various times been used as traditional medicine.[22] \nBased on our search results, spanning more than two centuries, we divide the scientific era into four periods (Figure 1E). Period Zero (1783\u20131840) marked the first-ever mention of Cannabis as a category of medicinal plant, in the years 1783[23] and 1787.[24] According to Europe PMC results, there were only 52 articles and 38 reviews in the next five decades. Most reports mentioned the botanical aspects of hemp and the quality of its fiber, with few observations about its use in traditional medicines. \nPeriod I (1840\u20131937) began with the detailed evidence-based report of the chemical properties and medicinal potential of Cannabis indica (hemp) by William O'Shaughnessy[2], followed by an array of medicinal reports in articles from 1923. We identified 183 reviews in the subsequent 96 years. Scientific endeavors to experiment, observe, and understand the diverse medicinal applications of cannabis were still in the early stages. However, the 1900s witnessed a series of legal regulations in the direction of the criminalization of cannabis. Cannabis was starting to be categorized into lists of narcotic drugs, and \"poisons rules,\" including the Pure Food and Drug Act of 1906, pushed for stricter measures for cannabis distribution. Later, the Second International Opium Convention of 1925 called for measures to regulate Indian hemp. Exports, unless exclusively for medical or scientific purposes or European hemp (for fiber), were banned. The Uniform State Narcotic Drug Act of 1925 and the Geneva Trafficking Conventions of 1936 resulted in criminalizing the cultivation, possession, manufacture, and distribution of cannabis derivatives. The Marihuana Tax Act of 1937 levied heavy taxes on the possession and selling of cannabis, excluding medical, and industrial use. As a consequence, the cultivation and procurement of cannabis for research purposes became increasingly difficult, severely limiting the research of medicinal cannabis during this era (see Figure 1E: Period I).\nDuring Period II (1937\u20131996), cannabis research suffered major restrictions, owing to legal regulations in the first two decades, until the identification of the first cannabinoid\u2014cannabidiolic acid or CBDA\u2014in 1954[6][25][26][27] and the isolation of the most psychoactive component of cannabis\u2014THC\u2014in 1964.[5] Other discoveries paved the way for decriminalization laws, including isolation of THC, discovery of the CB1[8] and CB2[28] receptors, and the emergence of the Compassionate Investigational New Drug program in 1978. The discovery of endocannabinoids and a growing understanding of the potential role of cannabis in the medicinal field also played a role during this period.[25][29] A significant uptick in published cannabis research was observed during this period, with 445 cannabis-related articles and 25 reviews being found between 1937 and 1964, ramping up to 8,888 articles and 773 reviews between 1964 and 1996 (see Figure 1E: Period II), although with a notably short period of decline in publications between 1973 and 1982.\nFinally, Period III (1996-2021) began with the historical Compassionate Use Act of 1996 in California approving medical cannabis. Post-legalization (1996 onwards), cannabis has been extensively explored for its diverse potential in the pharmaceutical and medicinal industries. During Period III, cannabis research witnessed unprecedented growth, with nearly 67,777 articles, 13,202 reviews, and 493 preprints showing up in Europe PMC, of which 97.01% articles were published since 2000 (see Figure 1E: Period III). Approval of the first cannabis-based inhaler spray in 2005[30][31] and publication of the first draft of the cannabis genome in 2011[32] in this era were the two major accomplishments that exponentially accelerated research development.\nThe trends of cannabis study in the diverse array of research articles and journals indicate the core interests of the scientific community. To further investigate the most researched field, the journals of cannabis articles were categorized into scientific and social areas. The journals related to social-, legal-, and policy-based studies were merged into the subject category of \"social research.\" The majority of broad science-based subjects were grouped into the following seven major categories: (i) medicinal, including all medical and medicinal subjects); (ii) pharmaceutical, comprised of pharmacology, pharmaceuticals, drug, toxicology, and chemical studies; (iii) neurosciences, comprised of neurological, brain-related, psychiatry, psychology, and cognitive studies; (iv) biochemistry, including biotechnology, microbiology, immunology, virology, and biochemistry; (v) genomics, including grouped genetic and genomic studies; (vi) plant biology, including plant sciences, agricultural, botanical aspects, plant-based pathogens, and environment studies; and lastly, (vii) bioinformatics, including data analytics. Journals that could not be classified into social research or science-based categories were excluded from downstream evaluation.\nThe science-based subject areas (74.47% of journals) were further compared for the corresponding number of articles and journals (Figure 1F). A distinct pattern was observed for the clinical aspects of cannabis, which remained a major focus from the very beginning. Some 94.76% of published articles addressed some sort of clinical aspect, including 64.51% articles addressing medicinal topics, 19.55% addressing pharmaceutical science topics, and 10.70% addressing the neurosciences. In contrast, plant biology and agricultural sciences comprised only 2.62% of articles, followed by 0.71% on genomics, and 0.07% on bioinformatics-based cannabis research. Genomics and bioinformatics are relatively new subjects, growing at a faster pace since the release of the first Cannabis draft genome in 2011. Recent advances in sequencing technologies have further propelled genomic and transcriptomic studies, with the purpose of dissecting the regulatory networks. The growth of genomic data in the public space has been met with the fast-paced development of bioinformatics tools for data analysis. In addition, the ongoing development of genomic tools using machine learning (ML) and artificial intelligence (AI) will facilitate improved genetic-level understanding of cannabis metabolism for the selective breeding of genetically modified cannabis with improved metabolic traits.\n\nCannabis sativa L. physiology and legal status \nPhysiological, morphological, and developmental aspects of the Cannabis plant are key in understanding its growth patterns and chemical profiles. However, plant growth and function are substantially influenced by abiotic factors and nutrient availability. Botanical aspects[33], plant architecture, and florogenesis of female C. sativa plants[34] with detailed trichome morphogenesis[35] has provided crucial insight into plant biology. However, it has also become increasingly important to determine the effect of abiotic factors on Cannabis growth and chemical yield, especially for large-scale commercial breeding programs. Hence, in-depth analysis of the effect of soil fertilization, salinity, temperature, and light conditions, as well as nutrient and water-use efficiency is key in establishing industrial-scale systems for the cultivation of hemp and marijuana varieties. \nThe first available records about the mineral nutrition of hemp plants were published by Tibeau et al. in 1936.[36] Later, in 1944, Clarence H. Nelson published the effect of varying soil temperature on hemp growth.[37] The first publication with a detailed response of greenhouse cultivated cannabis to nitrogen (N), phosphorus (P), and potassium (K) was published in 1977.[38] Furthermore, two parallel reports by van der Werf et al. in 1995 discussed the impact of nitrogen fertilization on sex expression in hemp[39], and the effect of temperature on leaf and canopy formation.[40] Importantly, most physiological studies in Period II and Period III (Figure 1A) were published for hemp, with a focus on photosynthetic response and biomass yield under varying conditions such as temperature, water availability, nitrogen, and mineral nutrition.[41][42][43][44][45][46] However, the first study to assess the chemical response of hemp plants wasn't published until 1997.[47]\nThe physiological response of drug-type medical Cannabis plants may differ from hemp plants, owing to the distinct genetic and chemical differences. Hence, a clear understanding of optimum factors for medical cannabis is inevitable for the efficient cultivation of plants with desired chemical composition. The first few studies that addressed medical cannabis and its photosynthetic response to photon flux densities, temperature, and CO2 conditions were published by Chandra et al. in 2008 and 2011.[48][49] Bernstein and others further addressed the growth and chemical response of medical cannabis to mineral nutrition, especially N, P, and K.[50][51][52][53] Saloner and Bernstein[52] reported optimum N concentration at 160 mg L\u22121, while N with lower levels showed several symptoms inducing necrosis and growth retardation and N with higher levels impacted in reducing concentrations of THCA and CBDA. Shiponi and Bernstein[51] showed a negative association of cannabinoid concentrations and yield with increasing P supply. Saloner et al.[50] further determined the genotype-dependent effect of K nutrition on medical cannabis, reporting 240 ppm K detrimental for the genotype Royal Medic and stimulant for the Desert Queen genotype, while 15 ppm K was insufficient for both genotypes. Further, in 2019, Bernstein et al.[53] discussed the combined effect of NPK nutrition upon cannabinoid concentration. \nIn addition to soil nutrients, the heavy metals uptake potential of hemp varieties has also been thoroughly investigated by multiple reports in the 2000s.[54][55][56][57][58][59][60][61] Industrial hemp varieties of C. sativa have also been shown to grow well in soils contaminated with heavy metals[54][56][57][58][59][61] and reported for their heavy metal accumulation. Several field projects have assessed the phytoremediation potential of hemp plants for the reclamation of contaminated and radioactive soils.[55][60]\nCannabis cultivars are classified into drug-type (marijuana), fiber-type (hemp), and neutral (zero cannabinoid) plants with distinct cannabinoid constitutions. Drug-type cultivars with THC\/CBD ratio \u226510 are classified as chemotype I, while those with THC\/CBD ratio ranging from 0.2 to 10 are grouped as chemotype II. In contrast, fiber-type cultivars with THC\/CBD ratio <0.2 are categorized as chemotype III. Chemotype IV also has low THC contents but with the potent percentage of CBG. Furthermore, the chemotypes producing very little to almost zero cannabinoid compounds (neutral) are grouped as chemotype V[62][63] and were first described by Mandolino et al. in 2004.[64] Apart from cannabinoid (THC, CBD) content, drug and fiber-type plants have significant genetic variation. Sawler et al. described that marijuana is genetically inclined toward sativa, and hemp has a similarity with the indica type.[65] Moreover, each plant type has unique applications, differentiating them from each other. For example, the fiber-type \"hemp\u201d plant has mostly food and industrial applications, including production dietary products, hemp oil, seeds, and fiber, while the \u201cmarijuana\u201d drug-type plant is used exclusively for medicinal and recreational purposes.\nDespite such a huge genetic and application diversity, both types of cannabis plants were placed under Schedule I of the Controlled Substances Act in 1970.[66] These restrictions had a serious impact on cannabis-related research, preventing the scientific community from studying the potential of diverse yielding traits for hemp. However, after 44 years, Section 7606 of the Agricultural Act of 2014 finally distinguished hemp from marijuana.[67] Approval of the law, along with the 2018 Farm Bill[68], opened the window for the scientific community in the U.S. to conduct research and cultivate hemp. Since then, most U.S. states[69] and more than 47 countries around the world have been growing hemp for research and industrial use.[70] On the other hand, marijuana research and legalization have been expanding at a comparatively slower rate, and till now only 16 countries have legalized medicinal cannabis.[71] Furthermore, a detailed study would be desirable to understand the gene function, the genetic composition, and the underlying mechanisms regulating the diversity of cannabinoids in both major varieties. Availability of the regeneration protocol[72] and transformation studies[73] could be utilized for the expression studies to unravel the mystery of these mechanisms, especially in trichomes.\n\nTrichomes and cannabinoid biosynthesis \nGlandular trichomes are the primary site for cannabinoid biosynthesis and accumulation[74] in C. sativa. The biosynthesis of cannabinoids[75][76] starts from the plastidial localized methylerythritol 4-phosphate (MEP) pathway, resulting in the formation of geranyl pyrophosphate (GPP)[77] and the fatty acid pathway leading to the production of olivetolic acid (OA).[78] GPP and OA in the presence of olivetolic acid cyclase (OLS)[79][80] and an aromatic prenyltransferase catalyze the reaction to form CBGA[79][81][82], which is the central precursor for cannabinoid biosynthesis. In 2011, van Bakel et al. analyzed the transcriptomic and genomic data and described the exclusive presence of the THCAS and CBDAS in the drug and hemp-type plant, respectively.[32] It is suggested that the activation of respective enzymes from the central precursor CBGA is responsible for regulating the THC and CBD concentration for each chemotype. However, the precise regulatory mechanism is still unknown.\nBesides biosynthesis, understanding the trichome physiology is also vital to elucidate the trafficking and localization of metabolites. For cannabinoid biosynthesis, there exist three major reactions: \n\nbiosynthesis of monoterpene precursor (GPP) via MEP and fatty acid intermediate (OA) from polyketide pathway,\nprenylation of the precursors, and\ncyclization.\nThe MEP pathway in plastid prenylation is localized in the chloroplast membrane, where the C-prenylated CBGA synthase is membrane-bound. The integration of the enzyme in the membrane seems essential, and the folding pattern is crucial for its functioning. Therefore, simple cloning and functional expression of this enzyme in a heterologous host such as yeast to generate the desired cannabinoids is challenging. Terpenoid cyclization reactions are the most complex reactions found in nature, and the biotransformation from CBGA to THCA by the THCA synthase is assumed to occur in the cytosol. This hypothetical model is under ongoing debate, and it might be likely that biocatalysis occurs in the extracellular oil container under a non-aqueous environment.[83] In 1992, Mahlberg and Kim postulated that THCA synthase is located in the outer membrane of the head cells or even attached on the outer membrane surface extending into the essential oil.[84] In recent studies, Liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) was used to detect a functional, active THCA and CBGA synthase in the exudates from glandular trichomes of cannabis.[85] Zirpel et al. described the need for an excellent understanding of protein chemistry and folding of these enzymes to produce the cannabinoid using a heterologous host.[86] Detailed knowledge of genetic regulatory mechanisms underlying cannabinoid biosynthesis is a future challenge. Identification of regulatory elements such as transcription factors (TFs) and microRNAs (miRNAs) could be utilized to understand the mechanistic insights of trichomes initiation, development, and densities. An in-depth understanding could be applied toward the breeding of genetically improved cannabis varieties with enhanced cannabinoids concentration in trichomes.\n\nDevelopments in cannabis genomics \nDrug- and fiber-type plants differ in biosynthesis, concentration, and composition of metabolites.[43] To determine the genetic variations regulating plant-specific differences, it is essential to compare the genomes. Advanced sequencing technologies, combined with continuously improving bioinformatics tools, have allowed rapid sequencing and analysis of multiple genomes and transcriptomes. The very first draft genome of C. sativa was released in 2011 by Bakel et al.[32] They sequenced the marijuana cultivar Purple Kush by using Illumina short reads and assembled them in combination with 454 reads. They also sequenced the fiber-type hemp cultivar Finola for a genome-level comparison. In addition to whole genome sequencing, the first complete mitochondrial reference genome was also obtained in 2016 from the cannabis hemp variety Carmagnola.[87] Later, in July 2016, two complete chloroplast genomes of marijuana (THC-dominant) African variety Yoruba Nigerian and Korean hemp non-drug variety (low THC) Cheungsam[88] were sequenced and used to determine the phylogenetic position of C. sativa relative to other members in the order Rosales. Furthermore, Vergara et al. released the complete chloroplast genomes of two Cannabis hemp varieties, the Carmagnola (Italian) and Dagestani (Russian), in September 2016 to determine their genetic distance compared with the closest Cannabaceae chloroplast of Humulus lupulus variety Saazer.[89]\nIncreasingly growing support for open data policies by multiple industries is improving transparency in cannabis agriculture. In 2016, the industrial lead in cannabis research from Courtagen Life Sciences and Phylos Bioscience independently generated the genomes of hybrid marijuana strain (THC-dominant) Chemdog91 (by Illumina GAII) and marijuana strain (CBD-dominant) Cannatonic (using PacBio), respectively. Phylos Bioscience also released genomic data on 850 cannabis strains as a part of the \u201cOpen Cannabis Project\u201d for plant breeding programs. With an objective to explore cannabis population genetics, Phylos Bioscience developed a three-dimensional interactive map of nearly 1,000 cannabis strains.[90] In 2017, the genome of hybrid marijuana cultivar Pineapple Banana Bubba Kush (PacBio) was released as part of the Cannabis Genomic Research Initiative. In 2018, Grassa et al. generated the first chromosome-level assembly for the genome of CBDRx, a high-CBD cultivar of C. sativa by using advanced long-read Oxford Nanopore Technology (ONT) and PacBio Single-Molecule Real-Time (SMRT) sequencing.[91] In 2019, Laverty et al. improved the initial draft assemblies[32] of drug-type Purple Kush and hemp-type Finola to the chromosome-level by using ultra-long PacBio reads.[92] In addition to genomes of high-CBD and -THC marijuana and hemp cultivars, a medicinal cannabis strain with a balanced THC\/CBD ratio was sequenced by Braich et al.[93]\nUntil 2020, nearly all cannabis genomes had been obtained from the hemp and marijuana cultivars, selectively bred for generations. However, cultivars lose genetic diversity owing to domestication and successive plant breeding for selected traits. In contrast, the wild-type genomes exhibit relatively high heterozygosity and genetic diversity, which might provide unique evolutionary insights into the cannabis genome. In 2020, Gao et al. sequenced the first samples of C. sativa wild-type \u201cJamaican Lion,\u201d growing in the geographically isolated Himalayan region in Tibet. Because these wild-type plants retained the ancestral genetic make-up, the data generated from this study was used as a tool to determine the inheritance patterns and evolutionary inference of cannabis.[94]\nThe published genomes of high-THC and -CBD marijuana cultivars, as well as hemp varieties, have exhibited inconsistent chromosomal nomenclature, arrangement, and a varying degree of gaps. By the end of 2020, Braich et al. had generated a relatively complete draft genome assembly for Cannbio-2, the medicinal cannabis strain with a balanced THC\/CBD ratio.[93] To present date, only 13 cannabis genomes are publicly available at the National Center for Biotechnological Information (NCBI). Of those 13, three assemblies are at the chromosome level, seven at the contig level, and one at the scaffold level. However, as of March 2021, the 1000 Cannabis Genomes Project comprises genomic data of some sort for nearly 1,000 samples from multiple cannabis strains. These datasets were the first genome data released on the Google Cloud Big Query database.\nThe continuous expansion of the list of cannabis genomes needs collaborative efforts toward curating the information. As such, academic and industry experts in diverse fields formed the International Cannabis Research Consortium (ICRC) during the annual PAG meeting in 2020. Despite several cannabis genome assemblies, the selection of a single standard reference genome is still a huge challenge for the scientific community, especially plant breeders. However, the ICRC proposed the CBDRX Cs10 assembly as the most complete reference for use in cannabis genome research.[91] Additionally, a member genomics company, NRGene, generated an integrated Cannabis and Hemp Genomic Database (CannaGENE) optimized and curated for the genomics-based breeding of cannabis varieties. Finally, in 2021, the first-ever open-access and comprehensive database of cannabis genome, the CannabisGDB, was released[95] with integrated bioinformatics tools for the analysis of datasets.\nOverall, the genomic data of diverse cannabis genotypes represent untapped reservoirs of genetic information which could be applied toward pan-genomic understanding of cannabis evolution and determining the effect of genetic variations upon the pathways, development, and concentration of cannabis derivatives. A detailed genetic atlas would facilitate the designing and further breeding of cannabis varieties for preferred metabolic yields.\n\nDevelopments in cannabis transcriptomics \nThe availability of several high-quality cannabis genomes made it easier to apply the transcriptome sequencing to elucidate detailed expression dynamics in a time-, tissue-, stage-, and chemotype-dependent manner. Furthermore, the differential expression analysis provides in-depth insight into co-related gene networks. In 2011, Bakel et al[32]. sequenced and compared the transcriptomes of marijuana variety Purple Kush (PK) and hemp cultivars Finola (FN) and USO-31. Gene expression analysis revealed preferential expression of cannabinoid and precursor pathway-associated genes in marijuana (PK). Expression of THCA synthase in the PK and CBDA synthase in FN was found to be consistent with the exclusive production of psychoactive THC in marijuana. In a recent study, transcriptomics of hemp-type plants was analyzed to determine the expression profile of the fiber-type plant at the various developmental stages.[96] Similarly, the transcriptome of marijuana flowers at different stages was captured and sequenced, notably with a gene expression pattern consistent with its cannabinoid contents.[32]\nAs glandular trichomes are the central reservoir for cannabinoids[74][97], the trichome transcriptome could yield valuable insight to determine the variation in cannabinoid biosynthesis, composition, and concentration between the drug- and fiber-type plants. Importantly, the identification of the differentially expressed genes could unravel the underlying molecular mechanisms of natural genetic and metabolic variation. The gene expression in trichomes of female plant strain Cannobio-2 was compared with genome-wide transcriptomics of female floral tissues at different stages of development, as well as other tissues including female and male flowers, leaves, and roots.[98] The extensive-expression atlas was applied toward the identification of genes expressed preferentially in various tissues at different developmental stages. Interestingly, the majority of genes involved in terpenoid and cannabinoids synthesis were significantly overexpressed in trichomes. In 2021, Grassa et al. used genomic and expression-associated expression of THCAS and CBDAS with THC:CBD ratio by Quantitative trait Loci (QTL) analysis of cannabis cultivars.[91]\nDatasets from similar genomics, transcriptomics, microbiome, and metagenomics studies of various cannabis strains are currently accessible from the Sequence Read Archive (SRA) repository at NCBI. In the past three years, there has been unprecedented growth in cannabis genome and transcriptome studies, as well as corresponding SRA entries. To date, there are over 4,571 BioSamples from multiple studies related to cannabis, of which 2,871 public BioSamples are exclusively for C. sativa, with 2,546 DNA and 325 RNA-Seq datasets in SRA. The SRA data for transcriptomics and metagenomics have been reportedly procured from various tissues, including seeds (3), flowers (116), leaves (138), shoot (13) stem (175), root (76), and trichomes (62), while genomic data lacks tissue-specific information. In-depth transcriptomic studies will be required in the future to improve the understanding of regulatory genetic networks.\n\nPatents for Cannabis sativa L. \nOne of the fundamental aspects of patents, especially in medical science or biotechnology, is to involve industrial partners in investing in research and development.[99] Cannabis-related patents have been issued by the United States Patent and Trademark Office (USPTO) since 1942. More than 1,500 applications have been filed just in the USPTO. Among them, approximately 500 applications got patent protection rights[100], and most of them were from the last decade. The exponential increase in the number of patents shows the future potential for the growing cannabis industry. Here, we analyzed the patents spatiotemporally and categorized them into four main classes: (i) patents related to cannabinoids as constituents, (ii) pharmaceutical applications, (iii) endocannabinoid pharmacology, and (iv) genome- and gene-related. Among the suggested four categories, the patents related to the pharmaceutical application were the most significant category, with 73 patents registered. These are further sub-grouped into the (i) preparation of the drugs, (ii) treatment, (iii) delivery technology, and (iv) detection method, each with 14, 33, 13, and 13 patents, respectively. Others have examined cannabis-related patents as well. For example, Gerra et al.[101] reviewed endocannabinoid-related patents, comprised of the CB1\/2 receptor (26), TRPV1 (6), and GPR119 (4) in 2010. The category of cannabinoids consists of (i) cannabinoid isolation, (ii) extraction, and (iii) synthesis- or biosynthesis-related patents, each with 6, 6, and 12 patents granted, respectively. For the division of the sequences, 15 patents are from enzyme inhibition, followed by the gene and the protein, each with two patents. Most of the patents are from the US (49.6%), followed by Great Britain (11%) and a variety of European countries[102] (Figure 2). In addition, 25 patents for fiber\/textile, 10 for foodstuff, five for the paper industry, three for architecture, one for biofuel, and three for plant breeding have been registered. Also, four patents each in the category of oil, extracts, and cosmetics have been filed.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 Cannabis patent development. (A) Number of patents registered for each category. Isolation, extraction, and biosynthesis belong to the category of cannabinoid-related patents. Pharmaceutical-related patents were subcategorized into preparation, treatment, delivery technology, and detection. CB receptor, TRPV1, and GPR119 were grouped into endocannabinoids. Three sub-groups\u2014e.g., enzymes, genes, and proteins\u2014are grouped for the category of sequence-related patents. (B) Distribution of the patents into four major categories. (C) Region-wise division of the patents registered for each category. (All the information shown here are up to 2017.)\n\n\n\nHowever, we have to keep in mind that a certain cannabinoid invention can be referred into more than one patent category. For instance, cannabinoids are highly hydrophobic by nature and thus they have low bioavailability in the human body. As a result, a new class of cannabinoid-glycosides has been created, whose representatives are produced through enzymatic glycosylation. This novel strategy led to increased aqueous solubility of the target cannabinoids and resulted in four patents (WO2017053574, US20190153461, US20190078168, and WO2020239784). Recently, a new method of producing one or more cannabosides by feeding an insect a cannabinoid was patented (WO2021146687). These new classes of cannabinoid glycosides generated vast structural diversity and have greatly improved water solubility, enabling new pharmaceutical formulations and multiple administration routes (oral, parenteral, or transdermal). The discovery of the genes encoding glycosyltransferases may belong to different categories of the cannabinoid patent family, that is, genes, enzymes, delivery technology, etc.\nThe exponential enhancement of the patent number during recent years in the diverse areas of cannabinoid applications is indicative of the increased commercial interest in this class of natural compounds. The various pharmaceutical applications will continue to shape primarily the path of future invention of cannabinoids.\n\nCannabis in COVID-19 \nC. sativa has become increasingly known for its potential anti-inflammatory properties.[103] The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus and its resulting disease, COVID-19, can result in life-threatening lung inflammation. A reduction of this inflammation is optimal, and means of reducing lung inflammation have been tested in the mice animal model. Interestingly, cannabinoid isolates such as CBD and THC have also been tested in humans, even long before the onset of the global pandemic owing to the spread of SARS-CoV-2.[104][105][106] Immune responses during severe cases of COVID-19 trigger the inflammation of human lung tissue, resulting in acute respiratory distress and failure. This immune response to the overproduction of pro-inflammatory cytokines is known as a cytokine storm.[107] Respiratory distress from COVID-19-induced lung inflammation is the leading cause of the disease's high mortality rate. Phyto-cannabinoids, especially CBD, have exhibited a remarkable anti-inflammatory effect through CB2 inhibitory activity and an agonistic effect on the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3).[108] Additionally, CBD, CBN, and THC have also been shown to exhibit some anti-viral effect against COVID-19 in cell-based assays, with the same potency as the standard clinical references (remdesivir and lopinavir).[109] However, the complete antiviral mechanism of cannabinoids against SAR-CoV-2 infection is still unknown. Therefore, detailed pharmacological research studies are urgently needed to explore the immunotherapy potential of cannabis against SARS-CoV-2 infection.\n\nConclusion and future prospective \nCannabis legalization fueled scientific research in cannabinoid compounds for their potential in medicinal, pharmaceutical, and neurological applications. However, with recent developments in sequencing technologies, there has been a paradigm shift in cannabis research toward the genomics of fiber- and drug-type plants. The remarkable growth in genomic data, combined with fast-paced development of AI-based bioinformatics and data analysis tools, has made it possible to explore the Cannabis plant at the genetic and molecular levels. Integrated omics studies combining genomic and expression data with metabolite profiles are now beginning to understand the genetic regulation of the cannabinoid biosynthesis pathway, especially by unraveling the association between the expression of cannabinoid genes with THC:CBD ratio and cannabinoid content. The knowledge could be further applied to genetically modified cannabis, with optimized pathways for preferred metabolite yield and composition. Advanced biotechnology methods could be further extended for recombinant production of cannabinoids in metabolically engineered hosts such as yeasts or bacteria. Currently, the recombinant production of THC in yeast is challenging, owing to unstable THCA and CBGA expression and high amounts of side products. However, in the future, the combination of genetic technologies to obtain enhanced expression rates will lead to enhanced cannabinoid yields in an economically feasible manner. In addition, cannabinoids have been recently shown to exhibit anti-inflammatory and immunosuppressing effects against the COVID-19 immune response. However, further evidence-based clinical studies are needed to determine the efficacy and safe dosage of cannabis extracts for treatment or prevention of COVID-19. Pharmacological research, coupled with rapidly evolving genome-based biotechnology, will further facilitate exploring the Cannabis plant for its tremendous potential in drug discovery.\n\nSupplemental information \nData S1 (.xls file)\nData S2 (.xls file)\nData S3 (.xls file)\nAcknowledgements \nAuthor contributions \nT.H. and O.K. designed the concept, while T.H. and G.J. performed a literature search and did bibliometric analysis. T.H. and G.J. wrote the sections \u201cHistory of cannabis research, Trends in past two centuries of cannabis research and Development in Cannabis Genomic and transcriptomes\u201d. T.H. an N.V. wrote the \u201cpatent\u201d section. 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PMID 33671463. https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1986 .   \n \n\n\u2191 Raj, Vinit; Park, Jae Gyu; Cho, Kiu-Hyung; Choi, Pilju; Kim, Taejung; Ham, Jungyeob; Lee, Jintae (1 January 2021). \"Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches\" (in en). International Journal of Biological Macromolecules 168: 474\u2013485. doi:10.1016\/j.ijbiomac.2020.12.020. PMC PMC7836687. PMID 33290767. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813020351783 .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. References aren't listed in the order they appear in the original, but they do for this version, by design. In some cases important information was missing from the references, and that information was added. A few references in the original are misattributed or had incorrect DOIs; they have been corrected for this version. A mention of the U.S. 2018 Farm Bill and several citations related to that bill, as well as one in regards to Section 7606 of the Agricultural Act of 2014, were added. This version is otherwise unchanged in compliance with the \"NoDerivatives\" portion of the original's license.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives<\/a>\nCategories: Pages containing cite templates with deprecated parametersCannaQAwiki journal articles (added in 2022)CannaQAwiki journal articles (all)CannaQAwiki journal articles on cannabis researchCannaQAwiki journal articles on cannabis testingNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inNavigationMain pageList of articlesRandom pageRecent changesHelpSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPrintable versionPermanent linkPage information This page was last edited on 5 April 2022, at 16:12.Content is available under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License unless otherwise noted.Privacy policyAbout CannaQAWikiDisclaimers\n","4e539c9ca5c42af2a2ca977a314b2e2f_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-170 ns-subject page-Journal_Cannabis_sativa_research_trends_challenges_and_new-age_perspectives rootpage-Journal_Cannabis_sativa_research_trends_challenges_and_new-age_perspectives skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:<i>Cannabis sativa<\/i> research trends, challenges, and new-age perspectives<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p><b>Background<\/b>: <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\"><i>Cannabis sativa<\/i> L.<\/a> is one of the oldest known medicinal plants, cultivated for at least 10,000 years for several agricultural and industrial applications. However, the plant became controversial owing to some psychoactive components that have adverse effects on human health. \n<\/p><p><b>Methods<\/b>: In this review, we analyze the trends in <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis\" title=\"Cannabis\" class=\"wiki-link\" data-key=\"a70b76268930d795518ff1f98d7e500d\">cannabis<\/a> research for the past two centuries. We discuss the historical transitions of cannabis from the category of \"herbal medicine\" to an <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_(drug)\" title=\"Cannabis (drug)\" class=\"wiki-link\" data-key=\"6500790ffdd84957d4b055c47e48efca\">illicit drug<\/a> and back to a medicinal product <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Legality_of_cannabis\" title=\"Legality of cannabis\" class=\"wiki-link\" data-key=\"b80036537100734fce629cc441653451\">post-legalization<\/a>. In addition, we address the new-age application of immuno-suppressive and anti-inflammatory cannabis extracts for the treatment of <a href=\"https:\/\/www.limswiki.org\/index.php\/COVID-19\" class=\"extiw wiki-link\" title=\"limswiki:COVID-19\" data-key=\"da9bd20c492b2a17074ad66c2fe25652\">COVID-19<\/a> inflammation. We further address the influence of the legal aspects of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_cultivation\" title=\"Cannabis cultivation\" class=\"wiki-link\" data-key=\"2a93fc4d018f9aaacd8e9024a56eaa13\">cannabis cultivation<\/a> for medicinal, pharmaceutical, and biotechnological research. Finally, we review the up-to-date cannabis-related genomic resources and advanced technologies for their potential application in genomic-based cannabis improvement. \n<\/p><p><b>Results<\/b>: Overall, this review discusses the diverse aspects of cannabis research developments, ranging from traditional use as herbal medicine to the latest potential in COVID-19, legal practices with updated patent status, and current state of the art genetic and genomic tools reshaping cannabis biotechnology in the modern agriculture and pharmaceutical industries.\n<\/p><p><b>Conclusions<\/b>: Remarkable growth in genomic data, combined with fast-paced development of <a href=\"https:\/\/www.limswiki.org\/index.php\/Artificial_intelligence\" class=\"extiw wiki-link\" title=\"limswiki:Artificial intelligence\" data-key=\"0c45a597361ca47e1cd8112af676276e\">artificial intelligence<\/a> (AI)-based data analysis tools have made it possible to explore the <i>Cannabis<\/i> plant at the genetic and molecular levels. In the future, the combination of these genetic technologies will make it possible to obtain enhanced expression rates, which will lead to enhanced <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">cannabinoid<\/a> yields in an economically feasible manner. Pharmacological research, coupled with rapidly evolving genome-based biotechnology, will further facilitate exploring the <i>Cannabis<\/i> plant for its tremendous potential in drug discovery.\n<\/p><p><b>Keywords<\/b>: cannabis, cannabis research, plant biology, plant genetics, genomics\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\"><i>Cannabis sativa<\/i> L.<\/a> is one of the earliest known cultivated plants since agricultural farming started around 10,000 years ago.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup> It is a multi-purpose crop plant with diverse agricultural and industrial applications, ranging from the production of paper, wood, and fiber, to its actual and potential use in the medicinal and pharmaceutical industries. The first-ever report to reveal the prospects of <i>C. sativa<\/i> L. as a medicinal plant was published in 1843 and described the use of plant extracts to treat patients suffering from tetanus, hydrophobia, and cholera.<sup id=\"rdp-ebb-cite_ref-:0_2-0\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup> However, the first chemical constituent identified was oxy-cannabis, in 1869.<sup id=\"rdp-ebb-cite_ref-3\" class=\"reference\"><a href=\"#cite_note-3\">[3]<\/a><\/sup> <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">Cannabinoids<\/a> were being isolated as early as 1896, followed by a variety of full identifications like:\n<\/p>\n<ul><li><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiol\" title=\"Cannabidiol\" class=\"wiki-link\" data-key=\"bbfcdd40d5eda5d20d1d5ab368c922a0\">cannabidiol<\/a> (CBD) in 1940<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup>,<\/li>\n<li><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinol\" title=\"Tetrahydrocannabinol\" class=\"wiki-link\" data-key=\"15f3b3e338baeb54c04c715818759ec9\">tetrahydrocannabinol<\/a> (THC) in 1964<sup id=\"rdp-ebb-cite_ref-:1_5-0\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:2_6-0\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup>,<\/li>\n<li><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerol\" title=\"Cannabigerol\" class=\"wiki-link\" data-key=\"6fc007b4c33a4c59a485b2c621035714\">cannabigerol<\/a> (CBG) in 1964<sup id=\"rdp-ebb-cite_ref-:1_5-1\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup>, and<\/li>\n<li><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabichromene\" title=\"Cannabichromene\" class=\"wiki-link\" data-key=\"1fa141abe89973bfa85a54e2632edf31\">cannabichromene<\/a> (CBC) in 1966.<sup id=\"rdp-ebb-cite_ref-7\" class=\"reference\"><a href=\"#cite_note-7\">[7]<\/a><\/sup><\/li><\/ul>\n<p>Identification of THC later led to an understanding of the endocannabinoid system, followed by the discovery of the first cannabinoid receptor (CB1) in 1988.<sup id=\"rdp-ebb-cite_ref-:3_8-0\" class=\"reference\"><a href=\"#cite_note-:3-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-9\" class=\"reference\"><a href=\"#cite_note-9\">[9]<\/a><\/sup> The CB1 receptor acts as a homeostatic regulator of neurotransmitters for pain relief mechanisms, but the same mode of action was responsible for the intoxicating effects from excessive cannabinoids use. This greater understanding of the mode of action of the CB1 receptor raised concerns about the adverse effects of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis\" title=\"Cannabis\" class=\"wiki-link\" data-key=\"a70b76268930d795518ff1f98d7e500d\">cannabis<\/a> use. Consequently, the plant was removed from the \"medicinal\" category and re-categorized exclusively to the category of \"<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_(drug)\" title=\"Cannabis (drug)\" class=\"wiki-link\" data-key=\"6500790ffdd84957d4b055c47e48efca\">illicit drug<\/a>.\"\n<\/p><p><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_cultivation\" title=\"Cannabis cultivation\" class=\"wiki-link\" data-key=\"2a93fc4d018f9aaacd8e9024a56eaa13\">Cultivation<\/a> and use of the <i>Cannabis<\/i> plant for recreational, medical, and industrial use were strictly banned, which severely limited the scientific research in the field. Owing to strict legal regulations, the plant remained unexplored for its incredible potential in drug discovery for an extended period until it was legalized for medical use first in California and later in many countries around the globe. Extensive research followed legalization in order to explore the chemodiversity of cannabinoids for potential clinical value. In total, more than one thousand compounds have been identified, including 278 cannabinoids, 174 <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Terpene\" title=\"Terpene\" class=\"wiki-link\" data-key=\"6bcbb95d582c08073101e9c4cfc91931\">terpenes<\/a>, 221 <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Terpenoid\" title=\"Terpenoid\" class=\"wiki-link\" data-key=\"ec93231d19f81064deeb38b392a0dadc\">terpenoids<\/a>, 19 <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Flavonoid\" title=\"Flavonoid\" class=\"wiki-link\" data-key=\"2680108c4b4b45ff6c819f1ff4d5e035\">flavonoids<\/a>, 63 flavonoid glycosides, 46 polyphenols, and 92 steroids\u2014have been identified.<sup id=\"rdp-ebb-cite_ref-:4_10-0\" class=\"reference\"><a href=\"#cite_note-:4-10\">[10]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_11-0\" class=\"reference\"><a href=\"#cite_note-:5-11\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_12-0\" class=\"reference\"><a href=\"#cite_note-:6-12\">[12]<\/a><\/sup> Nearly 278 of these compounds are cannabinoids and classified as phytocannabinoids plant-based) to distinguish them from endocannabinoids (non-plant). Cannabimimetic drugs binding to CB1 receptors in the endocannabinoid system can also be found in algae, bryophytes, and monilophytes.<sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-14\" class=\"reference\"><a href=\"#cite_note-14\">[14]<\/a><\/sup> The major cannabinoids in cannabis include THC, CBD, and CBC, as well as their precursors CBG and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinol\" title=\"Cannabinol\" class=\"wiki-link\" data-key=\"651d2d238facf7e91a42dc755b1cdb88\">cannabinol<\/a> (CBN).<sup id=\"rdp-ebb-cite_ref-15\" class=\"reference\"><a href=\"#cite_note-15\">[15]<\/a><\/sup> To date, 10 CBN-type, 17 CBG-type, 8 CBD-type, and 18 THC-type cannabinoids have been isolated.<sup id=\"rdp-ebb-cite_ref-:1_5-2\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup> <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerolic_acid\" title=\"Cannabigerolic acid\" class=\"wiki-link\" data-key=\"d0a5399af99137ebf5aa893d34531e49\">Cannabigerolic acid<\/a> (CBGA), a CBG-type cannabinoid, is the central precursor for the biosynthesis of psychoactive THC, non-psychoactive CBD, and CBC.<sup id=\"rdp-ebb-cite_ref-:4_10-1\" class=\"reference\"><a href=\"#cite_note-:4-10\">[10]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_11-1\" class=\"reference\"><a href=\"#cite_note-:5-11\">[11]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:6_12-1\" class=\"reference\"><a href=\"#cite_note-:6-12\">[12]<\/a><\/sup>\n<\/p><p>Cannabinoid <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Biosynthesis\" title=\"Biosynthesis\" class=\"wiki-link\" data-key=\"41066f127f35802943836be23f5c20c3\">biosynthesis<\/a> in plants occurs in specialized biosynthetic organs called glandular <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Trichome\" title=\"Trichome\" class=\"wiki-link\" data-key=\"40afd6e0542ec77b9084ef6d7bdb72bb\">trichomes<\/a><sup id=\"rdp-ebb-cite_ref-:7_16-0\" class=\"reference\"><a href=\"#cite_note-:7-16\">[16]<\/a><\/sup> on female <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Inflorescence\" title=\"Inflorescence\" class=\"wiki-link\" data-key=\"d8122354225ee6a932a086ca8a1b999f\">flowers<\/a> and leaves. Several studies use metabolic profiling of trichomes to demonstrate variation in trichome size, density, and relative concentration of cannabinoids.<sup id=\"rdp-ebb-cite_ref-:7_16-1\" class=\"reference\"><a href=\"#cite_note-:7-16\">[16]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-17\" class=\"reference\"><a href=\"#cite_note-17\">[17]<\/a><\/sup> However, the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Genetics\" title=\"Genetics\" class=\"wiki-link\" data-key=\"01a49b3130e92b8e6f43a515cf66cf43\">genetic<\/a> mechanisms underlying the developmental changes in trichomes and consecutive cannabinoid content are still unknown. Apart from natural and chemical biosynthesis methods<sup id=\"rdp-ebb-cite_ref-18\" class=\"reference\"><a href=\"#cite_note-18\">[18]<\/a><\/sup>, heterologous biosynthesis of cannabinoids has also been reported.<sup id=\"rdp-ebb-cite_ref-:8_19-0\" class=\"reference\"><a href=\"#cite_note-:8-19\">[19]<\/a><\/sup> However, the considerable amount of side products is still one of the major bottlenecks in cannabinoid production.<sup id=\"rdp-ebb-cite_ref-:8_19-1\" class=\"reference\"><a href=\"#cite_note-:8-19\">[19]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-20\" class=\"reference\"><a href=\"#cite_note-20\">[20]<\/a><\/sup>\n<\/p><p>This review highlights the latest research developments and challenges in <i>Cannabis<\/i> plant sciences, as well as the role of trichomes as biosynthetic sites, with a special focus on plant biology. Additionally, we discuss the existing legal practices with patent information for <i>C. sativa<\/i> L. We also discuss the new potential use of cannabinoids for <a href=\"https:\/\/www.limswiki.org\/index.php\/COVID-19\" class=\"extiw wiki-link\" title=\"limswiki:COVID-19\" data-key=\"da9bd20c492b2a17074ad66c2fe25652\">COVID-19<\/a> treatment. Finally, we address the available genomic and transcriptomic resources and discuss their potential toward the genetic improvement of cannabis. Overall, we provide the first in-depth review of diverse aspects of <i>C. sativa<\/i> L. from traditional medicinal use to genomics insights and research perspective to broad industrial applications.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Methods\">Methods<\/span><\/h2>\n<p>Cannabis-related publications were searched in four major scientific literature and citation databases of biomedical and life sciences journals: EMBL-EBI's <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/europepmc.org\/\" target=\"_blank\">Europe PMC<\/a> (Data S1, Supplemental information), Elsevier's <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.scopus.com\/\" target=\"_blank\">Scopus<\/a> (Data S2, Supplemental information), National Library of Medicine's <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/\" target=\"_blank\">PubMed Central<\/a> (Data S3, Supplemental information), and Clarivate's <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.webofscience.com\/wos\/\" target=\"_blank\">Web of Science<\/a>. The search criteria\u2014\u201ccannabis OR marijuana OR hemp OR cannabinoids OR cannabidiol OR cannabinol\u201d\u2014were used to examine available research articles. Some 80,979 (EuropePMC), 64,637 (Scopus), 43,182 (Web of Science), and 28,759 (PubMed Central) cannabis-related research articles were found. \n<\/p><p>The sheer difference in the number of articles could be attributed to the years for which the cannabis records are present in the databases. Europe PMC currently holds cannabis records dating back 239 years, with the oldest publication dating to 1783, whereas Scopus has data for 194 years (dating back to 1828), PubMed Central 182 years (dating back to 1840), and Web of Science 77 years (since 1945) (Figure 1A). Despite cannabis records only going back 77 years, the Web of Science record count exceeds PubMed Central's, owing to a data acquisition policy similar to Scopus, wherein all the cited references for a publication are pulled and listed in the database. \n<\/p><p>Another major reason for the different records in the archives could be owing to the source repositories and partner journals. Although PubMed Central has only 6.9 million articles from over 10,656 journals (as of April 2021), Scopus has more than 77.8 million records from nearly 23,500 journals, and Web of Science comprises over 171 million records, including journals, books, and proceedings. However, Europe PMC acquires data from multiple bibliographic repositories such as PubMed, MEDLINE, PubMed Central, AGRICOLA, and Chinese Biological Abstracts (CBA) (Figure 1D). It includes more than 45.6 million documents, including articles, books, preprints, patents, conference papers, and microPublications.\n<\/p><p>Cannabis citation <a href=\"https:\/\/www.limswiki.org\/index.php\/Metadata\" class=\"extiw wiki-link\" title=\"limswiki:Metadata\" data-key=\"f872d4d6272811392bafe802f3edf2d8\">metadata<\/a> was publicly available for bulk download from Europe PMC (6,586 journals), Scopus (8647 journals), and PubMed Central (3864 journals) (Figure 1B). Among the various article identifiers used such as DOI, PMCID, and PMID, the DOI was found for 85.62% of records at Europe PMC, 85.44% of records at Scopus, and 91.9% of records at PubMed Central. Since DOI was the only common identifier, it was used for the comparison of three datasets (Figure 1C). Cannabis records in Europe PMC comprised nearly 76.73% of PubMed Central and 49.75% of Scopus data (Figure 1C). Hence, metadata from Europe PMC was selected for downstream bibliometric analysis. The majority of cannabis-related records in Europe PMC were from MEDLINE (94.94%), followed by 4.29% from PubMed Central, with only 0.75% from Agricola and 0.02% from CBA (Figure 1D). The distribution of source databases indicates the most explored field in cannabis research for the last 239 years.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig1_Hussain_iScience2021_24-12.jpg\" class=\"image wiki-link\" data-key=\"760341454e14e3cae692c8ee7c43ed88\"><img alt=\"Fig1 Hussain iScience2021 24-12.jpg\" src=\"https:\/\/www.cannaqa.wiki\/images\/0\/09\/Fig1_Hussain_iScience2021_24-12.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> Cannabis research trend. (<b>A<\/b>) Timeline of cannabis records. Timeline and years from the earliest to the latest cannabis records in the literature databases of life science and biomedical journals are depicted with a color coded radial bar for Europe PMC (green), Scopus (blue), Pubmed Central (gray), and Web of Science (lilac). The publication year of the first available cannabis-related document in each database is marked by a vertical line at top of corresponding bar. The number of years from the oldest available article to the most recent publication in 2021 are indicated at the base of each bar. (<b>B<\/b>) Cannabis documents in the literature archives. The bar plot shows number of documents in the selected databases, with Y axis divided into two sections to show the journals (upper section) and articles (lower section). (<b>C<\/b>) Common citations in databases. Europe PMC, Scopus and Pubmed Central records were compared using DOI identifiers, and the number of shared and unique documents between three sets are shown as a Venn plot. The size of the circle corresponds to the number of articles with a DOI in each database. (<b>D<\/b>) Cannabis literature source in Europe PMC. Color-coded pie chart depicts the source repositories of cannabis articles in Europe PMC. The contribution (percentage of articles) from Medline (MED), AGRICOLA (AGR), PubMed Central (PMC) and Chinese Biological Abstracts (CBA) are shown by orange, gray, turquoise, and cyan color, respectively. (<b>E<\/b>) Cannabis research trends. The overall pattern of cannabis research from 1783 to 2021 is depicted by the trend line (log scaled), with each dot representing the number of articles (Y axis) per year (X axis). The research periods are categorized as Zero (1783\u20131840), I (1840\u20131937), II (1937\u20131996), and III (1996\u20132021), and they are separated by vertical dotted lines. The three major achievements\u2014(I) discovery of cannabinoids, ii) cannabinoid receptors, and iii) endocannabinoids\u2014that pushed the interest in cannabis are marked in pink color. The number of articles in 2021 are still growing and therefore depicted as a hollow enlarged dot. (<b>F<\/b>) Cannabis research subjects. A bubble plot depicts the most and least explored scientific subject areas, with size corresponding to the number of articles (Y axis) and journals (Y axis) in each category. A major proportion of cannabis research was related to medical and medicinal sciences, followed by pharmacology and pharmaceuticals, neurosciences and psychology, biochemistry and biotechnology, genetics and genomic sciences, agriculture and plant biology, and bioinformatics.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Trends_of_cannabis_research_from_1783_to_2021\">Trends of cannabis research from 1783 to 2021<\/span><\/h2>\n<p><i>C. sativa<\/i> L. originated in central Asia and later spread to Europe during its cultivation, with diverse applications. Archaeological evidence of early medical use was found in fossil records dating back to 315\u2013392 A.D.<sup id=\"rdp-ebb-cite_ref-21\" class=\"reference\"><a href=\"#cite_note-21\">[21]<\/a><\/sup> Researchers largely have a consensus that the plant has at various times been used as traditional medicine.<sup id=\"rdp-ebb-cite_ref-22\" class=\"reference\"><a href=\"#cite_note-22\">[22]<\/a><\/sup> \n<\/p><p>Based on our search results, spanning more than two centuries, we divide the scientific era into four periods (Figure 1E). Period Zero (1783\u20131840) marked the first-ever mention of <i>Cannabis<\/i> as a category of medicinal plant, in the years 1783<sup id=\"rdp-ebb-cite_ref-23\" class=\"reference\"><a href=\"#cite_note-23\">[23]<\/a><\/sup> and 1787.<sup id=\"rdp-ebb-cite_ref-24\" class=\"reference\"><a href=\"#cite_note-24\">[24]<\/a><\/sup> According to Europe PMC results, there were only 52 articles and 38 reviews in the next five decades. Most reports mentioned the botanical aspects of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Hemp\" title=\"Hemp\" class=\"wiki-link\" data-key=\"c23e30b6cf1df54f1dc338492c9f9da2\">hemp<\/a> and the quality of its fiber, with few observations about its use in traditional medicines. \n<\/p><p>Period I (1840\u20131937) began with the detailed evidence-based report of the chemical properties and medicinal potential of <i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_indica\" title=\"Cannabis indica\" class=\"wiki-link\" data-key=\"7ea23da7d68f4d25012bac401d531b8b\">Cannabis indica<\/a><\/i> (hemp) by William O'Shaughnessy<sup id=\"rdp-ebb-cite_ref-:0_2-1\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup>, followed by an array of medicinal reports in articles from 1923. We identified 183 reviews in the subsequent 96 years. Scientific endeavors to experiment, observe, and understand the diverse medicinal applications of cannabis were still in the early stages. However, the 1900s witnessed a series of legal regulations in the direction of the criminalization of cannabis. Cannabis was starting to be categorized into lists of narcotic drugs, and \"poisons rules,\" including the Pure Food and Drug Act of 1906, pushed for stricter measures for cannabis distribution. Later, the Second International Opium Convention of 1925 called for measures to regulate Indian hemp. Exports, unless exclusively for medical or scientific purposes or European hemp (for fiber), were banned. The Uniform State Narcotic Drug Act of 1925 and the Geneva Trafficking Conventions of 1936 resulted in criminalizing the cultivation, possession, manufacture, and distribution of cannabis derivatives. The Marihuana Tax Act of 1937 levied heavy taxes on the possession and selling of cannabis, excluding medical, and industrial use. As a consequence, the cultivation and procurement of cannabis for research purposes became increasingly difficult, severely limiting the research of medicinal cannabis during this era (see Figure 1E: Period I).\n<\/p><p>During Period II (1937\u20131996), cannabis research suffered major restrictions, owing to legal regulations in the first two decades, until the identification of the first cannabinoid\u2014<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiolic_acid\" title=\"Cannabidiolic acid\" class=\"wiki-link\" data-key=\"772927eeed478eff799c410179be18a1\">cannabidiolic acid<\/a> or CBDA\u2014in 1954<sup id=\"rdp-ebb-cite_ref-:2_6-1\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:9_25-0\" class=\"reference\"><a href=\"#cite_note-:9-25\">[25]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-26\" class=\"reference\"><a href=\"#cite_note-26\">[26]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-27\" class=\"reference\"><a href=\"#cite_note-27\">[27]<\/a><\/sup> and the isolation of the most psychoactive component of cannabis\u2014THC\u2014in 1964.<sup id=\"rdp-ebb-cite_ref-:1_5-3\" class=\"reference\"><a href=\"#cite_note-:1-5\">[5]<\/a><\/sup> Other discoveries paved the way for decriminalization laws, including isolation of THC, discovery of the CB1<sup id=\"rdp-ebb-cite_ref-:3_8-1\" class=\"reference\"><a href=\"#cite_note-:3-8\">[8]<\/a><\/sup> and CB2<sup id=\"rdp-ebb-cite_ref-28\" class=\"reference\"><a href=\"#cite_note-28\">[28]<\/a><\/sup> receptors, and the emergence of the Compassionate Investigational New Drug program in 1978. The discovery of endocannabinoids and a growing understanding of the potential role of cannabis in the medicinal field also played a role during this period.<sup id=\"rdp-ebb-cite_ref-:9_25-1\" class=\"reference\"><a href=\"#cite_note-:9-25\">[25]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-29\" class=\"reference\"><a href=\"#cite_note-29\">[29]<\/a><\/sup> A significant uptick in published cannabis research was observed during this period, with 445 cannabis-related articles and 25 reviews being found between 1937 and 1964, ramping up to 8,888 articles and 773 reviews between 1964 and 1996 (see Figure 1E: Period II), although with a notably short period of decline in publications between 1973 and 1982.\n<\/p><p>Finally, Period III (1996-2021) began with the historical Compassionate Use Act of 1996 in California approving medical cannabis. Post-legalization (1996 onwards), cannabis has been extensively explored for its diverse potential in the pharmaceutical and medicinal industries. During Period III, cannabis research witnessed unprecedented growth, with nearly 67,777 articles, 13,202 reviews, and 493 preprints showing up in Europe PMC, of which 97.01% articles were published since 2000 (see Figure 1E: Period III). Approval of the first cannabis-based inhaler spray in 2005<sup id=\"rdp-ebb-cite_ref-30\" class=\"reference\"><a href=\"#cite_note-30\">[30]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-31\" class=\"reference\"><a href=\"#cite_note-31\">[31]<\/a><\/sup> and publication of the first draft of the cannabis genome in 2011<sup id=\"rdp-ebb-cite_ref-:14_32-0\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup> in this era were the two major accomplishments that exponentially accelerated research development.\n<\/p><p>The trends of cannabis study in the diverse array of research articles and journals indicate the core interests of the scientific community. To further investigate the most researched field, the journals of cannabis articles were categorized into scientific and social areas. The journals related to social-, legal-, and policy-based studies were merged into the subject category of \"social research.\" The majority of broad science-based subjects were grouped into the following seven major categories: (i) <i>medicinal<\/i>, including all medical and medicinal subjects); (ii) <i>pharmaceutical<\/i>, comprised of pharmacology, pharmaceuticals, drug, toxicology, and chemical studies; (iii) <i>neurosciences<\/i>, comprised of neurological, brain-related, psychiatry, psychology, and cognitive studies; (iv) <i>biochemistry<\/i>, including biotechnology, microbiology, immunology, virology, and biochemistry; (v) <i>genomics<\/i>, including grouped genetic and genomic studies; (vi) <i>plant biology<\/i>, including plant sciences, agricultural, botanical aspects, plant-based pathogens, and environment studies; and lastly, (vii) <i><\/i>, including data analytics. Journals that could not be classified into social research or science-based categories were excluded from downstream evaluation.\n<\/p><p>The science-based subject areas (74.47% of journals) were further compared for the corresponding number of articles and journals (Figure 1F). A distinct pattern was observed for the clinical aspects of cannabis, which remained a major focus from the very beginning. Some 94.76% of published articles addressed some sort of clinical aspect, including 64.51% articles addressing medicinal topics, 19.55% addressing pharmaceutical science topics, and 10.70% addressing the neurosciences. In contrast, plant biology and agricultural sciences comprised only 2.62% of articles, followed by 0.71% on genomics, and 0.07% on bioinformatics-based cannabis research. Genomics and bioinformatics are relatively new subjects, growing at a faster pace since the release of the first <i>Cannabis<\/i> draft genome in 2011. Recent advances in sequencing technologies have further propelled genomic and transcriptomic studies, with the purpose of dissecting the regulatory networks. The growth of genomic data in the public space has been met with the fast-paced development of bioinformatics tools for data analysis. In addition, the ongoing development of genomic tools using (ML) and (AI) will facilitate improved genetic-level understanding of cannabis metabolism for the selective breeding of genetically modified cannabis with improved metabolic traits.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Cannabis_sativa_L._physiology_and_legal_status\"><i>Cannabis sativa<\/i> L. physiology and legal status<\/span><\/h2>\n<p>Physiological, morphological, and developmental aspects of the <i>Cannabis<\/i> plant are key in understanding its growth patterns and chemical profiles. However, plant growth and function are substantially influenced by abiotic factors and nutrient availability. Botanical aspects<sup id=\"rdp-ebb-cite_ref-33\" class=\"reference\"><a href=\"#cite_note-33\">[33]<\/a><\/sup>, plant architecture, and florogenesis of female <i>C. sativa<\/i> plants<sup id=\"rdp-ebb-cite_ref-34\" class=\"reference\"><a href=\"#cite_note-34\">[34]<\/a><\/sup> with detailed trichome morphogenesis<sup id=\"rdp-ebb-cite_ref-35\" class=\"reference\"><a href=\"#cite_note-35\">[35]<\/a><\/sup> has provided crucial insight into plant biology. However, it has also become increasingly important to determine the effect of abiotic factors on <i>Cannabis<\/i> growth and chemical yield, especially for large-scale commercial breeding programs. Hence, in-depth analysis of the effect of soil fertilization, salinity, temperature, and light conditions, as well as nutrient and water-use efficiency is key in establishing industrial-scale systems for the cultivation of hemp and marijuana varieties. \n<\/p><p>The first available records about the mineral nutrition of hemp plants were published by Tibeau <i>et al.<\/i> in 1936.<sup id=\"rdp-ebb-cite_ref-36\" class=\"reference\"><a href=\"#cite_note-36\">[36]<\/a><\/sup> Later, in 1944, Clarence H. Nelson published the effect of varying soil temperature on hemp growth.<sup id=\"rdp-ebb-cite_ref-37\" class=\"reference\"><a href=\"#cite_note-37\">[37]<\/a><\/sup> The first publication with a detailed response of greenhouse cultivated cannabis to nitrogen (N), phosphorus (P), and potassium (K) was published in 1977.<sup id=\"rdp-ebb-cite_ref-38\" class=\"reference\"><a href=\"#cite_note-38\">[38]<\/a><\/sup> Furthermore, two parallel reports by van der Werf <i>et al.<\/i> in 1995 discussed the impact of nitrogen fertilization on sex expression in hemp<sup id=\"rdp-ebb-cite_ref-39\" class=\"reference\"><a href=\"#cite_note-39\">[39]<\/a><\/sup>, and the effect of temperature on leaf and canopy formation.<sup id=\"rdp-ebb-cite_ref-40\" class=\"reference\"><a href=\"#cite_note-40\">[40]<\/a><\/sup> Importantly, most physiological studies in Period II and Period III (Figure 1A) were published for hemp, with a focus on photosynthetic response and biomass yield under varying conditions such as temperature, water availability, nitrogen, and mineral nutrition.<sup id=\"rdp-ebb-cite_ref-41\" class=\"reference\"><a href=\"#cite_note-41\">[41]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-42\" class=\"reference\"><a href=\"#cite_note-42\">[42]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:24_43-0\" class=\"reference\"><a href=\"#cite_note-:24-43\">[43]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-44\" class=\"reference\"><a href=\"#cite_note-44\">[44]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-45\" class=\"reference\"><a href=\"#cite_note-45\">[45]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-46\" class=\"reference\"><a href=\"#cite_note-46\">[46]<\/a><\/sup> However, the first study to assess the chemical response of hemp plants wasn't published until 1997.<sup id=\"rdp-ebb-cite_ref-47\" class=\"reference\"><a href=\"#cite_note-47\">[47]<\/a><\/sup>\n<\/p><p>The physiological response of drug-type medical <i>Cannabis<\/i> plants may differ from hemp plants, owing to the distinct genetic and chemical differences. Hence, a clear understanding of optimum factors for medical cannabis is inevitable for the efficient cultivation of plants with desired chemical composition. The first few studies that addressed medical cannabis and its photosynthetic response to photon flux densities, temperature, and CO<sub>2<\/sub> conditions were published by Chandra <i>et al.<\/i> in 2008 and 2011.<sup id=\"rdp-ebb-cite_ref-48\" class=\"reference\"><a href=\"#cite_note-48\">[48]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-49\" class=\"reference\"><a href=\"#cite_note-49\">[49]<\/a><\/sup> Bernstein and others further addressed the growth and chemical response of medical cannabis to mineral nutrition, especially N, P, and K.<sup id=\"rdp-ebb-cite_ref-:10_50-0\" class=\"reference\"><a href=\"#cite_note-:10-50\">[50]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:11_51-0\" class=\"reference\"><a href=\"#cite_note-:11-51\">[51]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:12_52-0\" class=\"reference\"><a href=\"#cite_note-:12-52\">[52]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:13_53-0\" class=\"reference\"><a href=\"#cite_note-:13-53\">[53]<\/a><\/sup> Saloner and Bernstein<sup id=\"rdp-ebb-cite_ref-:12_52-1\" class=\"reference\"><a href=\"#cite_note-:12-52\">[52]<\/a><\/sup> reported optimum N concentration at 160 mg L<sup>\u22121<\/sup>, while N with lower levels showed several symptoms inducing necrosis and growth retardation and N with higher levels impacted in reducing concentrations of THCA and CBDA. Shiponi and Bernstein<sup id=\"rdp-ebb-cite_ref-:11_51-1\" class=\"reference\"><a href=\"#cite_note-:11-51\">[51]<\/a><\/sup> showed a negative association of cannabinoid concentrations and yield with increasing P supply. Saloner <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:10_50-1\" class=\"reference\"><a href=\"#cite_note-:10-50\">[50]<\/a><\/sup> further determined the genotype-dependent effect of K nutrition on medical cannabis, reporting 240 ppm K detrimental for the genotype Royal Medic and stimulant for the Desert Queen genotype, while 15 ppm K was insufficient for both genotypes. Further, in 2019, Bernstein <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:13_53-1\" class=\"reference\"><a href=\"#cite_note-:13-53\">[53]<\/a><\/sup> discussed the combined effect of NPK nutrition upon cannabinoid concentration. \n<\/p><p>In addition to soil nutrients, the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Heavy_metals\" title=\"Heavy metals\" class=\"wiki-link\" data-key=\"a485b8274a229bee7a5d842d06729007\">heavy metals<\/a> uptake potential of hemp varieties has also been thoroughly investigated by multiple reports in the 2000s.<sup id=\"rdp-ebb-cite_ref-:15_54-0\" class=\"reference\"><a href=\"#cite_note-:15-54\">[54]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:16_55-0\" class=\"reference\"><a href=\"#cite_note-:16-55\">[55]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:17_56-0\" class=\"reference\"><a href=\"#cite_note-:17-56\">[56]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:18_57-0\" class=\"reference\"><a href=\"#cite_note-:18-57\">[57]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:19_58-0\" class=\"reference\"><a href=\"#cite_note-:19-58\">[58]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:20_59-0\" class=\"reference\"><a href=\"#cite_note-:20-59\">[59]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:21_60-0\" class=\"reference\"><a href=\"#cite_note-:21-60\">[60]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:22_61-0\" class=\"reference\"><a href=\"#cite_note-:22-61\">[61]<\/a><\/sup> Industrial hemp varieties of <i>C. sativa<\/i> have also been shown to grow well in soils contaminated with heavy metals<sup id=\"rdp-ebb-cite_ref-:15_54-1\" class=\"reference\"><a href=\"#cite_note-:15-54\">[54]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:17_56-1\" class=\"reference\"><a href=\"#cite_note-:17-56\">[56]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:18_57-1\" class=\"reference\"><a href=\"#cite_note-:18-57\">[57]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:19_58-1\" class=\"reference\"><a href=\"#cite_note-:19-58\">[58]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:20_59-1\" class=\"reference\"><a href=\"#cite_note-:20-59\">[59]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:22_61-1\" class=\"reference\"><a href=\"#cite_note-:22-61\">[61]<\/a><\/sup> and reported for their heavy metal accumulation. Several field projects have assessed the phytoremediation potential of hemp plants for the reclamation of contaminated and radioactive soils.<sup id=\"rdp-ebb-cite_ref-:16_55-1\" class=\"reference\"><a href=\"#cite_note-:16-55\">[55]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:21_60-1\" class=\"reference\"><a href=\"#cite_note-:21-60\">[60]<\/a><\/sup>\n<\/p><p>Cannabis cultivars are classified into drug-type (marijuana), fiber-type (hemp), and neutral (zero cannabinoid) plants with distinct cannabinoid constitutions. Drug-type cultivars with THC\/CBD ratio \u226510 are classified as chemotype I, while those with THC\/CBD ratio ranging from 0.2 to 10 are grouped as chemotype II. In contrast, fiber-type cultivars with THC\/CBD ratio <0.2 are categorized as chemotype III. Chemotype IV also has low THC contents but with the potent percentage of CBG. Furthermore, the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chemotype\" title=\"Chemotype\" class=\"wiki-link\" data-key=\"2cee49cb83af61d36357ce99efa5ab72\">chemotypes<\/a> producing very little to almost zero cannabinoid compounds (neutral) are grouped as chemotype V<sup id=\"rdp-ebb-cite_ref-62\" class=\"reference\"><a href=\"#cite_note-62\">[62]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-63\" class=\"reference\"><a href=\"#cite_note-63\">[63]<\/a><\/sup> and were first described by Mandolino <i>et al.<\/i> in 2004.<sup id=\"rdp-ebb-cite_ref-64\" class=\"reference\"><a href=\"#cite_note-64\">[64]<\/a><\/sup> Apart from cannabinoid (THC, CBD) content, drug and fiber-type plants have significant genetic variation. Sawler <i>et al.<\/i> described that marijuana is genetically inclined toward <i>sativa<\/i>, and hemp has a similarity with the <i>indica<\/i> type.<sup id=\"rdp-ebb-cite_ref-65\" class=\"reference\"><a href=\"#cite_note-65\">[65]<\/a><\/sup> Moreover, each plant type has unique applications, differentiating them from each other. For example, the fiber-type \"hemp\u201d plant has mostly food and industrial applications, including production dietary products, hemp oil, seeds, and fiber, while the \u201cmarijuana\u201d drug-type plant is used exclusively for medicinal and recreational purposes.\n<\/p><p>Despite such a huge genetic and application diversity, both types of cannabis plants were placed under Schedule I of the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Controlled_Substances_Act\" title=\"Controlled Substances Act\" class=\"wiki-link\" data-key=\"26d5a484acca5b4c5f416480c72c38e5\">Controlled Substances Act<\/a> in 1970.<sup id=\"rdp-ebb-cite_ref-66\" class=\"reference\"><a href=\"#cite_note-66\">[66]<\/a><\/sup> These restrictions had a serious impact on cannabis-related research, preventing the scientific community from studying the potential of diverse yielding traits for hemp. However, after 44 years, Section 7606 of the Agricultural Act of 2014 finally distinguished hemp from marijuana.<sup id=\"rdp-ebb-cite_ref-USDAStatement16_67-0\" class=\"reference\"><a href=\"#cite_note-USDAStatement16-67\">[67]<\/a><\/sup> Approval of the law, along with the 2018 Farm Bill<sup id=\"rdp-ebb-cite_ref-AbernethyHemp19_68-0\" class=\"reference\"><a href=\"#cite_note-AbernethyHemp19-68\">[68]<\/a><\/sup>, opened the window for the scientific community in the U.S. to conduct research and cultivate hemp. Since then, most U.S. states<sup id=\"rdp-ebb-cite_ref-NCSLState20_69-0\" class=\"reference\"><a href=\"#cite_note-NCSLState20-69\">[69]<\/a><\/sup> and more than 47 countries around the world have been growing hemp for research and industrial use.<sup id=\"rdp-ebb-cite_ref-70\" class=\"reference\"><a href=\"#cite_note-70\">[70]<\/a><\/sup> On the other hand, marijuana research and legalization have been expanding at a comparatively slower rate, and till now only 16 countries have legalized medicinal cannabis.<sup id=\"rdp-ebb-cite_ref-71\" class=\"reference\"><a href=\"#cite_note-71\">[71]<\/a><\/sup> Furthermore, a detailed study would be desirable to understand the gene function, the genetic composition, and the underlying mechanisms regulating the diversity of cannabinoids in both major varieties. Availability of the regeneration protocol<sup id=\"rdp-ebb-cite_ref-72\" class=\"reference\"><a href=\"#cite_note-72\">[72]<\/a><\/sup> and transformation studies<sup id=\"rdp-ebb-cite_ref-73\" class=\"reference\"><a href=\"#cite_note-73\">[73]<\/a><\/sup> could be utilized for the expression studies to unravel the mystery of these mechanisms, especially in trichomes.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Trichomes_and_cannabinoid_biosynthesis\">Trichomes and cannabinoid biosynthesis<\/span><\/h2>\n<p>Glandular trichomes are the primary site for cannabinoid biosynthesis and accumulation<sup id=\"rdp-ebb-cite_ref-:25_74-0\" class=\"reference\"><a href=\"#cite_note-:25-74\">[74]<\/a><\/sup> in <i>C. sativa<\/i>. The biosynthesis of cannabinoids<sup id=\"rdp-ebb-cite_ref-75\" class=\"reference\"><a href=\"#cite_note-75\">[75]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-76\" class=\"reference\"><a href=\"#cite_note-76\">[76]<\/a><\/sup> starts from the plastidial localized methylerythritol 4-phosphate (MEP) pathway, resulting in the formation of geranyl pyrophosphate (GPP)<sup id=\"rdp-ebb-cite_ref-77\" class=\"reference\"><a href=\"#cite_note-77\">[77]<\/a><\/sup> and the fatty acid pathway leading to the production of olivetolic acid (OA).<sup id=\"rdp-ebb-cite_ref-78\" class=\"reference\"><a href=\"#cite_note-78\">[78]<\/a><\/sup> GPP and OA in the presence of olivetolic acid cyclase (OLS)<sup id=\"rdp-ebb-cite_ref-:23_79-0\" class=\"reference\"><a href=\"#cite_note-:23-79\">[79]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-80\" class=\"reference\"><a href=\"#cite_note-80\">[80]<\/a><\/sup> and an aromatic prenyltransferase catalyze the reaction to form CBGA<sup id=\"rdp-ebb-cite_ref-:23_79-1\" class=\"reference\"><a href=\"#cite_note-:23-79\">[79]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-81\" class=\"reference\"><a href=\"#cite_note-81\">[81]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-82\" class=\"reference\"><a href=\"#cite_note-82\">[82]<\/a><\/sup>, which is the central precursor for cannabinoid biosynthesis. In 2011, van Bakel <i>et al.<\/i> analyzed the transcriptomic and genomic data and described the exclusive presence of the THCAS and CBDAS in the drug and hemp-type plant, respectively.<sup id=\"rdp-ebb-cite_ref-:14_32-1\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup> It is suggested that the activation of respective enzymes from the central precursor CBGA is responsible for regulating the THC and CBD concentration for each chemotype. However, the precise regulatory mechanism is still unknown.\n<\/p><p>Besides biosynthesis, understanding the trichome physiology is also vital to elucidate the trafficking and localization of metabolites. For cannabinoid biosynthesis, there exist three major reactions: \n<\/p>\n<ol><li>biosynthesis of monoterpene precursor (GPP) via MEP and fatty acid intermediate (OA) from polyketide pathway,<\/li>\n<li>prenylation of the precursors, and<\/li>\n<li>cyclization.<\/li><\/ol>\n<p>The MEP pathway in plastid prenylation is localized in the chloroplast membrane, where the C-prenylated CBGA synthase is membrane-bound. The integration of the enzyme in the membrane seems essential, and the folding pattern is crucial for its functioning. Therefore, simple cloning and functional expression of this enzyme in a heterologous host such as yeast to generate the desired cannabinoids is challenging. Terpenoid cyclization reactions are the most complex reactions found in nature, and the biotransformation from CBGA to THCA by the THCA synthase is assumed to occur in the cytosol. This hypothetical model is under ongoing debate, and it might be likely that biocatalysis occurs in the extracellular oil container under a non-aqueous environment.<sup id=\"rdp-ebb-cite_ref-83\" class=\"reference\"><a href=\"#cite_note-83\">[83]<\/a><\/sup> In 1992, Mahlberg and Kim postulated that THCA synthase is located in the outer membrane of the head cells or even attached on the outer membrane surface extending into the essential oil.<sup id=\"rdp-ebb-cite_ref-84\" class=\"reference\"><a href=\"#cite_note-84\">[84]<\/a><\/sup> In recent studies, <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Liquid_chromatography%E2%80%93mass_spectrometry\" title=\"Liquid chromatography\u2013mass spectrometry\" class=\"wiki-link\" data-key=\"e2eb804872f9ac16965fce8e49cfa3b6\">Liquid chromatography<\/a>\u2013<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tandem_mass_spectrometry\" title=\"Tandem mass spectrometry\" class=\"wiki-link\" data-key=\"573d237c370deba1a7ef999284ea1cf8\">tandem mass spectrometry<\/a> (LC-MS\/MS) was used to detect a functional, active THCA and CBGA synthase in the exudates from glandular trichomes of cannabis.<sup id=\"rdp-ebb-cite_ref-85\" class=\"reference\"><a href=\"#cite_note-85\">[85]<\/a><\/sup> Zirpel <i>et al.<\/i> described the need for an excellent understanding of protein chemistry and folding of these enzymes to produce the cannabinoid using a heterologous host.<sup id=\"rdp-ebb-cite_ref-86\" class=\"reference\"><a href=\"#cite_note-86\">[86]<\/a><\/sup> Detailed knowledge of genetic regulatory mechanisms underlying cannabinoid biosynthesis is a future challenge. Identification of regulatory elements such as transcription factors (TFs) and microRNAs (miRNAs) could be utilized to understand the mechanistic insights of trichomes initiation, development, and densities. An in-depth understanding could be applied toward the breeding of genetically improved cannabis varieties with enhanced cannabinoids concentration in trichomes.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Developments_in_cannabis_genomics\">Developments in cannabis genomics<\/span><\/h2>\n<p>Drug- and fiber-type plants differ in biosynthesis, concentration, and composition of metabolites.<sup id=\"rdp-ebb-cite_ref-:24_43-1\" class=\"reference\"><a href=\"#cite_note-:24-43\">[43]<\/a><\/sup> To determine the genetic variations regulating plant-specific differences, it is essential to compare the genomes. Advanced sequencing technologies, combined with continuously improving bioinformatics tools, have allowed rapid sequencing and analysis of multiple genomes and transcriptomes. The very first draft genome of <i>C. sativa<\/i> was released in 2011 by Bakel <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:14_32-2\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup> They sequenced the marijuana cultivar Purple Kush by using Illumina short reads and assembled them in combination with 454 reads. They also sequenced the fiber-type hemp cultivar Finola for a genome-level comparison. In addition to whole genome sequencing, the first complete mitochondrial reference genome was also obtained in 2016 from the cannabis hemp variety Carmagnola.<sup id=\"rdp-ebb-cite_ref-87\" class=\"reference\"><a href=\"#cite_note-87\">[87]<\/a><\/sup> Later, in July 2016, two complete chloroplast genomes of marijuana (THC-dominant) African variety Yoruba Nigerian and Korean hemp non-drug variety (low THC) Cheungsam<sup id=\"rdp-ebb-cite_ref-88\" class=\"reference\"><a href=\"#cite_note-88\">[88]<\/a><\/sup> were sequenced and used to determine the phylogenetic position of <i>C. sativa<\/i> relative to other members in the order Rosales. Furthermore, Vergara <i>et al.<\/i> released the complete chloroplast genomes of two <i>Cannabis<\/i> hemp varieties, the Carmagnola (Italian) and Dagestani (Russian), in September 2016 to determine their genetic distance compared with the closest <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabaceae\" title=\"Cannabaceae\" class=\"wiki-link\" data-key=\"5656d9c7cc7d9aac66fadf89750e914a\">Cannabaceae<\/a> chloroplast of <i>Humulus lupulus<\/i> variety Saazer.<sup id=\"rdp-ebb-cite_ref-89\" class=\"reference\"><a href=\"#cite_note-89\">[89]<\/a><\/sup>\n<\/p><p>Increasingly growing support for open data policies by multiple industries is improving transparency in cannabis agriculture. In 2016, the industrial lead in cannabis research from Courtagen Life Sciences and Phylos Bioscience independently generated the genomes of hybrid marijuana strain (THC-dominant) Chemdog91 (by Illumina GAII) and marijuana strain (CBD-dominant) Cannatonic (using PacBio), respectively. Phylos Bioscience also released genomic data on 850 cannabis strains as a part of the \u201cOpen Cannabis Project\u201d for plant breeding programs. With an objective to explore cannabis population genetics, Phylos Bioscience developed a three-dimensional interactive map of nearly 1,000 cannabis strains.<sup id=\"rdp-ebb-cite_ref-PBGalaxy_90-0\" class=\"reference\"><a href=\"#cite_note-PBGalaxy-90\">[90]<\/a><\/sup> In 2017, the genome of hybrid marijuana cultivar Pineapple Banana Bubba Kush (PacBio) was released as part of the Cannabis Genomic Research Initiative. In 2018, Grassa <i>et al.<\/i> generated the first chromosome-level assembly for the genome of CBDRx, a high-CBD cultivar of <i>C. sativa<\/i> by using advanced long-read Oxford Nanopore Technology (ONT) and PacBio Single-Molecule Real-Time (SMRT) sequencing.<sup id=\"rdp-ebb-cite_ref-:26_91-0\" class=\"reference\"><a href=\"#cite_note-:26-91\">[91]<\/a><\/sup> In 2019, Laverty <i>et al.<\/i> improved the initial draft assemblies<sup id=\"rdp-ebb-cite_ref-:14_32-3\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup> of drug-type Purple Kush and hemp-type Finola to the chromosome-level by using ultra-long PacBio reads.<sup id=\"rdp-ebb-cite_ref-92\" class=\"reference\"><a href=\"#cite_note-92\">[92]<\/a><\/sup> In addition to genomes of high-CBD and -THC marijuana and hemp cultivars, a medicinal cannabis strain with a balanced THC\/CBD ratio was sequenced by Braich <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-:27_93-0\" class=\"reference\"><a href=\"#cite_note-:27-93\">[93]<\/a><\/sup>\n<\/p><p>Until 2020, nearly all cannabis genomes had been obtained from the hemp and marijuana cultivars, selectively bred for generations. However, cultivars lose genetic diversity owing to domestication and successive plant breeding for selected traits. In contrast, the wild-type genomes exhibit relatively high heterozygosity and genetic diversity, which might provide unique evolutionary insights into the cannabis genome. In 2020, Gao <i>et al.<\/i> sequenced the first samples of <i>C. sativa<\/i> wild-type \u201cJamaican Lion,\u201d growing in the geographically isolated Himalayan region in Tibet. Because these wild-type plants retained the ancestral genetic make-up, the data generated from this study was used as a tool to determine the inheritance patterns and evolutionary inference of cannabis.<sup id=\"rdp-ebb-cite_ref-94\" class=\"reference\"><a href=\"#cite_note-94\">[94]<\/a><\/sup>\n<\/p><p>The published genomes of high-THC and -CBD marijuana cultivars, as well as hemp varieties, have exhibited inconsistent chromosomal nomenclature, arrangement, and a varying degree of gaps. By the end of 2020, Braich <i>et al.<\/i> had generated a relatively complete draft genome assembly for Cannbio-2, the medicinal cannabis strain with a balanced THC\/CBD ratio.<sup id=\"rdp-ebb-cite_ref-:27_93-1\" class=\"reference\"><a href=\"#cite_note-:27-93\">[93]<\/a><\/sup> To present date, only 13 cannabis genomes are publicly available at the National Center for Biotechnological Information (NCBI). Of those 13, three assemblies are at the chromosome level, seven at the contig level, and one at the scaffold level. However, as of March 2021, the 1000 Cannabis Genomes Project comprises genomic data of some sort for nearly 1,000 samples from multiple cannabis strains. These datasets were the first genome data released on the Google Cloud Big Query database.\n<\/p><p>The continuous expansion of the list of cannabis genomes needs collaborative efforts toward curating the information. As such, academic and industry experts in diverse fields formed the International Cannabis Research Consortium (ICRC) during the annual PAG meeting in 2020. Despite several cannabis genome assemblies, the selection of a single standard reference genome is still a huge challenge for the scientific community, especially plant breeders. However, the ICRC proposed the CBDRX Cs10 assembly as the most complete reference for use in cannabis genome research.<sup id=\"rdp-ebb-cite_ref-:26_91-1\" class=\"reference\"><a href=\"#cite_note-:26-91\">[91]<\/a><\/sup> Additionally, a member genomics company, NRGene, generated an integrated Cannabis and Hemp Genomic Database (CannaGENE) optimized and curated for the genomics-based breeding of cannabis varieties. Finally, in 2021, the first-ever open-access and comprehensive database of cannabis genome, the <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/gdb.supercann.net\" target=\"_blank\">CannabisGDB<\/a>, was released<sup id=\"rdp-ebb-cite_ref-95\" class=\"reference\"><a href=\"#cite_note-95\">[95]<\/a><\/sup> with integrated bioinformatics tools for the analysis of datasets.\n<\/p><p>Overall, the genomic data of diverse cannabis genotypes represent untapped reservoirs of genetic information which could be applied toward pan-genomic understanding of cannabis evolution and determining the effect of genetic variations upon the pathways, development, and concentration of cannabis derivatives. A detailed genetic atlas would facilitate the designing and further breeding of cannabis varieties for preferred metabolic yields.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Developments_in_cannabis_transcriptomics\">Developments in cannabis transcriptomics<\/span><\/h2>\n<p>The availability of several high-quality cannabis genomes made it easier to apply the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Transcriptome\" title=\"Transcriptome\" class=\"wiki-link\" data-key=\"054827308f8b6a6bc476d36105d57b80\">transcriptome<\/a> <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=DNA_sequencing#RNA_sequencing\" title=\"DNA sequencing\" class=\"wiki-link\" data-key=\"5181c006d55c0846541547fb213be810\">sequencing<\/a> to elucidate detailed expression dynamics in a time-, tissue-, stage-, and chemotype-dependent manner. Furthermore, the differential expression analysis provides in-depth insight into co-related gene networks. In 2011, Bakel <i>et al<\/i><sup id=\"rdp-ebb-cite_ref-:14_32-4\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup><i>.<\/i> sequenced and compared the transcriptomes of marijuana variety Purple Kush (PK) and hemp cultivars Finola (FN) and USO-31. Gene expression analysis revealed preferential expression of cannabinoid and precursor pathway-associated genes in marijuana (PK). Expression of THCA synthase in the PK and CBDA synthase in FN was found to be consistent with the exclusive production of psychoactive THC in marijuana. In a recent study, transcriptomics of hemp-type plants was analyzed to determine the expression profile of the fiber-type plant at the various developmental stages.<sup id=\"rdp-ebb-cite_ref-96\" class=\"reference\"><a href=\"#cite_note-96\">[96]<\/a><\/sup> Similarly, the transcriptome of marijuana flowers at different stages was captured and sequenced, notably with a gene expression pattern consistent with its cannabinoid contents.<sup id=\"rdp-ebb-cite_ref-:14_32-5\" class=\"reference\"><a href=\"#cite_note-:14-32\">[32]<\/a><\/sup>\n<\/p><p>As glandular trichomes are the central reservoir for cannabinoids<sup id=\"rdp-ebb-cite_ref-:25_74-1\" class=\"reference\"><a href=\"#cite_note-:25-74\">[74]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-97\" class=\"reference\"><a href=\"#cite_note-97\">[97]<\/a><\/sup>, the trichome transcriptome could yield valuable insight to determine the variation in cannabinoid biosynthesis, composition, and concentration between the drug- and fiber-type plants. Importantly, the identification of the differentially expressed genes could unravel the underlying molecular mechanisms of natural genetic and metabolic variation. The gene expression in trichomes of female plant strain Cannobio-2 was compared with genome-wide transcriptomics of female floral tissues at different stages of development, as well as other tissues including female and male flowers, leaves, and roots.<sup id=\"rdp-ebb-cite_ref-98\" class=\"reference\"><a href=\"#cite_note-98\">[98]<\/a><\/sup> The extensive-expression atlas was applied toward the identification of genes expressed preferentially in various tissues at different developmental stages. Interestingly, the majority of genes involved in terpenoid and cannabinoids synthesis were significantly overexpressed in trichomes. In 2021, Grassa <i>et al.<\/i> used genomic and expression-associated expression of THCAS and CBDAS with THC:CBD ratio by Quantitative trait Loci (QTL) analysis of cannabis cultivars.<sup id=\"rdp-ebb-cite_ref-:26_91-2\" class=\"reference\"><a href=\"#cite_note-:26-91\">[91]<\/a><\/sup>\n<\/p><p>Datasets from similar genomics, transcriptomics, microbiome, and metagenomics studies of various cannabis strains are currently accessible from the Sequence Read Archive (SRA) repository at NCBI. In the past three years, there has been unprecedented growth in cannabis genome and transcriptome studies, as well as corresponding SRA entries. To date, there are over 4,571 BioSamples from multiple studies related to cannabis, of which 2,871 public BioSamples are exclusively for <i>C. sativa<\/i>, with 2,546 DNA and 325 <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=RNA-Seq\" title=\"RNA-Seq\" class=\"wiki-link\" data-key=\"a950462d5c4d37e5f9d751dfd8557d04\">RNA-Seq<\/a> datasets in SRA. The SRA data for transcriptomics and metagenomics have been reportedly procured from various tissues, including seeds (3), flowers (116), leaves (138), shoot (13) stem (175), root (76), and trichomes (62), while genomic data lacks tissue-specific information. In-depth transcriptomic studies will be required in the future to improve the understanding of regulatory genetic networks.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Patents_for_Cannabis_sativa_L.\">Patents for <i>Cannabis sativa<\/i> L.<\/span><\/h2>\n<p>One of the fundamental aspects of patents, especially in medical science or biotechnology, is to involve industrial partners in investing in research and development.<sup id=\"rdp-ebb-cite_ref-99\" class=\"reference\"><a href=\"#cite_note-99\">[99]<\/a><\/sup> Cannabis-related patents have been issued by the United States Patent and Trademark Office (USPTO) since 1942. More than 1,500 applications have been filed just in the USPTO. Among them, approximately 500 applications got patent protection rights<sup id=\"rdp-ebb-cite_ref-100\" class=\"reference\"><a href=\"#cite_note-100\">[100]<\/a><\/sup>, and most of them were from the last decade. The exponential increase in the number of patents shows the future potential for the growing cannabis industry. Here, we analyzed the patents spatiotemporally and categorized them into four main classes: (i) patents related to cannabinoids as constituents, (ii) pharmaceutical applications, (iii) endocannabinoid pharmacology, and (iv) genome- and gene-related. Among the suggested four categories, the patents related to the pharmaceutical application were the most significant category, with 73 patents registered. These are further sub-grouped into the (i) preparation of the drugs, (ii) treatment, (iii) delivery technology, and (iv) detection method, each with 14, 33, 13, and 13 patents, respectively. Others have examined cannabis-related patents as well. For example, Gerra <i>et al.<\/i><sup id=\"rdp-ebb-cite_ref-101\" class=\"reference\"><a href=\"#cite_note-101\">[101]<\/a><\/sup> reviewed endocannabinoid-related patents, comprised of the CB1\/2 receptor (26), TRPV1 (6), and GPR119 (4) in 2010. The category of cannabinoids consists of (i) cannabinoid isolation, (ii) extraction, and (iii) synthesis- or biosynthesis-related patents, each with 6, 6, and 12 patents granted, respectively. For the division of the sequences, 15 patents are from enzyme inhibition, followed by the gene and the protein, each with two patents. Most of the patents are from the US (49.6%), followed by Great Britain (11%) and a variety of European countries<sup id=\"rdp-ebb-cite_ref-102\" class=\"reference\"><a href=\"#cite_note-102\">[102]<\/a><\/sup> (Figure 2). In addition, 25 patents for fiber\/textile, 10 for foodstuff, five for the paper industry, three for architecture, one for biofuel, and three for plant breeding have been registered. Also, four patents each in the category of oil, extracts, and cosmetics have been filed.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig2_Hussain_iScience2021_24-12.jpg\" class=\"image wiki-link\" data-key=\"36facff151954fffb19cb7d3d7da1191\"><img alt=\"Fig2 Hussain iScience2021 24-12.jpg\" src=\"https:\/\/www.cannaqa.wiki\/images\/b\/b0\/Fig2_Hussain_iScience2021_24-12.jpg\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> Cannabis patent development. (<b>A<\/b>) Number of patents registered for each category. Isolation, extraction, and biosynthesis belong to the category of cannabinoid-related patents. Pharmaceutical-related patents were subcategorized into preparation, treatment, delivery technology, and detection. CB receptor, TRPV1, and GPR119 were grouped into endocannabinoids. Three sub-groups\u2014e.g., enzymes, genes, and proteins\u2014are grouped for the category of sequence-related patents. (<b>B<\/b>) Distribution of the patents into four major categories. (<b>C<\/b>) Region-wise division of the patents registered for each category. (All the information shown here are up to 2017.)<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>However, we have to keep in mind that a certain cannabinoid invention can be referred into more than one patent category. For instance, cannabinoids are highly hydrophobic by nature and thus they have low bioavailability in the human body. As a result, a new class of cannabinoid-glycosides has been created, whose representatives are produced through enzymatic glycosylation. This novel strategy led to increased aqueous solubility of the target cannabinoids and resulted in four patents (WO2017053574, US20190153461, US20190078168, and WO2020239784). Recently, a new method of producing one or more cannabosides by feeding an insect a cannabinoid was patented (WO2021146687). These new classes of cannabinoid glycosides generated vast structural diversity and have greatly improved water solubility, enabling new pharmaceutical formulations and multiple administration routes (oral, parenteral, or transdermal). The discovery of the genes encoding glycosyltransferases may belong to different categories of the cannabinoid patent family, that is, genes, enzymes, delivery technology, etc.\n<\/p><p>The exponential enhancement of the patent number during recent years in the diverse areas of cannabinoid applications is indicative of the increased commercial interest in this class of natural compounds. The various pharmaceutical applications will continue to shape primarily the path of future invention of cannabinoids.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Cannabis_in_COVID-19\">Cannabis in COVID-19<\/span><\/h2>\n<p><i>C. sativa<\/i> has become increasingly known for its potential anti-inflammatory properties.<sup id=\"rdp-ebb-cite_ref-103\" class=\"reference\"><a href=\"#cite_note-103\">[103]<\/a><\/sup> The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus and its resulting disease, COVID-19, can result in life-threatening lung inflammation. A reduction of this inflammation is optimal, and means of reducing lung inflammation have been tested in the mice animal model. Interestingly, cannabinoid isolates such as CBD and THC have also been tested in humans, even long before the onset of the global pandemic owing to the spread of SARS-CoV-2.<sup id=\"rdp-ebb-cite_ref-104\" class=\"reference\"><a href=\"#cite_note-104\">[104]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-105\" class=\"reference\"><a href=\"#cite_note-105\">[105]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-106\" class=\"reference\"><a href=\"#cite_note-106\">[106]<\/a><\/sup> Immune responses during severe cases of COVID-19 trigger the inflammation of human lung tissue, resulting in acute respiratory distress and failure. This immune response to the overproduction of pro-inflammatory cytokines is known as a cytokine storm.<sup id=\"rdp-ebb-cite_ref-107\" class=\"reference\"><a href=\"#cite_note-107\">[107]<\/a><\/sup> Respiratory distress from COVID-19-induced lung inflammation is the leading cause of the disease's high mortality rate. Phyto-cannabinoids, especially CBD, have exhibited a remarkable anti-inflammatory effect through CB2 inhibitory activity and an agonistic effect on the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3).<sup id=\"rdp-ebb-cite_ref-108\" class=\"reference\"><a href=\"#cite_note-108\">[108]<\/a><\/sup> Additionally, CBD, CBN, and THC have also been shown to exhibit some anti-viral effect against COVID-19 in cell-based assays, with the same potency as the standard clinical references (remdesivir and lopinavir).<sup id=\"rdp-ebb-cite_ref-109\" class=\"reference\"><a href=\"#cite_note-109\">[109]<\/a><\/sup> However, the complete antiviral mechanism of cannabinoids against SAR-CoV-2 infection is still unknown. Therefore, detailed pharmacological research studies are urgently needed to explore the immunotherapy potential of cannabis against SARS-CoV-2 infection.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Conclusion_and_future_prospective\">Conclusion and future prospective<\/span><\/h2>\n<p>Cannabis legalization fueled scientific research in cannabinoid compounds for their potential in medicinal, pharmaceutical, and neurological applications. However, with recent developments in sequencing technologies, there has been a paradigm shift in cannabis research toward the genomics of fiber- and drug-type plants. The remarkable growth in genomic data, combined with fast-paced development of AI-based bioinformatics and data analysis tools, has made it possible to explore the <i>Cannabis<\/i> plant at the genetic and molecular levels. Integrated omics studies combining genomic and expression data with metabolite profiles are now beginning to understand the genetic regulation of the cannabinoid biosynthesis pathway, especially by unraveling the association between the expression of cannabinoid genes with THC:CBD ratio and cannabinoid content. The knowledge could be further applied to genetically modified cannabis, with optimized pathways for preferred metabolite yield and composition. Advanced biotechnology methods could be further extended for recombinant production of cannabinoids in metabolically engineered hosts such as yeasts or bacteria. Currently, the recombinant production of THC in yeast is challenging, owing to unstable THCA and CBGA expression and high amounts of side products. However, in the future, the combination of genetic technologies to obtain enhanced expression rates will lead to enhanced cannabinoid yields in an economically feasible manner. In addition, cannabinoids have been recently shown to exhibit anti-inflammatory and immunosuppressing effects against the COVID-19 immune response. However, further evidence-based clinical studies are needed to determine the efficacy and safe dosage of cannabis extracts for treatment or prevention of COVID-19. Pharmacological research, coupled with rapidly evolving genome-based biotechnology, will further facilitate exploring the <i>Cannabis<\/i> plant for its tremendous potential in drug discovery.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Supplemental_information\">Supplemental information<\/span><\/h2>\n<ul><li><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S2589004221013626-mmc1.xls\" target=\"_blank\">Data S1<\/a> (.xls file)<\/li>\n<li><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S2589004221013626-mmc2.xls\" target=\"_blank\">Data S2<\/a> (.xls file)<\/li>\n<li><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S2589004221013626-mmc3.xls\" target=\"_blank\">Data S3<\/a> (.xls file)<\/li><\/ul>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>T.H. and O.K. designed the concept, while T.H. and G.J. performed a literature search and did bibliometric analysis. T.H. and G.J. wrote the sections \u201cHistory of cannabis research, Trends in past two centuries of cannabis research and Development in Cannabis Genomic and transcriptomes\u201d. T.H. an N.V. wrote the \u201cpatent\u201d section. T.P. contributed in \u201cCannabis in covid-19\u201d section. O.K. supervised the study and all the authors contributed to the final manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflict_of_interest\">Conflict of interest<\/span><\/h3>\n<p>The authors declare no competing interests.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schultes, Richard Evans; Klein, William M; Plowman, Timothy; Lockwood, Tom E (28 February 1974). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.biodiversitylibrary.org\/part\/168565\" target=\"_blank\">\"Cannabis: an Example of Taxonomic Neglect\"<\/a>. <i>Botanical Museum leaflets, Harvard University<\/i> <b>23<\/b> (9): 337\u2013367. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5962%2Fp.168565\" target=\"_blank\">10.5962\/p.168565<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0006-8098\" target=\"_blank\">0006-8098<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.biodiversitylibrary.org\/part\/168565\" target=\"_blank\">https:\/\/www.biodiversitylibrary.org\/part\/168565<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis%3A+an+Example+of+Taxonomic+Neglect&rft.jtitle=Botanical+Museum+leaflets%2C+Harvard+University&rft.aulast=Schultes&rft.aufirst=Richard+Evans&rft.au=Schultes%2C%26%2332%3BRichard+Evans&rft.au=Klein%2C%26%2332%3BWilliam+M&rft.au=Plowman%2C%26%2332%3BTimothy&rft.au=Lockwood%2C%26%2332%3BTom+E&rft.date=28+February+1974&rft.volume=23&rft.issue=9&rft.pages=337%E2%80%93367&rft_id=info:doi\/10.5962%2Fp.168565&rft.issn=0006-8098&rft_id=https%3A%2F%2Fwww.biodiversitylibrary.org%2Fpart%2F168565&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-2\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_2-0\">2.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_2-1\">2.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">O'Shaughnessy, W. 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(1 July 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165614716300165\" target=\"_blank\">\"Beyond Cannabis: Plants and the Endocannabinoid System\"<\/a> (in en). <i>Trends in Pharmacological Sciences<\/i> <b>37<\/b> (7): 594\u2013605. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.tips.2016.04.005\" target=\"_blank\">10.1016\/j.tips.2016.04.005<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165614716300165\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165614716300165<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Beyond+Cannabis%3A+Plants+and+the+Endocannabinoid+System&rft.jtitle=Trends+in+Pharmacological+Sciences&rft.aulast=Russo&rft.aufirst=Ethan+B.&rft.au=Russo%2C%26%2332%3BEthan+B.&rft.date=1+July+2016&rft.volume=37&rft.issue=7&rft.pages=594%E2%80%93605&rft_id=info:doi\/10.1016%2Fj.tips.2016.04.005&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614716300165&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-10\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_10-0\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_10-1\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">ElSohly, Mahmoud A.; Slade, Desmond (1 December 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002432050500891X\" target=\"_blank\">\"Chemical constituents of marijuana: The complex mixture of natural cannabinoids\"<\/a> (in en). <i>Life Sciences<\/i> <b>78<\/b> (5): 539\u2013548. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.lfs.2005.09.011\" target=\"_blank\">10.1016\/j.lfs.2005.09.011<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002432050500891X\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002432050500891X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Chemical+constituents+of+marijuana%3A+The+complex+mixture+of+natural+cannabinoids&rft.jtitle=Life+Sciences&rft.aulast=ElSohly&rft.aufirst=Mahmoud+A.&rft.au=ElSohly%2C%26%2332%3BMahmoud+A.&rft.au=Slade%2C%26%2332%3BDesmond&rft.date=1+December+2005&rft.volume=78&rft.issue=5&rft.pages=539%E2%80%93548&rft_id=info:doi\/10.1016%2Fj.lfs.2005.09.011&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS002432050500891X&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-11\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_11-0\">11.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_11-1\">11.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gould, Julie (1 September 2015). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/525S2a\" target=\"_blank\">\"The cannabis crop\"<\/a> (in en). <i>Nature<\/i> <b>525<\/b> (7570): S2\u2013S3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2F525S2a\" target=\"_blank\">10.1038\/525S2a<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0028-0836\" target=\"_blank\">0028-0836<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/525S2a\" target=\"_blank\">http:\/\/www.nature.com\/articles\/525S2a<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+cannabis+crop&rft.jtitle=Nature&rft.aulast=Gould&rft.aufirst=Julie&rft.au=Gould%2C%26%2332%3BJulie&rft.date=1+September+2015&rft.volume=525&rft.issue=7570&rft.pages=S2%E2%80%93S3&rft_id=info:doi\/10.1038%2F525S2a&rft.issn=0028-0836&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2F525S2a&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-12\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_12-0\">12.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_12-1\">12.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFRadwanWanasChandraElSohly2017\">Radwan, Mohamed M.; Wanas, Amira S.; Chandra, Suman; ElSohly, Mahmoud A. (2017), Chandra, Suman; Lata, Hemant; ElSohly, Mahmoud A., eds., <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-54564-6_7\" target=\"_blank\">\"Natural Cannabinoids of Cannabis and Methods of Analysis\"<\/a> (in en), <i>Cannabis sativa L. - Botany and Biotechnology<\/i> (Cham: Springer International Publishing): 161\u2013182, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2F978-3-319-54564-6_7\" target=\"_blank\">10.1007\/978-3-319-54564-6_7<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-54563-9<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/978-3-319-54564-6_7\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/978-3-319-54564-6_7<\/a><\/span><span class=\"reference-accessdate\">. 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Hansen, Esben Halkj\u00e6r; Kayser, Oliver; Carlsen, Simon; Stehle, Felix (1 June 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/femsyr\/article\/doi\/10.1093\/femsyr\/fox037\/3861260\" target=\"_blank\">\"Designing microorganisms for heterologous biosynthesis of cannabinoids\"<\/a> (in en). <i>FEMS Yeast Research<\/i> <b>17<\/b> (4). <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Ffemsyr%2Ffox037\" target=\"_blank\">10.1093\/femsyr\/fox037<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1567-1364\" target=\"_blank\">1567-1364<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC5812543\" target=\"_blank\">PMC5812543<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28582498\" target=\"_blank\">28582498<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/femsyr\/article\/doi\/10.1093\/femsyr\/fox037\/3861260\" target=\"_blank\">https:\/\/academic.oup.com\/femsyr\/article\/doi\/10.1093\/femsyr\/fox037\/3861260<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Designing+microorganisms+for+heterologous+biosynthesis+of+cannabinoids&rft.jtitle=FEMS+Yeast+Research&rft.aulast=Carvalho&rft.aufirst=%C3%82ngela&rft.au=Carvalho%2C%26%2332%3B%C3%82ngela&rft.au=Hansen%2C%26%2332%3BEsben+Halkj%C3%A6r&rft.au=Kayser%2C%26%2332%3BOliver&rft.au=Carlsen%2C%26%2332%3BSimon&rft.au=Stehle%2C%26%2332%3BFelix&rft.date=1+June+2017&rft.volume=17&rft.issue=4&rft_id=info:doi\/10.1093%2Ffemsyr%2Ffox037&rft.issn=1567-1364&rft_id=info:pmc\/PMC5812543&rft_id=info:pmid\/28582498&rft_id=https%3A%2F%2Facademic.oup.com%2Ffemsyr%2Farticle%2Fdoi%2F10.1093%2Ffemsyr%2Ffox037%2F3861260&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-14\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-14\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Kumar, Amit; Premoli, Marika; Aria, Francesca; Bonini, Sara Anna; Maccarinelli, Giuseppina; Gianoncelli, Alessandra; Memo, Maurizio; Mastinu, Andrea (1 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00425-019-03138-x\" target=\"_blank\">\"Cannabimimetic plants: are they new cannabinoidergic modulators?\"<\/a> (in en). <i>Planta<\/i> <b>249<\/b> (6): 1681\u20131694. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00425-019-03138-x\" target=\"_blank\">10.1007\/s00425-019-03138-x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0935\" target=\"_blank\">0032-0935<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00425-019-03138-x\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00425-019-03138-x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabimimetic+plants%3A+are+they+new+cannabinoidergic+modulators%3F&rft.jtitle=Planta&rft.aulast=Kumar&rft.aufirst=Amit&rft.au=Kumar%2C%26%2332%3BAmit&rft.au=Premoli%2C%26%2332%3BMarika&rft.au=Aria%2C%26%2332%3BFrancesca&rft.au=Bonini%2C%26%2332%3BSara+Anna&rft.au=Maccarinelli%2C%26%2332%3BGiuseppina&rft.au=Gianoncelli%2C%26%2332%3BAlessandra&rft.au=Memo%2C%26%2332%3BMaurizio&rft.au=Mastinu%2C%26%2332%3BAndrea&rft.date=1+June+2019&rft.volume=249&rft.issue=6&rft.pages=1681%E2%80%931694&rft_id=info:doi\/10.1007%2Fs00425-019-03138-x&rft.issn=0032-0935&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00425-019-03138-x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-15\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-15\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Flores-Sanchez, Isvett Josefina; Verpoorte, Robert (1 October 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11101-008-9094-4\" target=\"_blank\">\"Secondary metabolism in cannabis\"<\/a> (in en). <i>Phytochemistry Reviews<\/i> <b>7<\/b> (3): 615\u2013639. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11101-008-9094-4\" target=\"_blank\">10.1007\/s11101-008-9094-4<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1568-7767\" target=\"_blank\">1568-7767<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11101-008-9094-4\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11101-008-9094-4<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Secondary+metabolism+in+cannabis&rft.jtitle=Phytochemistry+Reviews&rft.aulast=Flores-Sanchez&rft.aufirst=Isvett+Josefina&rft.au=Flores-Sanchez%2C%26%2332%3BIsvett+Josefina&rft.au=Verpoorte%2C%26%2332%3BRobert&rft.date=1+October+2008&rft.volume=7&rft.issue=3&rft.pages=615%E2%80%93639&rft_id=info:doi\/10.1007%2Fs11101-008-9094-4&rft.issn=1568-7767&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11101-008-9094-4&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-16\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_16-0\">16.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_16-1\">16.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Happyana, Nizar; Agnolet, Sara; Muntendam, Remco; Van Dam, Annie; Schneider, Bernd; Kayser, Oliver (1 March 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003194221200475X\" target=\"_blank\">\"Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR\"<\/a> (in en). <i>Phytochemistry<\/i> <b>87<\/b>: 51\u201359. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.phytochem.2012.11.001\" target=\"_blank\">10.1016\/j.phytochem.2012.11.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003194221200475X\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003194221200475X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+cannabinoids+in+laser-microdissected+trichomes+of+medicinal+Cannabis+sativa+using+LCMS+and+cryogenic+NMR&rft.jtitle=Phytochemistry&rft.aulast=Happyana&rft.aufirst=Nizar&rft.au=Happyana%2C%26%2332%3BNizar&rft.au=Agnolet%2C%26%2332%3BSara&rft.au=Muntendam%2C%26%2332%3BRemco&rft.au=Van+Dam%2C%26%2332%3BAnnie&rft.au=Schneider%2C%26%2332%3BBernd&rft.au=Kayser%2C%26%2332%3BOliver&rft.date=1+March+2013&rft.volume=87&rft.pages=51%E2%80%9359&rft_id=info:doi\/10.1016%2Fj.phytochem.2012.11.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS003194221200475X&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-17\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-17\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Small, Ernest; Naraine, Steve G. U. (1 February 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s10722-015-0254-2\" target=\"_blank\">\"Size matters: evolution of large drug-secreting resin glands in elite pharmaceutical strains of Cannabis sativa (marijuana)\"<\/a> (in en). <i>Genetic Resources and Crop Evolution<\/i> <b>63<\/b> (2): 349\u2013359. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs10722-015-0254-2\" target=\"_blank\">10.1007\/s10722-015-0254-2<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0925-9864\" target=\"_blank\">0925-9864<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s10722-015-0254-2\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s10722-015-0254-2<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Size+matters%3A+evolution+of+large+drug-secreting+resin+glands+in+elite+pharmaceutical+strains+of+Cannabis+sativa+%28marijuana%29&rft.jtitle=Genetic+Resources+and+Crop+Evolution&rft.aulast=Small&rft.aufirst=Ernest&rft.au=Small%2C%26%2332%3BErnest&rft.au=Naraine%2C%26%2332%3BSteve+G.+U.&rft.date=1+February+2016&rft.volume=63&rft.issue=2&rft.pages=349%E2%80%93359&rft_id=info:doi\/10.1007%2Fs10722-015-0254-2&rft.issn=0925-9864&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs10722-015-0254-2&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-18\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-18\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Bovens, M.; Schl\u00e4pfer, M.; Fiddian, S. et al. (2009) (in English). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/471464213\" target=\"_blank\"><i>Recommended methods for the identification and analysis of cannabis and cannabis products: manual for use by national drug testing laboratories<\/i><\/a>. New York: United Nations Office on Drugs and Crime. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-92-1-148242-3. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Online_Computer_Library_Center\" data-key=\"b53206e2204c7e657858a88b56c8ac4a\">OCLC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/oclc\/471464213\" target=\"_blank\">471464213<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/471464213\" target=\"_blank\">https:\/\/www.worldcat.org\/title\/mediawiki\/oclc\/471464213<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Recommended+methods+for+the+identification+and+analysis+of+cannabis+and+cannabis+products%3A+manual+for+use+by+national+drug+testing+laboratories&rft.aulast=Bovens%2C+M.%3B+Schl%C3%A4pfer%2C+M.%3B+Fiddian%2C+S.+et+al.&rft.au=Bovens%2C+M.%3B+Schl%C3%A4pfer%2C+M.%3B+Fiddian%2C+S.+et+al.&rft.date=2009&rft.place=New+York&rft.pub=United+Nations+Office+on+Drugs+and+Crime&rft.isbn=978-92-1-148242-3&rft_id=info:oclcnum\/471464213&rft_id=https%3A%2F%2Fwww.worldcat.org%2Ftitle%2Fmediawiki%2Foclc%2F471464213&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-19\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_19-0\">19.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_19-1\">19.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Luo, Xiaozhou; Reiter, Michael A.; d\u2019Espaux, Leo; Wong, Jeff; Denby, Charles M.; Lechner, Anna; Zhang, Yunfeng; Grzybowski, Adrian T. <i>et al.<\/i> (1 March 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41586-019-0978-9\" target=\"_blank\">\"Complete biosynthesis of cannabinoids and their unnatural analogues in yeast\"<\/a> (in en). <i>Nature<\/i> <b>567<\/b> (7746): 123\u2013126. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41586-019-0978-9\" target=\"_blank\">10.1038\/s41586-019-0978-9<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0028-0836\" target=\"_blank\">0028-0836<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41586-019-0978-9\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41586-019-0978-9<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Complete+biosynthesis+of+cannabinoids+and+their+unnatural+analogues+in+yeast&rft.jtitle=Nature&rft.aulast=Luo&rft.aufirst=Xiaozhou&rft.au=Luo%2C%26%2332%3BXiaozhou&rft.au=Reiter%2C%26%2332%3BMichael+A.&rft.au=d%E2%80%99Espaux%2C%26%2332%3BLeo&rft.au=Wong%2C%26%2332%3BJeff&rft.au=Denby%2C%26%2332%3BCharles+M.&rft.au=Lechner%2C%26%2332%3BAnna&rft.au=Zhang%2C%26%2332%3BYunfeng&rft.au=Grzybowski%2C%26%2332%3BAdrian+T.&rft.au=Harth%2C%26%2332%3BSimon&rft.date=1+March+2019&rft.volume=567&rft.issue=7746&rft.pages=123%E2%80%93126&rft_id=info:doi\/10.1038%2Fs41586-019-0978-9&rft.issn=0028-0836&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41586-019-0978-9&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-20\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-20\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Thomas, Fabian; 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Stark, Harley; Seligman, Jon; Levy, Rina; Werker, Ella; Breuer, Aviva; Mechoulam, Raphael (1 May 1993). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/363215a0\" target=\"_blank\">\"Early medical use of cannabis\"<\/a> (in en). <i>Nature<\/i> <b>363<\/b> (6426): 215\u2013215. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2F363215a0\" target=\"_blank\">10.1038\/363215a0<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0028-0836\" target=\"_blank\">0028-0836<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/363215a0\" target=\"_blank\">http:\/\/www.nature.com\/articles\/363215a0<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Early+medical+use+of+cannabis&rft.jtitle=Nature&rft.aulast=Zlas&rft.aufirst=Joe&rft.au=Zlas%2C%26%2332%3BJoe&rft.au=Stark%2C%26%2332%3BHarley&rft.au=Seligman%2C%26%2332%3BJon&rft.au=Levy%2C%26%2332%3BRina&rft.au=Werker%2C%26%2332%3BElla&rft.au=Breuer%2C%26%2332%3BAviva&rft.au=Mechoulam%2C%26%2332%3BRaphael&rft.date=1+May+1993&rft.volume=363&rft.issue=6426&rft.pages=215%E2%80%93215&rft_id=info:doi\/10.1038%2F363215a0&rft.issn=0028-0836&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2F363215a0&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-22\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-22\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bridgeman, Mary Barna; 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(1 March 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5312634\/\" target=\"_blank\">\"Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting\"<\/a>. <i>Pharmacy and Therapeutics<\/i> <b>42<\/b> (3): 180\u2013188. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1052-1372\" target=\"_blank\">1052-1372<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=5312634\" target=\"_blank\">5312634<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28250701\" target=\"_blank\">28250701<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5312634\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5312634\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Medicinal+Cannabis%3A+History%2C+Pharmacology%2C+And+Implications+for+the+Acute+Care+Setting&rft.jtitle=Pharmacy+and+Therapeutics&rft.aulast=Bridgeman&rft.aufirst=Mary+Barna&rft.au=Bridgeman%2C%26%2332%3BMary+Barna&rft.au=Abazia%2C%26%2332%3BDaniel+T.&rft.date=1+March+2017&rft.volume=42&rft.issue=3&rft.pages=180%E2%80%93188&rft.issn=1052-1372&rft_id=info:pmc\/5312634&rft_id=info:pmid\/28250701&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5312634%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-23\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-23\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\"><a rel=\"external_link\" class=\"external text\" 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href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5545489\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5545489\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Philosophical+Transactions+of+the+Royal+Society+of+London&rft.jtitle=The+London+Medical+Journal&rft.date=1783&rft.volume=4&rft.issue=1&rft.pages=1%E2%80%939&rft.issn=0952-4177&rft_id=info:pmc\/5545489&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5545489%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-24\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-24\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wright, William (1787). <a rel=\"external_link\" class=\"external text\" 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data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29139884\" target=\"_blank\">29139884<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5545524\/\" target=\"_blank\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5545524\/<\/a><\/span>.<\/span><span class=\"Z3988\" 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(2017), <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000016\" target=\"_blank\">\"The Cannabis Plant: Botanical Aspects\"<\/a> (in en), <i>Handbook of Cannabis and Related Pathologies<\/i> (Elsevier): 3\u201312, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fb978-0-12-800756-3.00001-6\" target=\"_blank\">10.1016\/b978-0-12-800756-3.00001-6<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-12-800756-3<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000016\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000016<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-04<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Cannabis+Plant%3A+Botanical+Aspects&rft.jtitle=Handbook+of+Cannabis+and+Related+Pathologies&rft.aulast=Farag&rft.aufirst=S.&rft.au=Farag%2C%26%2332%3BS.&rft.au=Kayser%2C%26%2332%3BO.&rft.date=2017&rft.pages=3%E2%80%9312&rft.pub=Elsevier&rft_id=info:doi\/10.1016%2Fb978-0-12-800756-3.00001-6&rft.isbn=978-0-12-800756-3&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FB9780128007563000016&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-34\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-34\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Spitzer-Rimon, Ben; Duchin, Shai; Bernstein, Nirit; Kamenetsky, Rina (2 April 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00350\/full\" target=\"_blank\">\"Architecture and Florogenesis in Female Cannabis sativa Plants\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>10<\/b>: 350. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2019.00350\" target=\"_blank\">10.3389\/fpls.2019.00350<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6454139\" target=\"_blank\">PMC6454139<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31001293\" target=\"_blank\">31001293<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00350\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00350\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Architecture+and+Florogenesis+in+Female+Cannabis+sativa+Plants&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Spitzer-Rimon&rft.aufirst=Ben&rft.au=Spitzer-Rimon%2C%26%2332%3BBen&rft.au=Duchin%2C%26%2332%3BShai&rft.au=Bernstein%2C%26%2332%3BNirit&rft.au=Kamenetsky%2C%26%2332%3BRina&rft.date=2+April+2019&rft.volume=10&rft.pages=350&rft_id=info:doi\/10.3389%2Ffpls.2019.00350&rft.issn=1664-462X&rft_id=info:pmc\/PMC6454139&rft_id=info:pmid\/31001293&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2019.00350%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-35\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-35\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hammond, Charles T.; Mahlberg, Paul G. (1 September 1977). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1977.tb11948.x\" target=\"_blank\">\"MORPHOGENESIS OF CAPITATE GLANDULAR HAIRS OF CANNABIS SATIVA (CANNABACEAE)\"<\/a> (in en). <i>American Journal of Botany<\/i> <b>64<\/b> (8): 1023\u20131031. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fj.1537-2197.1977.tb11948.x\" target=\"_blank\">10.1002\/j.1537-2197.1977.tb11948.x<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1977.tb11948.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1977.tb11948.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=MORPHOGENESIS+OF+CAPITATE+GLANDULAR+HAIRS+OF+CANNABIS+SATIVA+%28CANNABACEAE%29&rft.jtitle=American+Journal+of+Botany&rft.aulast=Hammond&rft.aufirst=Charles+T.&rft.au=Hammond%2C%26%2332%3BCharles+T.&rft.au=Mahlberg%2C%26%2332%3BPaul+G.&rft.date=1+September+1977&rft.volume=64&rft.issue=8&rft.pages=1023%E2%80%931031&rft_id=info:doi\/10.1002%2Fj.1537-2197.1977.tb11948.x&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fj.1537-2197.1977.tb11948.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-36\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-36\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tibeau, Sister Mary Etienne (1 October 1936). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/plphys\/article\/11\/4\/731-747\/6071549\" target=\"_blank\">\"TIME FACTOR IN UTILIZATION OF MINERAL NUTRIENTS BY HEMP\"<\/a> (in en). <i>Plant Physiology<\/i> <b>11<\/b> (4): 731\u2013747. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1104%2Fpp.11.4.731\" target=\"_blank\">10.1104\/pp.11.4.731<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0889\" target=\"_blank\">0032-0889<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC439254\" target=\"_blank\">PMC439254<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16653382\" target=\"_blank\">16653382<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/plphys\/article\/11\/4\/731-747\/6071549\" target=\"_blank\">https:\/\/academic.oup.com\/plphys\/article\/11\/4\/731-747\/6071549<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=TIME+FACTOR+IN+UTILIZATION+OF+MINERAL+NUTRIENTS+BY+HEMP&rft.jtitle=Plant+Physiology&rft.aulast=Tibeau&rft.aufirst=Sister+Mary+Etienne&rft.au=Tibeau%2C%26%2332%3BSister+Mary+Etienne&rft.date=1+October+1936&rft.volume=11&rft.issue=4&rft.pages=731%E2%80%93747&rft_id=info:doi\/10.1104%2Fpp.11.4.731&rft.issn=0032-0889&rft_id=info:pmc\/PMC439254&rft_id=info:pmid\/16653382&rft_id=https%3A%2F%2Facademic.oup.com%2Fplphys%2Farticle%2F11%2F4%2F731-747%2F6071549&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-37\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-37\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nelson, Clarence H. (1 April 1944). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/plphys\/article\/19\/2\/294-309\/6072537\" target=\"_blank\">\"GROWTH RESPONSES OF HEMP TO DIFFERENTIAL SOIL AND AIR TEMPERATURES\"<\/a> (in en). <i>Plant Physiology<\/i> <b>19<\/b> (2): 294\u2013309. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1104%2Fpp.19.2.294\" target=\"_blank\">10.1104\/pp.19.2.294<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0889\" target=\"_blank\">0032-0889<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC438156\" target=\"_blank\">PMC438156<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16653915\" target=\"_blank\">16653915<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/plphys\/article\/19\/2\/294-309\/6072537\" target=\"_blank\">https:\/\/academic.oup.com\/plphys\/article\/19\/2\/294-309\/6072537<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=GROWTH+RESPONSES+OF+HEMP+TO+DIFFERENTIAL+SOIL+AND+AIR+TEMPERATURES&rft.jtitle=Plant+Physiology&rft.aulast=Nelson&rft.aufirst=Clarence+H.&rft.au=Nelson%2C%26%2332%3BClarence+H.&rft.date=1+April+1944&rft.volume=19&rft.issue=2&rft.pages=294%E2%80%93309&rft_id=info:doi\/10.1104%2Fpp.19.2.294&rft.issn=0032-0889&rft_id=info:pmc\/PMC438156&rft_id=info:pmid\/16653915&rft_id=https%3A%2F%2Facademic.oup.com%2Fplphys%2Farticle%2F19%2F2%2F294-309%2F6072537&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-38\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-38\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Coffman, C. B.; Gentner, W. A. (1 September 1977). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.2134\/agronj1977.00021962006900050026x\" target=\"_blank\">\"Responses of Greenhouse\u2010grown Cannabis sativa L. to Nitrogen, Phosphorus, and Potassium 1\"<\/a> (in en). <i>Agronomy Journal<\/i> <b>69<\/b> (5): 832\u2013836. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2134%2Fagronj1977.00021962006900050026x\" target=\"_blank\">10.2134\/agronj1977.00021962006900050026x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0002-1962\" target=\"_blank\">0002-1962<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.2134\/agronj1977.00021962006900050026x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.2134\/agronj1977.00021962006900050026x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Responses+of+Greenhouse%E2%80%90grown+Cannabis+sativa+L.+to+Nitrogen%2C+Phosphorus%2C+and+Potassium+1&rft.jtitle=Agronomy+Journal&rft.aulast=Coffman&rft.aufirst=C.+B.&rft.au=Coffman%2C%26%2332%3BC.+B.&rft.au=Gentner%2C%26%2332%3BW.+A.&rft.date=1+September+1977&rft.volume=69&rft.issue=5&rft.pages=832%E2%80%93836&rft_id=info:doi\/10.2134%2Fagronj1977.00021962006900050026x&rft.issn=0002-1962&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.2134%2Fagronj1977.00021962006900050026x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-39\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-39\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">van der Werf, H. M. G.; van den Berg, W. (1 September 1995). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/BF00328684\" target=\"_blank\">\"Nitrogen fertilization and sex expression affect size variability of fibre hemp (Cannabis sativa L.)\"<\/a> (in en). <i>Oecologia<\/i> <b>103<\/b> (4): 462\u2013470. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2FBF00328684\" target=\"_blank\">10.1007\/BF00328684<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0029-8549\" target=\"_blank\">0029-8549<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/BF00328684\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/BF00328684<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nitrogen+fertilization+and+sex+expression+affect+size+variability+of+fibre+hemp+%28Cannabis+sativa+L.%29&rft.jtitle=Oecologia&rft.aulast=van+der+Werf&rft.aufirst=H.+M.+G.&rft.au=van+der+Werf%2C%26%2332%3BH.+M.+G.&rft.au=van+den+Berg%2C%26%2332%3BW.&rft.date=1+September+1995&rft.volume=103&rft.issue=4&rft.pages=462%E2%80%93470&rft_id=info:doi\/10.1007%2FBF00328684&rft.issn=0029-8549&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2FBF00328684&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-40\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-40\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Werf, H M G Van Der; Brouwer, K.; Wijlhuizen, M.; Withagen, J C M. (1 June 1995). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1744-7348.1995.tb05389.x\" target=\"_blank\">\"The effect of temperature on leaf appearance and canopy establishment in fibre hemp (Cannabis sativa L.)\"<\/a> (in en). <i>Annals of Applied Biology<\/i> <b>126<\/b> (3): 551\u2013561. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fj.1744-7348.1995.tb05389.x\" target=\"_blank\">10.1111\/j.1744-7348.1995.tb05389.x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0003-4746\" target=\"_blank\">0003-4746<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1744-7348.1995.tb05389.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1744-7348.1995.tb05389.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+effect+of+temperature+on+leaf+appearance+and+canopy+establishment+in+fibre+hemp+%28Cannabis+sativa+L.%29&rft.jtitle=Annals+of+Applied+Biology&rft.aulast=Werf&rft.aufirst=H+M+G+Van+Der&rft.au=Werf%2C%26%2332%3BH+M+G+Van+Der&rft.au=Brouwer%2C%26%2332%3BK.&rft.au=Wijlhuizen%2C%26%2332%3BM.&rft.au=Withagen%2C%26%2332%3BJ+C+M.&rft.date=1+June+1995&rft.volume=126&rft.issue=3&rft.pages=551%E2%80%93561&rft_id=info:doi\/10.1111%2Fj.1744-7348.1995.tb05389.x&rft.issn=0003-4746&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1744-7348.1995.tb05389.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-41\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-41\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Amaducci, S.; Errani, M.; Venturi, G. (2002). \"Response of hemp to plant population and nitrogen fertilisation\". <i>Italian Journal of Agronomy<\/i> <b>6<\/b> (2): 103\u201311.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Response+of+hemp+to+plant+population+and+nitrogen+fertilisation&rft.jtitle=Italian+Journal+of+Agronomy&rft.aulast=Amaducci%2C+S.%3B+Errani%2C+M.%3B+Venturi%2C+G.&rft.au=Amaducci%2C+S.%3B+Errani%2C+M.%3B+Venturi%2C+G.&rft.date=2002&rft.volume=6&rft.issue=2&rft.pages=103%E2%80%9311&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-42\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-42\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Aubin, Marie\u2010Pier; Seguin, Philippe; Vanasse, Anne; Tremblay, Ga\u00ebtan F.; Mustafa, Arif F.; Charron, Jean\u2010Benoit (1 December 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.2134\/cftm2015.0159\" target=\"_blank\">\"Industrial Hemp Response to Nitrogen, Phosphorus, and Potassium Fertilization\"<\/a> (in en). <i>Crop, Forage & Turfgrass Management<\/i> <b>1<\/b> (1): 1\u201310. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2134%2Fcftm2015.0159\" target=\"_blank\">10.2134\/cftm2015.0159<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2374-3832\" target=\"_blank\">2374-3832<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.2134\/cftm2015.0159\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.2134\/cftm2015.0159<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Industrial+Hemp+Response+to+Nitrogen%2C+Phosphorus%2C+and+Potassium+Fertilization&rft.jtitle=Crop%2C+Forage+%26+Turfgrass+Management&rft.aulast=Aubin&rft.aufirst=Marie%E2%80%90Pier&rft.au=Aubin%2C%26%2332%3BMarie%E2%80%90Pier&rft.au=Seguin%2C%26%2332%3BPhilippe&rft.au=Vanasse%2C%26%2332%3BAnne&rft.au=Tremblay%2C%26%2332%3BGa%C3%ABtan+F.&rft.au=Mustafa%2C%26%2332%3BArif+F.&rft.au=Charron%2C%26%2332%3BJean%E2%80%90Benoit&rft.date=1+December+2015&rft.volume=1&rft.issue=1&rft.pages=1%E2%80%9310&rft_id=info:doi\/10.2134%2Fcftm2015.0159&rft.issn=2374-3832&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2Fabs%2F10.2134%2Fcftm2015.0159&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:24-43\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:24_43-0\">43.0<\/a><\/sup> <sup><a href=\"#cite_ref-:24_43-1\">43.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Finnan, John; Burke, Brendan (1 November 2013). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12045\" target=\"_blank\">\"Nitrogen fertilization to optimize the greenhouse gas balance of hemp crops grown for biomass\"<\/a> (in en). <i>GCB Bioenergy<\/i> <b>5<\/b> (6): 701\u2013712. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fgcbb.12045\" target=\"_blank\">10.1111\/gcbb.12045<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12045\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12045<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nitrogen+fertilization+to+optimize+the+greenhouse+gas+balance+of+hemp+crops+grown+for+biomass&rft.jtitle=GCB+Bioenergy&rft.aulast=Finnan&rft.aufirst=John&rft.au=Finnan%2C%26%2332%3BJohn&rft.au=Burke%2C%26%2332%3BBrendan&rft.date=1+November+2013&rft.volume=5&rft.issue=6&rft.pages=701%E2%80%93712&rft_id=info:doi\/10.1111%2Fgcbb.12045&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fgcbb.12045&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-44\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-44\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Papastylianou, Panayiota; Kakabouki, Ioanna; Travlos, Ilias (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.notulaebotanicae.ro\/index.php\/nbha\/article\/view\/10862\" target=\"_blank\">\"Effect of Nitrogen Fertilization on Growth and Yield of Industrial Hemp (Cannabis sativa L.)\"<\/a>. <i>Notulae Botanicae Horti Agrobotanici Cluj-Napoca<\/i> <b>46<\/b> (1): 197\u2013201. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.15835%2Fnbha46110862\" target=\"_blank\">10.15835\/nbha46110862<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1842-4309\" target=\"_blank\">1842-4309<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.notulaebotanicae.ro\/index.php\/nbha\/article\/view\/10862\" target=\"_blank\">https:\/\/www.notulaebotanicae.ro\/index.php\/nbha\/article\/view\/10862<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effect+of+Nitrogen+Fertilization+on+Growth+and+Yield+of+Industrial+Hemp+%28Cannabis+sativa+L.%29&rft.jtitle=Notulae+Botanicae+Horti+Agrobotanici+Cluj-Napoca&rft.aulast=Papastylianou&rft.aufirst=Panayiota&rft.au=Papastylianou%2C%26%2332%3BPanayiota&rft.au=Kakabouki%2C%26%2332%3BIoanna&rft.au=Travlos%2C%26%2332%3BIlias&rft.date=1+January+2018&rft.volume=46&rft.issue=1&rft.pages=197%E2%80%93201&rft_id=info:doi\/10.15835%2Fnbha46110862&rft.issn=1842-4309&rft_id=https%3A%2F%2Fwww.notulaebotanicae.ro%2Findex.php%2Fnbha%2Farticle%2Fview%2F10862&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-45\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-45\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tang, Kailei; Struik, Paul C.; Amaducci, Stefano; Stomph, Tjeerd-Jan; Yin, Xinyou (1 October 2017). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12451\" target=\"_blank\">\"Hemp ( Cannabis sativa L.) leaf photosynthesis in relation to nitrogen content and temperature: implications for hemp as a bio-economically sustainable crop\"<\/a> (in en). <i>GCB Bioenergy<\/i> <b>9<\/b> (10): 1573\u20131587. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fgcbb.12451\" target=\"_blank\">10.1111\/gcbb.12451<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12451\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12451<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hemp+%28+Cannabis+sativa+L.%29+leaf+photosynthesis+in+relation+to+nitrogen+content+and+temperature%3A+implications+for+hemp+as+a+bio-economically+sustainable+crop&rft.jtitle=GCB+Bioenergy&rft.aulast=Tang&rft.aufirst=Kailei&rft.au=Tang%2C%26%2332%3BKailei&rft.au=Struik%2C%26%2332%3BPaul+C.&rft.au=Amaducci%2C%26%2332%3BStefano&rft.au=Stomph%2C%26%2332%3BTjeerd-Jan&rft.au=Yin%2C%26%2332%3BXinyou&rft.date=1+October+2017&rft.volume=9&rft.issue=10&rft.pages=1573%E2%80%931587&rft_id=info:doi\/10.1111%2Fgcbb.12451&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fgcbb.12451&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-46\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-46\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Tang, Kailei; Fracasso, Alessandra; Struik, Paul C.; Yin, Xinyou; Amaducci, Stefano (16 July 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2018.00951\/full\" target=\"_blank\">\"Water- and Nitrogen-Use Efficiencies of Hemp (Cannabis sativa L.) Based on Whole-Canopy Measurements and Modeling\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>9<\/b>: 951. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2018.00951\" target=\"_blank\">10.3389\/fpls.2018.00951<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6055055\" target=\"_blank\">PMC6055055<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30061905\" target=\"_blank\">30061905<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2018.00951\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2018.00951\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Water-+and+Nitrogen-Use+Efficiencies+of+Hemp+%28Cannabis+sativa+L.%29+Based+on+Whole-Canopy+Measurements+and+Modeling&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Tang&rft.aufirst=Kailei&rft.au=Tang%2C%26%2332%3BKailei&rft.au=Fracasso%2C%26%2332%3BAlessandra&rft.au=Struik%2C%26%2332%3BPaul+C.&rft.au=Yin%2C%26%2332%3BXinyou&rft.au=Amaducci%2C%26%2332%3BStefano&rft.date=16+July+2018&rft.volume=9&rft.pages=951&rft_id=info:doi\/10.3389%2Ffpls.2018.00951&rft.issn=1664-462X&rft_id=info:pmc\/PMC6055055&rft_id=info:pmid\/30061905&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2018.00951%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-47\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-47\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">B\u00f3csa, I..; M\u00e1th\u00e9, P.; Hangyel, L. (1997). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.internationalhempassociation.org\/jiha\/v4n2.html\" target=\"_blank\">\"Effects of nitrogen on tetrahydrocannabinol (THC) content\"<\/a>. <i>Journal of the International Hemp Association<\/i> <b>4<\/b> (2): 80\u201381<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.internationalhempassociation.org\/jiha\/v4n2.html\" target=\"_blank\">http:\/\/www.internationalhempassociation.org\/jiha\/v4n2.html<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effects+of+nitrogen+on+tetrahydrocannabinol+%28THC%29+content&rft.jtitle=Journal+of+the+International+Hemp+Association&rft.aulast=B%C3%B3csa%2C+I..%3B+M%C3%A1th%C3%A9%2C+P.%3B+Hangyel%2C+L.&rft.au=B%C3%B3csa%2C+I..%3B+M%C3%A1th%C3%A9%2C+P.%3B+Hangyel%2C+L.&rft.date=1997&rft.volume=4&rft.issue=2&rft.pages=80%E2%80%9381&rft_id=http%3A%2F%2Fwww.internationalhempassociation.org%2Fjiha%2Fv4n2.html&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-48\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-48\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chandra, Suman; Lata, Hemant; Khan, Ikhlas A.; Elsohly, Mahmoud A. (1 October 2008). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s12298-008-0027-x\" target=\"_blank\">\"Photosynthetic response of Cannabis sativa L. to variations in photosynthetic photon flux densities, temperature and CO2 conditions\"<\/a> (in en). <i>Physiology and Molecular Biology of Plants<\/i> <b>14<\/b> (4): 299\u2013306. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs12298-008-0027-x\" target=\"_blank\">10.1007\/s12298-008-0027-x<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0971-5894\" target=\"_blank\">0971-5894<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3550641\" target=\"_blank\">PMC3550641<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23572895\" target=\"_blank\">23572895<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s12298-008-0027-x\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s12298-008-0027-x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Photosynthetic+response+of+Cannabis+sativa+L.+to+variations+in+photosynthetic+photon+flux+densities%2C+temperature+and+CO2+conditions&rft.jtitle=Physiology+and+Molecular+Biology+of+Plants&rft.aulast=Chandra&rft.aufirst=Suman&rft.au=Chandra%2C%26%2332%3BSuman&rft.au=Lata%2C%26%2332%3BHemant&rft.au=Khan%2C%26%2332%3BIkhlas+A.&rft.au=Elsohly%2C%26%2332%3BMahmoud+A.&rft.date=1+October+2008&rft.volume=14&rft.issue=4&rft.pages=299%E2%80%93306&rft_id=info:doi\/10.1007%2Fs12298-008-0027-x&rft.issn=0971-5894&rft_id=info:pmc\/PMC3550641&rft_id=info:pmid\/23572895&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs12298-008-0027-x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-49\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-49\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Chandra, Suman; Lata, Hemant; Khan, Ikhlas A.; ElSohly, Mahmoud A. (1 July 2011). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s12298-011-0066-6\" target=\"_blank\">\"Photosynthetic response of Cannabis sativa L., an important medicinal plant, to elevated levels of CO2\"<\/a> (in en). <i>Physiology and Molecular Biology of Plants<\/i> <b>17<\/b> (3): 291\u2013295. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs12298-011-0066-6\" target=\"_blank\">10.1007\/s12298-011-0066-6<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0971-5894\" target=\"_blank\">0971-5894<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3550578\" target=\"_blank\">PMC3550578<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23573021\" target=\"_blank\">23573021<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s12298-011-0066-6\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s12298-011-0066-6<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Photosynthetic+response+of+Cannabis+sativa+L.%2C+an+important+medicinal+plant%2C+to+elevated+levels+of+CO2&rft.jtitle=Physiology+and+Molecular+Biology+of+Plants&rft.aulast=Chandra&rft.aufirst=Suman&rft.au=Chandra%2C%26%2332%3BSuman&rft.au=Lata%2C%26%2332%3BHemant&rft.au=Khan%2C%26%2332%3BIkhlas+A.&rft.au=ElSohly%2C%26%2332%3BMahmoud+A.&rft.date=1+July+2011&rft.volume=17&rft.issue=3&rft.pages=291%E2%80%93295&rft_id=info:doi\/10.1007%2Fs12298-011-0066-6&rft.issn=0971-5894&rft_id=info:pmc\/PMC3550578&rft_id=info:pmid\/23573021&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs12298-011-0066-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:10-50\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:10_50-0\">50.0<\/a><\/sup> <sup><a href=\"#cite_ref-:10_50-1\">50.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Saloner, Avia; Sacks, Mollie M.; Bernstein, Nirit (18 November 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.01369\/full\" target=\"_blank\">\"Response of Medical Cannabis (Cannabis sativa L.) Genotypes to K Supply Under Long Photoperiod\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>10<\/b>: 1369. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2019.01369\" target=\"_blank\">10.3389\/fpls.2019.01369<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6876614\" target=\"_blank\">PMC6876614<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31803198\" target=\"_blank\">31803198<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.01369\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.01369\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Response+of+Medical+Cannabis+%28Cannabis+sativa+L.%29+Genotypes+to+K+Supply+Under+Long+Photoperiod&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Saloner&rft.aufirst=Avia&rft.au=Saloner%2C%26%2332%3BAvia&rft.au=Sacks%2C%26%2332%3BMollie+M.&rft.au=Bernstein%2C%26%2332%3BNirit&rft.date=18+November+2019&rft.volume=10&rft.pages=1369&rft_id=info:doi\/10.3389%2Ffpls.2019.01369&rft.issn=1664-462X&rft_id=info:pmc\/PMC6876614&rft_id=info:pmid\/31803198&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2019.01369%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:11-51\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:11_51-0\">51.0<\/a><\/sup> <sup><a href=\"#cite_ref-:11_51-1\">51.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shiponi, Sivan; Bernstein, Nirit (15 July 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2021.657323\/full\" target=\"_blank\">\"The Highs and Lows of P Supply in Medical Cannabis: Effects on Cannabinoids, the Ionome, and Morpho-Physiology\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>12<\/b>: 657323. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2021.657323\" target=\"_blank\">10.3389\/fpls.2021.657323<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8320666\" target=\"_blank\">PMC8320666<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34335641\" target=\"_blank\">34335641<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2021.657323\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2021.657323\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Highs+and+Lows+of+P+Supply+in+Medical+Cannabis%3A+Effects+on+Cannabinoids%2C+the+Ionome%2C+and+Morpho-Physiology&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Shiponi&rft.aufirst=Sivan&rft.au=Shiponi%2C%26%2332%3BSivan&rft.au=Bernstein%2C%26%2332%3BNirit&rft.date=15+July+2021&rft.volume=12&rft.pages=657323&rft_id=info:doi\/10.3389%2Ffpls.2021.657323&rft.issn=1664-462X&rft_id=info:pmc\/PMC8320666&rft_id=info:pmid\/34335641&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticles%2F10.3389%2Ffpls.2021.657323%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:12-52\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:12_52-0\">52.0<\/a><\/sup> <sup><a href=\"#cite_ref-:12_52-1\">52.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Saloner, Avia; Bernstein, Nirit (17 November 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2020.572293\/full\" target=\"_blank\">\"Response of Medical Cannabis (Cannabis sativa L.) to Nitrogen Supply Under Long Photoperiod\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>11<\/b>: 572293. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2020.572293\" target=\"_blank\">10.3389\/fpls.2020.572293<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7704455\" target=\"_blank\">PMC7704455<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33312185\" target=\"_blank\">33312185<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2020.572293\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2020.572293\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Response+of+Medical+Cannabis+%28Cannabis+sativa+L.%29+to+Nitrogen+Supply+Under+Long+Photoperiod&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Saloner&rft.aufirst=Avia&rft.au=Saloner%2C%26%2332%3BAvia&rft.au=Bernstein%2C%26%2332%3BNirit&rft.date=17+November+2020&rft.volume=11&rft.pages=572293&rft_id=info:doi\/10.3389%2Ffpls.2020.572293&rft.issn=1664-462X&rft_id=info:pmc\/PMC7704455&rft_id=info:pmid\/33312185&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticles%2F10.3389%2Ffpls.2020.572293%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:13-53\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:13_53-0\">53.0<\/a><\/sup> <sup><a href=\"#cite_ref-:13_53-1\">53.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Bernstein, Nirit; Gorelick, Jonathan; Zerahia, Roei; Koch, Sraya (17 June 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00736\/full\" target=\"_blank\">\"Impact of N, P, K, and Humic Acid Supplementation on the Chemical Profile of Medical Cannabis (Cannabis sativa L)\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>10<\/b>: 736. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2019.00736\" target=\"_blank\">10.3389\/fpls.2019.00736<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6589925\" target=\"_blank\">PMC6589925<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31263470\" target=\"_blank\">31263470<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00736\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/article\/10.3389\/fpls.2019.00736\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Impact+of+N%2C+P%2C+K%2C+and+Humic+Acid+Supplementation+on+the+Chemical+Profile+of+Medical+Cannabis+%28Cannabis+sativa+L%29&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Bernstein&rft.aufirst=Nirit&rft.au=Bernstein%2C%26%2332%3BNirit&rft.au=Gorelick%2C%26%2332%3BJonathan&rft.au=Zerahia%2C%26%2332%3BRoei&rft.au=Koch%2C%26%2332%3BSraya&rft.date=17+June+2019&rft.volume=10&rft.pages=736&rft_id=info:doi\/10.3389%2Ffpls.2019.00736&rft.issn=1664-462X&rft_id=info:pmc\/PMC6589925&rft_id=info:pmid\/31263470&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticle%2F10.3389%2Ffpls.2019.00736%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:15-54\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:15_54-0\">54.0<\/a><\/sup> <sup><a href=\"#cite_ref-:15_54-1\">54.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Citterio, Sandra; Santagostino, Angela; Fumagalli, Pietro; Prato, Nadia; Ranalli, Paolo; Sgorbati, Sergio (2003). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1023\/A:1026113905129\" target=\"_blank\">\"Heavy metal tolerance and accumulation of Cd, Cr and Ni by Cannabis sativa L.\"<\/a>. <i>Plant and Soil<\/i> <b>256<\/b> (2): 243\u2013252. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1023%2FA%3A1026113905129\" target=\"_blank\">10.1023\/A:1026113905129<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1023\/A:1026113905129\" target=\"_blank\">http:\/\/link.springer.com\/10.1023\/A:1026113905129<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Heavy+metal+tolerance+and+accumulation+of+Cd%2C+Cr+and+Ni+by+Cannabis+sativa+L.&rft.jtitle=Plant+and+Soil&rft.aulast=Citterio&rft.aufirst=Sandra&rft.au=Citterio%2C%26%2332%3BSandra&rft.au=Santagostino%2C%26%2332%3BAngela&rft.au=Fumagalli%2C%26%2332%3BPietro&rft.au=Prato%2C%26%2332%3BNadia&rft.au=Ranalli%2C%26%2332%3BPaolo&rft.au=Sgorbati%2C%26%2332%3BSergio&rft.date=2003&rft.volume=256&rft.issue=2&rft.pages=243%E2%80%93252&rft_id=info:doi\/10.1023%2FA%3A1026113905129&rft_id=http%3A%2F%2Flink.springer.com%2F10.1023%2FA%3A1026113905129&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:16-55\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:16_55-0\">55.0<\/a><\/sup> <sup><a href=\"#cite_ref-:16_55-1\">55.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Ferrarini, Andrea; Fracasso, Alessandra; Spini, Giulia; Fornasier, Flavio; Taskin, Eren; Fontanella, Maria Chiara; Beone, Gian Maria; Amaducci, Stefano <i>et al.<\/i> (20 April 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.645893\/full\" target=\"_blank\">\"Bioaugmented Phytoremediation of Metal-Contaminated Soils and Sediments by Hemp and Giant Reed\"<\/a>. <i>Frontiers in Microbiology<\/i> <b>12<\/b>: 645893. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffmicb.2021.645893\" target=\"_blank\">10.3389\/fmicb.2021.645893<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-302X\" target=\"_blank\">1664-302X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8096354\" target=\"_blank\">PMC8096354<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33959108\" target=\"_blank\">33959108<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.645893\/full\" target=\"_blank\">https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.645893\/full<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Bioaugmented+Phytoremediation+of+Metal-Contaminated+Soils+and+Sediments+by+Hemp+and+Giant+Reed&rft.jtitle=Frontiers+in+Microbiology&rft.aulast=Ferrarini&rft.aufirst=Andrea&rft.au=Ferrarini%2C%26%2332%3BAndrea&rft.au=Fracasso%2C%26%2332%3BAlessandra&rft.au=Spini%2C%26%2332%3BGiulia&rft.au=Fornasier%2C%26%2332%3BFlavio&rft.au=Taskin%2C%26%2332%3BEren&rft.au=Fontanella%2C%26%2332%3BMaria+Chiara&rft.au=Beone%2C%26%2332%3BGian+Maria&rft.au=Amaducci%2C%26%2332%3BStefano&rft.au=Puglisi%2C%26%2332%3BEdoardo&rft.date=20+April+2021&rft.volume=12&rft.pages=645893&rft_id=info:doi\/10.3389%2Ffmicb.2021.645893&rft.issn=1664-302X&rft_id=info:pmc\/PMC8096354&rft_id=info:pmid\/33959108&rft_id=https%3A%2F%2Fwww.frontiersin.org%2Farticles%2F10.3389%2Ffmicb.2021.645893%2Ffull&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:17-56\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:17_56-0\">56.0<\/a><\/sup> <sup><a href=\"#cite_ref-:17_56-1\">56.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">van Ginneken, L.; Meers, E.; Guisson, R. et al. (2007). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/16486897.2007.9636935\" target=\"_blank\">\"Phytoremediation for heavy metal\u2010contaminated soils combined with bioenergy production\"<\/a>. <i>Journal of Environmental Engineering and Landscape Management<\/i> <b>15<\/b> (4): 227\u2013236. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F16486897.2007.9636935\" target=\"_blank\">10.1080\/16486897.2007.9636935<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/16486897.2007.9636935\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/16486897.2007.9636935<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Phytoremediation+for+heavy+metal%E2%80%90contaminated+soils+combined+with+bioenergy+production&rft.jtitle=Journal+of+Environmental+Engineering+and+Landscape+Management&rft.aulast=van+Ginneken%2C+L.%3B+Meers%2C+E.%3B+Guisson%2C+R.+et+al.&rft.au=van+Ginneken%2C+L.%3B+Meers%2C+E.%3B+Guisson%2C+R.+et+al.&rft.date=2007&rft.volume=15&rft.issue=4&rft.pages=227%E2%80%93236&rft_id=info:doi\/10.1080%2F16486897.2007.9636935&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Fabs%2F10.1080%2F16486897.2007.9636935&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:18-57\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:18_57-0\">57.0<\/a><\/sup> <sup><a href=\"#cite_ref-:18_57-1\">57.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Poursafa, Parinaz; Amin, MohammadMehdi; Hoseini, ParisaSeyed; Moattar, Faramarz; Rezaei, AmirHossein (2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ijehe.org\/text.asp?2012\/1\/1\/17\/96004\" target=\"_blank\">\"Ability of phytoremediation for absorption of strontium and cesium from soils using Cannabis sativa\"<\/a> (in en). <i>International Journal of Environmental Health Engineering<\/i> <b>1<\/b> (1): 17. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4103%2F2277-9183.96004\" target=\"_blank\">10.4103\/2277-9183.96004<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2277-9183\" target=\"_blank\">2277-9183<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.ijehe.org\/text.asp?2012\/1\/1\/17\/96004\" target=\"_blank\">http:\/\/www.ijehe.org\/text.asp?2012\/1\/1\/17\/96004<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Ability+of+phytoremediation+for+absorption+of+strontium+and+cesium+from+soils+using+Cannabis+sativa&rft.jtitle=International+Journal+of+Environmental+Health+Engineering&rft.aulast=Poursafa&rft.aufirst=Parinaz&rft.au=Poursafa%2C%26%2332%3BParinaz&rft.au=Amin%2C%26%2332%3BMohammadMehdi&rft.au=Hoseini%2C%26%2332%3BParisaSeyed&rft.au=Moattar%2C%26%2332%3BFaramarz&rft.au=Rezaei%2C%26%2332%3BAmirHossein&rft.date=2012&rft.volume=1&rft.issue=1&rft.pages=17&rft_id=info:doi\/10.4103%2F2277-9183.96004&rft.issn=2277-9183&rft_id=http%3A%2F%2Fwww.ijehe.org%2Ftext.asp%3F2012%2F1%2F1%2F17%2F96004&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:19-58\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:19_58-0\">58.0<\/a><\/sup> <sup><a href=\"#cite_ref-:19_58-1\">58.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Sakizadeh, Mohamad; Sharafabadi, Fatemeh Mehrabi; Shayegan, Eshagh; Ghorbani, Hadi (1 October 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/iopscience.iop.org\/article\/10.1088\/1755-1315\/44\/5\/052027\" target=\"_blank\">\"Concentrations and Soil-To-Plant Transfer Factor of Selenium in Soil and Plant Species from an Arid Area\"<\/a>. <i>IOP Conference Series: Earth and Environmental Science<\/i> <b>44<\/b>: 052027. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1088%2F1755-1315%2F44%2F5%2F052027\" target=\"_blank\">10.1088\/1755-1315\/44\/5\/052027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1755-1307\" target=\"_blank\">1755-1307<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/iopscience.iop.org\/article\/10.1088\/1755-1315\/44\/5\/052027\" target=\"_blank\">https:\/\/iopscience.iop.org\/article\/10.1088\/1755-1315\/44\/5\/052027<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Concentrations+and+Soil-To-Plant+Transfer+Factor+of+Selenium+in+Soil+and+Plant+Species+from+an+Arid+Area&rft.jtitle=IOP+Conference+Series%3A+Earth+and+Environmental+Science&rft.aulast=Sakizadeh&rft.aufirst=Mohamad&rft.au=Sakizadeh%2C%26%2332%3BMohamad&rft.au=Sharafabadi%2C%26%2332%3BFatemeh+Mehrabi&rft.au=Shayegan%2C%26%2332%3BEshagh&rft.au=Ghorbani%2C%26%2332%3BHadi&rft.date=1+October+2016&rft.volume=44&rft.pages=052027&rft_id=info:doi\/10.1088%2F1755-1315%2F44%2F5%2F052027&rft.issn=1755-1307&rft_id=https%3A%2F%2Fiopscience.iop.org%2Farticle%2F10.1088%2F1755-1315%2F44%2F5%2F052027&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:20-59\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:20_59-0\">59.0<\/a><\/sup> <sup><a href=\"#cite_ref-:20_59-1\">59.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Shi, Gangrong; Cai, Qingsheng (7 May 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/01904161003728669\" target=\"_blank\">\"ZINC TOLERANCE AND ACCUMULATION IN EIGHT OIL CROPS\"<\/a> (in en). <i>Journal of Plant Nutrition<\/i> <b>33<\/b> (7): 982\u2013997. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F01904161003728669\" target=\"_blank\">10.1080\/01904161003728669<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0190-4167\" target=\"_blank\">0190-4167<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/01904161003728669\" target=\"_blank\">http:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/01904161003728669<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ZINC+TOLERANCE+AND+ACCUMULATION+IN+EIGHT+OIL+CROPS&rft.jtitle=Journal+of+Plant+Nutrition&rft.aulast=Shi&rft.aufirst=Gangrong&rft.au=Shi%2C%26%2332%3BGangrong&rft.au=Cai%2C%26%2332%3BQingsheng&rft.date=7+May+2010&rft.volume=33&rft.issue=7&rft.pages=982%E2%80%93997&rft_id=info:doi\/10.1080%2F01904161003728669&rft.issn=0190-4167&rft_id=http%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Fabs%2F10.1080%2F01904161003728669&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:21-60\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:21_60-0\">60.0<\/a><\/sup> <sup><a href=\"#cite_ref-:21_60-1\">60.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rheay, Hanah T.; Omondi, Emmanuel C.; Brewer, Catherine E. (1 April 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12782\" target=\"_blank\">\"Potential of hemp ( Cannabis sativa L.) for paired phytoremediation and bioenergy production\"<\/a> (in en). <i>GCB Bioenergy<\/i> <b>13<\/b> (4): 525\u2013536. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fgcbb.12782\" target=\"_blank\">10.1111\/gcbb.12782<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1757-1693\" target=\"_blank\">1757-1693<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12782\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gcbb.12782<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Potential+of+hemp+%28+Cannabis+sativa+L.%29+for+paired+phytoremediation+and+bioenergy+production&rft.jtitle=GCB+Bioenergy&rft.aulast=Rheay&rft.aufirst=Hanah+T.&rft.au=Rheay%2C%26%2332%3BHanah+T.&rft.au=Omondi%2C%26%2332%3BEmmanuel+C.&rft.au=Brewer%2C%26%2332%3BCatherine+E.&rft.date=1+April+2021&rft.volume=13&rft.issue=4&rft.pages=525%E2%80%93536&rft_id=info:doi\/10.1111%2Fgcbb.12782&rft.issn=1757-1693&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fgcbb.12782&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:22-61\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:22_61-0\">61.0<\/a><\/sup> <sup><a href=\"#cite_ref-:22_61-1\">61.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vandenhove, H.; Van Hees, M. (1 January 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0265931X05000160\" target=\"_blank\">\"Fibre crops as alternative land use for radioactively contaminated arable land\"<\/a> (in en). <i>Journal of Environmental Radioactivity<\/i> <b>81<\/b> (2-3): 131\u2013141. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jenvrad.2005.01.002\" target=\"_blank\">10.1016\/j.jenvrad.2005.01.002<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0265931X05000160\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0265931X05000160<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Fibre+crops+as+alternative+land+use+for+radioactively+contaminated+arable+land&rft.jtitle=Journal+of+Environmental+Radioactivity&rft.aulast=Vandenhove&rft.aufirst=H.&rft.au=Vandenhove%2C%26%2332%3BH.&rft.au=Van+Hees%2C%26%2332%3BM.&rft.date=1+January+2005&rft.volume=81&rft.issue=2-3&rft.pages=131%E2%80%93141&rft_id=info:doi\/10.1016%2Fj.jenvrad.2005.01.002&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0265931X05000160&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-62\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-62\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Fidelia Cascini; Carola Aiello; GianLuca Di Tanna (3 April 2012). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1874-4737&volume=5&issue=1&spage=32\" target=\"_blank\">\"Increasing Delta-9-Tetrahydrocannabinol (?-9-THC) Content in Herbal Cannabis Over Time: Systematic Review and Meta-Analysis\"<\/a> (in en). <i>Current Drug Abuse Reviews<\/i> <b>5<\/b> (1): 32\u201340. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2174%2F1874473711205010032\" target=\"_blank\">10.2174\/1874473711205010032<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1874-4737&volume=5&issue=1&spage=32\" target=\"_blank\">http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1874-4737&volume=5&issue=1&spage=32<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Increasing+Delta-9-Tetrahydrocannabinol+%28%3F-9-THC%29+Content+in+Herbal+Cannabis+Over+Time%3A+Systematic+Review+and+Meta-Analysis&rft.jtitle=Current+Drug+Abuse+Reviews&rft.aulast=Fidelia+Cascini&rft.au=Fidelia+Cascini&rft.au=Carola+Aiello&rft.au=GianLuca+Di+Tanna&rft.date=3+April+2012&rft.volume=5&rft.issue=1&rft.pages=32%E2%80%9340&rft_id=info:doi\/10.2174%2F1874473711205010032&rft_id=http%3A%2F%2Fwww.eurekaselect.com%2Fopenurl%2Fcontent.php%3Fgenre%3Darticle%26issn%3D1874-4737%26volume%3D5%26issue%3D1%26spage%3D32&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-63\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-63\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFHartselEadesHickoryMakriyannis2016\">Hartsel, Joshua A.; Eades, Joshua; Hickory, Brian; Makriyannis, Alexandros (2016), <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B978012802147700053X\" target=\"_blank\">\"Cannabis sativa and Hemp\"<\/a> (in en), <i>Nutraceuticals<\/i> (Elsevier): 735\u2013754, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fb978-0-12-802147-7.00053-x\" target=\"_blank\">10.1016\/b978-0-12-802147-7.00053-x<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-12-802147-7<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B978012802147700053X\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B978012802147700053X<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-04<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis+sativa+and+Hemp&rft.jtitle=Nutraceuticals&rft.aulast=Hartsel&rft.aufirst=Joshua+A.&rft.au=Hartsel%2C%26%2332%3BJoshua+A.&rft.au=Eades%2C%26%2332%3BJoshua&rft.au=Hickory%2C%26%2332%3BBrian&rft.au=Makriyannis%2C%26%2332%3BAlexandros&rft.date=2016&rft.pages=735%E2%80%93754&rft.pub=Elsevier&rft_id=info:doi\/10.1016%2Fb978-0-12-802147-7.00053-x&rft.isbn=978-0-12-802147-7&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FB978012802147700053X&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-64\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-64\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mandolino, G.; Carboni, A. 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Tinker, Nicholas A.. ed. <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/dx.plos.org\/10.1371\/journal.pone.0133292\" target=\"_blank\">\"The Genetic Structure of Marijuana and Hemp\"<\/a> (in en). <i>PLOS ONE<\/i> <b>10<\/b> (8): e0133292. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1371%2Fjournal.pone.0133292\" target=\"_blank\">10.1371\/journal.pone.0133292<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1932-6203\" target=\"_blank\">1932-6203<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4550350\" target=\"_blank\">PMC4550350<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26308334\" target=\"_blank\">26308334<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/dx.plos.org\/10.1371\/journal.pone.0133292\" target=\"_blank\">https:\/\/dx.plos.org\/10.1371\/journal.pone.0133292<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Genetic+Structure+of+Marijuana+and+Hemp&rft.jtitle=PLOS+ONE&rft.aulast=Sawler&rft.aufirst=Jason&rft.au=Sawler%2C%26%2332%3BJason&rft.au=Stout%2C%26%2332%3BJake+M.&rft.au=Gardner%2C%26%2332%3BKyle+M.&rft.au=Hudson%2C%26%2332%3BDarryl&rft.au=Vidmar%2C%26%2332%3BJohn&rft.au=Butler%2C%26%2332%3BLaura&rft.au=Page%2C%26%2332%3BJonathan+E.&rft.au=Myles%2C%26%2332%3BSean&rft.date=26+August+2015&rft.volume=10&rft.issue=8&rft.pages=e0133292&rft_id=info:doi\/10.1371%2Fjournal.pone.0133292&rft.issn=1932-6203&rft_id=info:pmc\/PMC4550350&rft_id=info:pmid\/26308334&rft_id=https%3A%2F%2Fdx.plos.org%2F10.1371%2Fjournal.pone.0133292&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-66\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-66\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.law.cornell.edu\/uscode\/text\/21\/chapter-13\" target=\"_blank\">\"21 U.S. Code Chapter 13 - DRUG ABUSE PREVENTION AND CONTROL\"<\/a>. <i>Legal Information Institute<\/i>. Cornell Law School. 2021<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.law.cornell.edu\/uscode\/text\/21\/chapter-13\" target=\"_blank\">https:\/\/www.law.cornell.edu\/uscode\/text\/21\/chapter-13<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=21+U.S.+Code+Chapter+13+-+DRUG+ABUSE+PREVENTION+AND+CONTROL&rft.atitle=Legal+Information+Institute&rft.date=2021&rft.pub=Cornell+Law+School&rft_id=https%3A%2F%2Fwww.law.cornell.edu%2Fuscode%2Ftext%2F21%2Fchapter-13&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-USDAStatement16-67\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-USDAStatement16_67-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Office of the Secretary; Drug Enforcement Administration; Food and Drug Administration (12 August 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.federalregister.gov\/documents\/2016\/08\/12\/2016-19146\/statement-of-principles-on-industrial-hemp\" target=\"_blank\">\"Statement of Principles on Industrial Hemp\"<\/a>. <i>Federal Register<\/i>. pp. 53395-53396<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.federalregister.gov\/documents\/2016\/08\/12\/2016-19146\/statement-of-principles-on-industrial-hemp\" target=\"_blank\">https:\/\/www.federalregister.gov\/documents\/2016\/08\/12\/2016-19146\/statement-of-principles-on-industrial-hemp<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Statement+of+Principles+on+Industrial+Hemp&rft.atitle=Federal+Register&rft.aulast=Office+of+the+Secretary%3B+Drug+Enforcement+Administration%3B+Food+and+Drug+Administration&rft.au=Office+of+the+Secretary%3B+Drug+Enforcement+Administration%3B+Food+and+Drug+Administration&rft.date=12+August+2016&rft.pages=pp.+53395-53396&rft_id=https%3A%2F%2Fwww.federalregister.gov%2Fdocuments%2F2016%2F08%2F12%2F2016-19146%2Fstatement-of-principles-on-industrial-hemp&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-AbernethyHemp19-68\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-AbernethyHemp19_68-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Abernethy, A. 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(23 April 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/idpc.net\/publications\/2018\/04\/medicinal-cannabis-policies-and-practices-around-the-world\" target=\"_blank\">\"Medicinal cannabis policies and practices around the world\"<\/a>. International Drug Policy Consortium<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/idpc.net\/publications\/2018\/04\/medicinal-cannabis-policies-and-practices-around-the-world\" target=\"_blank\">https:\/\/idpc.net\/publications\/2018\/04\/medicinal-cannabis-policies-and-practices-around-the-world<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=Medicinal+cannabis+policies+and+practices+around+the+world&rft.atitle=&rft.aulast=Aguilar%2C+S.%3B+Guti%C3%A9rrez%2C+V.%3B+S%C3%A1nchez%2C+L.+et+al.&rft.au=Aguilar%2C+S.%3B+Guti%C3%A9rrez%2C+V.%3B+S%C3%A1nchez%2C+L.+et+al.&rft.date=23+April+2018&rft.pub=International+Drug+Policy+Consortium&rft_id=https%3A%2F%2Fidpc.net%2Fpublications%2F2018%2F04%2Fmedicinal-cannabis-policies-and-practices-around-the-world&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-72\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-72\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lata, Hemant; Chandra, Suman; Techen, Natascha; Khan, Ikhlas A.; ElSohly, Mahmoud A. (1 March 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S221478611530019X\" target=\"_blank\">\"In vitro mass propagation of Cannabis sativa L.: A protocol refinement using novel aromatic cytokinin meta-topolin and the assessment of eco-physiological, biochemical and genetic fidelity of micropropagated plants\"<\/a> (in en). <i>Journal of Applied Research on Medicinal and Aromatic Plants<\/i> <b>3<\/b> (1): 18\u201326. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jarmap.2015.12.001\" target=\"_blank\">10.1016\/j.jarmap.2015.12.001<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S221478611530019X\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S221478611530019X<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=In+vitro+mass+propagation+of+Cannabis+sativa+L.%3A+A+protocol+refinement+using+novel+aromatic+cytokinin+meta-topolin+and+the+assessment+of+eco-physiological%2C+biochemical+and+genetic+fidelity+of+micropropagated+plants&rft.jtitle=Journal+of+Applied+Research+on+Medicinal+and+Aromatic+Plants&rft.aulast=Lata&rft.aufirst=Hemant&rft.au=Lata%2C%26%2332%3BHemant&rft.au=Chandra%2C%26%2332%3BSuman&rft.au=Techen%2C%26%2332%3BNatascha&rft.au=Khan%2C%26%2332%3BIkhlas+A.&rft.au=ElSohly%2C%26%2332%3BMahmoud+A.&rft.date=1+March+2016&rft.volume=3&rft.issue=1&rft.pages=18%E2%80%9326&rft_id=info:doi\/10.1016%2Fj.jarmap.2015.12.001&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221478611530019X&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-73\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-73\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Schachtsiek, Julia; Warzecha, Heribert; Kayser, Oliver; Stehle, Felix (1 March 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-125087\" target=\"_blank\">\"Current Perspectives on Biotechnological Cannabinoid Production in Plants\"<\/a> (in en). <i>Planta Medica<\/i> <b>84<\/b> (04): 214\u2013220. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1055%2Fs-0043-125087\" target=\"_blank\">10.1055\/s-0043-125087<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0032-0943\" target=\"_blank\">0032-0943<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-125087\" target=\"_blank\">http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-125087<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Current+Perspectives+on+Biotechnological+Cannabinoid+Production+in+Plants&rft.jtitle=Planta+Medica&rft.aulast=Schachtsiek&rft.aufirst=Julia&rft.au=Schachtsiek%2C%26%2332%3BJulia&rft.au=Warzecha%2C%26%2332%3BHeribert&rft.au=Kayser%2C%26%2332%3BOliver&rft.au=Stehle%2C%26%2332%3BFelix&rft.date=1+March+2018&rft.volume=84&rft.issue=04&rft.pages=214%E2%80%93220&rft_id=info:doi\/10.1055%2Fs-0043-125087&rft.issn=0032-0943&rft_id=http%3A%2F%2Fwww.thieme-connect.de%2FDOI%2FDOI%3F10.1055%2Fs-0043-125087&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:25-74\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:25_74-0\">74.0<\/a><\/sup> <sup><a href=\"#cite_ref-:25_74-1\">74.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lanyon, Vicki S.; Turner, Jocelyn C.; Mahlberg, Paul G. (1 September 1981). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.journals.uchicago.edu\/doi\/10.1086\/337229\" target=\"_blank\">\"Quantitative Analysis of Cannabinoids in the Secretory Product from Capitate-Stalked Glands of Cannabis sativa L. (Cannabaceae)\"<\/a> (in en). <i>Botanical Gazette<\/i> <b>142<\/b> (3): 316\u2013319. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1086%2F337229\" target=\"_blank\">10.1086\/337229<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0006-8071\" target=\"_blank\">0006-8071<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.journals.uchicago.edu\/doi\/10.1086\/337229\" target=\"_blank\">https:\/\/www.journals.uchicago.edu\/doi\/10.1086\/337229<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Quantitative+Analysis+of+Cannabinoids+in+the+Secretory+Product+from+Capitate-Stalked+Glands+of+Cannabis+sativa+L.+%28Cannabaceae%29&rft.jtitle=Botanical+Gazette&rft.aulast=Lanyon&rft.aufirst=Vicki+S.&rft.au=Lanyon%2C%26%2332%3BVicki+S.&rft.au=Turner%2C%26%2332%3BJocelyn+C.&rft.au=Mahlberg%2C%26%2332%3BPaul+G.&rft.date=1+September+1981&rft.volume=142&rft.issue=3&rft.pages=316%E2%80%93319&rft_id=info:doi\/10.1086%2F337229&rft.issn=0006-8071&rft_id=https%3A%2F%2Fwww.journals.uchicago.edu%2Fdoi%2F10.1086%2F337229&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-75\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-75\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Andre, Christelle M.; Hausman, Jean-Francois; Guerriero, Gea (4 February 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/journal.frontiersin.org\/Article\/10.3389\/fpls.2016.00019\/abstract\" target=\"_blank\">\"Cannabis sativa: The Plant of the Thousand and One Molecules\"<\/a>. <i>Frontiers in Plant Science<\/i> <b>7<\/b>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3389%2Ffpls.2016.00019\" target=\"_blank\">10.3389\/fpls.2016.00019<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1664-462X\" target=\"_blank\">1664-462X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4740396\" target=\"_blank\">PMC4740396<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26870049\" target=\"_blank\">26870049<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/journal.frontiersin.org\/Article\/10.3389\/fpls.2016.00019\/abstract\" target=\"_blank\">http:\/\/journal.frontiersin.org\/Article\/10.3389\/fpls.2016.00019\/abstract<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis+sativa%3A+The+Plant+of+the+Thousand+and+One+Molecules&rft.jtitle=Frontiers+in+Plant+Science&rft.aulast=Andre&rft.aufirst=Christelle+M.&rft.au=Andre%2C%26%2332%3BChristelle+M.&rft.au=Hausman%2C%26%2332%3BJean-Francois&rft.au=Guerriero%2C%26%2332%3BGea&rft.date=4+February+2016&rft.volume=7&rft_id=info:doi\/10.3389%2Ffpls.2016.00019&rft.issn=1664-462X&rft_id=info:pmc\/PMC4740396&rft_id=info:pmid\/26870049&rft_id=http%3A%2F%2Fjournal.frontiersin.org%2FArticle%2F10.3389%2Ffpls.2016.00019%2Fabstract&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-76\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-76\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation\" id=\"rdp-ebb-CITEREFDegenhardtStehleKayser2017\">Degenhardt, F.; Stehle, F.; Kayser, O. (2017), <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000028\" target=\"_blank\">\"The Biosynthesis of Cannabinoids\"<\/a> (in en), <i>Handbook of Cannabis and Related Pathologies<\/i> (Elsevier): 13\u201323, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fb978-0-12-800756-3.00002-8\" target=\"_blank\">10.1016\/b978-0-12-800756-3.00002-8<\/a>, <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-12-800756-3<span class=\"printonly\">, <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000028\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780128007563000028<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 2022-04-04<\/span><\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Biosynthesis+of+Cannabinoids&rft.jtitle=Handbook+of+Cannabis+and+Related+Pathologies&rft.aulast=Degenhardt&rft.aufirst=F.&rft.au=Degenhardt%2C%26%2332%3BF.&rft.au=Stehle%2C%26%2332%3BF.&rft.au=Kayser%2C%26%2332%3BO.&rft.date=2017&rft.pages=13%E2%80%9323&rft.pub=Elsevier&rft_id=info:doi\/10.1016%2Fb978-0-12-800756-3.00002-8&rft.isbn=978-0-12-800756-3&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FB9780128007563000028&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-77\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-77\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Marks, M. David; Tian, Li; Wenger, Jonathan P.; Omburo, Stephanie N.; Soto-Fuentes, Wilfredo; He, Ji; Gang, David R.; Weiblen, George D. <i>et al.<\/i> (1 September 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jxb\/article-lookup\/doi\/10.1093\/jxb\/erp210\" target=\"_blank\">\"Identification of candidate genes affecting \u03949-tetrahydrocannabinol biosynthesis in Cannabis sativa\"<\/a> (in en). <i>Journal of Experimental Botany<\/i> <b>60<\/b> (13): 3715\u20133726. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fjxb%2Ferp210\" target=\"_blank\">10.1093\/jxb\/erp210<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1460-2431\" target=\"_blank\">1460-2431<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2736886\" target=\"_blank\">PMC2736886<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19581347\" target=\"_blank\">19581347<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jxb\/article-lookup\/doi\/10.1093\/jxb\/erp210\" target=\"_blank\">https:\/\/academic.oup.com\/jxb\/article-lookup\/doi\/10.1093\/jxb\/erp210<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+candidate+genes+affecting+%CE%949-tetrahydrocannabinol+biosynthesis+in+Cannabis+sativa&rft.jtitle=Journal+of+Experimental+Botany&rft.aulast=Marks&rft.aufirst=M.+David&rft.au=Marks%2C%26%2332%3BM.+David&rft.au=Tian%2C%26%2332%3BLi&rft.au=Wenger%2C%26%2332%3BJonathan+P.&rft.au=Omburo%2C%26%2332%3BStephanie+N.&rft.au=Soto-Fuentes%2C%26%2332%3BWilfredo&rft.au=He%2C%26%2332%3BJi&rft.au=Gang%2C%26%2332%3BDavid+R.&rft.au=Weiblen%2C%26%2332%3BGeorge+D.&rft.au=Dixon%2C%26%2332%3BRichard+A.&rft.date=1+September+2009&rft.volume=60&rft.issue=13&rft.pages=3715%E2%80%933726&rft_id=info:doi\/10.1093%2Fjxb%2Ferp210&rft.issn=1460-2431&rft_id=info:pmc\/PMC2736886&rft_id=info:pmid\/19581347&rft_id=https%3A%2F%2Facademic.oup.com%2Fjxb%2Farticle-lookup%2Fdoi%2F10.1093%2Fjxb%2Ferp210&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-78\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-78\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Raharjo, Tri J.; Chang, Wen-Te; Verberne, Marianne C.; Peltenburg-Looman, Anja M.G.; Linthorst, Huub J.M.; Verpoorte, Robert (1 April 2004). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0981942804000300\" target=\"_blank\">\"Cloning and over-expression of a cDNA encoding a polyketide synthase from Cannabis sativa\"<\/a> (in en). <i>Plant Physiology and Biochemistry<\/i> <b>42<\/b> (4): 291\u2013297. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.plaphy.2004.02.011\" target=\"_blank\">10.1016\/j.plaphy.2004.02.011<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0981942804000300\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0981942804000300<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cloning+and+over-expression+of+a+cDNA+encoding+a+polyketide+synthase+from+Cannabis+sativa&rft.jtitle=Plant+Physiology+and+Biochemistry&rft.aulast=Raharjo&rft.aufirst=Tri+J.&rft.au=Raharjo%2C%26%2332%3BTri+J.&rft.au=Chang%2C%26%2332%3BWen-Te&rft.au=Verberne%2C%26%2332%3BMarianne+C.&rft.au=Peltenburg-Looman%2C%26%2332%3BAnja+M.G.&rft.au=Linthorst%2C%26%2332%3BHuub+J.M.&rft.au=Verpoorte%2C%26%2332%3BRobert&rft.date=1+April+2004&rft.volume=42&rft.issue=4&rft.pages=291%E2%80%93297&rft_id=info:doi\/10.1016%2Fj.plaphy.2004.02.011&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0981942804000300&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:23-79\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:23_79-0\">79.0<\/a><\/sup> <sup><a href=\"#cite_ref-:23_79-1\">79.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gagne, Steve J.; Stout, Jake M.; Liu, Enwu; Boubakir, Zakia; Clark, Shawn M.; Page, Jonathan E. (31 July 2012). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1200330109\" target=\"_blank\">\"Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides\"<\/a> (in en). <i>Proceedings of the National Academy of Sciences<\/i> <b>109<\/b> (31): 12811\u201312816. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1073%2Fpnas.1200330109\" target=\"_blank\">10.1073\/pnas.1200330109<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0027-8424\" target=\"_blank\">0027-8424<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC3411943\" target=\"_blank\">PMC3411943<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22802619\" target=\"_blank\">22802619<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1200330109\" target=\"_blank\">https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1200330109<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+olivetolic+acid+cyclase+from+Cannabis+sativa+reveals+a+unique+catalytic+route+to+plant+polyketides&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences&rft.aulast=Gagne&rft.aufirst=Steve+J.&rft.au=Gagne%2C%26%2332%3BSteve+J.&rft.au=Stout%2C%26%2332%3BJake+M.&rft.au=Liu%2C%26%2332%3BEnwu&rft.au=Boubakir%2C%26%2332%3BZakia&rft.au=Clark%2C%26%2332%3BShawn+M.&rft.au=Page%2C%26%2332%3BJonathan+E.&rft.date=31+July+2012&rft.volume=109&rft.issue=31&rft.pages=12811%E2%80%9312816&rft_id=info:doi\/10.1073%2Fpnas.1200330109&rft.issn=0027-8424&rft_id=info:pmc\/PMC3411943&rft_id=info:pmid\/22802619&rft_id=https%3A%2F%2Fpnas.org%2Fdoi%2Ffull%2F10.1073%2Fpnas.1200330109&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-80\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-80\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Stout, Jake M.; Boubakir, Zakia; Ambrose, Stephen J.; Purves, Randy W.; Page, Jonathan E. 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Zenk, Meinhart H (8 May 1998). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/doi.wiley.com\/10.1016\/S0014-5793%2898%2900450-5\" target=\"_blank\">\"Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol\"<\/a> (in en). <i>FEBS Letters<\/i> <b>427<\/b> (2): 283\u2013285. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2FS0014-5793%2898%2900450-5\" target=\"_blank\">10.1016\/S0014-5793(98)00450-5<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/doi.wiley.com\/10.1016\/S0014-5793%2898%2900450-5\" target=\"_blank\">http:\/\/doi.wiley.com\/10.1016\/S0014-5793%2898%2900450-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Prenylation+of+olivetolate+by+a+hemp+transferase+yields+cannabigerolic+acid%2C+the+precursor+of+tetrahydrocannabinol&rft.jtitle=FEBS+Letters&rft.aulast=Fellermeier&rft.aufirst=Monika&rft.au=Fellermeier%2C%26%2332%3BMonika&rft.au=Zenk%2C%26%2332%3BMeinhart+H&rft.date=8+May+1998&rft.volume=427&rft.issue=2&rft.pages=283%E2%80%93285&rft_id=info:doi\/10.1016%2FS0014-5793%2898%2900450-5&rft_id=http%3A%2F%2Fdoi.wiley.com%2F10.1016%2FS0014-5793%252898%252900450-5&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-82\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-82\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Taura, Futoshi; Tanaka, Shinji; Taguchi, Chiho; Fukamizu, Tomohide; Tanaka, Hiroyuki; Shoyama, Yukihiro; Morimoto, Satoshi (18 June 2009). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/doi.wiley.com\/10.1016\/j.febslet.2009.05.024\" target=\"_blank\">\"Characterization of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway\"<\/a> (in en). <i>FEBS Letters<\/i> <b>583<\/b> (12): 2061\u20132066. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.febslet.2009.05.024\" target=\"_blank\">10.1016\/j.febslet.2009.05.024<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/doi.wiley.com\/10.1016\/j.febslet.2009.05.024\" target=\"_blank\">http:\/\/doi.wiley.com\/10.1016\/j.febslet.2009.05.024<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Characterization+of+olivetol+synthase%2C+a+polyketide+synthase+putatively+involved+in+cannabinoid+biosynthetic+pathway&rft.jtitle=FEBS+Letters&rft.aulast=Taura&rft.aufirst=Futoshi&rft.au=Taura%2C%26%2332%3BFutoshi&rft.au=Tanaka%2C%26%2332%3BShinji&rft.au=Taguchi%2C%26%2332%3BChiho&rft.au=Fukamizu%2C%26%2332%3BTomohide&rft.au=Tanaka%2C%26%2332%3BHiroyuki&rft.au=Shoyama%2C%26%2332%3BYukihiro&rft.au=Morimoto%2C%26%2332%3BSatoshi&rft.date=18+June+2009&rft.volume=583&rft.issue=12&rft.pages=2061%E2%80%932066&rft_id=info:doi\/10.1016%2Fj.febslet.2009.05.024&rft_id=http%3A%2F%2Fdoi.wiley.com%2F10.1016%2Fj.febslet.2009.05.024&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-83\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-83\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Lange, Kerstin; Schmid, Andreas; Julsing, Mattijs K. 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Kim, Eun-Soo (1 February 1992). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1992.tb13634.x\" target=\"_blank\">\"SECRETORY VESICLE FORMATION IN GLANDULAR TRICHOMES OF CANNABIS SATIVA (CANNABACEAE)\"<\/a> (in en). <i>American Journal of Botany<\/i> <b>79<\/b> (2): 166\u2013173. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1002%2Fj.1537-2197.1992.tb13634.x\" target=\"_blank\">10.1002\/j.1537-2197.1992.tb13634.x<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1992.tb13634.x\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1537-2197.1992.tb13634.x<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SECRETORY+VESICLE+FORMATION+IN+GLANDULAR+TRICHOMES+OF+CANNABIS+SATIVA+%28CANNABACEAE%29&rft.jtitle=American+Journal+of+Botany&rft.aulast=Mahlberg&rft.aufirst=Paul+G.&rft.au=Mahlberg%2C%26%2332%3BPaul+G.&rft.au=Kim%2C%26%2332%3BEun-Soo&rft.date=1+February+1992&rft.volume=79&rft.issue=2&rft.pages=166%E2%80%93173&rft_id=info:doi\/10.1002%2Fj.1537-2197.1992.tb13634.x&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1002%2Fj.1537-2197.1992.tb13634.x&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-85\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-85\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Rodziewicz, Pawe\u0142; Loroch, Stefan; Marczak, \u0141ukasz; Sickmann, Albert; Kayser, Oliver (1 July 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168945218314869\" target=\"_blank\">\"Cannabinoid synthases and osmoprotective metabolites accumulate in the exudates of Cannabis sativa L. glandular trichomes\"<\/a> (in en). <i>Plant Science<\/i> <b>284<\/b>: 108\u2013116. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.plantsci.2019.04.008\" target=\"_blank\">10.1016\/j.plantsci.2019.04.008<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168945218314869\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168945218314869<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabinoid+synthases+and+osmoprotective+metabolites+accumulate+in+the+exudates+of+Cannabis+sativa+L.+glandular+trichomes&rft.jtitle=Plant+Science&rft.aulast=Rodziewicz&rft.aufirst=Pawe%C5%82&rft.au=Rodziewicz%2C%26%2332%3BPawe%C5%82&rft.au=Loroch%2C%26%2332%3BStefan&rft.au=Marczak%2C%26%2332%3B%C5%81ukasz&rft.au=Sickmann%2C%26%2332%3BAlbert&rft.au=Kayser%2C%26%2332%3BOliver&rft.date=1+July+2019&rft.volume=284&rft.pages=108%E2%80%93116&rft_id=info:doi\/10.1016%2Fj.plantsci.2019.04.008&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168945218314869&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-86\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-86\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Zirpel, Bastian; Kayser, Oliver; Stehle, Felix (1 October 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168165618305698\" target=\"_blank\">\"Elucidation of structure-function relationship of THCA and CBDA synthase from Cannabis sativa L.\"<\/a> (in en). <i>Journal of Biotechnology<\/i> <b>284<\/b>: 17\u201326. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jbiotec.2018.07.031\" target=\"_blank\">10.1016\/j.jbiotec.2018.07.031<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168165618305698\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168165618305698<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Elucidation+of+structure-function+relationship+of+THCA+and+CBDA+synthase+from+Cannabis+sativa+L.&rft.jtitle=Journal+of+Biotechnology&rft.aulast=Zirpel&rft.aufirst=Bastian&rft.au=Zirpel%2C%26%2332%3BBastian&rft.au=Kayser%2C%26%2332%3BOliver&rft.au=Stehle%2C%26%2332%3BFelix&rft.date=1+October+2018&rft.volume=284&rft.pages=17%E2%80%9326&rft_id=info:doi\/10.1016%2Fj.jbiotec.2018.07.031&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168165618305698&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-87\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-87\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">White, Kristin H.; 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(1 January 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/23802359.2016.1155083\" target=\"_blank\">\"The complete mitochondrial genome for Cannabis sativa\"<\/a> (in en). <i>Mitochondrial DNA Part B<\/i> <b>1<\/b> (1): 715\u2013716. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F23802359.2016.1155083\" target=\"_blank\">10.1080\/23802359.2016.1155083<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2380-2359\" target=\"_blank\">2380-2359<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7871862\" target=\"_blank\">PMC7871862<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33644379\" target=\"_blank\">33644379<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/23802359.2016.1155083\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/23802359.2016.1155083<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+complete+mitochondrial+genome+for+Cannabis+sativa&rft.jtitle=Mitochondrial+DNA+Part+B&rft.aulast=White&rft.aufirst=Kristin+H.&rft.au=White%2C%26%2332%3BKristin+H.&rft.au=Vergara%2C%26%2332%3BDaniela&rft.au=Keepers%2C%26%2332%3BKyle+G.&rft.au=Kane%2C%26%2332%3BNolan+C.&rft.date=1+January+2016&rft.volume=1&rft.issue=1&rft.pages=715%E2%80%93716&rft_id=info:doi\/10.1080%2F23802359.2016.1155083&rft.issn=2380-2359&rft_id=info:pmc\/PMC7871862&rft_id=info:pmid\/33644379&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F23802359.2016.1155083&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-88\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-88\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Oh, Hyehyun; Seo, Boyoung; Lee, Seunghwan; Ahn, Dong-Ha; Jo, Euna; Park, Jin-Kyoung; Min, Gi-Sik (3 July 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1053117\" target=\"_blank\">\"Two complete chloroplast genome sequences of Cannabis sativa varieties\"<\/a> (in en). <i>Mitochondrial DNA Part A<\/i> <b>27<\/b> (4): 2835\u20132837. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3109%2F19401736.2015.1053117\" target=\"_blank\">10.3109\/19401736.2015.1053117<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2470-1394\" target=\"_blank\">2470-1394<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1053117\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1053117<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Two+complete+chloroplast+genome+sequences+of+Cannabis+sativa+varieties&rft.jtitle=Mitochondrial+DNA+Part+A&rft.aulast=Oh&rft.aufirst=Hyehyun&rft.au=Oh%2C%26%2332%3BHyehyun&rft.au=Seo%2C%26%2332%3BBoyoung&rft.au=Lee%2C%26%2332%3BSeunghwan&rft.au=Ahn%2C%26%2332%3BDong-Ha&rft.au=Jo%2C%26%2332%3BEuna&rft.au=Park%2C%26%2332%3BJin-Kyoung&rft.au=Min%2C%26%2332%3BGi-Sik&rft.date=3+July+2016&rft.volume=27&rft.issue=4&rft.pages=2835%E2%80%932837&rft_id=info:doi\/10.3109%2F19401736.2015.1053117&rft.issn=2470-1394&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.3109%2F19401736.2015.1053117&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-89\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-89\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Vergara, Daniela; 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(2 September 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1079905\" target=\"_blank\">\"The complete chloroplast genomes of Cannabis sativa and Humulus lupulus\"<\/a> (in en). <i>Mitochondrial DNA Part A<\/i> <b>27<\/b> (5): 3793\u20133794. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3109%2F19401736.2015.1079905\" target=\"_blank\">10.3109\/19401736.2015.1079905<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2470-1394\" target=\"_blank\">2470-1394<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1079905\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.3109\/19401736.2015.1079905<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+complete+chloroplast+genomes+of+Cannabis+sativa+and+Humulus+lupulus&rft.jtitle=Mitochondrial+DNA+Part+A&rft.aulast=Vergara&rft.aufirst=Daniela&rft.au=Vergara%2C%26%2332%3BDaniela&rft.au=White%2C%26%2332%3BKristin+H.&rft.au=Keepers%2C%26%2332%3BKyle+G.&rft.au=Kane%2C%26%2332%3BNolan+C.&rft.date=2+September+2016&rft.volume=27&rft.issue=5&rft.pages=3793%E2%80%933794&rft_id=info:doi\/10.3109%2F19401736.2015.1079905&rft.issn=2470-1394&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.3109%2F19401736.2015.1079905&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-PBGalaxy-90\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-PBGalaxy_90-0\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\"><a rel=\"external_link\" class=\"external text\" href=\"https:\/\/phylos.bio\/galaxy\/\" target=\"_blank\">\"Phylos Galaxy\"<\/a>. 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J. (1 May 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nph.17243\" target=\"_blank\">\"A new Cannabis genome assembly associates elevated cannabidiol (CBD) with hemp introgressed into marijuana\"<\/a> (in en). <i>New Phytologist<\/i> <b>230<\/b> (4): 1665\u20131679. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fnph.17243\" target=\"_blank\">10.1111\/nph.17243<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0028-646X\" target=\"_blank\">0028-646X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8248131\" target=\"_blank\">PMC8248131<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33521943\" target=\"_blank\">33521943<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nph.17243\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nph.17243<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+new+Cannabis+genome+assembly+associates+elevated+cannabidiol+%28CBD%29+with+hemp+introgressed+into+marijuana&rft.jtitle=New+Phytologist&rft.aulast=Grassa&rft.aufirst=Christopher+J.&rft.au=Grassa%2C%26%2332%3BChristopher+J.&rft.au=Weiblen%2C%26%2332%3BGeorge+D.&rft.au=Wenger%2C%26%2332%3BJonathan+P.&rft.au=Dabney%2C%26%2332%3BClemon&rft.au=Poplawski%2C%26%2332%3BShane+G.&rft.au=Timothy+Motley%2C%26%2332%3BS.&rft.au=Michael%2C%26%2332%3BTodd+P.&rft.au=Schwartz%2C%26%2332%3BC.+J.&rft.date=1+May+2021&rft.volume=230&rft.issue=4&rft.pages=1665%E2%80%931679&rft_id=info:doi\/10.1111%2Fnph.17243&rft.issn=0028-646X&rft_id=info:pmc\/PMC8248131&rft_id=info:pmid\/33521943&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fnph.17243&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-92\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-92\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Laverty, Kaitlin U.; Stout, Jake M.; Sullivan, Mitchell J.; Shah, Hardik; Gill, Navdeep; Holbrook, Larry; Deikus, Gintaras; Sebra, Robert <i>et al.<\/i> (1 January 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.242594.118\" target=\"_blank\">\"A physical and genetic map of Cannabis sativa identifies extensive rearrangements at the THC\/CBD acid synthase loci\"<\/a> (in en). <i>Genome Research<\/i> <b>29<\/b> (1): 146\u2013156. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1101%2Fgr.242594.118\" target=\"_blank\">10.1101\/gr.242594.118<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1088-9051\" target=\"_blank\">1088-9051<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6314170\" target=\"_blank\">PMC6314170<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30409771\" target=\"_blank\">30409771<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.242594.118\" target=\"_blank\">http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.242594.118<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+physical+and+genetic+map+of+Cannabis+sativa+identifies+extensive+rearrangements+at+the+THC%2FCBD+acid+synthase+loci&rft.jtitle=Genome+Research&rft.aulast=Laverty&rft.aufirst=Kaitlin+U.&rft.au=Laverty%2C%26%2332%3BKaitlin+U.&rft.au=Stout%2C%26%2332%3BJake+M.&rft.au=Sullivan%2C%26%2332%3BMitchell+J.&rft.au=Shah%2C%26%2332%3BHardik&rft.au=Gill%2C%26%2332%3BNavdeep&rft.au=Holbrook%2C%26%2332%3BLarry&rft.au=Deikus%2C%26%2332%3BGintaras&rft.au=Sebra%2C%26%2332%3BRobert&rft.au=Hughes%2C%26%2332%3BTimothy+R.&rft.date=1+January+2019&rft.volume=29&rft.issue=1&rft.pages=146%E2%80%93156&rft_id=info:doi\/10.1101%2Fgr.242594.118&rft.issn=1088-9051&rft_id=info:pmc\/PMC6314170&rft_id=info:pmid\/30409771&rft_id=http%3A%2F%2Fgenome.cshlp.org%2Flookup%2Fdoi%2F10.1101%2Fgr.242594.118&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:27-93\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:27_93-0\">93.0<\/a><\/sup> <sup><a href=\"#cite_ref-:27_93-1\">93.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Braich, Shivraj; Baillie, Rebecca C.; Spangenberg, German C.; Cogan, Noel O.I. (13 December 2020) (in en). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.12.13.422592\" target=\"_blank\"><i>A New and Improved Genome Sequence of Cannabis sativa<\/i><\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1101%2F2020.12.13.422592\" target=\"_blank\">10.1101\/2020.12.13.422592<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.12.13.422592\" target=\"_blank\">http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.12.13.422592<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=A+New+and+Improved+Genome+Sequence+of+Cannabis+sativa&rft.aulast=Braich&rft.aufirst=Shivraj&rft.au=Braich%2C%26%2332%3BShivraj&rft.au=Baillie%2C%26%2332%3BRebecca+C.&rft.au=Spangenberg%2C%26%2332%3BGerman+C.&rft.au=Cogan%2C%26%2332%3BNoel+O.I.&rft.date=13+December+2020&rft_id=info:doi\/10.1101%2F2020.12.13.422592&rft_id=http%3A%2F%2Fbiorxiv.org%2Flookup%2Fdoi%2F10.1101%2F2020.12.13.422592&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-94\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-94\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Gao, Shan; Wang, Baishi; Xie, Shanshan; Xu, Xiaoyu; Zhang, Jin; Pei, Li; Yu, Yongyi; Yang, Weifei <i>et al.<\/i> (1 December 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/hr\/article\/6445457\" target=\"_blank\">\"A high-quality reference genome of wild Cannabis sativa\"<\/a> (in en). <i>Horticulture Research<\/i> <b>7<\/b> (1): 73. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41438-020-0295-3\" target=\"_blank\">10.1038\/s41438-020-0295-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2662-6810\" target=\"_blank\">2662-6810<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7195422\" target=\"_blank\">PMC7195422<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32377363\" target=\"_blank\">32377363<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/hr\/article\/6445457\" target=\"_blank\">https:\/\/academic.oup.com\/hr\/article\/6445457<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+high-quality+reference+genome+of+wild+Cannabis+sativa&rft.jtitle=Horticulture+Research&rft.aulast=Gao&rft.aufirst=Shan&rft.au=Gao%2C%26%2332%3BShan&rft.au=Wang%2C%26%2332%3BBaishi&rft.au=Xie%2C%26%2332%3BShanshan&rft.au=Xu%2C%26%2332%3BXiaoyu&rft.au=Zhang%2C%26%2332%3BJin&rft.au=Pei%2C%26%2332%3BLi&rft.au=Yu%2C%26%2332%3BYongyi&rft.au=Yang%2C%26%2332%3BWeifei&rft.au=Zhang%2C%26%2332%3BYing&rft.date=1+December+2020&rft.volume=7&rft.issue=1&rft.pages=73&rft_id=info:doi\/10.1038%2Fs41438-020-0295-3&rft.issn=2662-6810&rft_id=info:pmc\/PMC7195422&rft_id=info:pmid\/32377363&rft_id=https%3A%2F%2Facademic.oup.com%2Fhr%2Farticle%2F6445457&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-95\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-95\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cai, Sen; Zhang, Zhiyuan; Huang, Suyun; Bai, Xu; Huang, Ziying; Zhang, Yiping Jason; Huang, Likun; Tang, Weiqi <i>et al.<\/i> (1 May 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pbi.13548\" target=\"_blank\">\"CannabisGDB: a comprehensive genomic database for Cannabis Sativa L\"<\/a> (in en). <i>Plant Biotechnology Journal<\/i> <b>19<\/b> (5): 857\u2013859. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fpbi.13548\" target=\"_blank\">10.1111\/pbi.13548<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1467-7644\" target=\"_blank\">1467-7644<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8131054\" target=\"_blank\">PMC8131054<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33462958\" target=\"_blank\">33462958<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pbi.13548\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pbi.13548<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=CannabisGDB%3A+a+comprehensive+genomic+database+for+Cannabis+Sativa+L&rft.jtitle=Plant+Biotechnology+Journal&rft.aulast=Cai&rft.aufirst=Sen&rft.au=Cai%2C%26%2332%3BSen&rft.au=Zhang%2C%26%2332%3BZhiyuan&rft.au=Huang%2C%26%2332%3BSuyun&rft.au=Bai%2C%26%2332%3BXu&rft.au=Huang%2C%26%2332%3BZiying&rft.au=Zhang%2C%26%2332%3BYiping+Jason&rft.au=Huang%2C%26%2332%3BLikun&rft.au=Tang%2C%26%2332%3BWeiqi&rft.au=Haughn%2C%26%2332%3BGeorge&rft.date=1+May+2021&rft.volume=19&rft.issue=5&rft.pages=857%E2%80%93859&rft_id=info:doi\/10.1111%2Fpbi.13548&rft.issn=1467-7644&rft_id=info:pmc\/PMC8131054&rft_id=info:pmid\/33462958&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fpbi.13548&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-96\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-96\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Guerriero, Gea; Behr, Marc; Legay, Sylvain; Mangeot-Peter, Lauralie; Zorzan, Simone; Ghoniem, Mohammad; Hausman, Jean-Francois (1 December 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41598-017-05200-8\" target=\"_blank\">\"Transcriptomic profiling of hemp bast fibres at different developmental stages\"<\/a> (in en). <i>Scientific Reports<\/i> <b>7<\/b> (1): 4961. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41598-017-05200-8\" target=\"_blank\">10.1038\/s41598-017-05200-8<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2045-2322\" target=\"_blank\">2045-2322<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC5504027\" target=\"_blank\">PMC5504027<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28694530\" target=\"_blank\">28694530<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41598-017-05200-8\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41598-017-05200-8<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Transcriptomic+profiling+of+hemp+bast+fibres+at+different+developmental+stages&rft.jtitle=Scientific+Reports&rft.aulast=Guerriero&rft.aufirst=Gea&rft.au=Guerriero%2C%26%2332%3BGea&rft.au=Behr%2C%26%2332%3BMarc&rft.au=Legay%2C%26%2332%3BSylvain&rft.au=Mangeot-Peter%2C%26%2332%3BLauralie&rft.au=Zorzan%2C%26%2332%3BSimone&rft.au=Ghoniem%2C%26%2332%3BMohammad&rft.au=Hausman%2C%26%2332%3BJean-Francois&rft.date=1+December+2017&rft.volume=7&rft.issue=1&rft.pages=4961&rft_id=info:doi\/10.1038%2Fs41598-017-05200-8&rft.issn=2045-2322&rft_id=info:pmc\/PMC5504027&rft_id=info:pmid\/28694530&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41598-017-05200-8&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-97\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-97\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Turner, J. C.; Hemphill, J. K.; Mahlberg, P. G. (1981). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/6914206\" target=\"_blank\">\"Interrelationships of glandular trichomes and cannabinoid content. I: Developing pistillate bracts of Cannabis sativa L. (Cannabaceae)\"<\/a>. <i>Bulletin on Narcotics<\/i> <b>33<\/b> (2): 59\u201369. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0007-523X\" target=\"_blank\">0007-523X<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/6914206\" target=\"_blank\">6914206<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/6914206\" target=\"_blank\">https:\/\/pubmed.ncbi.nlm.nih.gov\/6914206<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Interrelationships+of+glandular+trichomes+and+cannabinoid+content.+I%3A+Developing+pistillate+bracts+of+Cannabis+sativa+L.+%28Cannabaceae%29&rft.jtitle=Bulletin+on+Narcotics&rft.aulast=Turner&rft.aufirst=J.+C.&rft.au=Turner%2C%26%2332%3BJ.+C.&rft.au=Hemphill%2C%26%2332%3BJ.+K.&rft.au=Mahlberg%2C%26%2332%3BP.+G.&rft.date=1981&rft.volume=33&rft.issue=2&rft.pages=59%E2%80%9369&rft.issn=0007-523X&rft_id=info:pmid\/6914206&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F6914206&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-98\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-98\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Braich, Shivraj; Baillie, Rebecca C.; Jewell, Larry S.; Spangenberg, German C.; Cogan, Noel O. I. (1 December 2019). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41598-019-53023-6\" target=\"_blank\">\"Generation of a Comprehensive Transcriptome Atlas and Transcriptome Dynamics in Medicinal Cannabis\"<\/a> (in en). <i>Scientific Reports<\/i> <b>9<\/b> (1): 16583. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41598-019-53023-6\" target=\"_blank\">10.1038\/s41598-019-53023-6<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2045-2322\" target=\"_blank\">2045-2322<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6851104\" target=\"_blank\">PMC6851104<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31719627\" target=\"_blank\">31719627<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41598-019-53023-6\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41598-019-53023-6<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Generation+of+a+Comprehensive+Transcriptome+Atlas+and+Transcriptome+Dynamics+in+Medicinal+Cannabis&rft.jtitle=Scientific+Reports&rft.aulast=Braich&rft.aufirst=Shivraj&rft.au=Braich%2C%26%2332%3BShivraj&rft.au=Baillie%2C%26%2332%3BRebecca+C.&rft.au=Jewell%2C%26%2332%3BLarry+S.&rft.au=Spangenberg%2C%26%2332%3BGerman+C.&rft.au=Cogan%2C%26%2332%3BNoel+O.+I.&rft.date=1+December+2019&rft.volume=9&rft.issue=1&rft.pages=16583&rft_id=info:doi\/10.1038%2Fs41598-019-53023-6&rft.issn=2045-2322&rft_id=info:pmc\/PMC6851104&rft_id=info:pmid\/31719627&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41598-019-53023-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-99\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-99\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Cook-Deegan, Robert; Niehaus, Annie (1 December 2014). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s40142-014-0055-5\" target=\"_blank\">\"After Myriad: Genetic Testing in the Wake of Recent Supreme Court Decisions about Gene Patents\"<\/a> (in en). <i>Current Genetic Medicine Reports<\/i> <b>2<\/b> (4): 223\u2013241. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs40142-014-0055-5\" target=\"_blank\">10.1007\/s40142-014-0055-5<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2167-4876\" target=\"_blank\">2167-4876<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC4225052\" target=\"_blank\">PMC4225052<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25401053\" target=\"_blank\">25401053<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s40142-014-0055-5\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s40142-014-0055-5<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=After+Myriad%3A+Genetic+Testing+in+the+Wake+of+Recent+Supreme+Court+Decisions+about+Gene+Patents&rft.jtitle=Current+Genetic+Medicine+Reports&rft.aulast=Cook-Deegan&rft.aufirst=Robert&rft.au=Cook-Deegan%2C%26%2332%3BRobert&rft.au=Niehaus%2C%26%2332%3BAnnie&rft.date=1+December+2014&rft.volume=2&rft.issue=4&rft.pages=223%E2%80%93241&rft_id=info:doi\/10.1007%2Fs40142-014-0055-5&rft.issn=2167-4876&rft_id=info:pmc\/PMC4225052&rft_id=info:pmid\/25401053&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs40142-014-0055-5&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-100\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-100\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation web\">Weed, J. 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Zaimovic, Amir; Gerra, Maria; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo (1 January 2010). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1574-8898&volume=5&issue=1&spage=46\" target=\"_blank\">\"Pharmacology and Toxicology of Cannabis Derivatives and Endocannabinoid Agonists\"<\/a> (in en). <i>Recent Patents on CNS Drug Discovery<\/i> <b>5<\/b> (1): 46\u201352. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.2174%2F157488910789753521\" target=\"_blank\">10.2174\/157488910789753521<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1574-8898&volume=5&issue=1&spage=46\" target=\"_blank\">http:\/\/www.eurekaselect.com\/openurl\/content.php?genre=article&issn=1574-8898&volume=5&issue=1&spage=46<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmacology+and+Toxicology+of+Cannabis+Derivatives+and+Endocannabinoid+Agonists&rft.jtitle=Recent+Patents+on+CNS+Drug+Discovery&rft.aulast=Gerra&rft.aufirst=Gilberto&rft.au=Gerra%2C%26%2332%3BGilberto&rft.au=Zaimovic%2C%26%2332%3BAmir&rft.au=Gerra%2C%26%2332%3BMaria&rft.au=Ciccocioppo%2C%26%2332%3BRoberto&rft.au=Cippitelli%2C%26%2332%3BAndrea&rft.au=Serpelloni%2C%26%2332%3BGiovanni&rft.au=Somaini%2C%26%2332%3BLorenzo&rft.date=1+January+2010&rft.volume=5&rft.issue=1&rft.pages=46%E2%80%9352&rft_id=info:doi\/10.2174%2F157488910789753521&rft_id=http%3A%2F%2Fwww.eurekaselect.com%2Fopenurl%2Fcontent.php%3Fgenre%3Darticle%26issn%3D1574-8898%26volume%3D5%26issue%3D1%26spage%3D46&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-102\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-102\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Flores-Sanchez, Isvett Josefina; Ramos-Valdivia, Ana Carmela (1 August 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s11101-017-9498-0\" target=\"_blank\">\"A review from patents inspired by two plant genera: Uncaria and Hamelia\"<\/a> (in en). <i>Phytochemistry Reviews<\/i> <b>16<\/b> (4): 693\u2013723. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs11101-017-9498-0\" target=\"_blank\">10.1007\/s11101-017-9498-0<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1568-7767\" target=\"_blank\">1568-7767<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s11101-017-9498-0\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s11101-017-9498-0<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+review+from+patents+inspired+by+two+plant+genera%3A+Uncaria+and+Hamelia&rft.jtitle=Phytochemistry+Reviews&rft.aulast=Flores-Sanchez&rft.aufirst=Isvett+Josefina&rft.au=Flores-Sanchez%2C%26%2332%3BIsvett+Josefina&rft.au=Ramos-Valdivia%2C%26%2332%3BAna+Carmela&rft.date=1+August+2017&rft.volume=16&rft.issue=4&rft.pages=693%E2%80%93723&rft_id=info:doi\/10.1007%2Fs11101-017-9498-0&rft.issn=1568-7767&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs11101-017-9498-0&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-103\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-103\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Nagarkatti, Prakash; Pandey, Rupal; Rieder, Sadiye Amcaoglu; Hegde, Venkatesh L; Nagarkatti, Mitzi (1 October 2009). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.future-science.com\/doi\/10.4155\/fmc.09.93\" target=\"_blank\">\"Cannabinoids as novel anti-inflammatory drugs\"<\/a> (in en). <i>Future Medicinal Chemistry<\/i> <b>1<\/b> (7): 1333\u20131349. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.4155%2Ffmc.09.93\" target=\"_blank\">10.4155\/fmc.09.93<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1756-8919\" target=\"_blank\">1756-8919<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC2828614\" target=\"_blank\">PMC2828614<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20191092\" target=\"_blank\">20191092<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.future-science.com\/doi\/10.4155\/fmc.09.93\" target=\"_blank\">https:\/\/www.future-science.com\/doi\/10.4155\/fmc.09.93<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabinoids+as+novel+anti-inflammatory+drugs&rft.jtitle=Future+Medicinal+Chemistry&rft.aulast=Nagarkatti&rft.aufirst=Prakash&rft.au=Nagarkatti%2C%26%2332%3BPrakash&rft.au=Pandey%2C%26%2332%3BRupal&rft.au=Rieder%2C%26%2332%3BSadiye+Amcaoglu&rft.au=Hegde%2C%26%2332%3BVenkatesh+L&rft.au=Nagarkatti%2C%26%2332%3BMitzi&rft.date=1+October+2009&rft.volume=1&rft.issue=7&rft.pages=1333%E2%80%931349&rft_id=info:doi\/10.4155%2Ffmc.09.93&rft.issn=1756-8919&rft_id=info:pmc\/PMC2828614&rft_id=info:pmid\/20191092&rft_id=https%3A%2F%2Fwww.future-science.com%2Fdoi%2F10.4155%2Ffmc.09.93&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-104\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-104\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Petrosino, Stefania; Verde, Roberta; Vaia, Massimo; Allar\u00e0, Marco; Iuvone, Teresa; Di Marzo, Vincenzo (1 June 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/jpet.aspetjournals.org\/lookup\/doi\/10.1124\/jpet.117.244368\" target=\"_blank\">\"Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis\"<\/a> (in en). <i>Journal of Pharmacology and Experimental Therapeutics<\/i> <b>365<\/b> (3): 652\u2013663. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1124%2Fjpet.117.244368\" target=\"_blank\">10.1124\/jpet.117.244368<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0022-3565\" target=\"_blank\">0022-3565<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/jpet.aspetjournals.org\/lookup\/doi\/10.1124\/jpet.117.244368\" target=\"_blank\">http:\/\/jpet.aspetjournals.org\/lookup\/doi\/10.1124\/jpet.117.244368<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Anti-inflammatory+Properties+of+Cannabidiol%2C+a+Nonpsychotropic+Cannabinoid%2C+in+Experimental+Allergic+Contact+Dermatitis&rft.jtitle=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.aulast=Petrosino&rft.aufirst=Stefania&rft.au=Petrosino%2C%26%2332%3BStefania&rft.au=Verde%2C%26%2332%3BRoberta&rft.au=Vaia%2C%26%2332%3BMassimo&rft.au=Allar%C3%A0%2C%26%2332%3BMarco&rft.au=Iuvone%2C%26%2332%3BTeresa&rft.au=Di+Marzo%2C%26%2332%3BVincenzo&rft.date=1+June+2018&rft.volume=365&rft.issue=3&rft.pages=652%E2%80%93663&rft_id=info:doi\/10.1124%2Fjpet.117.244368&rft.issn=0022-3565&rft_id=http%3A%2F%2Fjpet.aspetjournals.org%2Flookup%2Fdoi%2F10.1124%2Fjpet.117.244368&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-105\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-105\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Pellati, Federica; Borgonetti, Vittoria; Brighenti, Virginia; Biagi, Marco; Benvenuti, Stefania; Corsi, Lorenzo (4 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.hindawi.com\/journals\/bmri\/2018\/1691428\/\" target=\"_blank\">\"Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer\"<\/a> (in en). <i>BioMed Research International<\/i> <b>2018<\/b>: 1\u201315. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1155%2F2018%2F1691428\" target=\"_blank\">10.1155\/2018\/1691428<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2314-6133\" target=\"_blank\">2314-6133<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6304621\" target=\"_blank\">PMC6304621<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30627539\" target=\"_blank\">30627539<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.hindawi.com\/journals\/bmri\/2018\/1691428\/\" target=\"_blank\">https:\/\/www.hindawi.com\/journals\/bmri\/2018\/1691428\/<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis+sativa+L.+and+Nonpsychoactive+Cannabinoids%3A+Their+Chemistry+and+Role+against+Oxidative+Stress%2C+Inflammation%2C+and+Cancer&rft.jtitle=BioMed+Research+International&rft.aulast=Pellati&rft.aufirst=Federica&rft.au=Pellati%2C%26%2332%3BFederica&rft.au=Borgonetti%2C%26%2332%3BVittoria&rft.au=Brighenti%2C%26%2332%3BVirginia&rft.au=Biagi%2C%26%2332%3BMarco&rft.au=Benvenuti%2C%26%2332%3BStefania&rft.au=Corsi%2C%26%2332%3BLorenzo&rft.date=4+December+2018&rft.volume=2018&rft.pages=1%E2%80%9315&rft_id=info:doi\/10.1155%2F2018%2F1691428&rft.issn=2314-6133&rft_id=info:pmc\/PMC6304621&rft_id=info:pmid\/30627539&rft_id=https%3A%2F%2Fwww.hindawi.com%2Fjournals%2Fbmri%2F2018%2F1691428%2F&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-106\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-106\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Almogi-Hazan, Osnat; Or, Reuven (23 June 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4448\" target=\"_blank\">\"Cannabis, the Endocannabinoid System and Immunity\u2014the Journey from the Bedside to the Bench and Back\"<\/a> (in en). <i>International Journal of Molecular Sciences<\/i> <b>21<\/b> (12): 4448. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fijms21124448\" target=\"_blank\">10.3390\/ijms21124448<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1422-0067\" target=\"_blank\">1422-0067<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7352399\" target=\"_blank\">PMC7352399<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32585801\" target=\"_blank\">32585801<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4448\" target=\"_blank\">https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4448<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis%2C+the+Endocannabinoid+System+and+Immunity%E2%80%94the+Journey+from+the+Bedside+to+the+Bench+and+Back&rft.jtitle=International+Journal+of+Molecular+Sciences&rft.aulast=Almogi-Hazan&rft.aufirst=Osnat&rft.au=Almogi-Hazan%2C%26%2332%3BOsnat&rft.au=Or%2C%26%2332%3BReuven&rft.date=23+June+2020&rft.volume=21&rft.issue=12&rft.pages=4448&rft_id=info:doi\/10.3390%2Fijms21124448&rft.issn=1422-0067&rft_id=info:pmc\/PMC7352399&rft_id=info:pmid\/32585801&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1422-0067%2F21%2F12%2F4448&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-107\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-107\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Esposito, Giuseppe; Pesce, Marcella; Seguella, Luisa; Sanseverino, Walter; Lu, Jie; Corpetti, Chiara; Sarnelli, Giovanni (1 November 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.15157\" target=\"_blank\">\"The potential of cannabidiol in the COVID\u201019 pandemic\"<\/a> (in en). <i>British Journal of Pharmacology<\/i> <b>177<\/b> (21): 4967\u20134970. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1111%2Fbph.15157\" target=\"_blank\">10.1111\/bph.15157<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0007-1188\" target=\"_blank\">0007-1188<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7300643\" target=\"_blank\">PMC7300643<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32519753\" target=\"_blank\">32519753<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.15157\" target=\"_blank\">https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.15157<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+potential+of+cannabidiol+in+the+COVID%E2%80%9019+pandemic&rft.jtitle=British+Journal+of+Pharmacology&rft.aulast=Esposito&rft.aufirst=Giuseppe&rft.au=Esposito%2C%26%2332%3BGiuseppe&rft.au=Pesce%2C%26%2332%3BMarcella&rft.au=Seguella%2C%26%2332%3BLuisa&rft.au=Sanseverino%2C%26%2332%3BWalter&rft.au=Lu%2C%26%2332%3BJie&rft.au=Corpetti%2C%26%2332%3BChiara&rft.au=Sarnelli%2C%26%2332%3BGiovanni&rft.date=1+November+2020&rft.volume=177&rft.issue=21&rft.pages=4967%E2%80%934970&rft_id=info:doi\/10.1111%2Fbph.15157&rft.issn=0007-1188&rft_id=info:pmc\/PMC7300643&rft_id=info:pmid\/32519753&rft_id=https%3A%2F%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fbph.15157&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-108\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-108\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Malinowska, Barbara; Baranowska-Kuczko, Marta; Kicman, Aleksandra; Schlicker, Eberhard (17 February 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1986\" target=\"_blank\">\"Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19\"<\/a> (in en). <i>International Journal of Molecular Sciences<\/i> <b>22<\/b> (4): 1986. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.3390%2Fijms22041986\" target=\"_blank\">10.3390\/ijms22041986<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1422-0067\" target=\"_blank\">1422-0067<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7922403\" target=\"_blank\">PMC7922403<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33671463\" target=\"_blank\">33671463<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1986\" target=\"_blank\">https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1986<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Opportunities%2C+Challenges+and+Pitfalls+of+Using+Cannabidiol+as+an+Adjuvant+Drug+in+COVID-19&rft.jtitle=International+Journal+of+Molecular+Sciences&rft.aulast=Malinowska&rft.aufirst=Barbara&rft.au=Malinowska%2C%26%2332%3BBarbara&rft.au=Baranowska-Kuczko%2C%26%2332%3BMarta&rft.au=Kicman%2C%26%2332%3BAleksandra&rft.au=Schlicker%2C%26%2332%3BEberhard&rft.date=17+February+2021&rft.volume=22&rft.issue=4&rft.pages=1986&rft_id=info:doi\/10.3390%2Fijms22041986&rft.issn=1422-0067&rft_id=info:pmc\/PMC7922403&rft_id=info:pmid\/33671463&rft_id=https%3A%2F%2Fwww.mdpi.com%2F1422-0067%2F22%2F4%2F1986&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-109\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-109\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Raj, Vinit; Park, Jae Gyu; Cho, Kiu-Hyung; Choi, Pilju; Kim, Taejung; Ham, Jungyeob; Lee, Jintae (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813020351783\" target=\"_blank\">\"Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches\"<\/a> (in en). <i>International Journal of Biological Macromolecules<\/i> <b>168<\/b>: 474\u2013485. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.ijbiomac.2020.12.020\" target=\"_blank\">10.1016\/j.ijbiomac.2020.12.020<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC7836687\" target=\"_blank\">PMC7836687<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33290767\" target=\"_blank\">33290767<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813020351783\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0141813020351783<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Assessment+of+antiviral+potencies+of+cannabinoids+against+SARS-CoV-2+using+computational+and+in+vitro+approaches&rft.jtitle=International+Journal+of+Biological+Macromolecules&rft.aulast=Raj&rft.aufirst=Vinit&rft.au=Raj%2C%26%2332%3BVinit&rft.au=Park%2C%26%2332%3BJae+Gyu&rft.au=Cho%2C%26%2332%3BKiu-Hyung&rft.au=Choi%2C%26%2332%3BPilju&rft.au=Kim%2C%26%2332%3BTaejung&rft.au=Ham%2C%26%2332%3BJungyeob&rft.au=Lee%2C%26%2332%3BJintae&rft.date=1+January+2021&rft.volume=168&rft.pages=474%E2%80%93485&rft_id=info:doi\/10.1016%2Fj.ijbiomac.2020.12.020&rft_id=info:pmc\/PMC7836687&rft_id=info:pmid\/33290767&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0141813020351783&rfr_id=info:sid\/en.wikipedia.org:Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. References aren't listed in the order they appear in the original, but they do for this version, by design. In some cases important information was missing from the references, and that information was added. A few references in the original are misattributed or had incorrect DOIs; they have been corrected for this version. A mention of the U.S. 2018 Farm Bill and several citations related to that bill, as well as one in regards to Section 7606 of the Agricultural Act of 2014, were added. This version is otherwise unchanged in compliance with the \"NoDerivatives\" portion of the original's license.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220628022804\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 1.016 seconds\nReal time usage: 1.070 seconds\nPreprocessor visited node count: 108355\/1000000\nPost\u2010expand include size: 953942\/2097152 bytes\nTemplate argument size: 285296\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 272267\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 945.861 1 -total\n 91.78% 868.113 1 Template:Reflist\n 76.21% 720.849 109 Template:Citation\/core\n 72.95% 690.007 97 Template:Cite_journal\n 12.88% 121.807 102 Template:Date\n 9.45% 89.421 234 Template:Citation\/identifier\n 4.33% 40.994 7 Template:Cite_web\n 3.51% 33.220 468 Template:Hide_in_print\n 3.28% 30.977 4 Template:Citation\n 2.93% 27.699 1 Template:Infobox_journal_article\n-->\n\n<!-- Saved in parser cache with key cannaqa_wiki:pcache:idhash:5660-0!canonical and timestamp 20220628022803 and revision id 17456. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n<\/body>","4e539c9ca5c42af2a2ca977a314b2e2f_images":["https:\/\/www.cannaqa.wiki\/images\/0\/09\/Fig1_Hussain_iScience2021_24-12.jpg","https:\/\/www.cannaqa.wiki\/images\/b\/b0\/Fig2_Hussain_iScience2021_24-12.jpg"],"4e539c9ca5c42af2a2ca977a314b2e2f_timestamp":1656439824,"60c6b04b4bcf2aea432c0203d99568af_type":"article","60c6b04b4bcf2aea432c0203d99568af_title":"Simultaneous quantification of 17 cannabinoids in cannabis inflorescence by liquid chromatography\u2013mass spectrometry (Hewavitharana et al. 2022)","60c6b04b4bcf2aea432c0203d99568af_url":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry","60c6b04b4bcf2aea432c0203d99568af_plaintext":"\n\nJournal:Simultaneous quantification of 17 cannabinoids in cannabis inflorescence by liquid chromatography\u2013mass spectrometryFrom CannaQAWikiJump to navigationJump to searchFull article title\n \nSimultaneous quantification of 17 cannabinoids in cannabis inflorescence by liquid chromatography\u2013mass spectrometryJournal\n \nSeparationsAuthor(s)\n \nHewavitharana, Amitha K.; Gloerfelt-Tarp, Francine; Nolan, Matthew; Barkla, Bronwyn J.; Purdy, Sarah; Kretzschmar, TobiasAuthor affiliation(s)\n \nSouthern Cross University, New South Wales Department of Primary IndustriesPrimary contact\n \nEmail: a dot hewavitharana at pharmacy dot uq dot edu dot auYear published\n \n2022Volume and issue\n \n9(4)Article #\n \n85DOI\n \n10.3390\/separations9040085ISSN\n \n2297-8739Distribution license\n \nCreative Commons Attribution 4.0 InternationalWebsite\n \nhttps:\/\/www.mdpi.com\/2297-8739\/9\/4\/85\/htmDownload\n \nhttps:\/\/www.mdpi.com\/2297-8739\/9\/4\/85\/pdf (PDF)\n\nContents \n\n1 Abstract \n2 Introduction \n3 Materials and methods \n\n3.1 Materials \n3.2 Sample preparation \n3.3 Optimization of the extraction \n3.4 Separation and detection \n3.5 Data analysis and calculations \n3.6 Extraction method used for routine analysis \n3.7 Preparation of samples for major cannabinoids: THC, THCA, CBD, CBDA \n3.8 Preparation of samples for minor cannabinoids \n3.9 Preparation of standard solutions \n3.10 Method validation \n\n\n4 Results and discussion \n\n4.1 Sample preparation \n4.2 Optimization of the extraction \n4.3 Optimization of chromatographic separation and mass spectrometry \n4.4 Data analysis and processing \n4.5 Method validation \n\n\n5 Conclusions \n6 Acknowledgements \n\n6.1 Author contributions \n6.2 Funding \n6.3 Conflicts of interest \n\n\n7 References \n8 Notes \n\n\n\nAbstract \nWith an increasing appreciation for the unique pharmacological properties associated with distinct, individual cannabinoids of Cannabis sativa, there is demand for accurate and reliable quantification for a growing number of them. Although recent methods are based on highly selective chromatography\u2013mass spectrometry technology, most are limited to a few cannabinoids, while relying on unnecessarily sophisticated and expensive ultra-high-performance liquid chromatography and tandem mass spectrometry. Here we report an optimized, simple extraction method followed by a reliable and simple high-performance liquid chromatography (HPLC) method for separation. The detection is performed using a time-of-flight mass spectrometer that is available in most natural products research laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well-suited for routine phytocannabinoid analysis for a range of applications. The method was validated in terms of detection and quantification limits, repeatability, and recoveries for a total of 17 cannabinoids. Detection limits were in the range 11\u2013520 pg when using a 1 \u00b5L sample injection volume, and the recovery percentages ranged from 85% to 108%. The validated method was subsequently applied to determine cannabinoid composition in the inflorescences of several medicinal Cannabis sativa varieties.\nKeywords: cannabinoids, phytocannabinoids, LC-MS, Cannabis sativa, tetrahydrocannabinol, THC, cannabidiol, CBD\n\nIntroduction \nCannabis sativa L. (Cannabis) is one of the oldest domesticated plants, cultivated for the purpose of food, fiber, psychoactives, and medicine. In recent years, its medicinal properties have gained a renewed interest given its therapeutic potential in the treatment of a variety of disease conditions. To date, over 100 different cannabinoids have been identified, with \u03949-tetrahydrocannabinol (THC), well known for its psychoactive properties, and others, such as cannabidiol (CBD), recognized for their therapeutic and medicinal value.[1][2]\nHistorically, cannabis samples were analyzed mostly in a legal or regulatory context for the purpose of determining \u03949-THC content. However, as more cannabinoids were identified and their pharmacological potential was examined, the quantification of cannabinoids other than \u03949-THC gained importance. Additional cannabinoids of interest now include \u03949-tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG), cannabigerolic acid (CBGA), \u03949-tetrahydrocannabivarin (THCV), \u03949-tetrahydrocannabivarinic acid (THCVA), cannabidivarin (CBDV), and cannabidivarinic acid (CBDVA).[2][3] A recent study on virus-neutralizing capabilities of naturally occurring cannabinoids (in acid form) even found that CBDA and CBGA are capable of binding to the spike protein of SARS-CoV-2, therefore making for possible candidates for the treatment and prevention of COVID-19.[4] Clearly, accurate methods of quantification are needed to determine the concentrations of both major and minor cannabinoids of pharmacological potential in cannabis inflorescence, the source of cannabinoids in the plant.\nDespite the rising demand and importance of accurate quantification of cannabinoids, the number of studies with a clear focus on analytical method development remains relatively small. This might be in part due to regulatory constraints, which necessitate specific licenses to handle this scheduled drug and limit the availability of standard compounds and test samples. Due to this, the cannabis testing industry remains poorly established, with only a relatively limited number of laboratories offering analytical services and a lack of standardized protocols for extraction and analysis.[5]\nTwo review articles published recently[6][7] contain critical evaluations of methods used for cannabinoid analysis and the recent trends; therefore, a detailed comparison of methods is not included here. Chromatographic techniques are generally used for the separation of cannabinoids. Liquid chromatography (LC) has gained preference over gas chromatography (GC) as LC avoids conversion of the acid forms of cannabinoids to their neutral forms, which occurs at the high temperatures used in GC.[8] Until recently, the detection of column-separated cannabinoids was predominantly carried out using UV spectrophotometry, which provides low specificity and makes baseline separation of all cannabinoids imperative. However, complete separation of structurally similar cannabinoids, especially isomeric compounds such as \u03948-THC and \u03949-THC, is challenging.[3] Due to the lack of specificity of UV detection, any unknown compound\/s co-eluting at the same retention time as the target cannabinoid can cause overestimation of its concentration. \nTo overcome this specificity problem, the detection method of choice has been changing to mass spectrometry (MS).[6][7] As MS detection can identify molecules according to differences in mass, the chromatographic separation becomes less important. However, since some of the major cannabinoids\u2014e.g., \u03948-THC, \u03949-THC, CBD, cannabichromene (CBC), and cannabicyclol (CBL)\u2014have the same molecular mass, chromatographic separation is still required. Most of the methods using MS detection of cannabinoids are based on tandem mass spectrometry (MS-MS).[6][7] However, there is no real advantage of using this approach over basic MS, as cannabinoids of the same molar masses produce similar fragmentation patterns in the second MS event, thus not providing additional selectivity. Therefore, baseline separation by chromatography followed by simple MS detection is well suited for the routine analysis of cannabinoids.\nAccording to a recent review of cannabinoid analysis, variability in extraction (solvent\/s, method, time, and temperature) significantly contributes to differential analytical results.[6] Most of the recent analytical methods have used ethanol for extraction of both acidic and neutral cannabinoids[3][9], although the method used for extraction varied in terms of sample to solvent ratio, the extraction technique, and the duration of extraction. Therefore, a study of the effects of these variables on the amounts of cannabinoids extracted is warranted.\nThe aims of this study were to develop a simple yet effective method for the extraction of cannabinoids from cannabis inflorescences, and to develop a reliable, robust and simple liquid chromatography\u2013mass spectrometry (LC\u2013MS) method that can be used for routine analysis of 17 phytocannabinoids for which standards are available. In this study, a time-of-flight mass spectrometer (TOF-MS) was used as the detector. The acquisition of spectral data was by simple MS mode rather than MS-MS because there was no advantage in using tandem MS. As many natural products laboratories are equipped with a TOF instrument (primarily used for qualitative analysis), a quantification method based on a TOF-MS would facilitate adoption of this method. The extraction conditions were optimized to develop a simple and robust method to extract cannabinoids from inflorescence, without altering the composition of cannabinoids. A separation method that uses a low flow rate enabled the use of (high-performance liquid chromatography (HPLC) rather than requiring an expensive ultra-high-performance liquid chromatography (UHPLC) system. The chromatographic separation of the cannabinoids with the same molar mass was made sufficiently robust so that small changes in column and\/or mobile phase do not cause the isobaric cannabinoids to co-elute.\n\nMaterials and methods \nMaterials \nProprietary medicinal cannabis samples of Cann Group Limited were supplied by New South Wales Department of Primary Industries (NSW DPI, Orange, Australia) under an Office of Drug Control (ODC) permit and received by Southern Cross University (SCU) under NSW Health authority. Samples of contrasting lines for THC\/A and CBD\/A content were used for method establishment and validation.\nAll cannabinoid reference standards were purchased from Novachem Pty. Ltd. (Heidelberg, Australia) as ampoules of 1,000 \u00b5g\/mL solutions. The standards for (\u00b1)-\u03949-tetrahydrocannabinolic acid A (\u03949-THCA-A), tetrahydrocannabivarinic acid (THCVA), cannabidiolic acid (CBDA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), cannabinolic Acid (CBNA), cannabichromenic acid (CBCA), (\u00b1)-cannabicyclol (CBL), and cannabicyclolic acid (CBLA) were supplied in acetonitrile. The standards for (\u2212)-\u03949-tetrahydrocannabinol (\u03949-THC), (\u2212)-\u03948-tetrahydrocannabinol (\u03948-THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabidivarin (CBDV), cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC) were supplied in methanol. Ibuprofen was purchased from Sigma-Aldrich Pty Ltd. (North Ryde, NSW, Australia). HPLC-grade ethanol (Scharlau, Scharlab S.L., Barcelona, Spain) was used for sample extractions, and LC-MS grade solvents (Honeywell Research Chemicals, Seelze, Germany) and MilliQ water (Merck Millipore, Billerica, MA, USA) were used to prepare mobile phase.\n\nSample preparation \nApical and mature female inflorescences were cut from the main stems, and any large stem pieces were removed. Samples were dried for approximately seven days at 24 \u00b0C under low humidity (50\u201358%) until a dry weight of 21% of the starting wet weight was achieved, after which they were weighed, double vacuum packed, and stored at ambient room temperature in the dark.\nTwo grams of inflorescence were ground to a fine powder using a 50 mL stainless steel screw top Retsch grinding canister, containing a single 20 mm stainless steel grinding ball, in a Retsch Mixer Mill MM301 (Retsch GmbH, Mettmann, Germany) at 30 rotations per second for 10 seconds. Ground samples were stored in polypropylene tubes at \u221220 \u00b0C until extracted for analysis (note: flash-cooling the grinding canister and ball in liquid nitrogen before adding the sample prior to grinding helped to prevent clumping of material, especially in high resin samples, thus producing a homogenous fine powder).\n\nOptimization of the extraction \nFor extraction, 0.1g of ground sample was accurately weighed into a 20 mL polypropylene centrifuge tube. An aliquot of 2.50, 5.00 or 10.00 mL of 100% ethanol was accurately pipetted into the tube. Three replicates were extracted for each volume added. The mixture was sonicated in an ultrasound bath (SONICLEAN, Soniclean\u00ae, Dudley Park, Australia) at 50\/60 Hz and 150 W for 15 minutes, then centrifuged at 3000 rpm (Sigma 3\u201316 L, Sigma Laborzentrifugen GmbH, Osterode am Harz, Germany) for 10 minutes. The supernatant was carefully removed and stored in an Eppendorf tube at \u221220 \u00b0C. The extract was diluted as necessary with 100% ethanol for instrumental analysis using HPLC-MS. Volumes of injection of 1, 2 and 4 \u00b5L (for 2.50, 5.00 and 10.00 mL extractions, respectively) were used to obtain the same peak area (if each treatment were to extract the same amount). Ten cannabinoids were used for comparison (CBDV, CBDA, CBG, CBD, THCV, CBGA, THCVA, CBN, \u03949-THC, THCA). The peak areas of each cannabinoid were divided by the mass of the sample, and the peak area per gram of sample was used for comparison.\n\nSeparation and detection \nThe chromatographic separation of cannabinoids was performed using UHPLC on an Agilent 1290 Infinity II series system (Agilent Technologies, Santa Clara, CA, USA). The UHPLC was coupled to an Agilent 6545 high-resolution accurate mass (HRAM) QToF mass spectrometer equipped with a dual nebulizer jet stream electrospray source for ionization (Agilent) and controlled using Agilent MassHunter Acquisition Software, Tokyo, Japan (Version 10.1). Separation was achieved using an Agilent Poroshell C18 2.7 \u00b5m particle size, narrow bore, 15 cm column, held at 30 \u00b0C. The chromatographic analysis was performed using 0.1% (v\/v) formic acid in 30% v\/v methanol in water (mobile phase A), and 0.1% formic acid (v\/v) in acetonitrile (mobile phase B), at a flow rate of 0.3 mL\/min. The column was pre-equilibrated with 47% (v\/v) A and 53% (v\/v) B. After injection (of 1 \u00b5L sample or standard), the composition of mobile phase was maintained at 53% (v\/v) B for the first 25 min. It was then changed from 53% (v\/v) B to 70% (v\/v) B over the next 15 minutes (to 40 minute mark), changed from 70% (v\/v) B to 97% (v\/v) B over the next two minutes (to 42 minute mark), and then held at 97% (v\/v) B for one minute (to 43 minute mark). The column was then returned to the starting composition of 53% (v\/v) B over the next one minute (to 44 minute mark). Finally, the column was re-equilibrated using 53% (v\/v) B for six minutes (to 50 minute mark) prior to the next injection. The injection volume was kept low to avoid peak distortion (as explained in the discussion).\nThe mass spectrometer was used in MS1-positive mode to scan from m\/z 190 to 370 for all samples at a scan rate of 1.5 spectra\/s. The general parameters of the source were: capillary voltage 4000 V, nozzle voltage 0 V, fragmentor voltage 180 V, skimmer voltage 45 V and octopole RF Peak voltage 750 V, nebulizer pressure 20 psi, drying gas 10 L\/minute, drying gas temperature 325 \u00b0C, sheath gas flow 12, and sheath gas temperature 400 \u00b0C.\n\nData analysis and calculations \nData analysis was performed using Agilent MassHunter Quantitative Analysis (for QToF) Software, Tokyo, Japan (Version 10.1). Each cannabinoid in a chromatogram of standard compounds was identified based on its spectrum and the retention time. A processing method was prepared to extract each peak based on the m\/z value of each compound within a \u00b10.03 m\/z window. Peaks were integrated and exported to EXCEL for calculations. External standard calibration was performed using a five-point calibration curve up to 12.5 \u00b5g\/mL concentration with 1 \u00b5L injections. The regression values obtained (slope and intercept) in EXCEL were formatted to contain the same number of significant figures as the peak area values to avoid rounding errors. Standards used in calibration were used as unknowns\/samples to predict concentrations and estimate the validity of the calibration. Concentrations calculated for the samples injected were checked to ensure that they were within the calibration\/linear range. If not, they were re-run after dilution. After multiplying by the dilution factor, concentrations were expressed as \u00b5g\/g of the sample using the exact mass of the sample used in extraction. Dilution factors (of the 5 mL extract) used for minor and major cannabinoids in this study were 2.5 and 200, respectively. A pooled sample of ground inflorescence was prepared using a mixture of high-THC and high-CBD plant material and used as the quality control (QC) sample with each batch of the samples analyzed.\n\nExtraction method used for routine analysis \nA sample of 0.1g ground cannabis inflorescence was accurately weighed into a 20 mL polypropylene centrifuge tube. A 5.00 mL aliquot of 100% ethanol was accurately pipetted into the tube. The mixture was sonicated in an ultrasound bath at 50\/60 Hz and 150 W for 30 minutes, then centrifuged at 3,000 rpm (Sigma 3\u201316 L, Germany) for 10 minutes. The supernatant was carefully removed and stored in a 2 mL Eppendorf tube at \u221220 \u00b0C. The extract was diluted as necessary (below) with 100% ethanol prior to the instrumental analysis using HPLC-MS.\n\n Preparation of samples for major cannabinoids: THC, THCA, CBD, CBDA \nThe extract was diluted 80 times by mixing 20 \u00b5L sample extract and 1580 \u00b5L ethanol. The extract was then further diluted by mixing 400 \u00b5L of the diluted extract, 40 \u00b5L of 0.025 mg\/mL Ibuprofen, and 560 \u00b5L ethanol in an HPLC vial to be used for LC-MS analysis. This resulted in a 200 times diluted extract containing 1 \u00b5g\/mL Ibuprofen (internal standard).\n\nPreparation of samples for minor cannabinoids \nThe extract was diluted by mixing 400 \u00b5L of the extract, 40 \u00b5L of 0.025 mg\/mL Ibuprofen, and 560 \u00b5L ethanol in an HPLC vial to be used for LC-MS analysis. This resulted in a 2.5 times diluted extract containing 1 \u00b5g\/mL Ibuprofen (internal standard).\n\nPreparation of standard solutions \nA 0.05 mg\/mL solution of 17 cannabinoid standards was prepared by mixing 100 \u00b5L each of the 17 cannabinoid stock standards (1 mg\/mL), and 300 \u00b5L of HPLC grade ethanol in a 2 mL Eppendorf tube. A 0.025 mg\/mL mix of standards was prepared by diluting the 0.05 mg\/mL solution and used as the working standard stock solution.\nIbuprofen was weighed into a 1.5 mL Eppendorf tube and dissolved in an appropriate volume of HPLC grade ethanol to make a 1 mg\/mL stock solution. This solution was diluted with an appropriate volume of ethanol to make the 0.025 mg\/mL working stock standard.\nFive calibration standards were prepared by diluting the appropriate volumes of 0.025 mg\/mL mix of 17 standards, and 0.025 mg\/mL Ibuprofen to contain 2.5, 5, 7.5, 10, and 12.5 \u00b5g\/mL cannabinoids and 1 \u00b5g\/mL Ibuprofen (internal standard).\n\nMethod validation \nLinearity for each cannabinoid was estimated by injecting 1\u00b5L each of five mixed standard solutions containing 0.5 to 12.5 \u00b5g\/mL of the 17 cannabinoids. The linearity was assessed by plotting the peak area of each cannabinoid versus the concentration. Limit of detection (LOD) and limit of quantification (LOQ) for each cannabinoid was determined based on the peak heights (and then the concentrations) corresponding to 3\u00d7 noise and 10\u00d7 noise, respectively. Repeatability was estimated by analyzing seven individual 0.1 g ground cannabis inflorescence samples (that were prepared by pooling samples containing high CBD and high THC levels), followed by the calculation of relative standard deviation of the concentrations determined for each cannabinoid. Recovery was determined by using the concentrations of each cannabinoid in spiked and un-spiked extracts using seven of the individual extracts prepared for the repeatability experiment. Each extract was spiked to give an added concentration that was below the mid-point of the calibration (linear) range.\n\nResults and discussion \nSample preparation \nA significantly larger (than the amount used for analysis) amount of inflorescence (2 g) was ground in order to minimize effects of within sample variation due to the architecture\/morphology of the inflorescence (containing bracts, stigma, sugar leaves, stem remnants, etc.) of varying trichome density. After homogenization by grinding, a representative 0.1 g sample was extracted for analysis.\n\nOptimization of the extraction \nEthanol has been the most common solvent of choice in recent studies of cannabinoid analysis, and the high extracting efficiency of ethanol is attributed to the high affinity of ethanol to the cannabinoid molecular structure.[6] Important advantages of using ethanol extraction for cannabinoid analysis are its general availability, low toxicity, low cost, and easy storage and handling. Furthermore, the concentrations determined by the analytical methods that used ethanol for extraction are likely in the range of concentrations used for actual extraction in formulations intended for human consumption, as ethanol is a common extraction solvent in preparations. An extraction that does not involve heat is more appropriate for cannabinoid extraction because heat can change the ratio of acid forms to neutral forms[8], thereby altering the composition of cannabinoids in the sample prior to analysis.\nAn optimization study of the extraction of cannabinoids from dried, ground cannabis inflorescence, using factorial design, found that the extraction solvent (80% methanol vs methanol-chloroform mixture), technique of extraction, and the time of extraction beyond 15 minutes did not significantly affect the amounts of cannabinoids extracted. The most significant variable that affected the amounts extracted was the sample to solvent ratio.[10] In recent methods that used ethanol as the extraction solvent, the ratio (grams of dried inflorescence\/mL ethanol) varied from 1\/100[9][11] to 1\/15.[3] Therefore, a study of the effect of this ratio on the amounts of cannabinoids extracted was warranted in order to establish an optimum extraction procedure prior to instrumental analysis. A systematic study of the effects of solvents other than the ones studied in the previous study[10], and extraction times below 15 minutes, was beyond the scope of this study.\nIn this study, the effect of the ratio \"grams of ground inflorescence \/ mL ethanol\" on the amount of cannabinoids extracted was studied using 0.1g of dried inflorescence in 2.5, 5, and 10 mL volumes of ethanol (ratios of 1\/25, 1\/50, and 1\/100, respectively), using triplicate extractions for each ratio. Volumes of injection of 1, 2, and 4 \u00b5L (respectively) were used to obtain the same peak area (if each treatment were to extract the same amount). Ten cannabinoids that were present in significant amounts in the sample were used for comparison (CBDV, CBDA, CBG, CBD, THCV, CBGA, THCVA, CBN, \u03949-THC, THCA). Peak area per gram of sample was used for comparison.\nAccording to the results of one-way ANOVA (plus a Duncan\u2019s multiple range test for the means), sample\/solvent ratio of 1\/100 extracted significantly lower (p < 0.05) amounts of all cannabinoids in comparison to the other two ratios. The amounts extracted with the ratios 1\/25 and 1\/50 were not significantly different (at p = 0.05) for all cannabinoids. However, the precision (based on the coefficient of variance) was better with the ratio 1\/50. Therefore, that ratio (0.1 g of ground inflorescence in 5 mL ethanol) was used for all extractions in this study.\n\nOptimization of chromatographic separation and mass spectrometry \nChromatographic separation for all cannabinoids was optimized, with the main emphasis on the baseline separation of the critical isomeric pair of \u03948-THC and \u03949-THC. Chromatographic separation with good resolution was also targeted for individual cannabinoids in two groups of isobaric compounds: CBD, \u03948-THC, \u03949-THC, CBC, CBL (m\/z = 315.2) and CBDA, THCA, CBLA, CBCA (m\/z = 359.2). In order to conduct these separations, a column with small particle size and\/or maximum possible length was important. However, because of the aim of making this separation suitable for HPLC rather than UHPLC, it was decided to use a poroshell-type column (a thin layer of porous stationary phase is coated on solid silica cores) that can produce resolutions similar to sub-2 \u00b5m body-porous stationary phase particles used in UHPLC columns, without having to use very high pressure. As the longest available LC-MS column (15 cm) was used in this separation, the high pressure required was compensated by using a low flow rate (0.3 mL\/min). Although the run time could have been shortened by using a higher flow rate, the flow rate was kept low in order to operate the LC in HPLC mode rather than UHPLC mode, particularly because our aim was to produce a method that can be run on a simple HPLC system. \nThe polarity of a C18 column is suitable for the separation when a low pH is used (when the acid forms are not ionized to produce highly polar carboxylates). The detector (MS) sensitivities for neutral compounds were much higher than those for acid forms at low pH. Another advantage of using low pH was, that the neutral forms of cannabinoids naturally occur at much lower concentrations compared to the acid forms. Therefore, the difference in sensitivities was well suited for analyzing a mixture of acids and neutrals without having to make additional dilutions to quantify the range of cannabinoids of interest. Formic acid (0.1%) was used to achieve a low pH of around three in the mobile phase. \nOrganic modifiers\u2014methanol and acetonitrile, from two different classes of selectivity\u2014were tested in different ratios and combinations to improve the selectivity factor of the separations.[12] The optimal separation of all 17 cannabinoids was achieved within the isocratic section at the beginning of the gradient using 53% v\/v methanol\/water (with 0.1% formic acid) as mobile phase A, and acetonitrile (with 0.1% formic acid) on a Poroshell C18 column with a particle size of 2.7 \u00b5m (as detailed under Section 2 above) (Figure 1). The m\/z values used for detection and the retention times for each cannabinoid are listed in Table 1. Since the samples and standards were in 100% organic solvent (ethanol), and the start of the gradient was only about 53% organic (weaker eluent strength), the chromatographic peaks were prone to distortion. With the column size and flow rate used in this study, we found that peak distortion could be prevented as long as the volume of injection was kept below 4 \u00b5L. The injection volume was kept at 1 \u00b5L throughout this study.\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 1 Chromatographic and mass spectrometric separation of Ibuprofen and 17 cannabinoids in a standard mixture. Top chromatogram shows the total ion chromatogram and the other chromatograms are extracted at the mass of compound\/s.\n\n\n\n\n\n\n\n\n\nTable 1. Retention time and precursor ions used to extract and integrate chromatographic peak of each cannabinoid. A \u00b10.03 m\/z window was used to extract spectral data.\n\n\nCompound\n\nPrecursor ion (m\/z)\n\nRetention time (minutes)\n\n\nIbuprofen\n\n251.1029\n\n3.0\n\n\nCBDV\n\n287.2021\n\n4.8\n\n\nTHCV\n\n287.2027\n\n9.6\n\n\nCBN\n\n311.2019\n\n16.8\n\n\nCBD\n\n315.2339\n\n9.4\n\n\n\u03948-THC\n\n315.2337\n\n23.4\n\n\n\u03949-THC\n\n315.2336\n\n21.8\n\n\nCBC\n\n315.2337\n\n31.2\n\n\nCBL\n\n315.2336\n\n26.1\n\n\nCBG\n\n317.2493\n\n9.4\n\n\nCBDVA\n\n331.1919\n\n5.0\n\n\nTHCVA\n\n331.1919\n\n16.6\n\n\nCBNA\n\n355.1920\n\n28.1\n\n\nCBDA\n\n359.2239\n\n8.9\n\n\nTHCA\n\n359.2237\n\n34.0\n\n\nCBLA\n\n359.2236\n\n36.8\n\n\nCBCA\n\n359.2238\n\n38.0\n\n\nCBGA\n\n361.2385\n\n11.0\n\n\n\nAs described above, our aim was to develop an MS detection method rather than a tandem MS detection method. This was partly to be able to use an inexpensive HPLC-MS system, and partly because there is no advantage in using MS-MS detection (the isobaric cannabinoids produced the same fragments in MS-MS therefore needed to be chromatographically separated). We used the QToF and its processing software to mimic a single ion monitoring (SIM) mode of detection and quantification that is normally used in quadrupole MS systems. Data was acquired as spectra in total ion current (TIC) mode within the range of m\/z 190\u2013370, and each cannabinoid peak was extracted (as listed in Table 1) from these spectra for processing. An advantage of using the TIC mode is the possibility of detection of other compounds that have their molar masses within the range of detection used. Since we started using this method to analyze samples from other projects, we were able to detect (and tentatively identify based on literature-reported mass values) some other cannabinoids, in some samples (data not shown). This could not have been possible with a quadrupole MS instrument that is usually used for quantification.\nSince there was concern regarding the source temperature (325 \u00b0C) causing decarboxylation of the acid forms[6][8][13], the presence of peaks for neutral forms were checked at the retention times of the acid forms. As evident from Figure 1, they were absent, confirming that the acid forms were not decarboxylated in MS. In the case of CBDA and CBD, which have very similar retention times, this was established by running only CBDA standard, and confirming the absence of a peak at m\/z of 315.2 (corresponding to CBD).\n\nData analysis and processing \nThe extract ion chromatography (EIC) option in Agilent MassHunter Quantitative Analysis (for QToF) software (Version 10.1) was used to extract peaks. We used a window of \u00b10.03 m\/z for EIC in this software, seeking to prevent MS line overlapping between CBD and CBG, which have the same retention time although they are 2 m\/z value apart. Since the sensitivities for (abundant) acid forms were deliberately suppressed (relative to the neutral forms), a single dilution of the extract by 2.5 times allowed all minor cannabinoid levels to fall within the calibration range. The extracts were required to be diluted by 200 times to make the concentrations of the major cannabinoids (CBD, CBDA, THC, THCA) to fall within the calibration\/linear range. We were able to quantify all 17 cannabinoids using only two dilutions because of the use of low pH elution to improve the sensitivities of neutral forms relative to those of acid forms, and because of the use of a low flowrate (therefore lower peak heights).\nMatrix effects (mostly by causing ion-suppression) are a major problem that impair the accuracy of LC-MS data.[14][15][16] As matrix effects cannot be completely eliminated in practice, the data is corrected for matrix effects by running a co-eluting internal standard for each analyte and subsequent calibration using internal standard method.[14][15] In our work, we did not correct for matrix effects because co-eluting compounds (stable isotope labelled analogues of the cannabinoids) were not yet commercially available for most of the cannabinoids. When available, they can easily be incorporated into to the current method, and the calibration can be carried out using an internal standard method. Until then, the data is not completely free of matrix effects. However, using lengthier retention times as well as achieving high resolution of all peaks in our method ensure minimal matrix effects because the likelihood of co-elution of matrix compounds with the peaks of interest is minimized. In addition, the high dilutions used, especially for the major cannabinoids (0.1 g sample diluted to 1 L), ensured negligible matrix effects on their concentration data.[15] The high sensitivity of the method enables the detection of very low concentrations, and therefore high dilution to minimize matrix effects was possible.\nUsing an internal standard that does not co-elute with the analyte is not an option in addressing LC-MS matrix effects.[16] This is because the matrix effects at each time point of the chromatogram are different for different matrices. This was the reason that the internal standard (Ibuprofen) used in method development was not used in actual calculations. However, if a study were undertaken using all samples containing the same matrix (e.g., studying the effect of some variable on the same plant matrix), Ibuprofen could be used as the internal standard to eliminate procedural errors (but with no effect on matrix effects).\n\nMethod validation \nThe LOD and LOQ, estimated based on 3\u00d7 and 10\u00d7 noise, respectively, ranged from 9 to 1734 picograms, as shown in Table 2. In general, acid forms of cannabinoids have higher LOD values (i.e., lower sensitivities) relative to the neutral forms. As discussed above, the suppression of sensitivities of acid forms (that are more abundant than the neutral forms) was deliberate in order to fit the MS responses of acid forms within the calibration range. In addition, Table 2 shows LOD and LOQ values calculated based on the concentrations of the extract that was injected to the column (with 1 \u00b5L volume of injection), and the concentrations in dried, ground inflorescence (based on 2.5-fold dilution of the 5 mL extract).\n\n\n\n\n\n\n\nTable 2. Linearity, detection limits, and quantification limits for 17 cannabinoids and Ibuprofen. * On column amounts; ** Concentration in extract; *** Concentration in sample.\n\n\nCompound\n\nLinearity (r2) and (Upper limit, in \u00b5g\/mL)\n\nLOD * (pg)\n\nLOD ** (\u00b5g\/mL)\n\nLOD *** (\u00b5g\/g)\n\nLOQ * (pg)\n\nLOQ ** (\u00b5g\/mL)\n\nLOQ *** (\u00b5g\/g)\n\n\nIbuprofen\n\n0.998 (10.0)\n\n-\n\n-\n\n-\n\n-\n\n-\n\n-\n\n\nCBDV\n\n0.998 (12.5)\n\n11.0\n\n0.011\n\n1.37\n\n36.6\n\n0.037\n\n4.57\n\n\nTHCV\n\n0.999 (12.5)\n\n9.43\n\n0.009\n\n1.18\n\n31.4\n\n0.031\n\n3.93\n\n\nCBN\n\n0.999 (12.5)\n\n72.9\n\n0.073\n\n9.11\n\n243\n\n0.243\n\n30.4\n\n\nCBD\n\n0.999 (12.5)\n\n17.4\n\n0.017\n\n2.17\n\n57.9\n\n0.058\n\n7.24\n\n\n\u03948-THC\n\n0.999 (12.5)\n\n31.4\n\n0.031\n\n3.93\n\n105\n\n0.011\n\n13.1\n\n\n\u03949-THC\n\n0.999 (12.5)\n\n23.4\n\n0.023\n\n2.93\n\n78.2\n\n0.078\n\n9.77\n\n\nCBC\n\n0.999 (12.5)\n\n60.8\n\n0.061\n\n7.60\n\n203\n\n0.020\n\n25.3\n\n\nCBL\n\n0.998 (12.5)\n\n43.9\n\n0.044\n\n5.49\n\n146\n\n0.146\n\n18.3\n\n\nCBG\n\n0.996 (12.5)\n\n27.0\n\n0.027\n\n3.37\n\n89.9\n\n0.090\n\n11.2\n\n\nCBDVA\n\n0.999 (12.5)\n\n181\n\n0.181\n\n22.6\n\n604\n\n0.604\n\n75.4\n\n\nTHCVA\n\n0.999 (12.5)\n\n98.3\n\n0.098\n\n12.3\n\n328\n\n0.328\n\n40.9\n\n\nCBNA\n\n0.998 (12.5)\n\n199\n\n0.199\n\n24.8\n\n662\n\n0.662\n\n82.7\n\n\nCBDA\n\n0.999 (12.5)\n\n125\n\n0.125\n\n15.7\n\n418\n\n0.418\n\n52.2\n\n\nTHCA\n\n0.999 (12.5)\n\n73.7\n\n0.074\n\n9.21\n\n246\n\n0.246\n\n30.7\n\n\nCBLA\n\n0.999 (12.5)\n\n239\n\n0.239\n\n29.8\n\n795\n\n0.795\n\n99.4\n\n\nCBCA\n\n0.999 (12.5)\n\n220\n\n0.220\n\n27.5\n\n735\n\n0.735\n\n91.8\n\n\nCBGA\n\n0.997 (12.5)\n\n520\n\n0.520\n\n65.0\n\n1734\n\n1.734\n\n218\n\n\n\nTable 2 also shows the linearity, along with the upper limits of concentrations. Good linearities (r2 of >0.99) were obtained for all cannabinoids for the concentration ranges used for calibration.\nThe repeatability values (n = 7), determined by analyzing multiple sub-samples of the pooled ground inflorescence and expressed as percentage standard deviations, are shown in Table 3. The chromatograms for the pooled sample are shown in Figure 2. The percentage standard deviations were larger for the cannabinoids that have high LOD values\/lower sensitivities. It is likely that lack of complete homogeneity of the ground samples, due to the formation of resin aggregates, contributed to the high RSD values. As suggested prior, snap-cooling the sample (in dry ice) before grinding produces homogeneous samples, although heat produced by friction during the grinding process might still cause resins to aggregate to some extent.\n\n\n\n\n\n\n\nTable 3. Repeatability (as mean value with standard deviation, in column 2, and as relative standard deviation, in column 3), and recovery for each cannabinoid (n = 7) in the pooled inflorescence sample. * Not detected; ** Values for \u00d7200 diluted extract shown (values for \u00d72.5 diluted extracts were 381 \u00b1 14.3, 3.76, and 29.0 \u00b1 5.24, respectively).\n\n\nCompound\n\nRepeatability\n\nRecovery\n\n\nMean \u00b1 SD (\u00b5g\/g)\n\nRSD (%)\n\nMean \u00b1 SD (%)\n\n\nCBDV\n\n50.5 \u00b1 2.21\n\n4.37\n\n101 \u00b1 3.15\n\n\nCBDVA\n\n144 \u00b1 8.67\n\n6.03\n\n96.3 \u00b1 6.27\n\n\nCBDA\n\n38,850 \u00b1 2973\n\n7.65\n\n94.8 \u00b1 11.0\n\n\nCBG **\n\n1084 \u00b1 91.7\n\n8.46\n\n97.9 \u00b1 4.09\n\n\nCBD\n\n15,110 \u00b1 973\n\n6.44\n\n99.0 \u00b1 5.82\n\n\nTHCV\n\n25.7 \u00b1 1.46\n\n5.67\n\n87.3 \u00b1 3.11\n\n\nCBGA\n\n399 \u00b1 20.2\n\n20.2\n\n108.5 \u00b1 9.47\n\n\nTHCVA\n\n324 \u00b1 23.0\n\n7.09\n\n99.4 \u00b1 6.26\n\n\nCBN\n\n68.2 \u00b1 3.66\n\n5.37\n\n101 \u00b1 2.07\n\n\n\u03948-THC\n\nND *\n\n-\n\n95.0 \u00b1 2.35\n\n\n\u03949-THC\n\n4748 \u00b1 232\n\n4.89\n\n102 \u00b1 4.30\n\n\nCBL\n\n14.7 \u00b1 0.58\n\n3.97\n\n99.3 \u00b1 3.61\n\n\nCBNA\n\n285 \u00b1 17.5\n\n6.14\n\n98.6 \u00b1 3.32\n\n\nCBC\n\n770 \u00b1 65.4\n\n8.49\n\n101 \u00b1 2.87\n\n\nTHCA\n\n43,681 \u00b1 5080\n\n11.6\n\n103 \u00b1 8.11\n\n\nCBLA\n\n196 \u00b1 11.0\n\n5.60\n\n101 \u00b1 5.82\n\n\nCBCA\n\n519 \u00b1 18.8\n\n3.62\n\n85.2 \u00b1 13.8\n\n\n\n\r\n\n\n\n\n\n\n\n\n\n\nFig. 2 Chromatographic and mass spectrometric separation of Ibuprofen and cannabinoids in a pooled sample of cannabis inflorescence. Top chromatogram shows the total ion chromatogram and the other chromatograms are extracted at the mass of compound\/s.\n\n\n\nThe mean recoveries, calculated using the percent ratio of observed\/spiked concentrations, are also shown in Table 3, along with their SD values (n = 7). In the case of CBG, both the low-dilution (\u00d72.5) and high-dilution (\u00d7200) produced peaks that were within the linear range. However, the recovery from low-dilution samples was about 30% compared to almost 100% recovery for the high-dilution samples. The mean concentration value was also about three times higher with the high dilution. This clearly demonstrates the ion-suppression effects on CBG, and the elimination of this effect by sample dilution, as discussed above.[14] As CBG and CBD have similar retention times, the CBG signal was suppressed by CBD in high CBD samples. In the pool sample used in Table 3, the CBD concentration is >10 times that of CBG.\nThe method was applied to quantify cannabinoids in several different samples containing high levels of CBD and high levels of THC. The concentrations of each cannabinoid quantified are listed in Table 4.\n\n\n\n\n\n\n\nTable 4. Concentration ranges (\u00b5g\/g) of cannabinoids found in two high-CBD and three high-THC samples. ND, not detected; <LOD, below detection limit; <LOQ, between detection and quantification limits.\n\n\nCompound\n\nHigh-CBD samples\n\nHigh-THC samples\n\n\nCBDV\n\n61.0\u201382.0\n\nND\n\n\nTHCV\n\n5.95\u20137.26\n\n38.2\u2013107\n\n\nCBN\n\n<LOQ\n\n105\u2013134\n\n\nCBD\n\n4090\u201328,713\n\n212\u2013382\n\n\n\u03948-THC\n\nND\n\nND\n\n\n\u03949-THC\n\n1705\u20132482\n\n11,936\u201320,476\n\n\nCBC\n\n928\u20131095\n\n153\u2013248\n\n\nCBL\n\nND\n\nND\n\n\nCBG\n\n376\u2013470\n\n519\u2013585\n\n\nCBDVA\n\n165\u2013216\n\nND\n\n\nTHCVA\n\n<LOQ\n\n160\u20131209\n\n\nCBNA\n\n<LOD\n\n342\u2013875\n\n\nCBDA\n\n10,258\u201364,992\n\n245\u2013363\n\n\nTHCA\n\n796\u20131518\n\n13,479\u201336,420\n\n\nCBLA\n\n196\u2013250\n\nND\n\n\nCBCA\n\n1732\u20132952\n\n998\u20131363\n\n\nCBGA\n\n1045\u20131234\n\n2956\u20136273\n\n\n\nConclusions \nAn optimised, simple extraction method followed by a reliable and simple LC-MS method, was developed and validated for the simultaneous quantification of 17 cannabinoids. The method can be used by natural products laboratories that are equipped with a TOF-MS detector. By using low flow rate, the separation was achieved at low pressure (HPLC rather than UHPLC) conditions. The disadvantage of using the low flow rate was the long run time. Detection was performed by simpler MS rather than MS-MS. Although there was no significant loss of selectivity due to using MS instead of MS-MS, the sensitivity is compromised as evident from relatively high LOD and LOQ values (\u00b5g\/mL levels compared to ng\/mL levels commonly achieved with MS-MS). The main advantage of using this approach is that the method can be easily adapted to use with a simple HPLC-MS (single quadrupole) system that is commonly used in routine analytical laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well suited for routine phytocannabinoid analysis across a range of applications in a variety of laboratory settings.\n\nAcknowledgements \nWe want to thank Cann Group Limited, lead industry partner on the CRC-P, for their valuable input and for providing proprietary germplasm for this research.\n\nAuthor contributions \nConceptualization A.K.H., T.K. and B.J.B.; methodology, A.K.H.; formal analysis A.K.H., F.G.-T. and M.N.; investigation, A.K.H., F.G.-T., S.P. and M.N.; writing\u2014original draft preparation, A.K.H. and T.K.; writing\u2014review and editing, B.J.B., F.G.-T., S.P. and M.N.; supervision, A.K.H. and T.K.; project administration, T.K. and S.P.; funding acquisition, B.J.B. and T.K. All authors have read and agreed to the published version of the manuscript.\n\nFunding \nThis project received grant funding from the Australian Government via the Department of Industry, Science, Energy and Resources, as part of the Cooperative Research Centres Project (CRC-P) program\u2014Round 7: Growing the medicinal cannabis industry\u2014precision farming to pharmaceuticals.\n\nConflicts of interest \nThe authors declare no conflict of interest.\n\nReferences \n\n\n\u2191 Chandra, Suman; ElSohly, Mahmoud A.; Lata, Hemant, eds. (2017). Cannabis sativa L. - Botany and Biotechnology (1st ed. 2017 ed.). Cham: Springer International Publishing : Imprint: Springer. ISBN 978-3-319-54564-6.   \n \n\n\u2191 2.0 2.1 Clarke, Robert C.; Merlin, Mark D. (1 November 2016). \"Cannabis Domestication, Breeding History, Present-day Genetic Diversity, and Future Prospects\" (in en). Critical Reviews in Plant Sciences 35 (5-6): 293\u2013327. doi:10.1080\/07352689.2016.1267498. ISSN 0735-2689. https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/07352689.2016.1267498 .   \n \n\n\u2191 3.0 3.1 3.2 3.3 Giese, Matthew W; Lewis, Mark A; Giese, Laura; Smith, Kevin M (1 November 2015). \"Method for the Analysis of Cannabinoids and Terpenes in Cannabis\" (in en). Journal of AOAC INTERNATIONAL 98 (6): 1503\u20131522. doi:10.5740\/jaoacint.15-116. ISSN 1060-3271. https:\/\/academic.oup.com\/jaoac\/article\/98\/6\/1503-1522\/5654599 .   \n \n\n\u2191 van Breemen, Richard B.; Muchiri, Ruth N.; Bates, Timothy A.; Weinstein, Jules B.; Leier, Hans C.; Farley, Scotland; Tafesse, Fikadu G. (28 January 2022). \"Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants\" (in en). Journal of Natural Products 85 (1): 176\u2013184. doi:10.1021\/acs.jnatprod.1c00946. ISSN 0163-3864. PMC PMC8768006. PMID 35007072. https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00946 .   \n \n\n\u2191 Welling, Matthew T.; Liu, Lei; Hazekamp, Arno; Dowell, Ashley; King, Graham J. (25 February 2019). \"Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry\" (in en). Medical Cannabis and Cannabinoids 2 (1): 1\u201313. doi:10.1159\/000496868. ISSN 2504-3889. PMC PMC8489335. PMID 34676328. https:\/\/www.karger.com\/Article\/FullText\/496868 .   \n \n\n\u2191 6.0 6.1 6.2 6.3 6.4 6.5 Citti, Cinzia; Braghiroli, Daniela; Vandelli, Maria Angela; Cannazza, Giuseppe (1 January 2018). \"Pharmaceutical and biomedical analysis of cannabinoids: A critical review\" (in en). Journal of Pharmaceutical and Biomedical Analysis 147: 565\u2013579. doi:10.1016\/j.jpba.2017.06.003. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708517311895 .   \n \n\n\u2191 7.0 7.1 7.2 Micalizzi, Giuseppe; Vento, Federica; Alibrando, Filippo; Donnarumma, Danilo; Dugo, Paola; Mondello, Luigi (1 January 2021). \"Cannabis Sativa L.: a comprehensive review on the analytical methodologies for cannabinoids and terpenes characterization\" (in en). Journal of Chromatography A 1637: 461864. doi:10.1016\/j.chroma.2020.461864. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967320311389 .   \n \n\n\u2191 8.0 8.1 8.2 Hewavitharana, A.K.; Golding, G.; Tempany, G.; King, G.; Holling, N. (1 May 2005). \"Quantitative GC-MS Analysis of \u03949-Tetrahydrocannabinol in Fiber Hemp Varieties\" (in en). Journal of Analytical Toxicology 29 (4): 258\u2013261. doi:10.1093\/jat\/29.4.258. ISSN 1945-2403. http:\/\/academic.oup.com\/jat\/article\/29\/4\/258\/730079\/Quantitative-GCMS-Analysis-of .   \n \n\n\u2191 9.0 9.1 ECA Foundation (8 April 2020). \"German Pharmacopoeia Monograph for Cannabis Extracts\". ECA Academy. ECA Foundation. https:\/\/www.gmp-compliance.org\/gmp-news\/german-pharmacopoeia-monograph-for-cannabis-extracts . Retrieved 28 February 2022 .   \n \n\n\u2191 10.0 10.1 Mudge, Elizabeth M.; Murch, Susan J.; Brown, Paula N. (1 May 2017). \"Leaner and greener analysis of cannabinoids\" (in en). Analytical and Bioanalytical Chemistry 409 (12): 3153\u20133163. doi:10.1007\/s00216-017-0256-3. ISSN 1618-2642. PMC PMC5395585. PMID 28233028. http:\/\/link.springer.com\/10.1007\/s00216-017-0256-3 .   \n \n\n\u2191 Berman, Paula; Futoran, Kate; Lewitus, Gil M.; Mukha, Dzmitry; Benami, Maya; Shlomi, Tomer; Meiri, David (1 December 2018). \"A new ESI-LC\/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis\" (in en). Scientific Reports 8 (1): 14280. doi:10.1038\/s41598-018-32651-4. ISSN 2045-2322. PMC PMC6155167. PMID 30250104. http:\/\/www.nature.com\/articles\/s41598-018-32651-4 .   \n \n\n\u2191 Skoog, Douglas A. (1985). Principles of instrumental analysis. Saunders golden sunburst series (3rd ed.). Philadelphia: Saunders College Pub. ISBN 978-0-03-001229-7.   \n \n\n\u2191 Wang, Mei; Wang, Yan-Hong; Avula, Bharathi; Radwan, Mohamed M.; Wanas, Amira S.; van Antwerp, John; Parcher, Jon F.; ElSohly, Mahmoud A. et al. (1 December 2016). \"Decarboxylation Study of Acidic Cannabinoids: A Novel Approach Using Ultra-High-Performance Supercritical Fluid Chromatography\/Photodiode Array-Mass Spectrometry\" (in en). Cannabis and Cannabinoid Research 1 (1): 262\u2013271. doi:10.1089\/can.2016.0020. ISSN 2378-8763. PMC PMC5549281. PMID 28861498. http:\/\/www.liebertpub.com\/doi\/10.1089\/can.2016.0020 .   \n \n\n\u2191 14.0 14.1 14.2 Taylor, Paul J. (1 April 2005). \"Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography\u2013electrospray\u2013tandem mass spectrometry\" (in en). Clinical Biochemistry 38 (4): 328\u2013334. doi:10.1016\/j.clinbiochem.2004.11.007. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009912004003364 .   \n \n\n\u2191 15.0 15.1 15.2 Hewavitharana, Amitha K. (1 January 2011). \"Matrix matching in liquid chromatography\u2013mass spectrometry with stable isotope labelled internal standards\u2014Is it necessary?\" (in en). Journal of Chromatography A 1218 (2): 359\u2013361. doi:10.1016\/j.chroma.2010.11.047. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967310016213 .   \n \n\n\u2191 16.0 16.1 Hewavitharana, A.K.; Shawn, P.N.; Smyth, H.D.C. et al. (July 2021). \"The Importance of Complete Overlapping of Analyte and Internal Standard Peaks in Eliminating Matrix Effects with Liquid Chromatography\u2013Mass Spectrometry (LC\u2013MS)\". LCGC North America 39 (7): 335\u201338. https:\/\/www.chromatographyonline.com\/view\/the-importance-of-complete-overlapping-of-analyte-and-internal-standard-peaks-in-eliminating-matrix-effects-with-liquid-chromatography-mass-spectrometry-lc-ms- .   \n \n\n\nNotes \nThis presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added.\n\n\n\n\n\nSource: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry<\/a>\nCategories: CannaQAwiki journal articles (added in 2022)CannaQAwiki journal articles (all)CannaQAwiki journal articles on cannabis cannabinoidsCannaQAwiki journal articles on cannabis testingNavigation menuPage actionsJournalDiscussionView sourceHistoryPage actionsJournalDiscussionMoreToolsIn other languagesPersonal toolsLog inNavigationMain pageList of articlesRandom pageRecent changesHelpSearch\u00a0 ToolsWhat links hereRelated changesSpecial pagesPrintable versionPermanent linkPage information This page was last edited on 15 June 2022, at 22:34.Content is available under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License unless otherwise noted.Privacy policyAbout CannaQAWikiDisclaimers\n","60c6b04b4bcf2aea432c0203d99568af_html":"<body class=\"mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-170 ns-subject page-Journal_Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography\u2013mass_spectrometry rootpage-Journal_Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography\u2013mass_spectrometry skin-monobook action-view skin--responsive\"><div id=\"rdp-ebb-globalWrapper\"><div id=\"rdp-ebb-column-content\"><div id=\"rdp-ebb-content\" class=\"mw-body\" role=\"main\"><a id=\"rdp-ebb-top\"><\/a>\n<h1 id=\"rdp-ebb-firstHeading\" class=\"firstHeading\" lang=\"en\">Journal:Simultaneous quantification of 17 cannabinoids in cannabis inflorescence by liquid chromatography\u2013mass spectrometry<\/h1><div id=\"rdp-ebb-bodyContent\" class=\"mw-body-content\"><!-- start content --><div id=\"rdp-ebb-mw-content-text\" lang=\"en\" dir=\"ltr\" class=\"mw-content-ltr\"><div class=\"mw-parser-output\">\n\n\n<h2><span class=\"mw-headline\" id=\"Abstract\">Abstract<\/span><\/h2>\n<p>With an increasing appreciation for the unique pharmacological properties associated with distinct, individual <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">cannabinoids<\/a> of <i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\">Cannabis sativa<\/a><\/i>, there is demand for accurate and reliable quantification for a growing number of them. Although recent methods are based on highly selective <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chromatography\" title=\"Chromatography\" class=\"wiki-link\" data-key=\"1b40e146652470be00cebaf949c68b24\">chromatography<\/a>\u2013<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Mass_spectrometry\" title=\"Mass spectrometry\" class=\"wiki-link\" data-key=\"18314b70982e52d5a81db4a757d6461f\">mass spectrometry<\/a> technology, most are limited to a few cannabinoids, while relying on unnecessarily sophisticated and expensive <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=High-performance_liquid_chromatography\" title=\"High-performance liquid chromatography\" class=\"wiki-link\" data-key=\"4c5d83ffa9785383c3eb0be7ea78dd2b\">ultra-high-performance liquid chromatography<\/a> and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tandem_mass_spectrometry\" title=\"Tandem mass spectrometry\" class=\"wiki-link\" data-key=\"573d237c370deba1a7ef999284ea1cf8\">tandem mass spectrometry<\/a>. Here we report an optimized, simple extraction method followed by a reliable and simple high-performance liquid chromatography (HPLC) method for separation. The detection is performed using a <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Time-of-flight_mass_spectrometry\" title=\"Time-of-flight mass spectrometry\" class=\"wiki-link\" data-key=\"ef7fd91770fcb12af7d71d544136e620\">time-of-flight mass spectrometer<\/a> that is available in most natural products research laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well-suited for routine phytocannabinoid analysis for a range of applications. The method was validated in terms of detection and quantification limits, repeatability, and recoveries for a total of 17 cannabinoids. Detection limits were in the range 11\u2013520 pg when using a 1 \u00b5L sample injection volume, and the recovery percentages ranged from 85% to 108%. The validated method was subsequently applied to determine cannabinoid composition in the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Inflorescence\" title=\"Inflorescence\" class=\"wiki-link\" data-key=\"d8122354225ee6a932a086ca8a1b999f\">inflorescences<\/a> of several medicinal <i>Cannabis sativa<\/i> varieties.\n<\/p><p><b>Keywords<\/b>: cannabinoids, phytocannabinoids, LC-MS, <i>Cannabis sativa<\/i>, tetrahydrocannabinol, THC, cannabidiol, CBD\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Introduction\">Introduction<\/span><\/h2>\n<p><i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_sativa\" title=\"Cannabis sativa\" class=\"wiki-link\" data-key=\"e003358742012354d1ff6002bc5781de\">Cannabis sativa<\/a><\/i> L. (<i><a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis\" title=\"Cannabis\" class=\"wiki-link\" data-key=\"a70b76268930d795518ff1f98d7e500d\">Cannabis<\/a><\/i>) is one of the oldest domesticated plants, cultivated for the purpose of food, fiber, <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Psychoactive_drug\" title=\"Psychoactive drug\" class=\"wiki-link\" data-key=\"abba12c7100bf1c8457208da20b4234b\">psychoactives<\/a>, and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabis_(drug)\" title=\"Cannabis (drug)\" class=\"wiki-link\" data-key=\"6500790ffdd84957d4b055c47e48efca\">medicine<\/a>. In recent years, its medicinal properties have gained a renewed interest given its therapeutic potential in the treatment of a variety of disease conditions. To date, over 100 different <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabinoid\" title=\"Cannabinoid\" class=\"wiki-link\" data-key=\"c224c3041748677fcdce5b5209900b7b\">cannabinoids<\/a> have been identified, with <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinol\" title=\"Tetrahydrocannabinol\" class=\"wiki-link\" data-key=\"15f3b3e338baeb54c04c715818759ec9\">\u0394<sup>9<\/sup>-tetrahydrocannabinol<\/a> (THC), well known for its psychoactive properties, and others, such as <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiol\" title=\"Cannabidiol\" class=\"wiki-link\" data-key=\"bbfcdd40d5eda5d20d1d5ab368c922a0\">cannabidiol<\/a> (CBD), recognized for their therapeutic and medicinal value.<sup id=\"rdp-ebb-cite_ref-1\" class=\"reference\"><a href=\"#cite_note-1\">[1]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:0_2-0\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup>\n<\/p><p>Historically, cannabis <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Sample_(material)\" title=\"Sample (material)\" class=\"wiki-link\" data-key=\"2d7596b7c3616db8f56af698be478d3d\">samples<\/a> were analyzed mostly in a legal or regulatory context for the purpose of determining \u0394<sup>9<\/sup>-THC content. However, as more cannabinoids were identified and their pharmacological potential was examined, the quantification of cannabinoids other than \u0394<sup>9<\/sup>-THC gained importance. Additional cannabinoids of interest now include <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabinolic_acid\" title=\"Tetrahydrocannabinolic acid\" class=\"wiki-link\" data-key=\"a047dcf0f7a85c57e1d2d308b56e5e4a\">\u0394<sup>9<\/sup>-tetrahydrocannabinolic acid<\/a> (THCA), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiol\" title=\"Cannabidiol\" class=\"wiki-link\" data-key=\"bbfcdd40d5eda5d20d1d5ab368c922a0\">cannabidiol<\/a> (CBD), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidiolic_acid\" title=\"Cannabidiolic acid\" class=\"wiki-link\" data-key=\"772927eeed478eff799c410179be18a1\">cannabidiolic acid<\/a> (CBDA), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerol\" title=\"Cannabigerol\" class=\"wiki-link\" data-key=\"6fc007b4c33a4c59a485b2c621035714\">cannabigerol<\/a> (CBG), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabigerolic_acid\" title=\"Cannabigerolic acid\" class=\"wiki-link\" data-key=\"d0a5399af99137ebf5aa893d34531e49\">cannabigerolic acid<\/a> (CBGA), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tetrahydrocannabivarin\" title=\"Tetrahydrocannabivarin\" class=\"wiki-link\" data-key=\"3d3d85708945bc2119701d78e7042afa\">\u0394<sup>9<\/sup>-tetrahydrocannabivarin<\/a> (THCV), \u0394<sup>9<\/sup>-tetrahydrocannabivarinic acid (THCVA), <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabidivarin\" title=\"Cannabidivarin\" class=\"wiki-link\" data-key=\"82cc8e549e09059f448fbd8d352b8f7f\">cannabidivarin<\/a> (CBDV), and cannabidivarinic acid (CBDVA).<sup id=\"rdp-ebb-cite_ref-:0_2-1\" class=\"reference\"><a href=\"#cite_note-:0-2\">[2]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:1_3-0\" class=\"reference\"><a href=\"#cite_note-:1-3\">[3]<\/a><\/sup> A recent study on virus-neutralizing capabilities of naturally occurring cannabinoids (in acid form) even found that CBDA and CBGA are capable of binding to the spike protein of SARS-CoV-2, therefore making for possible candidates for the treatment and prevention of COVID-19.<sup id=\"rdp-ebb-cite_ref-4\" class=\"reference\"><a href=\"#cite_note-4\">[4]<\/a><\/sup> Clearly, accurate methods of quantification are needed to determine the concentrations of both major and minor cannabinoids of pharmacological potential in cannabis <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Inflorescence\" title=\"Inflorescence\" class=\"wiki-link\" data-key=\"d8122354225ee6a932a086ca8a1b999f\">inflorescence<\/a>, the source of cannabinoids in the plant.\n<\/p><p>Despite the rising demand and importance of accurate quantification of cannabinoids, the number of studies with a clear focus on analytical method development remains relatively small. This might be in part due to <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Decriminalization_of_non-medical_cannabis_in_the_United_States\" title=\"Decriminalization of non-medical cannabis in the United States\" class=\"wiki-link\" data-key=\"938baf867922d8cbaae5d182229a581f\">regulatory constraints<\/a>, which necessitate specific licenses to handle this scheduled drug and limit the availability of standard compounds and test samples. Due to this, the cannabis testing industry remains poorly established, with only a relatively limited number of <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Laboratory\" title=\"Laboratory\" class=\"wiki-link\" data-key=\"ed14e6a67b4b14ad2c190c28455725f6\">laboratories<\/a> offering analytical services and a lack of standardized protocols for extraction and analysis.<sup id=\"rdp-ebb-cite_ref-5\" class=\"reference\"><a href=\"#cite_note-5\">[5]<\/a><\/sup>\n<\/p><p>Two review articles published recently<sup id=\"rdp-ebb-cite_ref-:2_6-0\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-0\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup> contain critical evaluations of methods used for cannabinoid analysis and the recent trends; therefore, a detailed comparison of methods is not included here. <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chromatography\" title=\"Chromatography\" class=\"wiki-link\" data-key=\"1b40e146652470be00cebaf949c68b24\">Chromatographic<\/a> techniques are generally used for the separation of cannabinoids. <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Chromatography#Liquid_chromatography\" title=\"Chromatography\" class=\"wiki-link\" data-key=\"da43e6566dd6693473e320ebadde934f\">Liquid chromatography<\/a> (LC) has gained preference over <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Gas_chromatography\" title=\"Gas chromatography\" class=\"wiki-link\" data-key=\"5094f035cb8bead5003deb9181e398b8\">gas chromatography<\/a> (GC) as LC avoids conversion of the acid forms of cannabinoids to their neutral forms, which occurs at the high temperatures used in GC.<sup id=\"rdp-ebb-cite_ref-:4_8-0\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup> Until recently, the detection of column-separated cannabinoids was predominantly carried out using <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Spectrophotometry\" title=\"Spectrophotometry\" class=\"wiki-link\" data-key=\"d3cee63e4f34b9fef1bd638cc1f5a66f\">UV spectrophotometry<\/a>, which provides low specificity and makes baseline separation of all cannabinoids imperative. However, complete separation of structurally similar cannabinoids, especially isomeric compounds such as \u0394<sup>8<\/sup>-THC and \u0394<sup>9<\/sup>-THC, is challenging.<sup id=\"rdp-ebb-cite_ref-:1_3-1\" class=\"reference\"><a href=\"#cite_note-:1-3\">[3]<\/a><\/sup> Due to the lack of specificity of UV detection, any unknown compound\/s co-eluting at the same retention time as the target cannabinoid can cause overestimation of its concentration. \n<\/p><p>To overcome this specificity problem, the detection method of choice has been changing to <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Mass_spectrometry\" title=\"Mass spectrometry\" class=\"wiki-link\" data-key=\"18314b70982e52d5a81db4a757d6461f\">mass spectrometry<\/a> (MS).<sup id=\"rdp-ebb-cite_ref-:2_6-1\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-1\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup> As MS detection can identify molecules according to differences in mass, the chromatographic separation becomes less important. However, since some of the major cannabinoids\u2014e.g., \u0394<sup>8<\/sup>-THC, \u0394<sup>9<\/sup>-THC, CBD, <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabichromene\" title=\"Cannabichromene\" class=\"wiki-link\" data-key=\"1fa141abe89973bfa85a54e2632edf31\">cannabichromene<\/a> (CBC), and <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Cannabicyclol\" title=\"Cannabicyclol\" class=\"wiki-link\" data-key=\"2ca85f204e15e09af8ec75c62146c2d1\">cannabicyclol<\/a> (CBL)\u2014have the same molecular mass, chromatographic separation is still required. Most of the methods using MS detection of cannabinoids are based on <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Tandem_mass_spectrometry\" title=\"Tandem mass spectrometry\" class=\"wiki-link\" data-key=\"573d237c370deba1a7ef999284ea1cf8\">tandem mass spectrometry<\/a> (MS-MS).<sup id=\"rdp-ebb-cite_ref-:2_6-2\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:3_7-2\" class=\"reference\"><a href=\"#cite_note-:3-7\">[7]<\/a><\/sup> However, there is no real advantage of using this approach over basic MS, as cannabinoids of the same molar masses produce similar fragmentation patterns in the second MS event, thus not providing additional selectivity. Therefore, baseline separation by chromatography followed by simple MS detection is well suited for the routine analysis of cannabinoids.\n<\/p><p>According to a recent review of cannabinoid analysis, variability in extraction (solvent\/s, method, time, and temperature) significantly contributes to differential analytical results.<sup id=\"rdp-ebb-cite_ref-:2_6-3\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> Most of the recent analytical methods have used <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Ethanol\" title=\"Ethanol\" class=\"wiki-link\" data-key=\"e0bdbbae89fcedde33e133fdfd2a2994\">ethanol<\/a> for extraction of both acidic and neutral cannabinoids<sup id=\"rdp-ebb-cite_ref-:1_3-2\" class=\"reference\"><a href=\"#cite_note-:1-3\">[3]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:5_9-0\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup>, although the method used for extraction varied in terms of sample to solvent ratio, the extraction technique, and the duration of extraction. Therefore, a study of the effects of these variables on the amounts of cannabinoids extracted is warranted.\n<\/p><p>The aims of this study were to develop a simple yet effective method for the extraction of cannabinoids from cannabis inflorescences, and to develop a reliable, robust and simple <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Liquid_chromatography%E2%80%93mass_spectrometry\" title=\"Liquid chromatography\u2013mass spectrometry\" class=\"wiki-link\" data-key=\"e2eb804872f9ac16965fce8e49cfa3b6\">liquid chromatography\u2013mass spectrometry<\/a> (LC\u2013MS) method that can be used for routine analysis of 17 phytocannabinoids for which standards are available. In this study, a <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Time-of-flight_mass_spectrometry\" title=\"Time-of-flight mass spectrometry\" class=\"wiki-link\" data-key=\"ef7fd91770fcb12af7d71d544136e620\">time-of-flight mass spectrometer<\/a> (TOF-MS) was used as the detector. The acquisition of spectral data was by simple MS mode rather than MS-MS because there was no advantage in using tandem MS. As many natural products laboratories are equipped with a TOF instrument (primarily used for qualitative analysis), a quantification method based on a TOF-MS would facilitate adoption of this method. The extraction conditions were optimized to develop a simple and robust method to extract cannabinoids from inflorescence, without altering the composition of cannabinoids. A separation method that uses a low flow rate enabled the use of (<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=High-performance_liquid_chromatography\" title=\"High-performance liquid chromatography\" class=\"wiki-link\" data-key=\"4c5d83ffa9785383c3eb0be7ea78dd2b\">high-performance liquid chromatography<\/a> (HPLC) rather than requiring an expensive ultra-high-performance liquid chromatography (UHPLC) system. The chromatographic separation of the cannabinoids with the same molar mass was made sufficiently robust so that small changes in column and\/or mobile phase do not cause the isobaric cannabinoids to co-elute.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Materials_and_methods\">Materials and methods<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Materials\">Materials<\/span><\/h3>\n<p>Proprietary medicinal cannabis samples of Cann Group Limited were supplied by New South Wales Department of Primary Industries (NSW DPI, Orange, Australia) under an Office of Drug Control (ODC) permit and received by Southern Cross University (SCU) under NSW Health authority. Samples of contrasting lines for THC\/A and CBD\/A content were used for method establishment and validation.\n<\/p><p>All cannabinoid reference standards were purchased from Novachem Pty. Ltd. (Heidelberg, Australia) as <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Ampoule\" title=\"Ampoule\" class=\"wiki-link\" data-key=\"a2972702561c17c42579e2ac948979d2\">ampoules<\/a> of 1,000 \u00b5g\/mL solutions. The standards for (\u00b1)-\u0394<sup>9<\/sup>-tetrahydrocannabinolic acid A (\u0394<sup>9<\/sup>-THCA-A), tetrahydrocannabivarinic acid (THCVA), cannabidiolic acid (CBDA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), cannabinolic Acid (CBNA), cannabichromenic acid (CBCA), (\u00b1)-cannabicyclol (CBL), and cannabicyclolic acid (CBLA) were supplied in <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Acetonitrile\" title=\"Acetonitrile\" class=\"wiki-link\" data-key=\"582d25d2e9d0fbfc0c2dcc54938b6798\">acetonitrile<\/a>. The standards for (\u2212)-\u0394<sup>9<\/sup>-tetrahydrocannabinol (\u0394<sup>9<\/sup>-THC), (\u2212)-\u0394<sup>8<\/sup>-tetrahydrocannabinol (\u03948-THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabidivarin (CBDV), cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC) were supplied in <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Methanol\" title=\"Methanol\" class=\"wiki-link\" data-key=\"e0e6fe7bacded0b162958a69f290a7bd\">methanol<\/a>. Ibuprofen was purchased from Sigma-Aldrich Pty Ltd. (North Ryde, NSW, Australia). HPLC-grade ethanol (Scharlau, Scharlab S.L., Barcelona, Spain) was used for sample extractions, and LC-MS grade solvents (Honeywell Research Chemicals, Seelze, Germany) and MilliQ water (Merck Millipore, Billerica, MA, USA) were used to prepare mobile phase.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Sample_preparation\">Sample preparation<\/span><\/h3>\n<p>Apical and mature female inflorescences were cut from the main stems, and any large stem pieces were removed. Samples were dried for approximately seven days at 24 \u00b0C under low humidity (50\u201358%) until a dry weight of 21% of the starting wet weight was achieved, after which they were weighed, double vacuum packed, and stored at ambient room temperature in the dark.\n<\/p><p>Two grams of inflorescence were ground to a fine powder using a 50 mL stainless steel screw top Retsch grinding canister, containing a single 20 mm stainless steel grinding ball, in a Retsch Mixer Mill MM301 (Retsch GmbH, Mettmann, Germany) at 30 rotations per second for 10 seconds. Ground samples were stored in polypropylene tubes at \u221220 \u00b0C until extracted for analysis (note: flash-cooling the grinding canister and ball in liquid nitrogen before adding the sample prior to grinding helped to prevent clumping of material, especially in high resin samples, thus producing a homogenous fine powder).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Optimization_of_the_extraction\">Optimization of the extraction<\/span><\/h3>\n<p>For extraction, 0.1g of ground sample was accurately weighed into a 20 mL polypropylene centrifuge tube. An aliquot of 2.50, 5.00 or 10.00 mL of 100% ethanol was accurately pipetted into the tube. Three replicates were extracted for each volume added. The mixture was sonicated in an ultrasound bath (SONICLEAN, Soniclean\u00ae, Dudley Park, Australia) at 50\/60 Hz and 150 W for 15 minutes, then centrifuged at 3000 rpm (Sigma 3\u201316 L, Sigma Laborzentrifugen GmbH, Osterode am Harz, Germany) for 10 minutes. The supernatant was carefully removed and stored in an Eppendorf tube at \u221220 \u00b0C. The extract was diluted as necessary with 100% ethanol for instrumental analysis using HPLC-MS. Volumes of injection of 1, 2 and 4 \u00b5L (for 2.50, 5.00 and 10.00 mL extractions, respectively) were used to obtain the same peak area (if each treatment were to extract the same amount). Ten cannabinoids were used for comparison (CBDV, CBDA, CBG, CBD, THCV, CBGA, THCVA, CBN, \u03949-THC, THCA). The peak areas of each cannabinoid were divided by the mass of the sample, and the peak area per gram of sample was used for comparison.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Separation_and_detection\">Separation and detection<\/span><\/h3>\n<p>The chromatographic separation of cannabinoids was performed using UHPLC on an Agilent 1290 Infinity II series system (Agilent Technologies, Santa Clara, CA, USA). The UHPLC was coupled to an Agilent 6545 high-resolution accurate mass (HRAM) QToF mass spectrometer equipped with a dual nebulizer jet stream electrospray source for ionization (Agilent) and controlled using Agilent MassHunter Acquisition Software, Tokyo, Japan (Version 10.1). Separation was achieved using an Agilent Poroshell C18 2.7 \u00b5m particle size, narrow bore, 15 cm column, held at 30 \u00b0C. The chromatographic analysis was performed using 0.1% (v\/v) formic acid in 30% v\/v methanol in water (mobile phase A), and 0.1% formic acid (v\/v) in acetonitrile (mobile phase B), at a flow rate of 0.3 mL\/min. The column was pre-equilibrated with 47% (v\/v) A and 53% (v\/v) B. After injection (of 1 \u00b5L sample or standard), the composition of mobile phase was maintained at 53% (v\/v) B for the first 25 min. It was then changed from 53% (v\/v) B to 70% (v\/v) B over the next 15 minutes (to 40 minute mark), changed from 70% (v\/v) B to 97% (v\/v) B over the next two minutes (to 42 minute mark), and then held at 97% (v\/v) B for one minute (to 43 minute mark). The column was then returned to the starting composition of 53% (v\/v) B over the next one minute (to 44 minute mark). Finally, the column was re-equilibrated using 53% (v\/v) B for six minutes (to 50 minute mark) prior to the next injection. The injection volume was kept low to avoid peak distortion (as explained in the discussion).\n<\/p><p>The mass spectrometer was used in MS1-positive mode to scan from <i>m\/z<\/i> 190 to 370 for all samples at a scan rate of 1.5 spectra\/s. The general parameters of the source were: capillary voltage 4000 V, nozzle voltage 0 V, fragmentor voltage 180 V, skimmer voltage 45 V and octopole RF Peak voltage 750 V, nebulizer pressure 20 psi, drying gas 10 L\/minute, drying gas temperature 325 \u00b0C, sheath gas flow 12, and sheath gas temperature 400 \u00b0C.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_analysis_and_calculations\">Data analysis and calculations<\/span><\/h3>\n<p>Data analysis was performed using Agilent MassHunter Quantitative Analysis (for QToF) Software, Tokyo, Japan (Version 10.1). Each cannabinoid in a chromatogram of standard compounds was identified based on its spectrum and the retention time. A processing method was prepared to extract each peak based on the <i>m\/z<\/i> value of each compound within a \u00b10.03 <i>m\/z<\/i> window. Peaks were integrated and exported to EXCEL for calculations. External standard calibration was performed using a five-point calibration curve up to 12.5 \u00b5g\/mL concentration with 1 \u00b5L injections. The regression values obtained (slope and intercept) in EXCEL were formatted to contain the same number of significant figures as the peak area values to avoid rounding errors. Standards used in calibration were used as unknowns\/samples to predict concentrations and estimate the validity of the calibration. Concentrations calculated for the samples injected were checked to ensure that they were within the calibration\/linear range. If not, they were re-run after dilution. After multiplying by the dilution factor, concentrations were expressed as \u00b5g\/g of the sample using the exact mass of the sample used in extraction. Dilution factors (of the 5 mL extract) used for minor and major cannabinoids in this study were 2.5 and 200, respectively. A pooled sample of ground inflorescence was prepared using a mixture of high-THC and high-CBD plant material and used as the <a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Quality_control\" title=\"Quality control\" class=\"wiki-link\" data-key=\"a50e0afa52af1b1741e5ca1c7d711282\">quality control<\/a> (QC) sample with each batch of the samples analyzed.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Extraction_method_used_for_routine_analysis\">Extraction method used for routine analysis<\/span><\/h3>\n<p>A sample of 0.1g ground cannabis inflorescence was accurately weighed into a 20 mL polypropylene centrifuge tube. A 5.00 mL aliquot of 100% ethanol was accurately pipetted into the tube. The mixture was sonicated in an ultrasound bath at 50\/60 Hz and 150 W for 30 minutes, then centrifuged at 3,000 rpm (Sigma 3\u201316 L, Germany) for 10 minutes. The supernatant was carefully removed and stored in a 2 mL Eppendorf tube at \u221220 \u00b0C. The extract was diluted as necessary (below) with 100% ethanol prior to the instrumental analysis using HPLC-MS.\n<\/p>\n<h3><span id=\"rdp-ebb-Preparation_of_samples_for_major_cannabinoids:_THC,_THCA,_CBD,_CBDA\"><\/span><span class=\"mw-headline\" id=\"Preparation_of_samples_for_major_cannabinoids:_THC.2C_THCA.2C_CBD.2C_CBDA\">Preparation of samples for major cannabinoids: THC, THCA, CBD, CBDA<\/span><\/h3>\n<p>The extract was diluted 80 times by mixing 20 \u00b5L sample extract and 1580 \u00b5L ethanol. The extract was then further diluted by mixing 400 \u00b5L of the diluted extract, 40 \u00b5L of 0.025 mg\/mL Ibuprofen, and 560 \u00b5L ethanol in an HPLC vial to be used for LC-MS analysis. This resulted in a 200 times diluted extract containing 1 \u00b5g\/mL Ibuprofen (internal standard).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Preparation_of_samples_for_minor_cannabinoids\">Preparation of samples for minor cannabinoids<\/span><\/h3>\n<p>The extract was diluted by mixing 400 \u00b5L of the extract, 40 \u00b5L of 0.025 mg\/mL Ibuprofen, and 560 \u00b5L ethanol in an HPLC vial to be used for LC-MS analysis. This resulted in a 2.5 times diluted extract containing 1 \u00b5g\/mL Ibuprofen (internal standard).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Preparation_of_standard_solutions\">Preparation of standard solutions<\/span><\/h3>\n<p>A 0.05 mg\/mL solution of 17 cannabinoid standards was prepared by mixing 100 \u00b5L each of the 17 cannabinoid stock standards (1 mg\/mL), and 300 \u00b5L of HPLC grade ethanol in a 2 mL Eppendorf tube. A 0.025 mg\/mL mix of standards was prepared by diluting the 0.05 mg\/mL solution and used as the working standard stock solution.\n<\/p><p>Ibuprofen was weighed into a 1.5 mL Eppendorf tube and dissolved in an appropriate volume of HPLC grade ethanol to make a 1 mg\/mL stock solution. This solution was diluted with an appropriate volume of ethanol to make the 0.025 mg\/mL working stock standard.\n<\/p><p>Five calibration standards were prepared by diluting the appropriate volumes of 0.025 mg\/mL mix of 17 standards, and 0.025 mg\/mL Ibuprofen to contain 2.5, 5, 7.5, 10, and 12.5 \u00b5g\/mL cannabinoids and 1 \u00b5g\/mL Ibuprofen (internal standard).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Method_validation\">Method validation<\/span><\/h3>\n<p>Linearity for each cannabinoid was estimated by injecting 1\u00b5L each of five mixed standard solutions containing 0.5 to 12.5 \u00b5g\/mL of the 17 cannabinoids. The linearity was assessed by plotting the peak area of each cannabinoid versus the concentration. Limit of detection (LOD) and limit of quantification (LOQ) for each cannabinoid was determined based on the peak heights (and then the concentrations) corresponding to 3\u00d7 noise and 10\u00d7 noise, respectively. Repeatability was estimated by analyzing seven individual 0.1 g ground cannabis inflorescence samples (that were prepared by pooling samples containing high CBD and high THC levels), followed by the calculation of relative standard deviation of the concentrations determined for each cannabinoid. Recovery was determined by using the concentrations of each cannabinoid in spiked and un-spiked extracts using seven of the individual extracts prepared for the repeatability experiment. Each extract was spiked to give an added concentration that was below the mid-point of the calibration (linear) range.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Results_and_discussion\">Results and discussion<\/span><\/h2>\n<h3><span class=\"mw-headline\" id=\"Sample_preparation_2\">Sample preparation<\/span><\/h3>\n<p>A significantly larger (than the amount used for analysis) amount of inflorescence (2 g) was ground in order to minimize effects of within sample variation due to the architecture\/morphology of the inflorescence (containing bracts, stigma, sugar leaves, stem remnants, etc.) of varying trichome density. After homogenization by grinding, a representative 0.1 g sample was extracted for analysis.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Optimization_of_the_extraction_2\">Optimization of the extraction<\/span><\/h3>\n<p>Ethanol has been the most common solvent of choice in recent studies of cannabinoid analysis, and the high extracting efficiency of ethanol is attributed to the high affinity of ethanol to the cannabinoid molecular structure.<sup id=\"rdp-ebb-cite_ref-:2_6-4\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup> Important advantages of using ethanol extraction for cannabinoid analysis are its general availability, low toxicity, low cost, and easy storage and handling. Furthermore, the concentrations determined by the analytical methods that used ethanol for extraction are likely in the range of concentrations used for actual extraction in formulations intended for human consumption, as ethanol is a common extraction solvent in preparations. An extraction that does not involve heat is more appropriate for cannabinoid extraction because heat can change the ratio of acid forms to neutral forms<sup id=\"rdp-ebb-cite_ref-:4_8-1\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup>, thereby altering the composition of cannabinoids in the sample prior to analysis.\n<\/p><p>An optimization study of the extraction of cannabinoids from dried, ground cannabis inflorescence, using factorial design, found that the extraction solvent (80% methanol vs methanol-chloroform mixture), technique of extraction, and the time of extraction beyond 15 minutes did not significantly affect the amounts of cannabinoids extracted. The most significant variable that affected the amounts extracted was the sample to solvent ratio.<sup id=\"rdp-ebb-cite_ref-:6_10-0\" class=\"reference\"><a href=\"#cite_note-:6-10\">[10]<\/a><\/sup> In recent methods that used ethanol as the extraction solvent, the ratio (grams of dried inflorescence\/mL ethanol) varied from 1\/100<sup id=\"rdp-ebb-cite_ref-:5_9-1\" class=\"reference\"><a href=\"#cite_note-:5-9\">[9]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-11\" class=\"reference\"><a href=\"#cite_note-11\">[11]<\/a><\/sup> to 1\/15.<sup id=\"rdp-ebb-cite_ref-:1_3-3\" class=\"reference\"><a href=\"#cite_note-:1-3\">[3]<\/a><\/sup> Therefore, a study of the effect of this ratio on the amounts of cannabinoids extracted was warranted in order to establish an optimum extraction procedure prior to instrumental analysis. A systematic study of the effects of solvents other than the ones studied in the previous study<sup id=\"rdp-ebb-cite_ref-:6_10-1\" class=\"reference\"><a href=\"#cite_note-:6-10\">[10]<\/a><\/sup>, and extraction times below 15 minutes, was beyond the scope of this study.\n<\/p><p>In this study, the effect of the ratio \"grams of ground inflorescence \/ mL ethanol\" on the amount of cannabinoids extracted was studied using 0.1g of dried inflorescence in 2.5, 5, and 10 mL volumes of ethanol (ratios of 1\/25, 1\/50, and 1\/100, respectively), using triplicate extractions for each ratio. Volumes of injection of 1, 2, and 4 \u00b5L (respectively) were used to obtain the same peak area (if each treatment were to extract the same amount). Ten cannabinoids that were present in significant amounts in the sample were used for comparison (CBDV, CBDA, CBG, CBD, THCV, CBGA, THCVA, CBN, \u03949-THC, THCA). Peak area per gram of sample was used for comparison.\n<\/p><p>According to the results of one-way ANOVA (plus a Duncan\u2019s multiple range test for the means), sample\/solvent ratio of 1\/100 extracted significantly lower (<i>p<\/i> < 0.05) amounts of all cannabinoids in comparison to the other two ratios. The amounts extracted with the ratios 1\/25 and 1\/50 were not significantly different (at <i>p<\/i> = 0.05) for all cannabinoids. However, the precision (based on the coefficient of variance) was better with the ratio 1\/50. Therefore, that ratio (0.1 g of ground inflorescence in 5 mL ethanol) was used for all extractions in this study.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Optimization_of_chromatographic_separation_and_mass_spectrometry\">Optimization of chromatographic separation and mass spectrometry<\/span><\/h3>\n<p>Chromatographic separation for all cannabinoids was optimized, with the main emphasis on the baseline separation of the critical isomeric pair of \u0394<sup>8<\/sup>-THC and \u0394<sup>9<\/sup>-THC. Chromatographic separation with good resolution was also targeted for individual cannabinoids in two groups of isobaric compounds: CBD, \u0394<sup>8<\/sup>-THC, \u0394<sup>9<\/sup>-THC, CBC, CBL (<i>m\/z<\/i> = 315.2) and CBDA, THCA, CBLA, CBCA (<i>m\/z<\/i> = 359.2). In order to conduct these separations, a column with small particle size and\/or maximum possible length was important. However, because of the aim of making this separation suitable for HPLC rather than UHPLC, it was decided to use a poroshell-type column (a thin layer of porous stationary phase is coated on solid silica cores) that can produce resolutions similar to sub-2 \u00b5m body-porous stationary phase particles used in UHPLC columns, without having to use very high pressure. As the longest available LC-MS column (15 cm) was used in this separation, the high pressure required was compensated by using a low flow rate (0.3 mL\/min). Although the run time could have been shortened by using a higher flow rate, the flow rate was kept low in order to operate the LC in HPLC mode rather than UHPLC mode, particularly because our aim was to produce a method that can be run on a simple HPLC system. \n<\/p><p>The polarity of a C18 column is suitable for the separation when a low pH is used (when the acid forms are not ionized to produce highly polar carboxylates). The detector (MS) sensitivities for neutral compounds were much higher than those for acid forms at low pH. Another advantage of using low pH was, that the neutral forms of cannabinoids naturally occur at much lower concentrations compared to the acid forms. Therefore, the difference in sensitivities was well suited for analyzing a mixture of acids and neutrals without having to make additional dilutions to quantify the range of cannabinoids of interest. Formic acid (0.1%) was used to achieve a low pH of around three in the mobile phase. \n<\/p><p>Organic modifiers\u2014methanol and acetonitrile, from two different classes of selectivity\u2014were tested in different ratios and combinations to improve the selectivity factor of the separations.<sup id=\"rdp-ebb-cite_ref-12\" class=\"reference\"><a href=\"#cite_note-12\">[12]<\/a><\/sup> The optimal separation of all 17 cannabinoids was achieved within the isocratic section at the beginning of the gradient using 53% v\/v methanol\/water (with 0.1% formic acid) as mobile phase A, and acetonitrile (with 0.1% formic acid) on a Poroshell C18 column with a particle size of 2.7 \u00b5m (as detailed under Section 2 above) (Figure 1). The <i>m\/z<\/i> values used for detection and the retention times for each cannabinoid are listed in Table 1. Since the samples and standards were in 100% organic solvent (ethanol), and the start of the gradient was only about 53% organic (weaker eluent strength), the chromatographic peaks were prone to distortion. With the column size and flow rate used in this study, we found that peak distortion could be prevented as long as the volume of injection was kept below 4 \u00b5L. The injection volume was kept at 1 \u00b5L throughout this study.\n<\/p><p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig1_Hewavitharana_Separations_9-4.png\" class=\"image wiki-link\" data-key=\"1dbd9f09b0986bf609dc2b2e3627cc6a\"><img alt=\"Fig1 Hewavitharana Separations 9-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/3\/33\/Fig1_Hewavitharana_Separations_9-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 1<\/b> Chromatographic and mass spectrometric separation of Ibuprofen and 17 cannabinoids in a standard mixture. Top chromatogram shows the total ion chromatogram and the other chromatograms are extracted at the mass of compound\/s.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 1.<\/b> Retention time and precursor ions used to extract and integrate chromatographic peak of each cannabinoid. A \u00b10.03 <i>m\/z<\/i> window was used to extract spectral data.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Compound\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Precursor ion (<i>m\/z<\/i>)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Retention time (minutes)\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ibuprofen\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">251.1029\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">287.2021\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">287.2027\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBN\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">311.2019\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBD\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">315.2339\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>8<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">315.2337\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">23.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>9<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">315.2336\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">21.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">315.2337\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">31.2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">315.2336\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">26.1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBG\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">317.2493\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">331.1919\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">331.1919\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">16.6\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBNA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">355.1920\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">28.1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">359.2239\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.9\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">359.2237\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">34.0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBLA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">359.2236\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">36.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">359.2238\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">38.0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBGA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">361.2385\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.0\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>As described above, our aim was to develop an MS detection method rather than a tandem MS detection method. This was partly to be able to use an inexpensive HPLC-MS system, and partly because there is no advantage in using MS-MS detection (the isobaric cannabinoids produced the same fragments in MS-MS therefore needed to be chromatographically separated). We used the QToF and its processing software to mimic a single ion monitoring (SIM) mode of detection and quantification that is normally used in quadrupole MS systems. Data was acquired as spectra in total ion current (TIC) mode within the range of <i>m\/z<\/i> 190\u2013370, and each cannabinoid peak was extracted (as listed in Table 1) from these spectra for processing. An advantage of using the TIC mode is the possibility of detection of other compounds that have their molar masses within the range of detection used. Since we started using this method to analyze samples from other projects, we were able to detect (and tentatively identify based on literature-reported mass values) some other cannabinoids, in some samples (data not shown). This could not have been possible with a quadrupole MS instrument that is usually used for quantification.\n<\/p><p>Since there was concern regarding the source temperature (325 \u00b0C) causing decarboxylation of the acid forms<sup id=\"rdp-ebb-cite_ref-:2_6-5\" class=\"reference\"><a href=\"#cite_note-:2-6\">[6]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:4_8-2\" class=\"reference\"><a href=\"#cite_note-:4-8\">[8]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-13\" class=\"reference\"><a href=\"#cite_note-13\">[13]<\/a><\/sup>, the presence of peaks for neutral forms were checked at the retention times of the acid forms. As evident from Figure 1, they were absent, confirming that the acid forms were not decarboxylated in MS. In the case of CBDA and CBD, which have very similar retention times, this was established by running only CBDA standard, and confirming the absence of a peak at <i>m\/z<\/i> of 315.2 (corresponding to CBD).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Data_analysis_and_processing\">Data analysis and processing<\/span><\/h3>\n<p>The extract ion chromatography (EIC) option in Agilent MassHunter Quantitative Analysis (for QToF) software (Version 10.1) was used to extract peaks. We used a window of \u00b10.03 <i>m\/z<\/i> for EIC in this software, seeking to prevent MS line overlapping between CBD and CBG, which have the same retention time although they are 2 <i>m\/z<\/i> value apart. Since the sensitivities for (abundant) acid forms were deliberately suppressed (relative to the neutral forms), a single dilution of the extract by 2.5 times allowed all minor cannabinoid levels to fall within the calibration range. The extracts were required to be diluted by 200 times to make the concentrations of the major cannabinoids (CBD, CBDA, THC, THCA) to fall within the calibration\/linear range. We were able to quantify all 17 cannabinoids using only two dilutions because of the use of low pH elution to improve the sensitivities of neutral forms relative to those of acid forms, and because of the use of a low flowrate (therefore lower peak heights).\n<\/p><p>Matrix effects (mostly by causing ion-suppression) are a major problem that impair the accuracy of LC-MS data.<sup id=\"rdp-ebb-cite_ref-:7_14-0\" class=\"reference\"><a href=\"#cite_note-:7-14\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:8_15-0\" class=\"reference\"><a href=\"#cite_note-:8-15\">[15]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:9_16-0\" class=\"reference\"><a href=\"#cite_note-:9-16\">[16]<\/a><\/sup> As matrix effects cannot be completely eliminated in practice, the data is corrected for matrix effects by running a co-eluting internal standard for each analyte and subsequent calibration using internal standard method.<sup id=\"rdp-ebb-cite_ref-:7_14-1\" class=\"reference\"><a href=\"#cite_note-:7-14\">[14]<\/a><\/sup><sup id=\"rdp-ebb-cite_ref-:8_15-1\" class=\"reference\"><a href=\"#cite_note-:8-15\">[15]<\/a><\/sup> In our work, we did not correct for matrix effects because co-eluting compounds (stable isotope labelled analogues of the cannabinoids) were not yet commercially available for most of the cannabinoids. When available, they can easily be incorporated into to the current method, and the calibration can be carried out using an internal standard method. Until then, the data is not completely free of matrix effects. However, using lengthier retention times as well as achieving high resolution of all peaks in our method ensure minimal matrix effects because the likelihood of co-elution of matrix compounds with the peaks of interest is minimized. In addition, the high dilutions used, especially for the major cannabinoids (0.1 g sample diluted to 1 L), ensured negligible matrix effects on their concentration data.<sup id=\"rdp-ebb-cite_ref-:8_15-2\" class=\"reference\"><a href=\"#cite_note-:8-15\">[15]<\/a><\/sup> The high sensitivity of the method enables the detection of very low concentrations, and therefore high dilution to minimize matrix effects was possible.\n<\/p><p>Using an internal standard that does not co-elute with the analyte is not an option in addressing LC-MS matrix effects.<sup id=\"rdp-ebb-cite_ref-:9_16-1\" class=\"reference\"><a href=\"#cite_note-:9-16\">[16]<\/a><\/sup> This is because the matrix effects at each time point of the chromatogram are different for different matrices. This was the reason that the internal standard (Ibuprofen) used in method development was not used in actual calculations. However, if a study were undertaken using all samples containing the same matrix (e.g., studying the effect of some variable on the same plant matrix), Ibuprofen could be used as the internal standard to eliminate procedural errors (but with no effect on matrix effects).\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Method_validation_2\">Method validation<\/span><\/h3>\n<p>The LOD and LOQ, estimated based on 3\u00d7 and 10\u00d7 noise, respectively, ranged from 9 to 1734 picograms, as shown in Table 2. In general, acid forms of cannabinoids have higher LOD values (i.e., lower sensitivities) relative to the neutral forms. As discussed above, the suppression of sensitivities of acid forms (that are more abundant than the neutral forms) was deliberate in order to fit the MS responses of acid forms within the calibration range. In addition, Table 2 shows LOD and LOQ values calculated based on the concentrations of the extract that was injected to the column (with 1 \u00b5L volume of injection), and the concentrations in dried, ground inflorescence (based on 2.5-fold dilution of the 5 mL extract).\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 2.<\/b> Linearity, detection limits, and quantification limits for 17 cannabinoids and Ibuprofen. * On column amounts; ** Concentration in extract; *** Concentration in sample.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Compound\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Linearity (r<sup>2<\/sup>) and (Upper limit, in \u00b5g\/mL)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOD * (pg)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOD ** (\u00b5g\/mL)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOD *** (\u00b5g\/g)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOQ * (pg)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOQ ** (\u00b5g\/mL)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">LOQ *** (\u00b5g\/g)\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">Ibuprofen\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.998 (10.0)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.998 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.011\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.37\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">36.6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.037\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4.57\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.43\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.009\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.18\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">31.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.031\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.93\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBN\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">72.9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.073\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.11\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">243\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.243\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">30.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBD\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">17.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.017\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.17\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">57.9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.058\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.24\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>8<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">31.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.031\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.93\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">105\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.011\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">13.1\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>9<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">23.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.023\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2.93\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">78.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.078\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.77\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">60.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.061\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.60\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">203\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.020\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">25.3\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.998 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">43.9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.044\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.49\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">146\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.146\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">18.3\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBG\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.996 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">27.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.027\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.37\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">89.9\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.090\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">181\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.181\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">22.6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">604\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.604\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">75.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">98.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.098\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">12.3\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">328\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.328\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">40.9\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBNA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.998 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">199\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.199\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">24.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">662\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.662\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">82.7\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">125\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.125\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">15.7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">418\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.418\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">52.2\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">73.7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.074\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">9.21\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">246\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.246\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">30.7\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBLA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">239\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.239\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">29.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">795\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.795\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">99.4\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.999 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">220\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.220\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">27.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">735\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.735\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">91.8\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBGA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.997 (12.5)\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">520\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">0.520\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">65.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1734\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1.734\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">218\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>Table 2 also shows the linearity, along with the upper limits of concentrations. Good linearities (r<sup>2<\/sup> of >0.99) were obtained for all cannabinoids for the concentration ranges used for calibration.\n<\/p><p>The repeatability values (<i>n<\/i> = 7), determined by analyzing multiple sub-samples of the pooled ground inflorescence and expressed as percentage standard deviations, are shown in Table 3. The chromatograms for the pooled sample are shown in Figure 2. The percentage standard deviations were larger for the cannabinoids that have high LOD values\/lower sensitivities. It is likely that lack of complete homogeneity of the ground samples, due to the formation of resin aggregates, contributed to the high RSD values. As suggested prior, snap-cooling the sample (in dry ice) before grinding produces homogeneous samples, although heat produced by friction during the grinding process might still cause resins to aggregate to some extent.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"8\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 3.<\/b> Repeatability (as mean value with standard deviation, in column 2, and as relative standard deviation, in column 3), and recovery for each cannabinoid (<i>n<\/i> = 7) in the pooled inflorescence sample. * Not detected; ** Values for \u00d7200 diluted extract shown (values for \u00d72.5 diluted extracts were 381 \u00b1 14.3, 3.76, and 29.0 \u00b1 5.24, respectively).\n<\/td><\/tr>\n<tr>\n<th rowspan=\"2\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Compound\n<\/th>\n<th colspan=\"2\" style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Repeatability\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Recovery\n<\/th><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mean \u00b1 SD (\u00b5g\/g)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">RSD (%)\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Mean \u00b1 SD (%)\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">50.5 \u00b1 2.21\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4.37\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">101 \u00b1 3.15\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">144 \u00b1 8.67\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6.03\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">96.3 \u00b1 6.27\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">38,850 \u00b1 2973\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.65\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">94.8 \u00b1 11.0\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBG **\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1084 \u00b1 91.7\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.46\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">97.9 \u00b1 4.09\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBD\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">15,110 \u00b1 973\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6.44\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">99.0 \u00b1 5.82\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">25.7 \u00b1 1.46\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.67\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">87.3 \u00b1 3.11\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBGA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">399 \u00b1 20.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">20.2\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">108.5 \u00b1 9.47\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">324 \u00b1 23.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">7.09\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">99.4 \u00b1 6.26\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBN\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">68.2 \u00b1 3.66\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.37\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">101 \u00b1 2.07\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>8<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND *\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">-\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">95.0 \u00b1 2.35\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>9<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4748 \u00b1 232\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4.89\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">102 \u00b1 4.30\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">14.7 \u00b1 0.58\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.97\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">99.3 \u00b1 3.61\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBNA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">285 \u00b1 17.5\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">6.14\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">98.6 \u00b1 3.32\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">770 \u00b1 65.4\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">8.49\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">101 \u00b1 2.87\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">43,681 \u00b1 5080\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11.6\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">103 \u00b1 8.11\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBLA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">196 \u00b1 11.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.60\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">101 \u00b1 5.82\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">519 \u00b1 18.8\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">3.62\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">85.2 \u00b1 13.8\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p><br \/>\n<a href=\"https:\/\/www.cannaqa.wiki\/index.php?title=File:Fig2_Hewavitharana_Separations_9-4.png\" class=\"image wiki-link\" data-key=\"4dfc77a7282b1b5659ff4d088154979a\"><img alt=\"Fig2 Hewavitharana Separations 9-4.png\" src=\"https:\/\/www.cannaqa.wiki\/images\/1\/1c\/Fig2_Hewavitharana_Separations_9-4.png\" decoding=\"async\" style=\"width: 100%;max-width: 400px;height: auto;\" \/><\/a>\n<\/p>\n<div style=\"clear:both;\"><\/div>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table border=\"0\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><blockquote><p><b>Fig. 2<\/b> Chromatographic and mass spectrometric separation of Ibuprofen and cannabinoids in a pooled sample of cannabis inflorescence. Top chromatogram shows the total ion chromatogram and the other chromatograms are extracted at the mass of compound\/s.<\/p><\/blockquote>\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<p>The mean recoveries, calculated using the percent ratio of observed\/spiked concentrations, are also shown in Table 3, along with their SD values (<i>n<\/i> = 7). In the case of CBG, both the low-dilution (\u00d72.5) and high-dilution (\u00d7200) produced peaks that were within the linear range. However, the recovery from low-dilution samples was about 30% compared to almost 100% recovery for the high-dilution samples. The mean concentration value was also about three times higher with the high dilution. This clearly demonstrates the ion-suppression effects on CBG, and the elimination of this effect by sample dilution, as discussed above.<sup id=\"rdp-ebb-cite_ref-:7_14-2\" class=\"reference\"><a href=\"#cite_note-:7-14\">[14]<\/a><\/sup> As CBG and CBD have similar retention times, the CBG signal was suppressed by CBD in high CBD samples. In the pool sample used in Table 3, the CBD concentration is >10 times that of CBG.\n<\/p><p>The method was applied to quantify cannabinoids in several different samples containing high levels of CBD and high levels of THC. The concentrations of each cannabinoid quantified are listed in Table 4.\n<\/p>\n<table style=\"\">\n<tbody><tr>\n<td style=\"vertical-align:top;\">\n<table class=\"wikitable\" border=\"1\" cellpadding=\"5\" cellspacing=\"0\" style=\"\">\n\n<tbody><tr>\n<td colspan=\"3\" style=\"background-color:white; padding-left:10px; padding-right:10px;\"><b>Table 4.<\/b> Concentration ranges (\u00b5g\/g) of cannabinoids found in two high-CBD and three high-THC samples. ND, not detected; <LOD, below detection limit; <LOQ, between detection and quantification limits.\n<\/td><\/tr>\n<tr>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">Compound\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">High-CBD samples\n<\/th>\n<th style=\"background-color:#e2e2e2; padding-left:10px; padding-right:10px;\">High-THC samples\n<\/th><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">61.0\u201382.0\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCV\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">5.95\u20137.26\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">38.2\u2013107\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBN\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><LOQ\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">105\u2013134\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBD\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">4090\u201328,713\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">212\u2013382\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>8<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">\u0394<sup>9<\/sup>-THC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1705\u20132482\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">11,936\u201320,476\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBC\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">928\u20131095\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">153\u2013248\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBL\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBG\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">376\u2013470\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">519\u2013585\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">165\u2013216\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCVA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><LOQ\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">160\u20131209\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBNA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\"><LOD\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">342\u2013875\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBDA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">10,258\u201364,992\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">245\u2013363\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">THCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">796\u20131518\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">13,479\u201336,420\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBLA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">196\u2013250\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">ND\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBCA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1732\u20132952\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">998\u20131363\n<\/td><\/tr>\n<tr>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">CBGA\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">1045\u20131234\n<\/td>\n<td style=\"background-color:white; padding-left:10px; padding-right:10px;\">2956\u20136273\n<\/td><\/tr>\n<\/tbody><\/table>\n<\/td><\/tr><\/tbody><\/table>\n<h2><span class=\"mw-headline\" id=\"Conclusions\">Conclusions<\/span><\/h2>\n<p>An optimised, simple extraction method followed by a reliable and simple LC-MS method, was developed and validated for the simultaneous quantification of 17 cannabinoids. The method can be used by natural products laboratories that are equipped with a TOF-MS detector. By using low flow rate, the separation was achieved at low pressure (HPLC rather than UHPLC) conditions. The disadvantage of using the low flow rate was the long run time. Detection was performed by simpler MS rather than MS-MS. Although there was no significant loss of selectivity due to using MS instead of MS-MS, the sensitivity is compromised as evident from relatively high LOD and LOQ values (\u00b5g\/mL levels compared to ng\/mL levels commonly achieved with MS-MS). The main advantage of using this approach is that the method can be easily adapted to use with a simple HPLC-MS (single quadrupole) system that is commonly used in routine analytical laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well suited for routine phytocannabinoid analysis across a range of applications in a variety of laboratory settings.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"Acknowledgements\">Acknowledgements<\/span><\/h2>\n<p>We want to thank Cann Group Limited, lead industry partner on the CRC-P, for their valuable input and for providing proprietary germplasm for this research.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Author_contributions\">Author contributions<\/span><\/h3>\n<p>Conceptualization A.K.H., T.K. and B.J.B.; methodology, A.K.H.; formal analysis A.K.H., F.G.-T. and M.N.; investigation, A.K.H., F.G.-T., S.P. and M.N.; writing\u2014original draft preparation, A.K.H. and T.K.; writing\u2014review and editing, B.J.B., F.G.-T., S.P. and M.N.; supervision, A.K.H. and T.K.; project administration, T.K. and S.P.; funding acquisition, B.J.B. and T.K. All authors have read and agreed to the published version of the manuscript.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Funding\">Funding<\/span><\/h3>\n<p>This project received grant funding from the Australian Government via the Department of Industry, Science, Energy and Resources, as part of the Cooperative Research Centres Project (CRC-P) program\u2014Round 7: Growing the medicinal cannabis industry\u2014precision farming to pharmaceuticals.\n<\/p>\n<h3><span class=\"mw-headline\" id=\"Conflicts_of_interest\">Conflicts of interest<\/span><\/h3>\n<p>The authors declare no conflict of interest.\n<\/p>\n<h2><span class=\"mw-headline\" id=\"References\">References<\/span><\/h2>\n<div class=\"reflist references-column-width\" style=\"-moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;\">\n<div class=\"mw-references-wrap mw-references-columns\"><ol class=\"references\">\n<li id=\"cite_note-1\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-1\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Chandra, Suman; ElSohly, Mahmoud A.; Lata, Hemant, eds. (2017). <i>Cannabis sativa L. - Botany and Biotechnology<\/i> (1st ed. 2017 ed.). Cham: Springer International Publishing : Imprint: Springer. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-3-319-54564-6.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Cannabis+sativa+L.+-+Botany+and+Biotechnology&rft.date=2017&rft.edition=1st+ed.+2017&rft.place=Cham&rft.pub=Springer+International+Publishing+%3A+Imprint%3A+Springer&rft.isbn=978-3-319-54564-6&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:0-2\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:0_2-0\">2.0<\/a><\/sup> <sup><a href=\"#cite_ref-:0_2-1\">2.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Clarke, Robert C.; Merlin, Mark D. (1 November 2016). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/07352689.2016.1267498\" target=\"_blank\">\"Cannabis Domestication, Breeding History, Present-day Genetic Diversity, and Future Prospects\"<\/a> (in en). <i>Critical Reviews in Plant Sciences<\/i> <b>35<\/b> (5-6): 293\u2013327. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1080%2F07352689.2016.1267498\" target=\"_blank\">10.1080\/07352689.2016.1267498<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0735-2689\" target=\"_blank\">0735-2689<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/07352689.2016.1267498\" target=\"_blank\">https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/07352689.2016.1267498<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis+Domestication%2C+Breeding+History%2C+Present-day+Genetic+Diversity%2C+and+Future+Prospects&rft.jtitle=Critical+Reviews+in+Plant+Sciences&rft.aulast=Clarke&rft.aufirst=Robert+C.&rft.au=Clarke%2C%26%2332%3BRobert+C.&rft.au=Merlin%2C%26%2332%3BMark+D.&rft.date=1+November+2016&rft.volume=35&rft.issue=5-6&rft.pages=293%E2%80%93327&rft_id=info:doi\/10.1080%2F07352689.2016.1267498&rft.issn=0735-2689&rft_id=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F07352689.2016.1267498&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:1-3\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:1_3-0\">3.0<\/a><\/sup> <sup><a href=\"#cite_ref-:1_3-1\">3.1<\/a><\/sup> <sup><a href=\"#cite_ref-:1_3-2\">3.2<\/a><\/sup> <sup><a href=\"#cite_ref-:1_3-3\">3.3<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Giese, Matthew W; Lewis, Mark A; Giese, Laura; Smith, Kevin M (1 November 2015). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/academic.oup.com\/jaoac\/article\/98\/6\/1503-1522\/5654599\" target=\"_blank\">\"Method for the Analysis of Cannabinoids and Terpenes in Cannabis\"<\/a> (in en). <i>Journal of AOAC INTERNATIONAL<\/i> <b>98<\/b> (6): 1503\u20131522. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.5740%2Fjaoacint.15-116\" target=\"_blank\">10.5740\/jaoacint.15-116<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1060-3271\" target=\"_blank\">1060-3271<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/academic.oup.com\/jaoac\/article\/98\/6\/1503-1522\/5654599\" target=\"_blank\">https:\/\/academic.oup.com\/jaoac\/article\/98\/6\/1503-1522\/5654599<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Method+for+the+Analysis+of+Cannabinoids+and+Terpenes+in+Cannabis&rft.jtitle=Journal+of+AOAC+INTERNATIONAL&rft.aulast=Giese&rft.aufirst=Matthew+W&rft.au=Giese%2C%26%2332%3BMatthew+W&rft.au=Lewis%2C%26%2332%3BMark+A&rft.au=Giese%2C%26%2332%3BLaura&rft.au=Smith%2C%26%2332%3BKevin+M&rft.date=1+November+2015&rft.volume=98&rft.issue=6&rft.pages=1503%E2%80%931522&rft_id=info:doi\/10.5740%2Fjaoacint.15-116&rft.issn=1060-3271&rft_id=https%3A%2F%2Facademic.oup.com%2Fjaoac%2Farticle%2F98%2F6%2F1503-1522%2F5654599&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-4\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-4\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">van Breemen, Richard B.; Muchiri, Ruth N.; Bates, Timothy A.; Weinstein, Jules B.; Leier, Hans C.; Farley, Scotland; Tafesse, Fikadu G. (28 January 2022). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00946\" target=\"_blank\">\"Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants\"<\/a> (in en). <i>Journal of Natural Products<\/i> <b>85<\/b> (1): 176\u2013184. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1021%2Facs.jnatprod.1c00946\" target=\"_blank\">10.1021\/acs.jnatprod.1c00946<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/0163-3864\" target=\"_blank\">0163-3864<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8768006\" target=\"_blank\">PMC8768006<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/35007072\" target=\"_blank\">35007072<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00946\" target=\"_blank\">https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.1c00946<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabinoids+Block+Cellular+Entry+of+SARS-CoV-2+and+the+Emerging+Variants&rft.jtitle=Journal+of+Natural+Products&rft.aulast=van+Breemen&rft.aufirst=Richard+B.&rft.au=van+Breemen%2C%26%2332%3BRichard+B.&rft.au=Muchiri%2C%26%2332%3BRuth+N.&rft.au=Bates%2C%26%2332%3BTimothy+A.&rft.au=Weinstein%2C%26%2332%3BJules+B.&rft.au=Leier%2C%26%2332%3BHans+C.&rft.au=Farley%2C%26%2332%3BScotland&rft.au=Tafesse%2C%26%2332%3BFikadu+G.&rft.date=28+January+2022&rft.volume=85&rft.issue=1&rft.pages=176%E2%80%93184&rft_id=info:doi\/10.1021%2Facs.jnatprod.1c00946&rft.issn=0163-3864&rft_id=info:pmc\/PMC8768006&rft_id=info:pmid\/35007072&rft_id=https%3A%2F%2Fpubs.acs.org%2Fdoi%2F10.1021%2Facs.jnatprod.1c00946&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-5\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-5\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Welling, Matthew T.; Liu, Lei; Hazekamp, Arno; Dowell, Ashley; King, Graham J. (25 February 2019). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.karger.com\/Article\/FullText\/496868\" target=\"_blank\">\"Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry\"<\/a> (in en). <i>Medical Cannabis and Cannabinoids<\/i> <b>2<\/b> (1): 1\u201313. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1159%2F000496868\" target=\"_blank\">10.1159\/000496868<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2504-3889\" target=\"_blank\">2504-3889<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC8489335\" target=\"_blank\">PMC8489335<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/34676328\" target=\"_blank\">34676328<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.karger.com\/Article\/FullText\/496868\" target=\"_blank\">https:\/\/www.karger.com\/Article\/FullText\/496868<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Developing+Robust+Standardised+Analytical+Procedures+for+Cannabinoid+Quantification%3A+Laying+the+Foundations+for+an+Emerging+Cannabis-Based+Pharmaceutical+Industry&rft.jtitle=Medical+Cannabis+and+Cannabinoids&rft.aulast=Welling&rft.aufirst=Matthew%C2%A0T.&rft.au=Welling%2C%26%2332%3BMatthew%C2%A0T.&rft.au=Liu%2C%26%2332%3BLei&rft.au=Hazekamp%2C%26%2332%3BArno&rft.au=Dowell%2C%26%2332%3BAshley&rft.au=King%2C%26%2332%3BGraham%C2%A0J.&rft.date=25+February+2019&rft.volume=2&rft.issue=1&rft.pages=1%E2%80%9313&rft_id=info:doi\/10.1159%2F000496868&rft.issn=2504-3889&rft_id=info:pmc\/PMC8489335&rft_id=info:pmid\/34676328&rft_id=https%3A%2F%2Fwww.karger.com%2FArticle%2FFullText%2F496868&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:2-6\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:2_6-0\">6.0<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-1\">6.1<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-2\">6.2<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-3\">6.3<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-4\">6.4<\/a><\/sup> <sup><a href=\"#cite_ref-:2_6-5\">6.5<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Citti, Cinzia; Braghiroli, Daniela; Vandelli, Maria Angela; Cannazza, Giuseppe (1 January 2018). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708517311895\" target=\"_blank\">\"Pharmaceutical and biomedical analysis of cannabinoids: A critical review\"<\/a> (in en). <i>Journal of Pharmaceutical and Biomedical Analysis<\/i> <b>147<\/b>: 565\u2013579. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.jpba.2017.06.003\" target=\"_blank\">10.1016\/j.jpba.2017.06.003<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708517311895\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708517311895<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmaceutical+and+biomedical+analysis+of+cannabinoids%3A+A+critical+review&rft.jtitle=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.aulast=Citti&rft.aufirst=Cinzia&rft.au=Citti%2C%26%2332%3BCinzia&rft.au=Braghiroli%2C%26%2332%3BDaniela&rft.au=Vandelli%2C%26%2332%3BMaria+Angela&rft.au=Cannazza%2C%26%2332%3BGiuseppe&rft.date=1+January+2018&rft.volume=147&rft.pages=565%E2%80%93579&rft_id=info:doi\/10.1016%2Fj.jpba.2017.06.003&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0731708517311895&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:3-7\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:3_7-0\">7.0<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-1\">7.1<\/a><\/sup> <sup><a href=\"#cite_ref-:3_7-2\">7.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Micalizzi, Giuseppe; Vento, Federica; Alibrando, Filippo; Donnarumma, Danilo; Dugo, Paola; Mondello, Luigi (1 January 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967320311389\" target=\"_blank\">\"Cannabis Sativa L.: a comprehensive review on the analytical methodologies for cannabinoids and terpenes characterization\"<\/a> (in en). <i>Journal of Chromatography A<\/i> <b>1637<\/b>: 461864. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.chroma.2020.461864\" target=\"_blank\">10.1016\/j.chroma.2020.461864<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967320311389\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967320311389<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cannabis+Sativa+L.%3A+a+comprehensive+review+on+the+analytical+methodologies+for+cannabinoids+and+terpenes+characterization&rft.jtitle=Journal+of+Chromatography+A&rft.aulast=Micalizzi&rft.aufirst=Giuseppe&rft.au=Micalizzi%2C%26%2332%3BGiuseppe&rft.au=Vento%2C%26%2332%3BFederica&rft.au=Alibrando%2C%26%2332%3BFilippo&rft.au=Donnarumma%2C%26%2332%3BDanilo&rft.au=Dugo%2C%26%2332%3BPaola&rft.au=Mondello%2C%26%2332%3BLuigi&rft.date=1+January+2021&rft.volume=1637&rft.pages=461864&rft_id=info:doi\/10.1016%2Fj.chroma.2020.461864&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0021967320311389&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:4-8\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:4_8-0\">8.0<\/a><\/sup> <sup><a href=\"#cite_ref-:4_8-1\">8.1<\/a><\/sup> <sup><a href=\"#cite_ref-:4_8-2\">8.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hewavitharana, A.K.; Golding, G.; Tempany, G.; King, G.; Holling, N. (1 May 2005). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/academic.oup.com\/jat\/article\/29\/4\/258\/730079\/Quantitative-GCMS-Analysis-of\" target=\"_blank\">\"Quantitative GC-MS Analysis of \u03949-Tetrahydrocannabinol in Fiber Hemp Varieties\"<\/a> (in en). <i>Journal of Analytical Toxicology<\/i> <b>29<\/b> (4): 258\u2013261. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1093%2Fjat%2F29.4.258\" target=\"_blank\">10.1093\/jat\/29.4.258<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1945-2403\" target=\"_blank\">1945-2403<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/academic.oup.com\/jat\/article\/29\/4\/258\/730079\/Quantitative-GCMS-Analysis-of\" target=\"_blank\">http:\/\/academic.oup.com\/jat\/article\/29\/4\/258\/730079\/Quantitative-GCMS-Analysis-of<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Quantitative+GC-MS+Analysis+of+%CE%949-Tetrahydrocannabinol+in+Fiber+Hemp+Varieties&rft.jtitle=Journal+of+Analytical+Toxicology&rft.aulast=Hewavitharana&rft.aufirst=A.K.&rft.au=Hewavitharana%2C%26%2332%3BA.K.&rft.au=Golding%2C%26%2332%3BG.&rft.au=Tempany%2C%26%2332%3BG.&rft.au=King%2C%26%2332%3BG.&rft.au=Holling%2C%26%2332%3BN.&rft.date=1+May+2005&rft.volume=29&rft.issue=4&rft.pages=258%E2%80%93261&rft_id=info:doi\/10.1093%2Fjat%2F29.4.258&rft.issn=1945-2403&rft_id=http%3A%2F%2Facademic.oup.com%2Fjat%2Farticle%2F29%2F4%2F258%2F730079%2FQuantitative-GCMS-Analysis-of&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:5-9\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:5_9-0\">9.0<\/a><\/sup> <sup><a href=\"#cite_ref-:5_9-1\">9.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation web\">ECA Foundation (8 April 2020). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.gmp-compliance.org\/gmp-news\/german-pharmacopoeia-monograph-for-cannabis-extracts\" target=\"_blank\">\"German Pharmacopoeia Monograph for Cannabis Extracts\"<\/a>. <i>ECA Academy<\/i>. ECA Foundation<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.gmp-compliance.org\/gmp-news\/german-pharmacopoeia-monograph-for-cannabis-extracts\" target=\"_blank\">https:\/\/www.gmp-compliance.org\/gmp-news\/german-pharmacopoeia-monograph-for-cannabis-extracts<\/a><\/span><span class=\"reference-accessdate\">. Retrieved 28 February 2022<\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.btitle=German+Pharmacopoeia+Monograph+for+Cannabis+Extracts&rft.atitle=ECA+Academy&rft.aulast=ECA+Foundation&rft.au=ECA+Foundation&rft.date=8+April+2020&rft.pub=ECA+Foundation&rft_id=https%3A%2F%2Fwww.gmp-compliance.org%2Fgmp-news%2Fgerman-pharmacopoeia-monograph-for-cannabis-extracts&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:6-10\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:6_10-0\">10.0<\/a><\/sup> <sup><a href=\"#cite_ref-:6_10-1\">10.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Mudge, Elizabeth M.; Murch, Susan J.; Brown, Paula N. (1 May 2017). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/link.springer.com\/10.1007\/s00216-017-0256-3\" target=\"_blank\">\"Leaner and greener analysis of cannabinoids\"<\/a> (in en). <i>Analytical and Bioanalytical Chemistry<\/i> <b>409<\/b> (12): 3153\u20133163. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1007%2Fs00216-017-0256-3\" target=\"_blank\">10.1007\/s00216-017-0256-3<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/1618-2642\" target=\"_blank\">1618-2642<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC5395585\" target=\"_blank\">PMC5395585<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28233028\" target=\"_blank\">28233028<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/link.springer.com\/10.1007\/s00216-017-0256-3\" target=\"_blank\">http:\/\/link.springer.com\/10.1007\/s00216-017-0256-3<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Leaner+and+greener+analysis+of+cannabinoids&rft.jtitle=Analytical+and+Bioanalytical+Chemistry&rft.aulast=Mudge&rft.aufirst=Elizabeth+M.&rft.au=Mudge%2C%26%2332%3BElizabeth+M.&rft.au=Murch%2C%26%2332%3BSusan+J.&rft.au=Brown%2C%26%2332%3BPaula+N.&rft.date=1+May+2017&rft.volume=409&rft.issue=12&rft.pages=3153%E2%80%933163&rft_id=info:doi\/10.1007%2Fs00216-017-0256-3&rft.issn=1618-2642&rft_id=info:pmc\/PMC5395585&rft_id=info:pmid\/28233028&rft_id=http%3A%2F%2Flink.springer.com%2F10.1007%2Fs00216-017-0256-3&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-11\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-11\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Berman, Paula; Futoran, Kate; Lewitus, Gil M.; Mukha, Dzmitry; Benami, Maya; Shlomi, Tomer; Meiri, David (1 December 2018). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.nature.com\/articles\/s41598-018-32651-4\" target=\"_blank\">\"A new ESI-LC\/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis\"<\/a> (in en). <i>Scientific Reports<\/i> <b>8<\/b> (1): 14280. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1038%2Fs41598-018-32651-4\" target=\"_blank\">10.1038\/s41598-018-32651-4<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2045-2322\" target=\"_blank\">2045-2322<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC6155167\" target=\"_blank\">PMC6155167<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30250104\" target=\"_blank\">30250104<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.nature.com\/articles\/s41598-018-32651-4\" target=\"_blank\">http:\/\/www.nature.com\/articles\/s41598-018-32651-4<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+new+ESI-LC%2FMS+approach+for+comprehensive+metabolic+profiling+of+phytocannabinoids+in+Cannabis&rft.jtitle=Scientific+Reports&rft.aulast=Berman&rft.aufirst=Paula&rft.au=Berman%2C%26%2332%3BPaula&rft.au=Futoran%2C%26%2332%3BKate&rft.au=Lewitus%2C%26%2332%3BGil+M.&rft.au=Mukha%2C%26%2332%3BDzmitry&rft.au=Benami%2C%26%2332%3BMaya&rft.au=Shlomi%2C%26%2332%3BTomer&rft.au=Meiri%2C%26%2332%3BDavid&rft.date=1+December+2018&rft.volume=8&rft.issue=1&rft.pages=14280&rft_id=info:doi\/10.1038%2Fs41598-018-32651-4&rft.issn=2045-2322&rft_id=info:pmc\/PMC6155167&rft_id=info:pmid\/30250104&rft_id=http%3A%2F%2Fwww.nature.com%2Farticles%2Fs41598-018-32651-4&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-12\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-12\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation book\">Skoog, Douglas A. (1985). <i>Principles of instrumental analysis<\/i>. Saunders golden sunburst series (3rd ed.). Philadelphia: Saunders College Pub. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Book_Number\" data-key=\"f64947ba21e884434bd70e8d9e60bae6\">ISBN<\/a> 978-0-03-001229-7.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Principles+of+instrumental+analysis&rft.aulast=Skoog&rft.aufirst=Douglas+A.&rft.au=Skoog%2C%26%2332%3BDouglas+A.&rft.date=1985&rft.series=Saunders+golden+sunburst+series&rft.edition=3rd&rft.place=Philadelphia&rft.pub=Saunders+College+Pub&rft.isbn=978-0-03-001229-7&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-13\"><span class=\"mw-cite-backlink\"><a href=\"#cite_ref-13\">\u2191<\/a><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Wang, Mei; Wang, Yan-Hong; Avula, Bharathi; Radwan, Mohamed M.; Wanas, Amira S.; van Antwerp, John; Parcher, Jon F.; ElSohly, Mahmoud A. <i>et al.<\/i> (1 December 2016). <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.liebertpub.com\/doi\/10.1089\/can.2016.0020\" target=\"_blank\">\"Decarboxylation Study of Acidic Cannabinoids: A Novel Approach Using Ultra-High-Performance Supercritical Fluid Chromatography\/Photodiode Array-Mass Spectrometry\"<\/a> (in en). <i>Cannabis and Cannabinoid Research<\/i> <b>1<\/b> (1): 262\u2013271. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1089%2Fcan.2016.0020\" target=\"_blank\">10.1089\/can.2016.0020<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/International_Standard_Serial_Number\" data-key=\"a5dec3e4d005e654c29ad167ab53f53a\">ISSN<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.worldcat.org\/issn\/2378-8763\" target=\"_blank\">2378-8763<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Central\" data-key=\"c85bdffd69dd30e02024b9cc3d7679e2\">PMC<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.pubmedcentral.gov\/articlerender.fcgi?tool=pmcentrez&artid=PMC5549281\" target=\"_blank\">PMC5549281<\/a>. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/PubMed_Identifier\" data-key=\"1d34e999f13d8801964a6b3e9d7b4e30\">PMID<\/a> <a rel=\"external_link\" class=\"external text\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28861498\" target=\"_blank\">28861498<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"http:\/\/www.liebertpub.com\/doi\/10.1089\/can.2016.0020\" target=\"_blank\">http:\/\/www.liebertpub.com\/doi\/10.1089\/can.2016.0020<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Decarboxylation+Study+of+Acidic+Cannabinoids%3A+A+Novel+Approach+Using+Ultra-High-Performance+Supercritical+Fluid+Chromatography%2FPhotodiode+Array-Mass+Spectrometry&rft.jtitle=Cannabis+and+Cannabinoid+Research&rft.aulast=Wang&rft.aufirst=Mei&rft.au=Wang%2C%26%2332%3BMei&rft.au=Wang%2C%26%2332%3BYan-Hong&rft.au=Avula%2C%26%2332%3BBharathi&rft.au=Radwan%2C%26%2332%3BMohamed+M.&rft.au=Wanas%2C%26%2332%3BAmira+S.&rft.au=van+Antwerp%2C%26%2332%3BJohn&rft.au=Parcher%2C%26%2332%3BJon+F.&rft.au=ElSohly%2C%26%2332%3BMahmoud+A.&rft.au=Khan%2C%26%2332%3BIkhlas+A.&rft.date=1+December+2016&rft.volume=1&rft.issue=1&rft.pages=262%E2%80%93271&rft_id=info:doi\/10.1089%2Fcan.2016.0020&rft.issn=2378-8763&rft_id=info:pmc\/PMC5549281&rft_id=info:pmid\/28861498&rft_id=http%3A%2F%2Fwww.liebertpub.com%2Fdoi%2F10.1089%2Fcan.2016.0020&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:7-14\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:7_14-0\">14.0<\/a><\/sup> <sup><a href=\"#cite_ref-:7_14-1\">14.1<\/a><\/sup> <sup><a href=\"#cite_ref-:7_14-2\">14.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Taylor, Paul J. (1 April 2005). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009912004003364\" target=\"_blank\">\"Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography\u2013electrospray\u2013tandem mass spectrometry\"<\/a> (in en). <i>Clinical Biochemistry<\/i> <b>38<\/b> (4): 328\u2013334. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.clinbiochem.2004.11.007\" target=\"_blank\">10.1016\/j.clinbiochem.2004.11.007<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009912004003364\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009912004003364<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Matrix+effects%3A+the+Achilles+heel+of+quantitative+high-performance+liquid+chromatography%E2%80%93electrospray%E2%80%93tandem+mass+spectrometry&rft.jtitle=Clinical+Biochemistry&rft.aulast=Taylor&rft.aufirst=Paul+J.&rft.au=Taylor%2C%26%2332%3BPaul+J.&rft.date=1+April+2005&rft.volume=38&rft.issue=4&rft.pages=328%E2%80%93334&rft_id=info:doi\/10.1016%2Fj.clinbiochem.2004.11.007&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0009912004003364&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:8-15\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:8_15-0\">15.0<\/a><\/sup> <sup><a href=\"#cite_ref-:8_15-1\">15.1<\/a><\/sup> <sup><a href=\"#cite_ref-:8_15-2\">15.2<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hewavitharana, Amitha K. (1 January 2011). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967310016213\" target=\"_blank\">\"Matrix matching in liquid chromatography\u2013mass spectrometry with stable isotope labelled internal standards\u2014Is it necessary?\"<\/a> (in en). <i>Journal of Chromatography A<\/i> <b>1218<\/b> (2): 359\u2013361. <a rel=\"nofollow\" class=\"external text wiki-link\" href=\"http:\/\/en.wikipedia.org\/wiki\/Digital_object_identifier\" data-key=\"ae6d69c760ab710abc2dd89f3937d2f4\">doi<\/a>:<a rel=\"external_link\" class=\"external text\" href=\"http:\/\/dx.doi.org\/10.1016%2Fj.chroma.2010.11.047\" target=\"_blank\">10.1016\/j.chroma.2010.11.047<\/a><span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967310016213\" target=\"_blank\">https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021967310016213<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Matrix+matching+in+liquid+chromatography%E2%80%93mass+spectrometry+with+stable+isotope+labelled+internal+standards%E2%80%94Is+it+necessary%3F&rft.jtitle=Journal+of+Chromatography+A&rft.aulast=Hewavitharana&rft.aufirst=Amitha+K.&rft.au=Hewavitharana%2C%26%2332%3BAmitha+K.&rft.date=1+January+2011&rft.volume=1218&rft.issue=2&rft.pages=359%E2%80%93361&rft_id=info:doi\/10.1016%2Fj.chroma.2010.11.047&rft_id=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0021967310016213&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<li id=\"cite_note-:9-16\"><span class=\"mw-cite-backlink\">\u2191 <sup><a href=\"#cite_ref-:9_16-0\">16.0<\/a><\/sup> <sup><a href=\"#cite_ref-:9_16-1\">16.1<\/a><\/sup><\/span> <span class=\"reference-text\"><span class=\"citation Journal\">Hewavitharana, A.K.; Shawn, P.N.; Smyth, H.D.C. et al. (July 2021). <a rel=\"external_link\" class=\"external text\" href=\"https:\/\/www.chromatographyonline.com\/view\/the-importance-of-complete-overlapping-of-analyte-and-internal-standard-peaks-in-eliminating-matrix-effects-with-liquid-chromatography-mass-spectrometry-lc-ms-\" target=\"_blank\">\"The Importance of Complete Overlapping of Analyte and Internal Standard Peaks in Eliminating Matrix Effects with Liquid Chromatography\u2013Mass Spectrometry (LC\u2013MS)\"<\/a>. <i>LCGC North America<\/i> <b>39<\/b> (7): 335\u201338<span class=\"printonly\">. <a rel=\"external_link\" class=\"external free\" href=\"https:\/\/www.chromatographyonline.com\/view\/the-importance-of-complete-overlapping-of-analyte-and-internal-standard-peaks-in-eliminating-matrix-effects-with-liquid-chromatography-mass-spectrometry-lc-ms-\" target=\"_blank\">https:\/\/www.chromatographyonline.com\/view\/the-importance-of-complete-overlapping-of-analyte-and-internal-standard-peaks-in-eliminating-matrix-effects-with-liquid-chromatography-mass-spectrometry-lc-ms-<\/a><\/span>.<\/span><span class=\"Z3988\" title=\"ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Importance+of+Complete+Overlapping+of+Analyte+and+Internal+Standard+Peaks+in+Eliminating+Matrix+Effects+with+Liquid+Chromatography%E2%80%93Mass+Spectrometry+%28LC%E2%80%93MS%29&rft.jtitle=LCGC+North+America&rft.aulast=Hewavitharana%2C+A.K.%3B+Shawn%2C+P.N.%3B+Smyth%2C+H.D.C.+et+al.&rft.au=Hewavitharana%2C+A.K.%3B+Shawn%2C+P.N.%3B+Smyth%2C+H.D.C.+et+al.&rft.date=July+2021&rft.volume=39&rft.issue=7&rft.pages=335%E2%80%9338&rft_id=https%3A%2F%2Fwww.chromatographyonline.com%2Fview%2Fthe-importance-of-complete-overlapping-of-analyte-and-internal-standard-peaks-in-eliminating-matrix-effects-with-liquid-chromatography-mass-spectrometry-lc-ms-&rfr_id=info:sid\/en.wikipedia.org:Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\"><span style=\"display: none;\"> <\/span><\/span>\n<\/span>\n<\/li>\n<\/ol><\/div><\/div>\n<h2><span class=\"mw-headline\" id=\"Notes\">Notes<\/span><\/h2>\n<p>This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added.\n<\/p>\n<!-- \nNewPP limit report\nCached time: 20220627183149\nCache expiry: 86400\nDynamic content: false\nComplications: []\nCPU time usage: 0.261 seconds\nReal time usage: 0.318 seconds\nPreprocessor visited node count: 17924\/1000000\nPost\u2010expand include size: 156100\/2097152 bytes\nTemplate argument size: 48680\/2097152 bytes\nHighest expansion depth: 25\/40\nExpensive parser function count: 0\/100\nUnstrip recursion depth: 0\/20\nUnstrip post\u2010expand size: 43302\/5000000 bytes\n-->\n<!--\nTransclusion expansion time report (%,ms,calls,template)\n100.00% 230.636 1 -total\n 78.42% 180.869 1 Template:Reflist\n 58.61% 135.184 16 Template:Citation\/core\n 46.51% 107.276 13 Template:Cite_journal\n 17.58% 40.542 2 Template:Cite_book\n 11.87% 27.365 1 Template:Infobox_journal_article\n 10.94% 25.239 16 Template:Date\n 9.90% 22.843 1 Template:Infobox\n 9.19% 21.191 32 Template:Citation\/identifier\n 5.45% 12.576 80 Template:Infobox\/row\n-->\n\n<!-- Saved in parser cache with key cannaqa_wiki:pcache:idhash:5678-0!canonical and timestamp 20220627183149 and revision id 17514. Serialized with JSON.\n -->\n<\/div><\/div><div class=\"printfooter\">Source: <a rel=\"external_link\" class=\"external\" href=\"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry\">https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry<\/a><\/div>\n<!-- end content --><div class=\"visualClear\"><\/div><\/div><\/div><div class=\"visualClear\"><\/div><\/div><!-- end of the left (by default at least) column --><div class=\"visualClear\"><\/div><\/div>\n<\/body>","60c6b04b4bcf2aea432c0203d99568af_images":["https:\/\/www.cannaqa.wiki\/images\/3\/33\/Fig1_Hewavitharana_Separations_9-4.png","https:\/\/www.cannaqa.wiki\/images\/1\/1c\/Fig2_Hewavitharana_Separations_9-4.png"],"60c6b04b4bcf2aea432c0203d99568af_timestamp":1656439823,"6b03770f3ae1d0327e8eb69d5900fa48":{"type":"chapter","title":"1. Cannabis analysis and research","key":"6b03770f3ae1d0327e8eb69d5900fa48"}},"link":"https:\/\/www.limswiki.org\/index.php\/Book:LIMSjournal_-_Summer_2022","price_currency":"","price_amount":"","book_size":"","download_url":"https:\/\/www.limsforum.com?ebb_action=book_download&book_id=103423","language":"","cta_button_content":"","toc":[{"type":"chapter","name":"1. Cannabis analysis and research","id":"6b03770f3ae1d0327e8eb69d5900fa48","children":[{"type":"article","name":"Simultaneous quantification of 17 cannabinoids in cannabis inflorescence by liquid chromatography\u2013mass spectrometry (Hewavitharana et al. 2022)","id":"60c6b04b4bcf2aea432c0203d99568af","pageUrl":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Simultaneous_quantification_of_17_cannabinoids_in_cannabis_inflorescence_by_liquid_chromatography%E2%80%93mass_spectrometry"},{"type":"article","name":"Cannabis sativa research trends, challenges, and new-age perspectives (Hussain et al. 2021)","id":"4e539c9ca5c42af2a2ca977a314b2e2f","pageUrl":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Cannabis_sativa_research_trends,_challenges,_and_new-age_perspectives"},{"type":"article","name":"Potential of NIRS technology for the determination of cannabinoid content in industrial hemp (Cannabis sativa L.) (Jar\u00e9n et al. 2022)","id":"e54c0b7e681c5437811a012a24acebea","pageUrl":"https:\/\/www.cannaqa.wiki\/index.php?title=Journal:Potential_of_NIRS_technology_for_the_determination_of_cannabinoid_content_in_industrial_hemp_(Cannabis_sativa_L.)"}]},{"type":"chapter","name":"2. Clinical informatics","id":"cc883ed5b173beeb241cab635b32933a","children":[{"type":"article","name":"DigiPatICS: Digital pathology transformation of the Catalan Health Institute network of eight hospitals - Planning, implementation, and preliminary results (Temprana-Salvado et al. 2022)","id":"ef9487ab4d88db8c29a49a38ec04aec1","pageUrl":"https:\/\/www.limswiki.org\/index.php\/Journal:DigiPatICS:_Digital_pathology_transformation_of_the_Catalan_Health_Institute_network_of_eight_hospitals_-_Planning,_implementation,_and_preliminary_results"},{"type":"article","name":"A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operations (Tomlinson et al. 2022)","id":"215d8425e45c087c83287d3b78268e65","pageUrl":"https:\/\/www.limswiki.org\/index.php\/Journal:A_model_for_design_and_implementation_of_a_laboratory_information_management_system_specific_to_molecular_pathology_laboratory_operations"},{"type":"article","name":"Health informatics: Engaging modern healthcare units: A brief overview (Yogesh and Karthikeyan 2022)","id":"c4564a9f0e02ca2559e204e61f391fbd","pageUrl":"https:\/\/www.limswiki.org\/index.php\/Journal:Health_informatics:_Engaging_modern_healthcare_units:_A_brief_overview"}]},{"type":"chapter","name":"3. Data interoperability and provenance","id":"e36b36956c80f568d26bd459dd75ac3d","children":[{"type":"article","name":"Using knowledge graph structures for semantic interoperability in electronic health records data exchanges (Sachdeva and Bhalla 2022)","id":"5c4c23816cc524a349b691a9b6846809","pageUrl":"https:\/\/www.limswiki.org\/index.php\/Journal:Using_knowledge_graph_structures_for_semantic_interoperability_in_electronic_health_records_data_exchanges"},{"type":"article","name":"Structure-based knowledge acquisition from electronic lab notebooks for research data provenance documentation (Schr\u00f6der et al. 2022)","id":"d40238949d238978e30434ffe18aa050","pageUrl":"https:\/\/www.limswiki.org\/index.php\/Journal:Structure-based_knowledge_acquisition_from_electronic_lab_notebooks_for_research_data_provenance_documentation"}]},{"type":"chapter","name":"4. 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