BioDrugs最新文献

{"title":"Demand- Versus Supply-Side Policies in Market Penetration of Biosimilars: Which is More Effective?","authors":"Gyeongseon Shin, Heejin Han, Gyeyoung Choi, Donghwan Lee, SeungJin Bae","doi":"10.1007/s40259-025-00721-5","DOIUrl":"https://doi.org/10.1007/s40259-025-00721-5","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of demand- and supply-side policies on the biosimilar market penetration and identify effective strategies for promoting biosimilar uptake in eight high-income countries.</p><p><strong>Methods: </strong>We analyzed biosimilar market penetration for infliximab, rituximab, and trastuzumab in six European countries-France, Germany, Italy, Spain, Sweden, and the UK-and two Asian countries-Japan and South Korea. Biosimilar market penetration was measured using two indicators: biosimilar market share and the time required for biosimilars to reach the majority point (> 50% market share). Policies were categorized into demand- and supply-side measures, and weights were applied to reflect the extent and timing of policy implementation. Spearman correlation examined the relationship between policy implementation and biosimilar market penetration.</p><p><strong>Results: </strong>Sweden, Italy, and the UK showed the highest biosimilar market shares, adopting various demand-side policies, while Japan and South Korea exhibited slower biosimilar adoption with fewer or no demand-side policies. Biosimilars in most European countries reached the majority point within 5-6 quarters, while projections for Japan and South Korea exceeded 30 quarters. Correlation analysis revealed that adoption of demand-side policies was significantly associated with higher market share (r_s = 0.69, p < 0.001) and shorter time to reach the majority point (r_s = - 0.62, p < 0.01). In contrast, supply-side policies showed a weaker and less consistent association.</p><p><strong>Conclusions: </strong>Demand-side policies, such as financial incentives and prescribing guidelines, are significantly associated with rapid and widespread biosimilar adoption, while supply-side policies had limited impact. Policymakers should prioritize demand-side measures to improve biosimilar uptake and reduce healthcare expenditures effectively.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Biosimilar Monoclonal Antibodies and Their Reference Products Approved in Japan to Reveal the Quality Characteristics in Post-approval Phase.","authors":"Hiroko Shibata, Akira Harazono, Masato Kiyoshi, Yoshiro Saito, Akiko Ishii-Watabe","doi":"10.1007/s40259-025-00722-4","DOIUrl":"https://doi.org/10.1007/s40259-025-00722-4","url":null,"abstract":"<p><strong>Background: </strong>Promoting the use of biosimilars is a global issue from the perspective of reducing medical costs. In Japan, the replacement of original biopharmaceuticals with biosimilars has not progressed as expected. To promote the use of biosimilar monoclonal antibodies, it is necessary to increase the public's understanding of biosimilars by evaluating and confirming the quality of biosimilar products. However, there are limited data to compare among multiple biosimilars and/or the reference, and among their product lots.</p><p><strong>Objective: </strong>In this study, we evaluated quality attributes of multiple lots of reference products and their biosimilars to determine the extent of distribution in quality attributes between products as well as the quality consistencies from lot to lot.</p><p><strong>Methods: </strong>As the quality attributes, the glycosylation profile, charge heterogeneity, binding affinity for the antigen and Fcγ receptors, and high-molecular-weight species and subvisible particles were measured.</p><p><strong>Results: </strong>The degree of similarity in quality attributes with a reference product was different for each biosimilar product. We confirmed the differences between reference and biosimilar product reported in previous articles or review reports, and that some quality attributes of biosimilars were out of the quality ranges of reference products. Although lot-to-lot variations and trends at some degrees were observed for some products, no clear drifts among lots were observed.</p><p><strong>Conclusion: </strong>Analyzing several lots of these products enabled us to capture a profile of quality characteristics for each product. Overall, the extent of variability of each quality attribute among reference products and biosimilars was revealed by this study for the first time.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fomivirsen, Patisiran, and Givosiran Odyssey: How the Success Stories May Pave the Way for Future Clinical Translation of Nucleic Acid Drugs.","authors":"Mona Mansouri, Kimia Mansouri, Zahra Taheri, Samira Hossaini Alhashemi, Ali Dehshahri","doi":"10.1007/s40259-025-00711-7","DOIUrl":"10.1007/s40259-025-00711-7","url":null,"abstract":"<p><p>Over the past 25 years, the approval of several nucleic acid-based drugs by the US Food and Drug Administration (FDA) has marked a significant milestone, establishing nucleic acid drugs as a viable therapeutic modality. These groundbreaking discoveries are the result of some crucial points in the timeline of nucleic acid drug development. The inventions used in fomivirsen (Vitravene; Isis Pharmaceuticals) development paved the road for structural backbone modifications as well as nucleobase and sugar modifications. The approval of patisiran (Onpattro; Alnylam) demonstrated an effective and safe delivery system for small interfering RNA (siRNA), extending potential applications to other nucleic acids such as messenger RNA (mRNA). Givosiran (Givlaari; Alnylam) further revolutionized the field with a carrier-free, targeted platform, utilizing N-Acetylgalactosamine (GalNAc)-siRNA conjugates to enable efficient delivery, expanding therapeutic applications beyond rare genetic disorders to more common conditions such as hyperlipidemia and hypertension. In this review paper, we highlight the evolution of nucleic acid-based drug development, focusing on the pioneering agents fomivirsen, patisiran, and givosiran, and discuss the ongoing challenges in advancing these therapeutics and vaccines.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"359-371"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress and Challenges in the Treatment of Fabry Disease.","authors":"Malte Lenders, Elise Raphaela Menke, Eva Brand","doi":"10.1007/s40259-025-00723-3","DOIUrl":"https://doi.org/10.1007/s40259-025-00723-3","url":null,"abstract":"<p><p>Fabry disease is a rare but life-threatening, X-linked, inherited lysosomal storage disorder in which globotriaosylceramide is insufficiently metabolized because of reduced α-galactosidase A activity. Cellular globotriaosylceramide accumulation causes a multisystemic disease, which, if left untreated, reduces life expectancy in female and male individuals by around 10 and 20 years, respectively, leading to progressive renal failure, hypertrophic cardiomyopathy, cardiac arrhythmia, and premature cerebral infarction. The method of choice for confirming the diagnosis is the determination of reduced α-galactosidase A activity in leukocytes in male individuals and the molecular genetic detection of a disease-causing mutation in female individuals. Current approved treatment includes enzyme replacement therapy (agalsidase alfa [0.2 mg/kg body weight], agalsidase beta or pegunigalsidase alfa [both 1.0 mg/kg body weight]) every other week intravenously or, if a responding ('amenable') α-galactosidase A mutation is present, oral pharmacological chaperone therapy (migalastat 123 mg, every other day). Future therapeutic options may include substrate reduction therapy, gene therapy, messenger RNA therapy, and/or vesicle-packaged enzyme replacement therapy. This review presents current and future treatment options with advantages and disadvantages of the different treatment options.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilar Policies and Their Impact on Market Penetration of Adalimumab, Etanercept and Infliximab: A Policy Synthesis and Descriptive Analysis in 13 OECD Countries.","authors":"Alexander C T Tam, Jasleen Badesha, Daphne P Guh, Nick Bansback, Kevin K Peter, Aidan Hollis, Paul Grootendorst, Sang-Cheol Bae, Aslam H Anis, Wei Zhang","doi":"10.1007/s40259-025-00709-1","DOIUrl":"10.1007/s40259-025-00709-1","url":null,"abstract":"<p><strong>Background: </strong>Different biosimilar-promoting policies have been implemented worldwide to improve biosimilar uptake and reduce expenditures on costly biologics.</p><p><strong>Objective: </strong>The aim was to review biosimilar-promoting policies in 13 countries, and examine biosimilar uptake and expenditure reduction for adalimumab, etanercept, and infliximab, among countries with different biosimilar-promoting policies.</p><p><strong>Methods: </strong>Quarterly IQVIA MIDAS sales data from 2012 to 2023 for the three originators and their biosimilars in 13 countries were used. Two countries for a given setting (retail or hospital) and originator were paired if they differed only on one specific policy. Biosimilar uptake and relative expenditure reduction were compared between pairs. Biosimilar uptake was calculated by dividing the sales volume of biosimilars by the total sales volume of biosimilars and their corresponding originator. Expenditure reduction was the difference between the actual expenditure in 2023 and the but-for-biosimilar expenditure (based on the price of the originator in the year before biosimilar launch).</p><p><strong>Results: </strong>Biosimilar uptake and relative expenditure reduction have grown over time across the three originators in all country-settings. We identified ten country-setting-anti-tumor necrosis factor (anti-TNF) pairs for three policies: tendering, price link, and quotas. All three policies appeared to facilitate greater biosimilar uptake, but this did not consistently translate to greater expenditure reductions. Tendering facilitated greater reductions in three out of four paired comparisons in the retail setting and zero of two comparisons in the hospital setting. Price link with low discount rates (- 20 to - 25% of originator price) and prescribing quotas facilitated greater reductions in one of three comparisons and zero of one comparison in the hospital setting, respectively.</p><p><strong>Conclusions: </strong>Procurement of biosimilars through tendering could potentially reduce spending on anti-TNFs in the retail setting, whereas price links at low discounts did not appear to help. The impact of prescribing quotas needs to be further investigated.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"461-476"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.","authors":"Miaomiao Chen, Yuli Zhou, Kaicheng Bao, Siyu Chen, Guoqing Song, Siliang Wang","doi":"10.1007/s40259-025-00712-6","DOIUrl":"10.1007/s40259-025-00712-6","url":null,"abstract":"<p><p>The development of immune checkpoint inhibitors has revolutionized the treatment of patients with cancer. Targeting the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1(PD-L1) interaction using monoclonal antibodies has emerged as a prominent focus in tumor therapy with rapid advancements. However, the efficacy of anti-PD-1/PD-L1 treatment is hindered by primary or acquired resistance, limiting the effectiveness of single-drug approaches. Moreover, combining PD-1/PD-L1 with other immune drugs, targeted therapies, or chemotherapy significantly enhances response rates while exacerbating adverse reactions. Multispecific antibodies, capable of binding to different epitopes, offer improved antitumor efficacy while reducing drug-related side effects, serving as a promising therapeutic approach in cancer treatment. Several bispecific antibodies (bsAbs) targeting PD-1/PD-L1 have received regulatory approval, and many more are currently in clinical development. Additionally, tri-specific antibodies (TsAbs) and tetra-specific antibodies (TetraMabs) are under development. This review comprehensively explores the fundamental structure, preclinical principles, clinical trial progress, and challenges associated with bsAbs targeting PD-1/PD-L1.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"427-444"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Investigation of CM326 from Preclinical Studies to Randomized Phase I Clinical Trials in Healthy Adults.","authors":"Yujing Di, Ling Yang, Jianfei Zhou, Libo Zhang, Yanqiu Huang, Yingmin Jia, Hongyue Yan, Li Chen, Qiaoyun Hou, Bo Chen, Zhu Luo, Jie Hou","doi":"10.1007/s40259-025-00714-4","DOIUrl":"10.1007/s40259-025-00714-4","url":null,"abstract":"<p><strong>Background: </strong>Thymic stromal lymphopoietin (TSLP) plays a pivotal role in immune responses. CM326 is a humanized monoclonal antibody targeting TSLP.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the preclinical characterization, safety, tolerability, pharmacokinetics, and immunogenicity of CM326 in healthy adults.</p><p><strong>Methods: </strong>In vitro pharmacologic activity of CM326 was compared with that of tezepelumab. In vivo efficacy of CM326 was assessed in allergic cynomolgus monkeys. Subjects in single ascending dose trials were randomized 2:1 (22 mg), 4:1 (55/110/220/440/660/880 mg), and 3:1 (330 mg) to receive CM326 or placebo subcutaneously. Subjects in multiple ascending dose trials were randomized 4:1 (55/110/220 mg every 2 weeks [Q2W], 220 mg Q4W) and 3:1 (440 mg Q2W) to receive CM326 or placebo.</p><p><strong>Results: </strong>CM326 revealed higher potency over tezepelumab in blocking T_h2-driven inflammation in vitro and ameliorated lung function and normalized the inflammatory microenvironment in vivo. CM326 was well tolerated with no discernible safety signals. CM326 showed linear pharmacokinetics over the dose range 22-880 mg. Mean accumulation ratio of AUC was 4.04, 3.87, and 3.74 for 55 mg, 110 mg, and 220 mg Q2W after six doses and 2.16 for 440 mg Q2W after three doses. The mean accumulation ratio of maximum concentration (C_max) was 3.66 and 1.52 for 220 mg Q2W and Q4W, respectively. Anti-drug antibodies (ADAs) were positive in 2/58 subjects after a single dose of CM326, 2/12 receiving placebo and 3/44 receiving CM326 after multiple doses.</p><p><strong>Conclusions: </strong>CM326 improved T_h2 inflammation preclinically and demonstrated an acceptable safety profile with linear pharmacokinetics and low immunogenicity in healthy adults.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifiers: NCT04842201 (registered on 8 April 2021), NCT05171348 (registered on 9 December 2021), NCT05715333 (registered on 27 January 2023).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"487-498"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.","authors":"Torleif Tollefsrud Gjølberg, Simone Mester, Gaia Calamera, Jenny Skjermo Telstad, Inger Sandlie, Jan Terje Andersen","doi":"10.1007/s40259-025-00708-2","DOIUrl":"10.1007/s40259-025-00708-2","url":null,"abstract":"<p><p>Autoimmune diseases are highly prevalent and affect people at all ages, women more often than men. The most prominent immunological manifestation is the production of antibodies directed against self-antigens. In many cases, these antibodies (Abs) drive the pathogenesis by attacking the body's own healthy cells, causing serious health problems that may be life threatening. Most autoantibodies are of the immunoglobulin G (IgG) isotype, which has a long plasma half-life and potent effector functions. Thus, there is a need for specific treatment options that rapidly eliminate these pathogenic IgG auto-Abs. In this review, we discuss how the neonatal Fc receptor (FcRn) acts as a regulator of the high levels of not only IgG Abs, but also albumin, by rescuing both these soluble proteins from cellular catabolism, and how a molecular and cellular understanding of this complex biology has spurred an intense interest in the development of FcRn-targeting strategies for the treatment of IgG-driven autoimmune diseases. We find that this emerging therapeutic class demonstrates efficacy within several autoimmune diseases with distinct pathophysiology. This offers hope for both new therapeutic avenues for highly prevalent diseases currently treated by other means, and rare diseases with no approved therapies to date. In addition, we elaborate on studies that have led to approval of the first FcRn antagonists, the clinical progress and structural design of molecules in the pipeline, their position in the overall therapeutic landscape of autoimmunity, the design of next-generation antagonists as well as the use of this receptor-targeting principle for other therapeutic applications.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"373-409"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles and Immune Activation in Solid Organ Transplantation: The Impact of Immunosuppression.","authors":"Weicheng Xu, Karin Boer, Dennis A Hesselink, Carla C Baan","doi":"10.1007/s40259-025-00713-5","DOIUrl":"10.1007/s40259-025-00713-5","url":null,"abstract":"<p><p>Recent advances in extracellular vesicle (EV) research in organ transplantation have highlighted the crucial role of donor-derived EVs in triggering alloimmune responses, ultimately contributing to transplant rejection. Following transplantation, EVs carrying donor major histocompatibility complex (MHC) molecules activate recipient antigen-presenting cells (APCs), initiating both alloreactive and regulatory T-cell responses. While immunosuppressive drugs are essential for preventing rejection, they may also influence the biogenesis and release of EVs from donor cells. This review examines the impact of maintenance immunosuppressive therapy on EV biogenesis and release post-transplantation. In addition, EV release and uptake may be influenced by specific factors such as the patient's end-stage organ disease and the transplant procedure itself. In-vitro studies using primary human parenchymal and immune cells-integrated with cutting-edge multi-omics techniques, including genomics, proteomics, lipidomics, and single-EV analysis-will offer deeper insights into EV biology and the mechanisms by which immunosuppressive agents regulate EV-initiated immune processes. A detailed understanding of how organ failure, the transplantation procedure and immunosuppressive drugs affect the biology of EVs may uncover new roles for EVs in immune activation and regulation in patients, ultimately leading to improved immunosuppressive strategies and better transplant outcomes.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"445-459"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining a Framework for Sustainable Global Biosimilars Markets Using Findings from a Targeted Literature Review.","authors":"Joshua A Roth, Victoria W Dayer, Mireia Jofre-Bonet, Alistair McGuire, Sean D Sullivan","doi":"10.1007/s40259-025-00710-8","DOIUrl":"10.1007/s40259-025-00710-8","url":null,"abstract":"<p><p>A biosimilar is a biologic medication that is highly similar to and has no clinically meaningful differences from an existing approved biologic referred to as \"reference product.\" From the introduction of the first biosimilar in 2006 to today, a variety of challenges to biosimilar development and uptake have arisen across global markets, threatening sustainability. Consequences of an unsustainable market can include drug shortages, limited competition, and less innovation. However, there are few frameworks to facilitate systematic evaluation and action to address these threats. This study used a contemporary, targeted review of the global biosimilars literature to establish the key dimensions of biosimilar market sustainability. The most commonly referenced stakeholder groups were healthcare payers, government/legal/regulatory authorities, healthcare providers, biologic manufacturers, patients, and biologic purchasers. The most prevalent sustainability dimensions discussed were pricing and cost-savings, legal and regulatory barriers to market entry and access, manufacturer processes, provider choice in selecting biologic therapy, knowledge and preferences, and procurement processes. We incorporated these findings into a framework of biosimilar market sustainability dimensions that should be considered by stakeholders looking to ensure the long-term viability of the market.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"411-425"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}