Pub Date : 2024-10-08DOI: 10.1038/s41575-024-00989-y
Christopher Ma, Vipul Jairath, Brian G. Feagan, Laurent Peyrin-Biroulet, Silvio Danese, Bruce E. Sands, Remo Panaccione
Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn’s disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice. In this Review, Ma and colleagues discuss the evolution in clinical trial designs for inflammatory bowel disease (IBD), their implications for clinical care, and identify future directions for the next generation of IBD studies.
{"title":"Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease","authors":"Christopher Ma, Vipul Jairath, Brian G. Feagan, Laurent Peyrin-Biroulet, Silvio Danese, Bruce E. Sands, Remo Panaccione","doi":"10.1038/s41575-024-00989-y","DOIUrl":"10.1038/s41575-024-00989-y","url":null,"abstract":"Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn’s disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice. In this Review, Ma and colleagues discuss the evolution in clinical trial designs for inflammatory bowel disease (IBD), their implications for clinical care, and identify future directions for the next generation of IBD studies.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"792-808"},"PeriodicalIF":45.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00989-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1038/s41575-024-00981-6
Robert Hutkins, Jens Walter, Glenn R. Gibson, Cassandre Bedu-Ferrari, Karen Scott, Daniel J. Tancredi, Anisha Wijeyesekera, Mary Ellen Sanders
Microbiomes provide key contributions to health and potentially important therapeutic targets. Conceived nearly 30 years ago, the prebiotic concept posits that targeted modulation of host microbial communities through the provision of selectively utilized growth substrates provides an effective approach to improving health. Although the basic tenets of this concept remain the same, it is timely to address certain challenges pertaining to prebiotics, including establishing that prebiotic-induced microbiota modulation causes the health outcome, determining which members within a complex microbial community directly utilize specific substrates in vivo and when those microbial effects sufficiently satisfy selectivity requirements, and clarification of the scientific principles on which the term ‘prebiotic’ is predicated to inspire proper use. In this Expert Recommendation, we provide a framework for the classification of compounds as prebiotics. We discuss ecological principles by which substrates modulate microbiomes and methodologies useful for characterizing such changes. We then propose statistical approaches that can be used to establish causal links between selective effects on the microbiome and health effects on the host, which can help address existing challenges. We use this information to provide the minimum criteria needed to classify compounds as prebiotics. Furthermore, communications to consumers and regulatory approaches to prebiotics worldwide are discussed. Prebiotics selectively modulate the composition or function of the microbiome, thereby improving health. This Expert Recommendation presents a framework to classify defined compounds as prebiotics, discusses principles of host microbial ecology, and proposes statistical methods to link microbiome changes with health outcomes to infer causality.
{"title":"Classifying compounds as prebiotics — scientific perspectives and recommendations","authors":"Robert Hutkins, Jens Walter, Glenn R. Gibson, Cassandre Bedu-Ferrari, Karen Scott, Daniel J. Tancredi, Anisha Wijeyesekera, Mary Ellen Sanders","doi":"10.1038/s41575-024-00981-6","DOIUrl":"10.1038/s41575-024-00981-6","url":null,"abstract":"Microbiomes provide key contributions to health and potentially important therapeutic targets. Conceived nearly 30 years ago, the prebiotic concept posits that targeted modulation of host microbial communities through the provision of selectively utilized growth substrates provides an effective approach to improving health. Although the basic tenets of this concept remain the same, it is timely to address certain challenges pertaining to prebiotics, including establishing that prebiotic-induced microbiota modulation causes the health outcome, determining which members within a complex microbial community directly utilize specific substrates in vivo and when those microbial effects sufficiently satisfy selectivity requirements, and clarification of the scientific principles on which the term ‘prebiotic’ is predicated to inspire proper use. In this Expert Recommendation, we provide a framework for the classification of compounds as prebiotics. We discuss ecological principles by which substrates modulate microbiomes and methodologies useful for characterizing such changes. We then propose statistical approaches that can be used to establish causal links between selective effects on the microbiome and health effects on the host, which can help address existing challenges. We use this information to provide the minimum criteria needed to classify compounds as prebiotics. Furthermore, communications to consumers and regulatory approaches to prebiotics worldwide are discussed. Prebiotics selectively modulate the composition or function of the microbiome, thereby improving health. This Expert Recommendation presents a framework to classify defined compounds as prebiotics, discusses principles of host microbial ecology, and proposes statistical methods to link microbiome changes with health outcomes to infer causality.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 1","pages":"54-70"},"PeriodicalIF":45.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1038/s41575-024-00990-5
Alina M. Allen, Juan Pablo Arab, Vincent Wai-Sun Wong
To coincide with the 20th anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management. They comment on how MASLD research and clinical management has changed over the past 20 years, the strengths and limitations of the MASLD field today, and their predictions for progress over the next 20 years. In this Viewpoint, Alina M. Allen, Juan Pablo Arab and Vincent Wai-Sun Wong reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management.
在《Nature Reviews Gastroenterology & Hepatology》杂志创刊 20 周年之际，我们请三位专家回顾了代谢功能障碍相关性脂肪肝 (MASLD) 研究和临床管理的过去、现在和未来。他们评论了过去 20 年来 MASLD 研究和临床管理的变化、当今 MASLD 领域的优势和局限性，以及他们对未来 20 年进展的预测。在本视点中，Alina M. Allen、Juan Pablo Arab 和 Vincent Wai-Sun Wong 回顾了代谢功能障碍相关性脂肪肝（MASLD）研究和临床管理的过去、现在和未来。
{"title":"MASLD: a disease in flux","authors":"Alina M. Allen, Juan Pablo Arab, Vincent Wai-Sun Wong","doi":"10.1038/s41575-024-00990-5","DOIUrl":"10.1038/s41575-024-00990-5","url":null,"abstract":"To coincide with the 20th anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management. They comment on how MASLD research and clinical management has changed over the past 20 years, the strengths and limitations of the MASLD field today, and their predictions for progress over the next 20 years. In this Viewpoint, Alina M. Allen, Juan Pablo Arab and Vincent Wai-Sun Wong reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"747-750"},"PeriodicalIF":45.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00990-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1038/s41575-024-00980-7
Jessica E. S. Shay, Ömer H. Yilmaz
Diet and nutritional metabolites exhibit wide-ranging effects on health and disease partly by altering tissue composition and function. With rapidly rising rates of obesity, there is particular interest in how obesogenic diets influence tissue homeostasis and risk of tumorigenesis; epidemiologically, these diets have a positive correlation with various cancers, including colorectal cancer. The gastrointestinal tract is a highly specialized, continuously renewing tissue with a fundamental role in nutrient uptake and is, in turn, influenced by diet composition and host metabolic state. Intestinal stem cells are found at the base of the intestinal crypt and can generate all mature lineages that comprise the intestinal epithelium and are uniquely influenced by host diet, metabolic by-products and energy dynamics. Similarly, tumour growth and metabolism can also be shaped by nutrient availability and host diet. In this Review, we discuss how different diets and metabolic changes influence intestinal stem cells in homeostatic and pathological conditions, as well as tumorigenesis. We also discuss how dietary changes and composition affect the intestinal epithelium and its surrounding microenvironment. In this Review, Shay and Yilmaz describe how diet and metabolism influence intestinal stem cells in health and disease, including tumorigenesis. The effect of dietary changes such as calorie restriction, intermittent fasting, high-fat diets and ketogenic diets on intestinal stem cells is discussed.
{"title":"Dietary and metabolic effects on intestinal stem cells in health and disease","authors":"Jessica E. S. Shay, Ömer H. Yilmaz","doi":"10.1038/s41575-024-00980-7","DOIUrl":"10.1038/s41575-024-00980-7","url":null,"abstract":"Diet and nutritional metabolites exhibit wide-ranging effects on health and disease partly by altering tissue composition and function. With rapidly rising rates of obesity, there is particular interest in how obesogenic diets influence tissue homeostasis and risk of tumorigenesis; epidemiologically, these diets have a positive correlation with various cancers, including colorectal cancer. The gastrointestinal tract is a highly specialized, continuously renewing tissue with a fundamental role in nutrient uptake and is, in turn, influenced by diet composition and host metabolic state. Intestinal stem cells are found at the base of the intestinal crypt and can generate all mature lineages that comprise the intestinal epithelium and are uniquely influenced by host diet, metabolic by-products and energy dynamics. Similarly, tumour growth and metabolism can also be shaped by nutrient availability and host diet. In this Review, we discuss how different diets and metabolic changes influence intestinal stem cells in homeostatic and pathological conditions, as well as tumorigenesis. We also discuss how dietary changes and composition affect the intestinal epithelium and its surrounding microenvironment. In this Review, Shay and Yilmaz describe how diet and metabolism influence intestinal stem cells in health and disease, including tumorigenesis. The effect of dietary changes such as calorie restriction, intermittent fasting, high-fat diets and ketogenic diets on intestinal stem cells is discussed.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 1","pages":"23-38"},"PeriodicalIF":45.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1038/s41575-024-00978-1
Xiaogang Feng , Pascal Flüchter, Jeshua C. De Tenorio, Christoph Schneider
Tuft cells have gained substantial attention over the past 10 years due to numerous reports linking them with type 2 immunity and microorganism-sensing capacity in many mucosal tissues. This heightened interest is fuelled by their unique ability to produce an array of biological effector molecules, including IL-25, allergy-related eicosanoids, and the neurotransmitter acetylcholine, enabling downstream responses in diverse cell types. Operating through G protein-coupled receptor-mediated signalling pathways reminiscent of type II taste cells in oral taste buds, tuft cells emerge as chemosensory sentinels that integrate luminal conditions, eliciting appropriate responses in immune, epithelial and neuronal populations. How tuft cells promote tissue alterations and adaptation to the variety of stimuli at mucosal surfaces has been explored in multiple studies in the past few years. Since the initial recognition of the role of tuft cells, the discovery of diverse tuft cell effector functions and associated feedback loops have also revealed the complexity of tuft cell biology. Although earlier work largely focused on extraintestinal tissues, novel genetic tools and recent mechanistic studies on intestinal tuft cells established fundamental concepts of tuft cell activation and functions. This Review is an overview of intestinal tuft cells, providing insights into their development, signalling and interaction modules in immunity and other states. Tuft cells have important roles in type 2 immunity and antimicrobial responses in mucosal tissues. This Review provides an overview of intestinal tuft cells, providing insights into their phenotype, function and role in the intestine in immunity and other states.
在过去的 10 年中，簇状细胞受到了广泛关注，因为有大量报道称簇状细胞与许多粘膜组织的 2 型免疫和微生物感应能力有关。它们能产生一系列生物效应分子，包括 IL-25、与过敏相关的类二十烷酸和神经递质乙酰胆碱，从而在不同类型的细胞中产生下游反应。簇细胞通过 G 蛋白偶联受体介导的信号通路运作，让人联想到口腔味蕾中的 II 型味觉细胞，簇细胞作为化学感觉哨兵整合腔内条件，引起免疫、上皮和神经元群体的适当反应。在过去几年中，多项研究探讨了簇细胞如何促进组织改变和适应粘膜表面的各种刺激。自最初认识到丛细胞的作用以来，对丛细胞多种效应器功能和相关反馈回路的发现也揭示了丛细胞生物学的复杂性。虽然早期的工作主要集中在肠外组织，但新型遗传工具和最近对肠道簇细胞的机理研究确立了簇细胞活化和功能的基本概念。本综述概述了肠簇细胞，深入探讨了它们在免疫和其他状态下的发育、信号传递和相互作用模块。
{"title":"Tuft cells in the intestine, immunity and beyond","authors":"Xiaogang Feng \u0000 , Pascal Flüchter, Jeshua C. De Tenorio, Christoph Schneider","doi":"10.1038/s41575-024-00978-1","DOIUrl":"10.1038/s41575-024-00978-1","url":null,"abstract":"Tuft cells have gained substantial attention over the past 10 years due to numerous reports linking them with type 2 immunity and microorganism-sensing capacity in many mucosal tissues. This heightened interest is fuelled by their unique ability to produce an array of biological effector molecules, including IL-25, allergy-related eicosanoids, and the neurotransmitter acetylcholine, enabling downstream responses in diverse cell types. Operating through G protein-coupled receptor-mediated signalling pathways reminiscent of type II taste cells in oral taste buds, tuft cells emerge as chemosensory sentinels that integrate luminal conditions, eliciting appropriate responses in immune, epithelial and neuronal populations. How tuft cells promote tissue alterations and adaptation to the variety of stimuli at mucosal surfaces has been explored in multiple studies in the past few years. Since the initial recognition of the role of tuft cells, the discovery of diverse tuft cell effector functions and associated feedback loops have also revealed the complexity of tuft cell biology. Although earlier work largely focused on extraintestinal tissues, novel genetic tools and recent mechanistic studies on intestinal tuft cells established fundamental concepts of tuft cell activation and functions. This Review is an overview of intestinal tuft cells, providing insights into their development, signalling and interaction modules in immunity and other states. Tuft cells have important roles in type 2 immunity and antimicrobial responses in mucosal tissues. This Review provides an overview of intestinal tuft cells, providing insights into their phenotype, function and role in the intestine in immunity and other states.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"852-868"},"PeriodicalIF":45.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1038/s41575-024-00985-2
Nature Reviews Gastroenterology & Hepatology is launching a new Series on justice, equity, diversity and inclusion in an effort to increase awareness and advance equitable health.
{"title":"Justice, equity, diversity and inclusion in gastroenterology and hepatology","authors":"","doi":"10.1038/s41575-024-00985-2","DOIUrl":"10.1038/s41575-024-00985-2","url":null,"abstract":"Nature Reviews Gastroenterology & Hepatology is launching a new Series on justice, equity, diversity and inclusion in an effort to increase awareness and advance equitable health.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 10","pages":"661-661"},"PeriodicalIF":45.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00985-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20DOI: 10.1038/s41575-024-00993-2
Katrina Ray
{"title":"A resource for the food microbiome and its links with the human microbiome","authors":"Katrina Ray","doi":"10.1038/s41575-024-00993-2","DOIUrl":"10.1038/s41575-024-00993-2","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"746-746"},"PeriodicalIF":45.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Therapeutic advances in inflammatory bowel disease (IBD) have been universally directed towards patients with established disease to control inflammation, ameliorate symptoms and hinder disease progression, but preventing IBD development or delaying its onset are highly attractive. This Comment discusses the emerging approaches and future promises of interventional disease prevention trials in IBD.
{"title":"Disease prevention trials in IBD: feasibility to future outlook","authors":"Sailish Honap, Nelly Agrinier, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1038/s41575-024-00984-3","DOIUrl":"10.1038/s41575-024-00984-3","url":null,"abstract":"Therapeutic advances in inflammatory bowel disease (IBD) have been universally directed towards patients with established disease to control inflammation, ameliorate symptoms and hinder disease progression, but preventing IBD development or delaying its onset are highly attractive. This Comment discusses the emerging approaches and future promises of interventional disease prevention trials in IBD.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 1","pages":"1-2"},"PeriodicalIF":45.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1038/s41575-024-00986-1
Soumaya Kouidhi, Ovokeraye H. Oduaran
The current state of microbiome research in Africa can be leveraged to encourage the development and implementation of standardized processes for data collection and management. In this Comment, we provide some recommendations to enable the research community to fully harness the richness of the microbiome of African populations and potential opportunities therein.
{"title":"Strengthening the foundation of African microbiome research: strategies for standardized data collection","authors":"Soumaya Kouidhi, Ovokeraye H. Oduaran","doi":"10.1038/s41575-024-00986-1","DOIUrl":"10.1038/s41575-024-00986-1","url":null,"abstract":"The current state of microbiome research in Africa can be leveraged to encourage the development and implementation of standardized processes for data collection and management. In this Comment, we provide some recommendations to enable the research community to fully harness the richness of the microbiome of African populations and potential opportunities therein.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"742-743"},"PeriodicalIF":45.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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