Biomarker InsightsPub Date : 2021-05-14eCollection Date: 2021-01-01DOI: 10.1177/11772719211016359
Susanne Gjørup Sækmose, René Holst, Tine Lottenburger, Henriette Ytting, Hans Jørgen Nielsen, Peter Junker, Anders Schlosser, Grith Lykke Sorensen
{"title":"Circadian, Week-to-Week, and Physical Exercise-Induced Variation of Serum Microfibrillar-Associated Protein 4.","authors":"Susanne Gjørup Sækmose, René Holst, Tine Lottenburger, Henriette Ytting, Hans Jørgen Nielsen, Peter Junker, Anders Schlosser, Grith Lykke Sorensen","doi":"10.1177/11772719211016359","DOIUrl":"https://doi.org/10.1177/11772719211016359","url":null,"abstract":"<p><p>Serum microfibrillar-associated protein 4 (sMFAP4) has been investigated as a biomarker for various diseases and is demonstrated to show significant gradual increase with severity of liver fibrosis. Ideal biomarkers used for disease diagnosis or prognosis should display deviating levels in affected individuals only and be robust to factors unrelated to the disease. Here we show the impact of normal physiological variation of sMFAP4 by characterizing the circadian variation, week-to-week variation, and physical exercise-induced levels. Serum samples from 3 groups of healthy volunteers were drawn: 7 times during a 24-hour period, 5 times during a 3-week period, and before and after a standardized physical exercise challenge. sMFAP4 was determined by AlphaLISA. Statistical analysis was performed using mixed effects modeling of repeated measurements. Circadian variation of sMFAP4 was demonstrated, with time of peak and nadir values depending on age and gender. For males, the peak values were observed during nighttime whereas for females, peak values were observed in the morning. Individual sMFAP4 levels remained stable over a period of 3 weeks and physical exercise inferred a mild negative influence. In conclusion, the circadian sMFAP4 variation was significant, and the levels could be influenced by physical activity. However, these variations were of limited magnitude relative to previously observed disease-induced levels in support of the biomarker potential of sMFAP4.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211016359"},"PeriodicalIF":3.8,"publicationDate":"2021-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/11772719211016359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38936847","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":"Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches.","authors":"Ameneh Jafari, Amirhesam Babajani, Mostafa Rezaei-Tavirani","doi":"10.1177/11772719211013352","DOIUrl":"10.1177/11772719211013352","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211013352"},"PeriodicalIF":3.8,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/e8/10.1177_11772719211013352.PMC8114757.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38933381","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}
Biomarker InsightsPub Date : 2021-04-30eCollection Date: 2021-01-01DOI: 10.1177/11772719211013359
Cassandra Griffin, Ricardo Vilain, Simon King, Sandy Nixon, Alisha Gooley, Samara Bray, James Lynam, Marjorie M Walker, Rodney J Scott, Christine Paul
{"title":"Mind Over Matter: Confronting Challenges in Post-Mortem Brain Biobanking for Glioblastoma Multiforme.","authors":"Cassandra Griffin, Ricardo Vilain, Simon King, Sandy Nixon, Alisha Gooley, Samara Bray, James Lynam, Marjorie M Walker, Rodney J Scott, Christine Paul","doi":"10.1177/11772719211013359","DOIUrl":"https://doi.org/10.1177/11772719211013359","url":null,"abstract":"<p><p>Over the past 10 years, there has been limited progress for the treatment of brain cancer and outcomes for patients are not much improved. For brain cancer researchers, a major obstacle to biomarker driven research is limited access to brain cancer tissue for research purposes. The Mark Hughes Foundation Brain Biobank is one of the first post-mortem adult brain banks in Australia to operate with protocols specifically developed for brain cancer. Located within the Hunter New England Local Health District and operated by Hunter Cancer Biobank, the boundaries of service provided by the Brain Bank extend well into the surrounding regional and rural areas of the Local Health District and beyond. Brain cancer biobanking is challenging. There are conflicting international guidelines for best practice and unanswered questions relating to scientific, psychosocial and operational practices. To address this challenge, a best practice model was developed, informed by a consensus of existing data but with consideration of the difficulties associated with operating in regional or resource poor settings. The regional application of this model was challenged following the presentation of a donor located in a remote area, 380km away from the biobank. This required biobank staff to overcome numerous obstacles including long distance patient transport, lack of palliative care staff, death in the home and limited rural outreach services. Through the establishment of shared goals, contingency planning and the development of an informal infrastructure, the donation was facilitated within the required timeframe. This experience demonstrates the importance of collaboration and networking to overcome resource insufficiency and geographical challenges in rural cancer research programmes.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211013359"},"PeriodicalIF":3.8,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/11772719211013359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930049","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}
Biomarker InsightsPub Date : 2021-04-20eCollection Date: 2021-01-01DOI: 10.1177/11772719211009513
Valerie Speirs
{"title":"Quality Considerations When Using Tissue Samples for Biomarker Studies in Cancer Research.","authors":"Valerie Speirs","doi":"10.1177/11772719211009513","DOIUrl":"10.1177/11772719211009513","url":null,"abstract":"<p><p>Tissue obtained from biobanks is frequently employed in biomarker studies. Biomarkers define objective, measurable characteristics of biological and biomedical procedures and have been used as indicators of clinical outcome. This article outlines some of the steps scientists should consider when embarking on biomarker research in cancer research using samples from biobanks and the importance and challenges of linking clinical data to biological samples.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211009513"},"PeriodicalIF":3.8,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38877424","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}
Biomarker InsightsPub Date : 2021-04-20eCollection Date: 2021-01-01DOI: 10.1177/11772719211011173
Agata Będzichowska, Katarzyna Jobs, Małgorzata Kloc, Anna Bujnowska, Bolesław Kalicki
{"title":"The Assessment of the Usefulness of Selected Markers in the Diagnosis of Chronic Kidney Disease in Children.","authors":"Agata Będzichowska, Katarzyna Jobs, Małgorzata Kloc, Anna Bujnowska, Bolesław Kalicki","doi":"10.1177/11772719211011173","DOIUrl":"10.1177/11772719211011173","url":null,"abstract":"<p><strong>Introduction: </strong>The kidney deterioration, which starts in childhood often leads to end-stage renal failure in the future. Therefore, searching for an early, sensitive, and specific biomarkers became a paramount for chronic kidney disease diagnosis. The aim of this study was the assessment of markers: KIM-1, FGF-23, NAG, NGAL, and uromodulin for diagnosis of preclinical phase of the disease in children.</p><p><strong>Patients and methods: </strong>59 children (15 boys, 44 girls from 6 months to 17 years old) with kidney disorders, which had clinical indications for renoscintigraphy, were included in the study. All patients were divided depending on the result of renoscintigraphy (renal scarring vs normal kidney picture) and depending on the level of estimated glomerular filtration rate (glomerular hyperfiltration vs normal filtration rate). The concentration of uromoduline, KIM-1, FGF-23, NAG, and NGAL in serum and of NGAL and uromoduline in urine were measured in all studied groups.</p><p><strong>Results: </strong>The children with glomerular hyperfiltration had a statistically significantly higher serum values of FGF-23 and NGAL than the children with normal filtration rate (<i>P</i> < .05). There were no statistically significant differences in serum concentrations of tested markers in children with renal scars in comparison to children with normal renal image. There was no statistically significant difference in the concentration of tested markers in urine.</p><p><strong>Conclusions: </strong>The study confirmed the possible usefulness of FGF-23 and NGAL in detecting the preclinical-stage of renal disease associated with glomerular hyperfiltration in children. The study do not allow to indicate markers, which could be useful in the early diagnosis of kidney damage visible in the scintigraphic examination.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211011173"},"PeriodicalIF":3.8,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/13/10.1177_11772719211011173.PMC8060753.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38877425","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}
Biomarker InsightsPub Date : 2021-03-30eCollection Date: 2021-01-01DOI: 10.1177/11772719211006666
Diane Elizabeth Bender, Maximilian O Schaettler, Kathleen Cf Sheehan, Tanner M Johanns, Gavin P Dunn
{"title":"Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms.","authors":"Diane Elizabeth Bender, Maximilian O Schaettler, Kathleen Cf Sheehan, Tanner M Johanns, Gavin P Dunn","doi":"10.1177/11772719211006666","DOIUrl":"https://doi.org/10.1177/11772719211006666","url":null,"abstract":"<p><p>We compared the performance of two 96-well multiplex immunoassay platforms in assessing plasma cytokine concentrations in patients with glioblastoma (GBM; n = 27), individuals with melanoma, breast or lung cancer metastases to the brain (n = 17), and healthy volunteers (n = 11). Assays included a bead-based fluorescence MILLIPLEX<sup>®</sup> assay/Luminex (LMX) platform and 4 planar electrochemiluminescence kits from Meso Scale Discovery (MSD). The LMX kit evaluated 21 cytokines and the 3 MSD kits evaluated 20 cytokines in total, with 19 overlapping human cytokines between platforms (GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IL-23, MIP-1α, MIP-1β, MIP-3α, TNFα). The MSD platform had lower LLoQs (lower limits of quantification) than LMX for 17/19 cytokines, and higher LLoQs for IFN-γ and IL-21. The ULoQs were higher in LMX versus MSD assays for 17/19 shared analytes, but lower than MSD for IL-17A and IL-21. With LMX, all 19 shared analytes were quantifiable in each of 55 samples. Although MSD recombinant protein standard curves indicated lower LLoQs than LMX for most cytokines, MSD detected 7/19 (37%) native analytes in <75% of samples, including 0% detection for IL-21 and 8% for IL-23. The LMX platform categorized identical samples at greater concentrations than the MSD system for most analytes (MIP-1β the sole exception), sometimes by orders of magnitude. This mismatched quantification paradigm was supported by Bland-Altman analysis. LMX identified significantly elevated levels of 10 of 19 circulating cytokines in GBM: GM-CSF, IFN-γ, IL-1β, IL-5, IL-10, IL-17A, IL-21, IL-23, MIP-1α, and MIP-3α, consistent with prior findings and confirming the utility of applying appropriate multiplex immunoassay technologies toward developing a cytokine signature profile for GBM.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211006666"},"PeriodicalIF":3.8,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/11772719211006666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25591522","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}
Biomarker InsightsPub Date : 2021-03-27eCollection Date: 2021-01-01DOI: 10.1177/11772719211005745
Carmel M Quinn, Mamta Porwal, Nicola S Meagher, Anusha Hettiaratchi, Carl Power, Jitendra Jonnaggadala, Sue McCullough, Stephanie Macmillan, Katrina Tang, Winston Liauw, David Goldstein, Nikolajs Zeps, Philip J Crowe
{"title":"Moving with the Times: The Health Science Alliance (HSA) Biobank, Pathway to Sustainability.","authors":"Carmel M Quinn, Mamta Porwal, Nicola S Meagher, Anusha Hettiaratchi, Carl Power, Jitendra Jonnaggadala, Sue McCullough, Stephanie Macmillan, Katrina Tang, Winston Liauw, David Goldstein, Nikolajs Zeps, Philip J Crowe","doi":"10.1177/11772719211005745","DOIUrl":"https://doi.org/10.1177/11772719211005745","url":null,"abstract":"<p><p>Human biobanks are recognised as vital components of translational research infrastructure. With the growth in personalised and precision medicine, and the associated expansion of biomarkers and novel therapeutics under development, it is critical that researchers can access a strong collection of patient biospecimens, annotated with clinical data. Biobanks globally are undertaking transformation of their operating models in response to changing research needs; transition from a 'classic' model representing a largely retrospective collection of pre-defined specimens to a more targeted, prospective collection model, although there remains a research need for both models to co-exist. Here we introduce the Health Science Alliance (HSA) Biobank, established in 2012 as a classic biobank, now transitioning to a hybrid operational model. Some of the past and current challenges encountered are discussed including clinical annotation, specimen utilisation and biobank sustainability, along with the measures the HSA Biobank is taking to address these challenges. We describe new directions being explored, going beyond traditional specimen collection into areas involving bioimages, microbiota and live cell culture. The HSA Biobank is working in collaboration with clinicians, pathologists and researchers, piloting a sustainable, robust platform with the potential to integrate future needs.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"16 ","pages":"11772719211005745"},"PeriodicalIF":3.8,"publicationDate":"2021-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/11772719211005745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930047","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}
Biomarker InsightsPub Date : 2020-12-08eCollection Date: 2020-01-01DOI: 10.1177/1177271920974652
Mariya Gromova, Annegret Vaggelas, Gabriele Dallmann, Diane Seimetz
{"title":"Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape.","authors":"Mariya Gromova, Annegret Vaggelas, Gabriele Dallmann, Diane Seimetz","doi":"10.1177/1177271920974652","DOIUrl":"https://doi.org/10.1177/1177271920974652","url":null,"abstract":"<p><p>Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current global regulatory landscape is presented in this article with particular emphasis on the validation and qualification of biomarkers, as well as legal framework for companion diagnostics. Furthermore, this article shows how the number of approved drugs with at least 1 biomarker used during development (biomarker acceptance) is affected by the recent advances in the biomarker regulations. More than half of analysed approvals were supported by biomarker data and there has been a slight increase in acceptance of biomarkers in recent years, even though the growth is not continuous. For certain pharmacotherapeutic groups, approvals with biomarkers are more common than without. Examples include immunosuppressants, immunostimulants, drugs used in diabetes, antithrombotic drugs, antineoplastic agents and antivirals. As a conclusion, potential benefits, challenges and opportunities of using biomarkers in drug discovery and development in the current regulatory landscape are summarised and discussed.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920974652"},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920974652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38732988","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}
Biomarker InsightsPub Date : 2020-12-01eCollection Date: 2020-01-01DOI: 10.1177/1177271920976146
Ibrahim Ali, Sara T Ibrahim, Rajkumar Chinnadurai, Darren Green, Maarten Taal, Tony D Whetton, Philip A Kalra
{"title":"A Paradigm to Discover Biomarkers Associated With Chronic Kidney Disease Progression.","authors":"Ibrahim Ali, Sara T Ibrahim, Rajkumar Chinnadurai, Darren Green, Maarten Taal, Tony D Whetton, Philip A Kalra","doi":"10.1177/1177271920976146","DOIUrl":"https://doi.org/10.1177/1177271920976146","url":null,"abstract":"<p><p>Biomarker discovery in the field of risk prediction in chronic kidney disease (CKD) embraces the prospect of improving our ability to risk stratify future adverse outcomes and thereby guide patient care in a new era of personalised medicine. However, many studies that report biomarkers predictive of CKD progression share a key methodological limitation: failure to characterise patients' renal progression precisely. This weakens any observable association between a biomarker and an outcome poorly defined by a patient's change in renal function over time. In this commentary, we discuss the need for a better approach in this research arena and describe a compelling strategy that has the advantage of offering robust and meaningful biomarker exploration relevant to CKD progression.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920976146"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920976146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716776","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}
Biomarker InsightsPub Date : 2020-11-25eCollection Date: 2020-01-01DOI: 10.1177/1177271920976367
Rawan Tarawneh
{"title":"Biomarkers: Our Path Towards a Cure for Alzheimer Disease.","authors":"Rawan Tarawneh","doi":"10.1177/1177271920976367","DOIUrl":"https://doi.org/10.1177/1177271920976367","url":null,"abstract":"<p><p>Over the last decade, biomarkers have significantly improved our understanding of the pathophysiology of Alzheimer disease (AD) and provided valuable tools to examine different disease mechanisms and their progression over time. While several markers of amyloid, tau, neuronal, synaptic, and axonal injury, inflammation, and immune dysregulation in AD have been identified, there is a relative paucity of biomarkers which reflect other disease mechanisms such as oxidative stress, mitochondrial injury, vascular or endothelial injury, and calcium-mediated excitotoxicity. Importantly, there is an urgent need to standardize methods for biomarker assessments across different centers, and to identify dynamic biomarkers which can monitor disease progression over time and/or response to potential disease-modifying treatments. The updated research framework for AD, proposed by the National Institute of Aging- Alzheimer's Association (NIA-AA) Work Group, emphasizes the importance of incorporating biomarkers in AD research and defines AD as a biological construct consisting of amyloid, tau, and neurodegeneration which spans pre-symptomatic and symptomatic stages. As results of clinical trials of AD therapeutics have been disappointing, it has become increasingly clear that the success of future AD trials will require the incorporation of biomarkers in participant selection, prognostication, monitoring disease progression, and assessing response to treatments. We here review the current state of fluid AD biomarkers, and discuss the advantages and limitations of the updated NIA-AA research framework. Importantly, the integration of biomarker data with clinical, cognitive, and imaging domains through a systems biology approach will be essential to adequately capture the molecular, genetic, and pathological heterogeneity of AD and its spatiotemporal evolution over time.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920976367"},"PeriodicalIF":3.8,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920976367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38688446","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}