BMJ Open Science最新文献

{"title":"Technological advances in preclinical meta-research.","authors":"Alexandra Bannach-Brown, Kaitlyn Hair, Zsanett Bahor, Nadia Soliman, Malcolm Macleod, Jing Liao","doi":"10.1136/bmjos-2020-100131","DOIUrl":"10.1136/bmjos-2020-100131","url":null,"abstract":"","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100131"},"PeriodicalIF":0.0,"publicationDate":"2021-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710953","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":"Development and uptake of an online systematic review platform: the early years of the CAMARADES Systematic Review Facility (SyRF).","authors":"Zsanett Bahor, Jing Liao, Gillian Currie, Can Ayder, Malcolm Macleod, Sarah K McCann, Alexandra Bannach-Brown, Kimberley Wever, Nadia Soliman, Qianying Wang, Lee Doran-Constant, Laurie Young, Emily S Sena, Chris Sena","doi":"10.1136/bmjos-2020-100103","DOIUrl":"10.1136/bmjos-2020-100103","url":null,"abstract":"<p><p>Preclinical research is a vital step in the drug discovery pipeline and more generally in helping to better understand human disease aetiology and its management. Systematic reviews (SRs) can be powerful in summarising and appraising this evidence concerning a specific research question, to highlight areas of improvements, areas for further research and areas where evidence may be sufficient to take forward to other research domains, for instance clinical trial. Guidance and tools for preclinical research synthesis remain limited despite their clear utility. We aimed to create an online end-to-end platform primarily for conducting SRs of preclinical studies, that was flexible enough to support a wide variety of experimental designs, was adaptable to different research questions, would allow users to adopt emerging automated tools and support them during their review process using best practice. In this article, we introduce the Systematic Review Facility (https://syrf.org.uk), which was launched in 2016 and designed to support primarily preclinical SRs from small independent projects to large, crowdsourced projects. We discuss the architecture of the app and its features, including the opportunity to collaborate easily, to efficiently manage projects, to screen and annotate studies for important features (metadata), to extract outcome data into a secure database, and tailor these steps to each project. We introduce how we are working to leverage the use of automation tools and allow the integration of these services to accelerate and automate steps in the systematic review workflow.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100103"},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39710951","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":"What is the optimum design for my animal experiment?","authors":"Natasha A Karp,&nbsp;Derek Fry","doi":"10.1136/bmjos-2020-100126","DOIUrl":"https://doi.org/10.1136/bmjos-2020-100126","url":null,"abstract":"<p><p>Within preclinical research, attention has focused on experimental design and how current practices can lead to poor reproducibility. There are numerous decision points when designing experiments. Ethically, when working with animals we need to conduct a harm-benefit analysis to ensure the animal use is justified for the scientific gain. Experiments should be robust, not use more or fewer animals than necessary, and truly add to the knowledge base of science. Using case studies to explore these decision points, we consider how individual experiments can be designed in several different ways. We use the Experimental Design Assistant (EDA) graphical summary of each experiment to visualise the design differences and then consider the strengths and weaknesses of each design. Through this format, we explore key and topical experimental design issues such as pseudo-replication, blocking, covariates, sex bias, inference space, standardisation fallacy and factorial designs. There are numerous articles discussing these critical issues in the literature, but here we bring together these topics and explore them using real-world examples allowing the implications of the choice of design to be considered. Fundamentally, there is no perfect experiment; choices must be made which will have an impact on the conclusions that can be drawn. We need to understand the limitations of an experiment's design and when we report the experiments, we need to share the caveats that inherently exist.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":"5 1","pages":"e100126"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/bmjos-2020-100126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266678","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":"Multicentre translational Trial of Remote Ischaemic Conditioning in Acute Ischaemic Stroke (TRICS): protocol of multicentre, parallel group, randomised, preclinical trial in female and male rat and mouse from the Italian Stroke Organization (ISO) Basic Science network.","authors":"Mauro Tettamanti,&nbsp;Simone Beretta,&nbsp;Giuseppe Pignataro,&nbsp;Stefano Fumagalli,&nbsp;Carlo Perego,&nbsp;Luigi Sironi,&nbsp;Felicita Pedata,&nbsp;Diana Amantea,&nbsp;Marco Bacigaluppi,&nbsp;Antonio Vinciguerra,&nbsp;Alessia Valente,&nbsp;Susanna Diamanti,&nbsp;Jacopo Mariani,&nbsp;Martina Viganò,&nbsp;Francesco Santangelo,&nbsp;Chiara Paola Zoia,&nbsp;Virginia Rogriguez-Menendez,&nbsp;Laura Castiglioni,&nbsp;Joanna Rzemieniec,&nbsp;Ilaria Dettori,&nbsp;Irene Bulli,&nbsp;Elisabetta Coppi,&nbsp;Giorgia Serena Gullotta,&nbsp;Giacinto Bagetta,&nbsp;Gianvito Martino,&nbsp;Carlo Ferrarese,&nbsp;Maria Grazia De Simoni","doi":"10.1136/bmjos-2020-100063","DOIUrl":"https://doi.org/10.1136/bmjos-2020-100063","url":null,"abstract":"<p><strong>Introduction: </strong>Multicentre preclinical randomised controlled trials (pRCT) are emerging as a necessary step to confirm efficacy and improve translation into the clinic. The aim of this project is to perform two multicentre pRCTs (one in rats and one in mice) to investigate the efficacy of remote ischaemic conditioning (RIC) in an experimental model of severe ischaemic stroke.</p><p><strong>Methods and analysis: </strong>Seven research laboratories within the Italian Stroke Organization (ISO) Basic Science network will participate in the study. Transient endovascular occlusion of the proximal right middle cerebral artery will be performed in two species (rats and mice) and in both sexes. Animals will be randomised to receive RIC by transient surgical occlusion of the right femoral artery, or sham surgery, after reperfusion. Blinded outcome assessment will be performed for dichotomised functional neuroscore (primary endpoint) and infarct volume (secondary endpoint) at 48 hours. A sample size of 80 animals per species will yield 82% power to detect a significant difference of 30% in the primary outcome in both pRCTs. Analyses will be performed in a blind status and according to an intention-to-treat paradigm. The results of this study will provide robust, translationally oriented, high-quality evidence on the efficacy of RIC in multiple species of rodents with large ischaemic stroke.</p><p><strong>Ethics and dissemination: </strong>This is approved by the Animal Welfare Regulatory Body of the University of Milano Bicocca, under project license from the Italian Ministry of Health. Trial results will be subject to publication according to the definition of the outcome presented in this protocol.</p><p><strong>Trial registration number: </strong>PCTE0000177.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100063"},"PeriodicalIF":0.0,"publicationDate":"2020-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/bmjos-2020-100063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39696249","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":"<i>Crocodylus porosus</i>: a potential source of anticancer molecules.","authors":"Shareni Jeyamogan,&nbsp;Naveed Ahmed Khan,&nbsp;K Sagathevan,&nbsp;Ruqaiyyah Siddiqui","doi":"10.1136/bmjos-2019-100040","DOIUrl":"https://doi.org/10.1136/bmjos-2019-100040","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains a global threat resulting in significant morbidity and mortality despite advances in therapeutic interventions, suggesting urgency for identification of anticancer agents. Crocodiles thrive in polluted habitat, feed on germ-infested meat, are exposed to carcinogenic heavy metals, are the very few species to survive the catastrophic Cretaceous-Paleogene extinction event, yet have a prolonged lifespan and rarely been reported to develop cancer. Therefore, we hypothesised that animals living in polluted environments such as crocodiles possess anticancer molecules/mechanisms.</p><p><strong>Methods: </strong><i>Crocodylus porosus</i> was procured, blood collected, dissected and lysates prepared from internal organs. Organ lysates and sera were tested for growth inhibition, cytotoxic effects and cell survival against HeLa, PC3 and MCF7 cells and subjected to liquid chromatography mass spectrometry. RNA transcriptome analysis and differential gene analysis were performed using Galaxy Bioinformatics.</p><p><strong>Results: </strong>Sera exhibited potent growth inhibition and cytotoxic effects against cancer cells. 80 molecules were detected from <i>C. porosus</i> and 19 molecules were putatively identified. Additionally, more than 100 potential anticancer peptides were identified from sera using bioinformatics based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition. Following transcriptome analysis, 14 genes in treated HeLa cells, 51 genes in treated MCF7 cells and 2 genes in treated PC3 cells, were found to be expressed, compared with untreated controls.</p><p><strong>Conclusion: </strong>Animals residing in polluted milieus are an unexploited source for prospective pharmaceutical drugs, and could lead to identification of novel antitumour compound(s) and/or further understanding of the mechanisms of cancer resistance.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100040"},"PeriodicalIF":0.0,"publicationDate":"2020-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/bmjos-2019-100040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835814","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":"Publication rate in preclinical research: a plea for preregistration.","authors":"Mira van der Naald, Steven Wenker, Pieter A Doevendans, Kimberley E Wever, Steven A J Chamuleau","doi":"10.1136/bmjos-2019-100051","DOIUrl":"10.1136/bmjos-2019-100051","url":null,"abstract":"<p><strong>Objectives: </strong>The ultimate goal of biomedical research is the development of new treatment options for patients. Animal models are used if questions cannot be addressed otherwise. Currently, it is widely believed that a large fraction of performed studies are never published, but there are no data that directly address this question.</p><p><strong>Methods: </strong>We have tracked a selection of animal study protocols approved in the University Medical Center Utrecht in the Netherlands, to assess whether these have led to a publication with a follow-up period of 7 years.</p><p><strong>Results: </strong>We found that 60% of all animal study protocols led to at least one publication (full text or abstract). A total of 5590 animals were used in these studies, of which 26% was reported in the resulting publications.</p><p><strong>Conclusions: </strong>The data presented here underline the need for preclinical preregistration, in view of the risk of reporting and publication bias in preclinical research. We plea that all animal study protocols should be prospectively registered on an online, accessible platform to increase transparency and data sharing. To facilitate this, we have developed a platform dedicated to animal study protocol registration: www.preclinicaltrials.eu.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100051"},"PeriodicalIF":0.0,"publicationDate":"2020-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39696247","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":"In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol.","authors":"Elda Righi,&nbsp;Luigia Scudeller,&nbsp;Margherita Chiamenti,&nbsp;Kamilia Abdelraouf,&nbsp;Thomas Lodise,&nbsp;Elena Carrara,&nbsp;Alessia Savoldi,&nbsp;Dario Menghin,&nbsp;Gloria Pellizzari,&nbsp;Sally Ellis,&nbsp;Francois Franceschi,&nbsp;Laura Piddock,&nbsp;Chiara Rebuffi,&nbsp;Maurizio Sanguinetti,&nbsp;Evelina Tacconelli","doi":"10.1136/bmjos-2019-100055","DOIUrl":"https://doi.org/10.1136/bmjos-2019-100055","url":null,"abstract":"<p><strong>Objective: </strong>There is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i> and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.</p><p><strong>Methods and analysis: </strong>This protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE's risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I² test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.</p><p><strong>Dissemination: </strong>This systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.</p><p><strong>Prospero registration number: </strong>CRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104).</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100055"},"PeriodicalIF":0.0,"publicationDate":"2020-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/bmjos-2019-100055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39696248","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 ARRIVE guidelines 2.0: updated guidelines for reporting animal research.","authors":"Nathalie Percie du Sert, Viki Hurst, Amrita Ahluwalia, Sabina Alam, Marc T Avey, Monya Baker, William J Browne, Alejandra Clark, Innes C Cuthill, Ulrich Dirnagl, Michael Emerson, Paul Garner, Stephen T Holgate, David W Howells, Natasha A Karp, Stanley E Lazic, Katie Lidster, Catriona J MacCallum, Malcolm Macleod, Esther J Pearl, Ole H Petersen, Frances Rawle, Penny Reynolds, Kieron Rooney, Emily S Sena, Shai D Silberberg, Thomas Steckler, Hanno Würbel","doi":"10.1136/bmjos-2020-100115","DOIUrl":"10.1136/bmjos-2020-100115","url":null,"abstract":"<p><p>Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into two sets, the 'ARRIVE Essential 10', which constitutes the minimum requirement, and the 'Recommended Set', which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":"4 1","pages":"e100115"},"PeriodicalIF":0.0,"publicationDate":"2020-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10611472","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":"Systematic review of guidelines for internal validity in the design, conduct and analysis of preclinical biomedical experiments involving laboratory animals.","authors":"Jan Vollert, Esther Schenker, Malcolm Macleod, Anton Bespalov, Hanno Wuerbel, Martin Michel, Ulrich Dirnagl, Heidrun Potschka, Ann-Marie Waldron, Kimberley Wever, Thomas Steckler, Tom van de Casteele, Bruce Altevogt, Annesha Sil, Andrew S C Rice","doi":"10.1136/bmjos-2019-100046","DOIUrl":"10.1136/bmjos-2019-100046","url":null,"abstract":"<p><p>Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency and internal validity of preclinical studies, mostly publishing expert consensus and experience. While many of the points raised in these various guidelines are identical or similar, they differ in detail and rigour. Most of them focus on reporting, only few of them cover the planning and conduct of studies. The aim of this systematic review is to identify existing experimental design, conduct, analysis and reporting guidelines relating to preclinical animal research. A systematic search in PubMed, Embase and Web of Science retrieved 13 863 unique results. After screening these on title and abstract, 613 papers entered the full-text assessment stage, from which 60 papers were retained. From these, we extracted unique 58 recommendations on the planning, conduct and reporting of preclinical animal studies. Sample size calculations, adequate statistical methods, concealed and randomised allocation of animals to treatment, blinded outcome assessment and recording of animal flow through the experiment were recommended in more than half of the publications. While we consider these recommendations to be valuable, there is a striking lack of experimental evidence on their importance and relative effect on experiments and effect sizes.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100046"},"PeriodicalIF":0.0,"publicationDate":"2020-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835817","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":"Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?","authors":"Sarah K McCann, Catherine B Lawrence","doi":"10.1136/bmjos-2019-100013","DOIUrl":"10.1136/bmjos-2019-100013","url":null,"abstract":"<p><p>Stroke is a significant cause of mortality and morbidity for which there are limited treatment options. Virtually all drug interventions that have been successful preclinically in experimental stroke have failed to translate to an effective treatment in the clinical setting. In this review, we examine one of the factors likely contributing to this lack of translation, the failure of preclinical studies to consider fully the advanced age and comorbidities (eg, hypertension or diabetes) present in most patients with stroke. Age and comorbidities affect the likelihood of suffering a stroke, disease progression and the response to treatment. Analysing data from preclinical systematic reviews of interventions for ischaemic stroke we show that only 11.4% of studies included an aged or comorbid model, with hypertension being the most frequent. The degree of protection (% reduction in infarct volume) varied depending on the comorbidity and the type of intervention. We consider reasons for the lack of attention to comorbid and aged animals in stroke research and discuss the value of testing a potential therapy in models representing a range of comorbidities that affect patients with stroke. These models can help establish any limits to a treatment's efficacy and inform the design of clinical trials in appropriate patient populations.</p>","PeriodicalId":9212,"journal":{"name":"BMJ Open Science","volume":" ","pages":"e100013"},"PeriodicalIF":0.0,"publicationDate":"2020-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835812","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}