{"title":"Perspective of the Pharmaceuticals and Medical Devices Agency on Drug Development for Childhood Myopia.","authors":"Mitsuru Arima, Motomasa Atsumi, Kumiko Takeuchi, Takumi Aoki, Emi Inagaki, Yosuke Kobayashi, Takuya Kageyama, Kazuki Izumi, Atsushi Yoshimura, Wataru Asakura","doi":"10.1002/cpt.70086","DOIUrl":"https://doi.org/10.1002/cpt.70086","url":null,"abstract":"<p><p>Pathologic myopia represents a global public health concern, with increasing prevalence and vision loss risk. Myopia typically develops in childhood and progresses more rapidly with earlier onset. Clinical trials exploring treatments for decelerating myopia progression are underway. In Japan, 0.025% atropine ophthalmic solution (RYJUSEA®) has been approved. This review outlines the evaluation process by the Pharmaceuticals and Medical Devices Agency (PMDA) and highlights challenges for future drug development.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211213","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}
Peter Ashcroft, Sarah McFann, Alex Ferguson, Arthur Van De Vyver, Suzanne Gaudet, Eshita Khera, Jan-Frederik Schlender
{"title":"Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.","authors":"Peter Ashcroft, Sarah McFann, Alex Ferguson, Arthur Van De Vyver, Suzanne Gaudet, Eshita Khera, Jan-Frederik Schlender","doi":"10.1002/cpt.70077","DOIUrl":"https://doi.org/10.1002/cpt.70077","url":null,"abstract":"<p><p>T-cell engaging antibodies (TCEs) and chimeric antigen receptor (CAR) T cells (CAR-T cells) are among precision medicine therapies that have revolutionized the treatment of hematologic cancers. Their success in oncology has piqued interest in translating this promise into additional indications, such as autoimmune disorders. This review discusses the foundational principles for mechanistic modeling to provide a unified assessment framework for cross-modality (i.e., CAR-T cells vs. TCEs) and cross-indication (i.e., oncology vs. immunology) translation. This framework captures the unique elements of each modality, such as CAR-T cellular kinetics, TCE pharmacokinetics, and complex formation with target cells, as well as shared elements such as B-cell kinetics and biodistribution across indications. We describe how this integrated approach can lead to informed decision making for more personalized and effective treatment strategies with these immune therapies.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211209","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}
Katarzyna Lipinska, Danny van Weelij, Bart Lagerwaard, Linda Rutgrink, Eduard Vardianu, Petra Naster, Lina Pérez-Breva, Paul Bodfish, Megan Heath, Yvonne van Rijswick, Diederick E Grobbee, Mira G P Zuidgeest
{"title":"Selecting and Preparing Clinical Sites for the Successful Conduct of Decentralized Clinical Trial Activities-Findings From the Trials@Home RADIAL Proof-of-Concept Trial.","authors":"Katarzyna Lipinska, Danny van Weelij, Bart Lagerwaard, Linda Rutgrink, Eduard Vardianu, Petra Naster, Lina Pérez-Breva, Paul Bodfish, Megan Heath, Yvonne van Rijswick, Diederick E Grobbee, Mira G P Zuidgeest","doi":"10.1002/cpt.70075","DOIUrl":"https://doi.org/10.1002/cpt.70075","url":null,"abstract":"<p><p>Decentralized clinical trials (DCTs) offer opportunities to improve trial accessibility, participant convenience, and efficiency, yet may pose significant operational challenges for clinical trial sites. This paper presents the operational insights gained from selecting, training, and supporting clinical sites within the RADIAL proof-of-concept trial, part of the Trials@Home project. RADIAL was a multicenter, low-intervention phase IV trial comparing conventional, hybrid, and fully decentralized approaches for individuals with type 2 diabetes mellitus across six European countries. Site selection involved detailed feasibility assessments evaluating operational capabilities, recruitment potential, technological readiness, and willingness to implement decentralized elements. Despite proactive training, including ongoing support via a centralized helpdesk, sites faced initial difficulties with technology management and participant onboarding. Contractual complexities were prominent, particularly regarding clearly delineating responsibilities and data handling in agreements involving third-party providers. Moreover, integrating third-party services necessitated meticulous oversight strategies and continuous stakeholder coordination to ensure regulatory compliance and efficient trial management. Our experiences underscore essential considerations for future DCT implementations: proactive stakeholder alignment; tailored, timely, and ongoing training and support; intuitive technology design informed by clinical user input; robust, centralized oversight structures; and clearly defined delegation frameworks for third-party engagements. Addressing these operational considerations will facilitate smoother transitions toward decentralized clinical research models, maximizing their potential benefits while managing associated complexities effectively-especially for clinical site staff.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204988","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}
Suguru Okami, Kako Shimotsumagari, Yasunari Sadatsuki
{"title":"Evolving Real-World Data and Evidence Use for New Drugs and Regenerative Medical Products Approvals in Japan-An Analysis of the 6-Year Trend.","authors":"Suguru Okami, Kako Shimotsumagari, Yasunari Sadatsuki","doi":"10.1002/cpt.70081","DOIUrl":"https://doi.org/10.1002/cpt.70081","url":null,"abstract":"<p><p>Several regulatory initiatives have been made to clarify the acceptability and requirements of real-world data and real-world evidence (RWD/E) for the benefit/risk assessment of new medical products in Japan. The objectives of this review were to characterize the use of RWD/E in regulatory applications of new medical products and to describe the longitudinal trends of how use cases evolved in conjunction with regulatory initiatives in the most recent 6 years in Japan. New drugs and regenerative medical products applications approved by the Ministry of Labour, Health, and Welfare between January 1, 2019, and December 31, 2024, were included (N = 674). Of these, 158 (23.4%) applications contained RWD/E. The number of RWD/E use cases increased continuously over the period from 21 (18.1%) of applications in 2019 to 38 (30.4%) of applications in 2024. 75% of use cases categorized as the main study were used to provide comparator arms in clinical trials. Most of the cases were employed because a randomized controlled trial was ethically difficult or infeasible. In pediatric drug applications, RWD/E were leveraged to address the low feasibility of clinical trials and ethical concerns, with a relatively higher use for safety purposes (40%) observed. Alongside the development of regulatory initiatives, the findings confirm the increasing number and variety of RWD/E utilization. The requirements for the regulatory use of RWD/E differ based on its purposes and context. Insights from accumulated cases may help clarify regulatory requirements and deepen our understanding of the value of RWD/E use in developing new medicines.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184360","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}
Naomi Gronich, Naama Geva-Zatorsky, Rachel Herren, Libusha Kelly, Ziv Cohen, Haiying Zhou, Yi-Ching Chen, Khalid Shah, Talin A Robinson-Catala, Grecia Frisby, Jason H Karnes, Lisl Shoda
{"title":"Pharmacomicrobiomics.","authors":"Naomi Gronich, Naama Geva-Zatorsky, Rachel Herren, Libusha Kelly, Ziv Cohen, Haiying Zhou, Yi-Ching Chen, Khalid Shah, Talin A Robinson-Catala, Grecia Frisby, Jason H Karnes, Lisl Shoda","doi":"10.1002/cpt.70066","DOIUrl":"https://doi.org/10.1002/cpt.70066","url":null,"abstract":"<p><p>Oral medications encounter gut commensal microbes that participate directly and indirectly in drug effects through metabolism, interactions with drug metabolites, or production of substrates that compete with drugs for drug-metabolizing enzymes, consequently influencing drug pharmacokinetics. The microbiota can also affect drug efficacy or toxicity by modulating the immune system; for example, variability in response to cancer immunotherapy, such as anti-PD-1 and anti-CTLA-4 therapies, is increasingly attributed to differences in gut microbial composition and function. These conditions indicate the need and opportunity to intentionally leverage the microbiome for drug effect; as such, the study of how intra- and inter-individual differences in the microbiome affect drug response has gained a definition termed pharmacomicrobiomics. While the need is clear, clinical studies evaluating pharmacomicrobiomic interactions are challenging due to microbiome variability, multiple potential confounders, no standardization of statistical and bioinformatics methods, and the reluctance of potential clinical study participants. In this review, we make the case for pharmacomicrobiomic clinical studies; for the use of modeling and simulation to provide a quantitative framework for data integration, hypothesis testing, and translational-to-late-stage clinical predictions; and the application of real-world data to support both using a within-subject comparison approach. We argue that an integrated and cohesive approach can address the large \"inherent\" inter-individual variability in the microbiome, attributed to factors such as age, lifestyle choices, environmental factors, chemical and biological exposures, and disease. In summary, there are many challenges to pharmacomicrobiomics research but also enormous potential to improve the development and utilization of pharmaceutical products.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184399","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":"Impact of Antihypertensive Treatment on Outcomes of Adjuvant Bevacizumab for Ovarian Cancer (IATRO), Results from a Nationwide Emulated Clinical Trial.","authors":"Floriane Jochum, Élise Dumas, Joe-Elie Salem, Stéphane Ederhy, Anne-Sophie Hamy, Lise Lecointre, Enora Laas, Fabien Reyal, Fabrice Lecuru, Cherif Akladios, Paul Gougis","doi":"10.1002/cpt.70067","DOIUrl":"https://doi.org/10.1002/cpt.70067","url":null,"abstract":"<p><p>Antiangiogenic therapy with bevacizumab improves outcomes in ovarian cancer but induces hypertension, leading to major adverse cardiovascular events (MACE). While calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEi) are recommended for managing bevacizumab-associated hypertension, their impacts on cancer progression and cardiovascular outcomes are unclear. This study compared the effects of CCBs and ACEi on progression-free survival (PFS) in ovarian cancer patients treated with adjuvant bevacizumab. The incidence of MACE and overall survival (OS) were also evaluated. We conducted an emulated clinical trial using data from January 1, 2011, to January 1, 2021, from the French National Health Data System (SNDS), covering 98.8% of the French population. Patients with FIGO stage III to IV ovarian cancer who underwent cytoreductive surgery and adjuvant chemotherapy with bevacizumab, treated with CCBs or ACEi monotherapy within 6 months after surgery, were included. Out of 4,165 patients treated with bevacizumab, 454 met inclusion criteria for the main analysis: 273 in the CCBs group and 181 in the ACEi group. CCBs use was associated with a longer median PFS compared to ACEi (21.8 vs. 18.2 months) and a higher 3-year PFS rate (difference of 8.2 percentage points, 95% CI: 2.0%; 14.8%). No significant difference in OS was observed between groups. Cardiovascular complications were more frequent with CCBs compared to ACEi, particularly congestive heart failure (difference in 3-year incidence of MACE: -4.5 percentage points; 95% CI: -8.2%; -1.1%). These findings emphasize the need for a balanced approach to managing hypertension in cancer patients, considering both oncologic and cardiologic outcomes.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147045","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":"History and Evolution of Innovations in Clinical Pharmacology.","authors":"Lawrence J Lesko, Piet H van der Graaf","doi":"10.1002/cpt.70048","DOIUrl":"https://doi.org/10.1002/cpt.70048","url":null,"abstract":"<p><p>Foundational scientific discoveries and inventions, with some dating back nearly 80 years laid the groundwork for many of today's innovations in clinical pharmacology. Beginning in the 1970 to 1980's, these discoveries began to rapidly mature, leading to widespread adoption in new and generic drug development and in regulatory decision-making. Over time, there has been a gradual transition toward a greater focus on quantitative modeling and simulation technologies, reinforced by enormous improvements in data collection in preclinical studies with translational bridges to relevant information derived from early phase human clinical trials. These innovations have opened the door to may improvements such as more precise assessments of dosage form performance, optimized dose selection to maximize the benefit-to-risk of numerous therapies, more in-depth understanding of drug-drug interactions, and informed dosage adjustments in specific populations. This review traces the history and evolution of innovations in clinical pharmacology through the lens of the interconnected pharmaceutical industry-regulatory agency relationship. It discusses three categories of innovations: established, in progress, and emerging, and discusses how specific innovations have played out, or are expected to shape, the future of the drug development and regulatory science enterprise tasked with bringing effective, safe, and needed new and novel therapies to the marketplace.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129737","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}
Megan Heath, Amos J de Jong, Shaun Magorrian-Spence, Chao Jin, Danny R van Weelij, Lucas Pagnier, Yvonne van Rijswick, Volker Haufe, Bart Lagerwaard, Mira G P Zuidgeest
{"title":"The Supply of Investigational Medicinal Product and Management of Study Materials for Decentralized Participants-Insights from the Trials@Home RADIAL Proof-of-Concept Trial.","authors":"Megan Heath, Amos J de Jong, Shaun Magorrian-Spence, Chao Jin, Danny R van Weelij, Lucas Pagnier, Yvonne van Rijswick, Volker Haufe, Bart Lagerwaard, Mira G P Zuidgeest","doi":"10.1002/cpt.70072","DOIUrl":"https://doi.org/10.1002/cpt.70072","url":null,"abstract":"<p><p>Decentralized clinical trials (DCTs), which move trial activities to participants' homes or direct surroundings, offer potential advantages over conventional site-based trials through reduced participant burden and improved accessibility. The direct-to-participant (DtP) delivery of investigational medicinal products (IMPs) and other study materials and collection of biological samples requires careful planning and execution to ensure participant safety and data integrity. Here, we report operational experiences from the RADIAL proof-of-concept trial, a three-arm parallel-group study conducted across six European countries comparing conventional, hybrid, and fully decentralized approaches in type 2 diabetes patients. The study implemented two DtP IMP models: clinical trial site-to-participant and central pharmacy-to-participant delivery, with comprehensive logistics tracking and temperature monitoring. In RADIAL, 68 DtP IMP shipments were executed with a 94% successful delivery rate. Four shipments (6%) failed due to participant unavailability, temperature excursions, defective monitoring equipment, or courier loss. The central pharmacy model demonstrated inventory savings compared with conventional site-based distribution. Biological sample collection for HbA1c assessment was done through drop-off, which proved more challenging in the remote arm. Key challenges related to DCT logistics as experienced in RADIAL included unclear importer/exporter responsibilities, regulatory divergence across countries, participant material management, and sample drop-off reliability. DtP IMP delivery and biological sample collection are feasible in European DCTs but require enhanced planning, clear vendor responsibilities, and robust contingency procedures. Success depends on appropriate participant training, reliable courier services, temperature control systems, and accessible biological sample collection methods.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129735","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}
Alan Shi, Cole Cornwell, Kyunghee Yang, Paul M Beringer
{"title":"Quantitative Systems Toxicology Predicts Ivacaftor-Induced Oxidative Stress Contributes to CFTR Modulator Hepatotoxicity.","authors":"Alan Shi, Cole Cornwell, Kyunghee Yang, Paul M Beringer","doi":"10.1002/cpt.70073","DOIUrl":"https://doi.org/10.1002/cpt.70073","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a chronic hereditary disease that affects tens of thousands of people worldwide. The introduction of CFTR modulator therapies such as elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved the quality of life of people with CF. However, ETI has been shown in clinical trials to cause elevations in liver enzymes, and real-world cases of drug-induced liver injury (DILI) have also been reported. The mechanism of ETI-mediated DILI is currently unknown, hindering the development of more effective mitigation strategies for this adverse reaction. Through in vitro assays and quantitative systems toxicology modeling using DILIsym, this study revealed that ivacaftor contributed most significantly to ETI-mediated DILI, primarily via reactive oxygen species production, resulting in mitochondrial dysfunction due to electron transport chain inhibition. DILIsym modeling also predicted liver enzyme elevations following daily dosing of ETI at a comparable frequency (6.0%) to that of clinical data (8.0%). Simulations of the therapeutic effects of DILI mitigation strategies for ETI showed that dose reduction and antioxidant administration may significantly reduce the frequency of liver enzyme elevations due to ETI.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123862","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}
Sten Hanke, Dimitrios Giannikopoulos, Bernhard Neumayer, Tea Vedenkannas, Robert Davey, Lampros Mpaltadoros, Brian Guthrie, Rebecca Jackson, Bart Lagerwaard, Mira Zuidgeest
{"title":"Operationalizing Decentralized Clinical Trials: Technology Insights from the Trials@Home RADIAL Proof-of-Concept Trial.","authors":"Sten Hanke, Dimitrios Giannikopoulos, Bernhard Neumayer, Tea Vedenkannas, Robert Davey, Lampros Mpaltadoros, Brian Guthrie, Rebecca Jackson, Bart Lagerwaard, Mira Zuidgeest","doi":"10.1002/cpt.70070","DOIUrl":"https://doi.org/10.1002/cpt.70070","url":null,"abstract":"<p><p>While decentralized clinical trials (DCTs) hold great promise for improving trial accessibility and efficiency, the effective deployment of DCT elements requires robust technological infrastructure and careful system integration. Although several innovative technologies are now available for implementing DCT elements, most existing setups integrate single-vendor solutions, which restrict the potential for tailored trial designs as well as seamless interoperability between different platforms and solutions. This paper presents operational learnings from the Trials@Home RADIAL proof-of-concept trial. RADIAL implemented a modular, multi-vendor technology package. RADIAL adopted a deliberate strategy to avoid a monolithic \"one-vendor-for-all\" solution, instead selecting technologies and integrating them only where it added clear value. Core systems-such as eConsent and Bluetooth glucometer-were fully integrated into the central platform, while other components were deliberately managed outside the core system. The aim was to implement and validate a multi-vendor technology setup and generate learnings that would help DCT trialist in designing DCTs, especially in terms of technology selection and integration. Key challenges arose from Bring Your Own Device (BYOD) variability, immature device technologies, and infrastructure limitations at clinical sites-particularly affecting components like telemedicine. The results emphasize the significance of investing in participant support infrastructure, as well as early cross-functional support, while automated, multichannel notifications seem to guide participant engagement. Finally, embedding compliance by planning early streamlines documentation through a clear governance model seemed to enhance agility and reduce burden.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084513","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}