Digital Biomarkers最新文献

{"title":"Defining and Developing the Workforce Needed for Success in the Digital Era of Medicine.","authors":"Jennifer C Goldsack,&nbsp;Cole A Zanetti","doi":"10.1159/000512382","DOIUrl":"https://doi.org/10.1159/000512382","url":null,"abstract":"<p><p>Artificial intelligence offers the promise of transforming biomedical research and helping clinicians put the \"care\" back in healthcare. Digital medicine is on its way to becoming just plain medicine. But who will digitize how we define health and disease? And who will deploy this knowledge to improve the lives of patients that medicine - and digital medicine - exists to serve? Here we define the emerging field of digital medicine and identify the disciplines and skills needed for success. We examine the current and projected skills gaps. We also consider the impact of the culture clash that occurs at the intersection of healthcare and technology, and the lack of diversity in the workforce of both of these fields. We conclude by describing the requirements for the skills pivot needed to ensure that the digital transformation of healthcare is successful: (1) big tent thinking to recognize the critical importance of new technical skills alongside more traditional clinical disciplines, (2) the integration of clinical and technical skill sets within educational curricula, companies, and professional institutions, and (3) a commitment to diversity that goes beyond lip service.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"136-142"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science.","authors":"Diane Stephenson, Robert Alexander, Varun Aggarwal, Reham Badawy, Lisa Bain, Roopal Bhatnagar, Bastiaan R Bloem, Babak Boroojerdi, Jackson Burton, Jesse M Cedarbaum, Josh Cosman, David T Dexter, Marissa Dockendorf, E Ray Dorsey, Ariel V Dowling, Luc J W Evers, Katherine Fisher, Mark Frasier, Luis Garcia-Gancedo, Jennifer C Goldsack, Derek Hill, Janice Hitchcock, Michele T Hu, Michael P Lawton, Susan J Lee, Michael Lindemann, Ken Marek, Nitin Mehrotra, Marjan J Meinders, Michael Minchik, Lauren Oliva, Klaus Romero, George Roussos, Robert Rubens, Sakshi Sadar, Joseph Scheeren, Eiichi Sengoku, Tanya Simuni, Glenn Stebbins, Kirsten I Taylor, Beatrice Yang, Neta Zach","doi":"10.1159/000512500","DOIUrl":"10.1159/000512500","url":null,"abstract":"<p><p>Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson's Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"28-49"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768153/pdf/dib-0004-0028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Digital Navigators in Promoting Clinical Care and Technology Integration into Practice.","authors":"Hannah Wisniewski, Tristan Gorrindo, Natali Rauseo-Ricupero, Don Hilty, John Torous","doi":"10.1159/000510144","DOIUrl":"10.1159/000510144","url":null,"abstract":"<p><p>As the role of technology expands in healthcare, so does the need to support its implementation and integration into the clinic. The concept of a new team member, the digital navigator, able to assume this role is introduced as a solution. With a digital navigator, any clinic today can take advantage of digital health and smartphone tools to augment and expand existing telehealth and face to face care. The role of a digital navigator is suitable as an entry level healthcare role, additional training for an experienced clinician, and well suited to peer specialists. To facilitate the training of digital navigators, we draw upon our experience in creating the role and across health education to introduce a 10-h curriculum designed to train digital navigators across 5 domains: (1) core smartphone skills, (2) basic technology troubleshooting, (3) app evaluation, (4) clinical terminology and data, and (5) engagement techniques. This paper outlines the curricular content, skills, and modules for this training and features a rich online supplementary Appendix with step by step instructions and resources.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"119-135"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768140/pdf/dib-0004-0119.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Roadmap to Inform Development, Validation and Approval of Digital Mobility Outcomes: The Mobilise-D Approach.","authors":"Lynn Rochester,&nbsp;Claudia Mazzà,&nbsp;Arne Mueller,&nbsp;Brian Caulfield,&nbsp;Marie McCarthy,&nbsp;Clemens Becker,&nbsp;Ram Miller,&nbsp;Paolo Piraino,&nbsp;Marco Viceconti,&nbsp;Wilhelmus P Dartee,&nbsp;Judith Garcia-Aymerich,&nbsp;Aida A Aydemir,&nbsp;Beatrix Vereijken,&nbsp;Valdo Arnera,&nbsp;Nadir Ammour,&nbsp;Michael Jackson,&nbsp;Tilo Hache,&nbsp;Ronenn Roubenoff","doi":"10.1159/000512513","DOIUrl":"https://doi.org/10.1159/000512513","url":null,"abstract":"<p><p>Health care has had to adapt rapidly to COVID-19, and this in turn has highlighted a pressing need for tools to facilitate remote visits and monitoring. Digital health technology, including body-worn devices, offers a solution using digital outcomes to measure and monitor disease status and provide outcomes meaningful to both patients and health care professionals. Remote monitoring of physical mobility is a prime example, because mobility is among the most advanced modalities that can be assessed digitally and remotely. Loss of mobility is also an important feature of many health conditions, providing a read-out of health as well as a target for intervention. Real-world, continuous digital measures of mobility (digital mobility outcomes or DMOs) provide an opportunity for novel insights into health care conditions complementing existing mobility measures. Accepted and approved DMOs are not yet widely available. The need for large collaborative efforts to tackle the critical steps to adoption is widely recognised. Mobilise-D is an example. It is a multidisciplinary consortium of 34 institutions from academia and industry funded through the European Innovative Medicines Initiative 2 Joint Undertaking. Members of Mobilise-D are collaborating to address the critical steps for DMOs to be adopted in clinical trials and ultimately health care. To achieve this, the consortium has developed a roadmap to inform the development, validation and approval of DMOs in Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease and recovery from proximal femoral fracture. Here we aim to describe the proposed approach and provide a high-level view of the ongoing and planned work of the Mobilise-D consortium. Ultimately, Mobilise-D aims to stimulate widespread adoption of DMOs through the provision of device agnostic software, standards and robust validation in order to bring digital outcomes from concept to use in clinical trials and health care.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"13-27"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Digital Health.","authors":"Ieuan Clay","doi":"10.1159/000511705","DOIUrl":"https://doi.org/10.1159/000511705","url":null,"abstract":"","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38816764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Path Forward for Digital Measures: Suppressing the Desire to Compare Apples and Pineapples.","authors":"Carrie R Houts,&nbsp;Bray Patrick-Lake,&nbsp;Ieuan Clay,&nbsp;R J Wirth","doi":"10.1159/000511586","DOIUrl":"https://doi.org/10.1159/000511586","url":null,"abstract":"<p><p>Digital measures are becoming more prevalent in clinical development. Methods for robust evaluation are increasingly well defined, yet the primary barrier for digital measures to transition beyond exploratory usage often relies on a comparison to the existing standards. This article focuses on how researchers should approach the complex issue of comparing across assessment modalities. We discuss comparisons of subjective versus objective assessments, or performance-based versus behavioral measures, and we pay particular attention to the situation where the expected association may be poor or nonlinear. We propose that, rather than seeking to replace the standard, research should focus on a structured understanding of how the new measure augments established assessments, with the ultimate goal of developing a more complete understanding of what is meaningful to patients.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38816766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Collaborative Aging Research Using Technology Initiative: An Open, Sharable, Technology-Agnostic Platform for the Research Community.","authors":"Zachary Beattie,&nbsp;Lyndsey M Miller,&nbsp;Carlos Almirola,&nbsp;Wan-Tai M Au-Yeung,&nbsp;Hannah Bernard,&nbsp;Kevin E Cosgrove,&nbsp;Hiroko H Dodge,&nbsp;Charlene J Gamboa,&nbsp;Ona Golonka,&nbsp;Sarah Gothard,&nbsp;Sam Harbison,&nbsp;Stephanie Irish,&nbsp;Judith Kornfeld,&nbsp;Jonathan Lee,&nbsp;Jennifer Marcoe,&nbsp;Nora C Mattek,&nbsp;Charlie Quinn,&nbsp;Christina Reynolds,&nbsp;Thomas Riley,&nbsp;Nathaniel Rodrigues,&nbsp;Nicole Sharma,&nbsp;Mary Alice Siqueland,&nbsp;Neil W Thomas,&nbsp;Timothy Truty,&nbsp;Rachel Wall,&nbsp;Katherine Wild,&nbsp;Chao-Yi Wu,&nbsp;Jason Karlawish,&nbsp;Nina B Silverberg,&nbsp;Lisa L Barnes,&nbsp;Sara Czaja,&nbsp;Lisa C Silbert,&nbsp;Jeffrey Kaye","doi":"10.1159/000512208","DOIUrl":"https://doi.org/10.1159/000512208","url":null,"abstract":"<p><strong>Introduction: </strong>Future digital health research hinges on methodologies to conduct remote clinical assessments and in-home monitoring. The Collaborative Aging Research Using Technology (CART) initiative was introduced to establish a digital technology research platform that could widely assess activity in the homes of diverse cohorts of older adults and detect meaningful change longitudinally. This paper reports on the built end-to-end design of the CART platform, its functionality, and the resulting research capabilities.</p><p><strong>Methods: </strong>CART platform development followed a principled design process aiming for scalability, use case flexibility, longevity, and data privacy protection while allowing sharability. The platform, comprising ambient technology, wearables, and other sensors, was deployed in participants' homes to provide continuous, long-term (months to years), and ecologically valid data. Data gathered from CART homes were sent securely to a research server for analysis and future data sharing.</p><p><strong>Results: </strong>The CART system was created, iteratively tested, and deployed to 232 homes representing four diverse cohorts (African American, Latinx, low-income, and predominantly rural-residing veterans) of older adults (<i>n</i> = 301) across the USA. Multiple measurements of wellness such as cognition (e.g., mean daily computer use time = 160-169 min), physical mobility (e.g., mean daily transitions between rooms = 96-155), sleep (e.g., mean nightly sleep duration = 6.3-7.4 h), and level of social engagement (e.g., reports of overnight visitors = 15-45%) were collected across cohorts.</p><p><strong>Conclusion: </strong>The CART initiative resulted in a minimally obtrusive digital health-enabled system that met the design principles while allowing for data capture over extended periods and can be widely used by the research community. The ability to monitor and manage health digitally within the homes of older adults is an important alternative to in-person assessments in many research contexts. Further advances will come with wider, shared use of the CART system in additional settings, within different disease contexts, and by diverse research teams.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 Suppl 1","pages":"100-118"},"PeriodicalIF":0.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38817110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Speech-Based Digital Biomarkers: Review and Recommendations.","authors":"Jessica Robin,&nbsp;John E Harrison,&nbsp;Liam D Kaufman,&nbsp;Frank Rudzicz,&nbsp;William Simpson,&nbsp;Maria Yancheva","doi":"10.1159/000510820","DOIUrl":"https://doi.org/10.1159/000510820","url":null,"abstract":"<p><p>Speech represents a promising novel biomarker by providing a window into brain health, as shown by its disruption in various neurological and psychiatric diseases. As with many novel digital biomarkers, however, rigorous evaluation is currently lacking and is required for these measures to be used effectively and safely. This paper outlines and provides examples from the literature of evaluation steps for speech-based digital biomarkers, based on the recent V3 framework (Goldsack et al., 2020). The V3 framework describes 3 components of evaluation for digital biomarkers: verification, analytical validation, and clinical validation. Verification includes assessing the quality of speech recordings and comparing the effects of hardware and recording conditions on the integrity of the recordings. Analytical validation includes checking the accuracy and reliability of data processing and computed measures, including understanding test-retest reliability, demographic variability, and comparing measures to reference standards. Clinical validity involves verifying the correspondence of a measure to clinical outcomes which can include diagnosis, disease progression, or response to treatment. For each of these sections, we provide recommendations for the types of evaluation necessary for speech-based biomarkers and review published examples. The examples in this paper focus on speech-based biomarkers, but they can be used as a template for digital biomarker development more generally.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 3","pages":"99-108"},"PeriodicalIF":0.0,"publicationDate":"2020-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38315669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A COVID-19 Multipurpose Platform.","authors":"Nikos Petrellis","doi":"10.1159/000511704","DOIUrl":"10.1159/000511704","url":null,"abstract":"<p><strong>Background: </strong>Contactless symptom tracking is essential for the diagnosis of COVID-19 cases that need hospitalization. Indications from sensors and user descriptions have to be combined in order to make the right decisions.</p><p><strong>Methods: </strong>The proposed multipurpose platform Coronario combines sensory information from different sources for a valid diagnosis following a dynamically adaptable protocol. The information exchanged can also be exploited for the advancement of research on COVID-19. The platform consists of mobile and desktop applications, sensor infrastructure, and cloud services. It may be used by patients in pre- and post-hospitalization stages, vulnerable populations, medical practitioners, and researchers.</p><p><strong>Results: </strong>The supported audio processing is used to demonstrate how the Coronario platform can assist research on the nature of COVID-19. Cough sounds are classified as a case study, with 90% accuracy.</p><p><strong>Discussion/conclusions: </strong>The dynamic adaptation to new medical protocols is one of the main advantages of the developed platform, making it particularly useful for several target groups of patients that require different screening methods. A medical protocol determines the structure of the questionnaires, the medical sensor sampling strategy and, the alert rules.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 3","pages":"89-98"},"PeriodicalIF":0.0,"publicationDate":"2020-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38588391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Thorough Examination of Morning Activity Patterns in Adults with Arthritis and Healthy Controls Using Actigraphy Data.","authors":"Alison Keogh,&nbsp;Niladri Sett,&nbsp;Seamas Donnelly,&nbsp;Ronan Mullan,&nbsp;Diana Gheta,&nbsp;Martina Maher-Donnelly,&nbsp;Vittorio Illiano,&nbsp;Francesc Calvo,&nbsp;Jonas F Dorn,&nbsp;Brian Mac Namee,&nbsp;Brian Caulfield","doi":"10.1159/000509724","DOIUrl":"https://doi.org/10.1159/000509724","url":null,"abstract":"<p><strong>Background: </strong>Wearable sensors allow researchers to remotely capture digital health data, including physical activity, which may identify digital biomarkers to differentiate healthy and clinical cohorts. To date, research has focused on high-level data (e.g., overall step counts) which may limit our insights to <i>whether</i> people move differently, rather than <i>how</i> they move differently.</p><p><strong>Objective: </strong>This study therefore aimed to use actigraphy data to thoroughly examine activity patterns during the first hours following waking in arthritis patients (<i>n</i> = 45) and healthy controls (<i>n</i> = 30).</p><p><strong>Methods: </strong>Participants wore an Actigraph GT9X Link for 28 days. Activity counts were analysed and compared over varying epochs, ranging from 15 min to 4 h, starting with waking in the morning. The sum, and a measure of rate of change of cumulative activity in the period immediately after waking (area under the curve [AUC]) for each time period, was calculated for each participant, each day, and individual and group means were calculated. Two-tailed independent <i>t</i> tests determined differences between the groups.</p><p><strong>Results: </strong>No differences were seen for summed activity counts across any time period studied. However, differences were noted in the AUC analysis for the discrete measures of relative activity. Specifically, within the first 15, 30, 45, and 60 min following waking, the AUC for activity counts was significantly higher in arthritis patients compared to controls, particularly at the 30 min period (<i>t</i> = -4.24, <i>p</i> = 0.0002). Thus, while both cohorts moved the same amount, the way in which they moved was different.</p><p><strong>Conclusion: </strong>This study is the first to show that a detailed analysis of actigraphy variables could identify activity pattern changes associated with arthritis, where the high-level daily summaries did not. Results suggest discrete variables derived from raw data may be useful to help identify clinical cohorts and should be explored further to determine if they may be effective clinical biomarkers.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"4 3","pages":"78-88"},"PeriodicalIF":0.0,"publicationDate":"2020-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000509724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38591452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}