Clinical Pharmacology & Therapeutics最新文献

{"title":"Statins Safety Signals: From Precautions to Proportionate Evidence-Based Labeling","authors":"Médéa Locquet,&nbsp;Jonathan Douxfils,&nbsp;Patrizio Lancellotti,&nbsp;Jean-Michel Dogné","doi":"10.1002/cpt.70419","DOIUrl":"10.1002/cpt.70419","url":null,"abstract":"<p>The recent Cholesterol Treatment Trialists' Collaboration meta-analysis provides the most comprehensive randomized evidence to date regarding statin-associated adverse drug reactions, substantially narrowing the list of harms confidently attributable to statins. Beyond its clinical implications, the analysis highlights important challenges in pharmacovigilance and regulatory risk communication. Precautionary labeling based on low-certainty evidence may inadvertently amplify nocebo effects, reduce adherence to preventive therapies, and contribute to avoidable cardiovascular burden, particularly among vulnerable populations.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"120 4","pages":"852-854"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597019","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":"Pediatric Extrapolation in Neuropsychiatric Drug Development: Leveraging Pharmacokinetic and Pharmacodynamic Strategies to Facilitate FDA Approvals","authors":"Anantha Ram Nookala,&nbsp;William A. Murphy,&nbsp;Nimishraj Panse,&nbsp;Michael Bewernitz,&nbsp;Atul Bhattaram,&nbsp;Poonam Delvadia,&nbsp;Venkateswaran C. Pillai,&nbsp;Deep Kwatra,&nbsp;Yun Xu,&nbsp;Ramana Uppoor,&nbsp;Mehul Mehta,&nbsp;Sreedharan Sabarinath,&nbsp;Gopichand Gottipati","doi":"10.1002/cpt.70412","DOIUrl":"10.1002/cpt.70412","url":null,"abstract":"<p>Pediatric extrapolation enables the application of adult efficacy data to pediatric populations when sufficient similarity is established in disease pathophysiology, pharmacologic response, and drug exposure. When these conditions are met, extrapolation can reduce or eliminate the need for dedicated pediatric efficacy trials, facilitating more efficient pediatric drug development. In this paper, we examined US Food and Drug Administration (FDA) pediatric drug approvals in neurology, analgesia, and psychiatry from 2014 to 2025 that utilized exposure matching to support extrapolation approaches. We identified 33 unique drug products that successfully implemented pharmacokinetic-based exposure matching strategies across neuropsychiatric indications. Population pharmacokinetic modeling emerged as the predominant strategy for pediatric dose optimization, incorporating developmental considerations such as allometric scaling and enzyme maturation functions. FDA General Advice Letters proved instrumental in facilitating adoption of complete pediatric extrapolation approaches, demonstrating the critical role of regulatory guidance in expediting pediatric drug development. Case examples spanned broad age ranges, from mechanistically informed neonatal applications utilizing enzyme maturation modeling (risdiplam) to adolescent populations where adult dosing regimens proved adequate (brexanolone, nipocalimab). Additionally, pharmacodynamic biomarkers were pivotal in pediatric extrapolation of eculizumab and nipocalimab efficacy for the treatment of generalized myasthenia gravis, highlighting promising future directions for the field. These cases demonstrate how achieving comparable pharmacokinetics and, when necessary, pharmacodynamics profiles between adult and pediatric populations can support efficient regulatory approval without dedicated pediatric efficacy studies. The regulatory pathways established for select neuropsychiatric indications provide a compelling framework for expanding extrapolation approaches to other therapeutic areas.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"120 4","pages":"890-913"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628911","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":"Repurposing Registries: Completeness of Real-World Data for Regulatory and HTA Purposes in Three Cancer-Focused Registries","authors":"Manon C. Wilpshaar,&nbsp;Doranne Hilarius,&nbsp;Luisa Prada,&nbsp;Ansgar Weltermann,&nbsp;Christine Leopold","doi":"10.1002/cpt.70368","DOIUrl":"10.1002/cpt.70368","url":null,"abstract":"<p>Despite developments in supporting the identification and selection of fit-for-purpose registries, a translational gap remains between the original purposes of clinically focused registries and their current and future expected use in policymaking. This study aimed to assess the extent to which cancer-focused registries collect essential data elements for regulatory and Health Technology Assessment (HTA) processes. Using literature and expert input, a reference dataset of essential data elements was developed. Completeness of data elements in this reference dataset was evaluated on the example of three European, cancer-focused registries, varying in type, coverage, and health system: the Cancer Centre Upper Austria (CCUA) registry, the Dutch Medication Audit (DMA), and the Portuguese Oncology Institute of Porto (RIC IPO Porto) registry. The evaluated registries exhibit clear differences in inclusion criteria driven by their specific aims. Data elements related to comorbidities, concomitant therapies, patient-reported outcome measures (PROMs), resource use, and safety outcomes were lacking partly or completely in all evaluated registries, highlighting the importance of developing disease-specific core datasets to which registry holders can benchmark their data collection. This study also highlights that the initial aims and design of registries impact their strengths and weaknesses in supporting regulatory and HTA decision-making. Optimally repurposing registry data requires capacity building for registry holders and regulatory/HTA stakeholders focusing on mutual understanding of aims, needs, and limitations. Additional research should address data interoperability, standardization, and data quality across registries.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"120 4","pages":"943-954"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306413","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":"Navigating the Prescription Drug Information System","authors":"Irina V. Wang,&nbsp;Courtney Davis,&nbsp;Robin Forrest,&nbsp;Avi Cherla,&nbsp;Maximilian Siebert,&nbsp;Janice Cowden,&nbsp;Sophia Walker,&nbsp;Tamar Krishnamurti,&nbsp;Florence T. Bourgeois,&nbsp;Steven Woloshin,&nbsp;Anita K. Wagner,&nbsp;Huseyin Naci","doi":"10.1002/cpt.70401","DOIUrl":"10.1002/cpt.70401","url":null,"abstract":"<p>Information on new prescription drugs is increasingly complex and fragmented, posing challenges for healthcare professionals, patients, and payers. Clinicians require concise, actionable guidance to support prescribing decisions, while patients seek to balance benefits and harms when making decisions aligned with their treatment goals. Payers need comparative effectiveness data to inform coverage decisions that shape access and resource allocation. However, inadequacies in drug information communication often lead to overestimation of benefits and underestimation of harms. In this White Paper, we explore how information about newly approved drugs is generated, disseminated, and interpreted. We examine the information needs of healthcare professionals, patients, and payers and the influence of regulatory standards on available evidence. Focusing on regulated communication channels, such as prescription drug labeling, medication guides, and clinical trial snapshots, we highlight the foundational role of regulatory agencies in setting evidence standards and legitimizing drug information. We also consider alternative information sources, including pharmaceutical advertising, which coexist with regulated content. Against a backdrop of increasing uncertainty of drug approval evidence, we identify documented principles that regulators can adopt to meet drug information needs. Recommendations for improvements aim to better serve patients, support clinical decision making, and promote ethical healthcare resource allocation. While centered on the US context, the paper draws parallels with the European information landscape.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"120 4","pages":"855-870"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589652","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":"Operationalizing Precision Medicine in Drug Development: Predictive Biomarkers, Companion Diagnostics, and Regulatory Pathways","authors":"Ingrid Holst-Laubjerg,&nbsp;José M.A. Moreira","doi":"10.1002/cpt.70423","DOIUrl":"10.1002/cpt.70423","url":null,"abstract":"<p>Precision medicine offers the opportunity to improve the benefit–risk profile of new therapies by prospectively identifying patients most likely to respond or least likely to experience harm; however, its systematic integration into drug development remains inconsistent outside oncology. Key barriers include timely generation of robust predictive biomarker hypotheses (i.e., hypotheses regarding treatment-by-biomarker interactions), appropriate validation strategies, and coordinated development of companion diagnostics within increasingly complex FDA, European Medicines Agency, and In Vitro Diagnostic Regulation regulatory frameworks. This review presents a pragmatic operational framework to guide the incorporation of precision medicine into drug development across therapeutic areas. We outline structured approaches for early biomarker hypothesis generation and prephase II evidence development; define five clinical development scenarios based on the strength of the biomarker signal—front-loaded enrichment, precision-medicine-enabled phase II, adaptive phase II, adaptive phase III, and back-loaded confirmatory enrichment; and summarize regulatory and lifecycle considerations for companion diagnostics. Examples from oncology and emerging applications in cardiovascular and metabolic diseases illustrate evolving regulatory expectations and common industry challenges. We also discuss opportunities to extend precision medicine beyond predictive biomarkers to diagnostic, prognostic, and safety biomarkers, as well as digitally derived signatures. Treating precision medicine as a core component of drug development—rather than an optional enhancement—can improve clinical trial efficiency, support commercial viability, and ensure that patients derive meaningful clinical benefit. Early, structured biomarker planning; integrated clinical–diagnostic strategies; and iterative collaboration among sponsors, regulators, HTA bodies, payers, and patients are critical for translating biomarker insights into de-risked pivotal trials and aligned regulatory and market-access decisions.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"120 4","pages":"914-929"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682740","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":"Clinical Impact of Target-Mediated Drug Disposition of Small Molecules with Focus on Early Phase I Study Designs.","authors":"Francesca Tessaro, Neil John Parrott, Matthias B Wittwer, Franziska Schaedeli Stark, Andrés Olivares-Morales, Michael Derks, Stefan Sturm","doi":"10.1002/cpt.70474","DOIUrl":"10.1002/cpt.70474","url":null,"abstract":"","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954580","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":"Phase I Evaluation of Siltartoxatug, a First-in-Class Anti-Tetanus Monoclonal Antibody: Safety, Pharmacokinetics and Pharmacodynamics in Healthy Australian and Chinese Populations.","authors":"Xinyu Liu, Zhigang Liu, Xiaohu Kuang, Yueming Wang, Xiaoyi Liu, Jiyuan Ding, Xia Zhou, Xin Zhou, Qianyu Liang, Meizhuo Zhang, Hao Zhao, Qingqing Tan, Weihong Zheng, Huaxin Liao, Charlotte Lemech, Wanmei Wang","doi":"10.1002/cpt.70467","DOIUrl":"10.1002/cpt.70467","url":null,"abstract":"<p><p>Siltartoxatug, a first-in-class monoclonal antibody targeting tetanus toxin for post-exposure prophylaxis, was evaluated in two phase I trials in Australian and Chinese healthy adults. In these randomized, double-blind, placebo-controlled, dose-escalation studies, participants received a single intramuscular injection of siltartoxatug (10-250 μg/kg) or placebo. The primary objectives were to assess safety, with secondary goals evaluating pharmacokinetics (PK) and immunogenicity, and pharmacodynamics (PD) as an exploratory. Siltartoxatug demonstrated an excellent safety profile across all doses, with adverse event (AE) rates comparable to placebo and no serious adverse events (SAE) attributed to the drug. PK analysis revealed dose-proportional exposure, and the PK profile exhibited characteristics typical of an IgG1 monoclonal antibody. PK parameters were highly consistent between Australian and Chinese trials, indicating no apparent ethnic differences in drug disposition. A single dose rapidly induced protective anti-tetanus antibody titers (≥ 0.01 IU/mL), with all participants in the 100 and 250 μg/kg cohorts achieving seroprotection within 48 hours post-dose; 100% seroprotection was sustained through 105 days in the 250 μg/kg cohort, and remained high (≥ 83.3%) through Day 85 in the 100 μg/kg cohort. Immunogenicity was minimal. These findings collectively highlighted siltartoxatug's potential as a next-generation passive immunizing agent. The consistent PK/PD profiles between Australian and Chinese populations suggested no apparent ethnic differences, providing a foundation for extrapolating efficacy findings from the Chinese trials to other racial groups.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910397","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":"How to Optimize Healthy Volunteer Screening and Enrolment in Clinical Trials: A Qualitative and Quantitative Approach to Evaluate Processes and Healthy Volunteers' Perceptions.","authors":"Evelyn Krohmer, Manuela König, Cathrin J Vogt, Marina Streckebein, Sybille Baumann, Max Blumenstock, Ruwen Böhm, Fabian Müller, Nadja Struß, Viktoria S Wurmbach, Antje Blank","doi":"10.1002/cpt.70462","DOIUrl":"10.1002/cpt.70462","url":null,"abstract":"<p><p>Healthy volunteers (HVs) are essential for phase I trials, yet their recruitment and screening remain resource-intensive and ethically complex. High screening failure (SF) rates highlight the need to evaluate and understand all aspects of the enrolment processes. We analyzed SF patterns in a large German HV cohort and explored participants' motivations, risk perceptions, and expectations regarding trial participation and screening procedure. We retrospectively evaluated screening results from phase I trials (2012-2022) at Heidelberg University Hospital. Additionally, we performed a prospective mixed-methods assessment with semi-structured interviews and a questionnaire evaluating recruitment, informed consent (IC), motivation, and decision making, distributed to experienced volunteers of four trial sites (October 2024-August 2025). Across 30 phase I trials, 900 volunteers were screened with a SF rate of 31.9% (n = 287), mainly due to laboratory abnormalities, medical history of concern, and organizational issues. Results from five semi-structured interviews and the questionnaire survey (n = 196) showed an overall acceptable satisfaction with the IC process, but identified areas of improvement in weighting of topics and risk perception. Although financial compensation was voted as the most important motivation, the decision process is multifactorial and an interplay of compensation, organizational aspects, and expected risks. We identified trial characteristics that are modifiable to facilitate interest in trial participation and provide data-driven recommendations to improve the ethical, efficient, and operational conduct of phase I trials. Furthermore, the results underline the relevance of addressing public perceptions and misconceptions surrounding clinical trials to improve willingness to engage in early-phase research.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910361","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":"Exposure-Response Analysis of Enfortumab Vedotin Plus Pembrolizumab as First-Line Therapy for Locally Advanced or Metastatic Urothelial Cancer.","authors":"Vaishali L Chudasama, Helen Kastrissios, Hossam Kadry, Daping Zhang, Salaheldin Hamed, Srinivasu Poondru, Souvik Bhattacharya, Russ Wada, Amit Garg, Yen Lin Chia","doi":"10.1002/cpt.70466","DOIUrl":"10.1002/cpt.70466","url":null,"abstract":"<p><p>Enfortumab vedotin is a nectin-4-directed antibody-drug conjugate currently approved in combination with pembrolizumab for the first-line treatment of locally advanced or metastatic urothelial cancer. Here we describe the exposure-response relationship between enfortumab vedotin exposures and efficacy/safety endpoints in patients who received ≥1 dose of enfortumab vedotin 1.25 mg/kg (on days 1 and 8 of a 21-day dosing cycle) plus pembrolizumab (recommended dosage) and had evaluable pharmacokinetics in the EV-103 (N = 121) and EV-302 (N = 432) studies. Overall, most patients were older (median age of 69 years), White (74%), and male (77%), with median body weight in EV-103 (79 kg) trending higher than that in EV-302 (75 kg). Higher exposures of enfortumab vedotin were associated with consistently higher objective response rates across all exposure quartiles in both studies, and longer survival than chemotherapy in EV-302. Increased and faster incidence of treatment-related adverse events (Grade ≥ 3 hyperglycemia, Grade ≥ 3 skin reactions, and Grade ≥ 2 peripheral neuropathy) was also observed with increased exposures. However, dose modifications were effective in managing most adverse events, with most patients having at least partial resolution (hyperglycemia, >75%; skin reactions, >85%; and peripheral neuropathy, >50%). Responses attained with higher early cycle exposure were not impacted by subsequent dose modifications. Overall, exposure-response analysis supports the use of enfortumab vedotin at a starting dose of 1.25 mg/kg and in combination with pembrolizumab for first-line treatment of locally advanced or metastatic urothelial cancer.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917585","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":"Constructing an External Control Arm Using the French REALYSA Cohort to Replicate Outcomes of a Randomized Trial Arm in Advanced Hodgkin Lymphoma.","authors":"Olivia Febvey-Combes, Cédric Rossi, Behrouz Kassai, Tesla Murairi Mirimo, Loïc Chartier, Fanny Cherblanc, Emeline Cugnod, Hervé Ghesquières, Aurélien Belot","doi":"10.1002/cpt.70470","DOIUrl":"10.1002/cpt.70470","url":null,"abstract":"<p><p>External control (EC) arms using routine data can be used as comparators in clinical trials under certain conditions. The objective of this study was to assess the ability of an EC arm to replicate outcomes of a randomized controlled trial (RCT) arm receiving the same treatment strategy in advanced stage classical Hodgkin lymphoma and serve as comparator in future trials. Using the prospective real-world data in lymphoma and survival in adults (REALYSA) cohort, we constructed an EC arm by applying eligibility criteria of the AHL2011 phase III RCT. Propensity score (PS) weighting was used to balance baseline characteristics between the EC arm and the RCT arm that received the same treatment. Progression-free survival (PFS) and overall response rate (ORR) at the end of first-line treatment were estimated in both arms. Hazard ratio (HR) for PFS and odds ratio (OR) for ORR were estimated using the EC arm as reference. A sensitivity analysis evaluated PS matching. Four hundred and ten RCT patients and 191 EC patients were analyzed. After PS weighting, patients' characteristics were well-balanced between arms. PFS estimates were similar in RCT and EC arms with an HR close to 1 (HR, 0.98; 95% CI, 0.59-1.62). ORR estimates were comparable in both arms. Weighting performed better than matching. Using PS weighting gave similar outcomes in the EC arm compared with the RCT arm. Our results suggest that EC studies using routine care data could be considered in the development of strategies for advanced Hodgkin lymphoma.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899917","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}