Cancer Chemotherapy and Pharmacology最新文献

{"title":"Acknowledgement to reviewers 2023.","authors":"","doi":"10.1007/s00280-025-04762-z","DOIUrl":"https://doi.org/10.1007/s00280-025-04762-z","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"43"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: HER-2 SMASH.","authors":"Celal Alandağ, Ayşegül Öztürk, Fatih Yulak, Zeynep Deniz Şahin İnan, Mustafa Özkaraca, Burak Batuhan Lacın, Ahmet Altun","doi":"10.1007/s00280-025-04765-w","DOIUrl":"https://doi.org/10.1007/s00280-025-04765-w","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"42"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid.","authors":"Jesper Heldrup, Archie Bleyer, Laura Ramsey, Lauren Schaff, Brooke Bernhardt, Stefan Schwartz, Etienne Chatelut, Miriam Hwang, Carolina Ten, Martin Guscott, Scott Howard","doi":"10.1007/s00280-025-04749-w","DOIUrl":"10.1007/s00280-025-04749-w","url":null,"abstract":"<p><strong>Purpose: </strong>Folinic acid (FA) rescue protocols to counter the adverse effects of high-dose methotrexate (HDMTX) vary widely, and the risk of over-rescue and potential adverse effects of excessive FA (e.g., hypercalcemia) are under-recognized issues when providing augmented rescue in cases of delayed methotrexate elimination (DME). This opinion summary defines over-rescue, describes its potential adverse impacts, highlights the risk of hypercalcemia associated with excessive FA dosing in patients with acute kidney injury (AKI) from HDMTX, and provides recommendations to improve safety and efficacy of FA rescue in patients receiving HDMTX.</p><p><strong>Methods: </strong>A multidisciplinary panel of experts with clinical experience in HDMTX treatment convened in three roundtable meetings to coalesce expert opinion and best published evidence on the pharmacology and clinical effects and interactions of FA and HDMTX.</p><p><strong>Results: </strong>The type of FA (calcium folinate, calcium levofolinate, sodium levofolinate), dose, and frequency of FA administration may be factors for over-rescue and the development of hypercalcemia due to their respective pharmacokinetic characteristics, especially in cases of DME requiring augmented FA rescue.</p><p><strong>Conclusion: </strong>Clinicians are reminded of the possibility of over-rescue with FA and its impact on subsequent HDMTX courses, types of FA available and their durations of action, and avoid providing too frequent doses. In the setting of AKI and DME requiring high doses of FA, use of sodium levofolinate or calcium levofolinate may be considered to reduce the risk of hypercalcemia associated with calcium folinate.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"41"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant treatment with Capecitabine in patients who received orthotopic liver transplantation with incidental diagnosis of intrahepatic cholangiocarcinoma. Implications on DPYD polymorphisms assessment: report of two cases and review of the literature.","authors":"Carolina Liguori, Simona Magi, Alessandra Mandolesi, Andrea Agostini, Gianluca Svegliati-Baroni, Andrea Benedetti Cacciaguerra, Alessandro Parisi, Elisa Tiberi, Marco Vivarelli, Andrea Giovagnoni, Gaia Goteri, Pasqualina Castaldo, Rossana Berardi, Riccardo Giampieri","doi":"10.1007/s00280-025-04756-x","DOIUrl":"10.1007/s00280-025-04756-x","url":null,"abstract":"<p><p>In recent years, assessing dihydropyrimidine dehydrogenase (DPD) activity has become crucial for cancer patients undergoing 5-fluorouracil (5FU)-based chemotherapy due to the life-threatening toxicity associated with reduced DPD function. The methods for evaluating DPD activity have evolved, with the analysis of DPYD polymorphisms in blood samples becoming the preferred approach. As the indications for liver transplantation are increasing-particularly due to a rise in cases of cholangiocarcinoma (CCA) and non-resectable colorectal liver metastasis-more cancer patients with a history of liver transplantation may experience disease relapse. Furthermore, 5-fluorouracil chemotherapy is a standard treatment for both cancers. This growing need to evaluate DPD activity in transplanted livers arises because standard tests conducted on blood samples reflect the activity of native liver tissue and may produce misleading results. This paper presents two clinical cases from 2022 to 2023 involving patients who underwent successful liver transplants but were later diagnosed with intrahepatic CCA in the explanted liver. Both patients were subsequently prescribed capecitabine as adjuvant chemotherapy, making it essential to assess DPD activity in donor liver tissue to ensure safe treatment protocols. However, there are currently no established guidelines for this specific patient group. If we follow standard clinical practice, this critical analysis will be insufficient, as it only describes the DPD activity of the native liver. It is imperative to determine the DPD activity of the transplanted liver. In summary, this case report highlights the importance of managing this complex situation effectively.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"40"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Bruton's Tyrosine Kinase (BTK) inhibition with alternative doses of ibrutinib in subjects with Chronic Lymphocytic Leukemia (CLL).","authors":"Aziz Ouerdani, Belén Valenzuela, Nicoline Treijtel, Nahor Haddish-Berhane, Sanjay Desphande, Srimathi Srinivasan, Emma Smith, Juan José Perez Ruixo","doi":"10.1007/s00280-025-04753-0","DOIUrl":"10.1007/s00280-025-04753-0","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate alternative ibrutinib dosing regimens that maintain Bruton's tyrosine kinase (BTK) receptor occupancy over the entire dosing interval for CLL patients using a model-based approach.</p><p><strong>Methods: </strong>Ibrutinib inhibits B-cell proliferation via irreversible binding of BTK. As IC₅₀ is not an appropriate parameter to describe the potency of the inhibition in the presence of a covalent binding inhibitor. A BTK covalent binding model was developed using k_inact/K_I as key parameter to account for covalent binding. The ibrutinib-BTK covalent binding model was used to describe the effect of daily doses of 140, 280, 420 and 560 mg on the proportion of subjects with more than 90% BTK inhibition at steady state trough concentrations. Predictive performance of the model was assessed using the available ibrutinib BTK inhibition data following QD dosing. Model-based predictions were used to identify the minimum ibrutinib QD dose that provides more than 90% inhibition in more than 90% of the subjects.</p><p><strong>Results: </strong>The covalent binding model was able to describe the data and predicted that ibrutinib QD dose reduced from 420 mg to 280 mg or 140 mg may inhibit de novo synthetized BTK efficiently in a CLL population.</p><p><strong>Conclusion: </strong>Using a model-based approach showed that reducing the ibrutinib dosing regimen to 280 mg QD or even 140 mg in case of adverse events could maintain BTK inhibition over the entire dosing interval.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"38"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetic modeling of asciminib in support of exposure-response and ethnic sensitivity analyses in patients with chronic myeloid leukemia.","authors":"Christelle Darstein, Deokyong Yoon, Yiqun Yang, Shruti Kapoor, Kohinoor Dasgupta, Shengyuan Wu, Yasunori Kawakita, Matthias Hoch, Kai Grosch, Sherwin K B Sy","doi":"10.1007/s00280-025-04755-y","DOIUrl":"https://doi.org/10.1007/s00280-025-04755-y","url":null,"abstract":"<p><strong>Background: </strong>The original population pharmacokinetics (popPK) model for asciminib in patients with chronic myeloid leukemia in chronic phase (CML-CP) was refined to address drug development needs in support of drug submission, namely, attainment of target drug exposure in specific patient populations, populating individual daily exposures for exposure-response analyses of key efficacy and safety endpoints, confirmation of comparability in exposure between 40 mg b.i.d. and 80 mg q.d., and assessment of ethnic insensitivity.</p><p><strong>Methods: </strong>Participants from two organ dysfunction studies, patients with CML in blast and acute phases and acute lymphoblastic leukemia and patients from a phase III efficacy study in newly diagnosed Ph + CML-CP, and data from a dedicated phase II study in the Chinese patients previously treated with at least two prior tyrosine kinase inhibitors, and a phase IIIb study comparing two dose regimens of asciminib (40 mg b.i.d. and 80 mg q.d.) were included in the revised popPK model. Covariates evaluated were line of therapy, baseline renal and hepatic functions, Chinese or Japanese ethnicity.</p><p><strong>Results: </strong>The apparent clearance and steady-state volume of distribution of asciminib were 6.84 L/h and 110 L, respectively, for a typical individual of 70 kg weight and 90 mL/min absolute glomerular filtration rate. Both the 40 mg b.i.d. and 80 mg q.d. resulted in a steady-state daily AUC of 12,600 ng.h/mL, and there was no difference between lines of therapy. Effects of renal or hepatic impairment on clearance were not clinically relevant. Chinese and Japanese exhibited similar PK as that of the global population.</p><p><strong>Conclusions: </strong>The 40 mg b.i.d. and 80 mg q.d. regimens are comparable in their daily exposure, supporting the use of the two dosing regimens in newly diagnosed and previously treated CML-CP patients. The PK of asciminib is insensitive to ethnic differences and no dose adjustment is required for severe renal and hepatic impaired patients.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"39"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world pharmacokinetics of trametinib in pediatric low-grade glioma.","authors":"Laurie Pagnot, Isaline Granger, Jérôme Guitton, Bertrand Favier, Antony Ceraulo, Cécile Faure-Conter, Pierre Leblond, Michael Philippe","doi":"10.1007/s00280-025-04761-0","DOIUrl":"https://doi.org/10.1007/s00280-025-04761-0","url":null,"abstract":"<p><strong>Purpose: </strong>Trametinib, a MEK1/2 inhibitor, has emerged as a promising treatment for pediatric patients with low-grade gliomas (LGG). However, trametinib exhibits significant inter-individual pharmacokinetic (PK) variability, and studies in adults demonstrated an exposure-efficacy relationship. This study aimed to evaluate the PK profile of trametinib in pediatric routine care and explore potential exposure-outcome relationships.</p><p><strong>Methods: </strong>We analyzed PK data from 65 blood samples from 19 children receiving trametinib, either as single agent or in combination with dabrafenib. A trough concentration (Cmin) range of 8-15 ng/mL was considered, based on average exposure reported in the largest pediatric study.</p><p><strong>Results: </strong>The mean Cmin was 8.82 ng/ml, with 64.6% of samples falling within the predefined target range, while 35.4% were below it. Regarding tolerance, 84.2% of patients experienced treatment-related toxicities, predominantly skin and subcutaneous tissue disorders. Efficacy data were limited.</p><p><strong>Conclusion: </strong>These findings underscore the necessity of therapeutic drug monitoring in pediatric patients to optimize treatment efficacy and minimize toxicity, highlighting trametinib's potential for personalized dosing strategies in this population.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"35"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1 study of the combination of BH3-mimetic, navitoclax, and mTORC1/2 inhibitor, vistusertib, in patients with advanced solid tumors.","authors":"Susan C Scott, Anna Farago, W Victoria Lai, Marianna Zahurak, Michelle A Rudek, Judy Murray, Michael A Carducci, Tamar Uziel, Naoko Takebe, Steven D Gore, Charles M Rudin, Christine L Hann","doi":"10.1007/s00280-025-04760-1","DOIUrl":"https://doi.org/10.1007/s00280-025-04760-1","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the, safety, tolerability and recommended phase 2 dosing of the combination of navitoclax, a dual Bcl-2/xL inhibitor, and vistusertib, a TORC1/2 inhibitor.</p><p><strong>Methods: </strong>Patients with advanced solid tumors received navitoclax plus vistusertib following a 3 + 3 dose escalation design. To mitigate thrombocytopenia, a known toxicity of navitoclax, all patients received lead-in dosing of navitoclax alone at 150 mg orally daily for a minimum of 7 days. In addition to safety and tolerability, pharmacokinetics of navitoclax and vistusertib were evaluated.</p><p><strong>Results: </strong>14 patients received combination treatment which was well-tolerated at dose level 1 (navitoclax 150 mg orally daily plus vistusertib 35 mg orally twice daily). The main dose-limiting toxicity, grade 3 serum aminotransferase elevation, occurred in two of five patients at dose level 2 (navitoclax 250 mg orally daily plus vistusertib 35 mg orally twice daily). Navitoclax and vistusertib exposures appeared consistent with levels reported in prior studies of each agent. No responses were observed among the 8 response evaluable patients.</p><p><strong>Conclusions: </strong>A tolerable dose of navitoclax at 150 mg orally daily plus vistusertib at 35 mg orally twice daily was identified in patients with advanced solid tumors and established as the recommended phase 2 dose (RP2D). Further efficacy assessment of this combination, in a planned phase 2 expansion in patients with relapsed small cell lung cancer, was terminated due to discontinuation of vistusertib.</p><p><strong>Trial registration: </strong>NCT03366103 (First posted December 8, 2017).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"37"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-informed development of a cost-saving dosing regimen for enfortumab vedotin.","authors":"Catharina Jp Op 't Hoog, Amy Rieborn, Dirk Jan Ar Moes, Jeroen Jma Hendrikx, Michiel S van der Heijden, Mira D Franken, Tom van der Hulle, Michel van Kruchten, Annelieke Ecab Willemsen, Stijn Lw Koolen, Emmy Boerrigter, Rob Ter Heine","doi":"10.1007/s00280-025-04764-x","DOIUrl":"10.1007/s00280-025-04764-x","url":null,"abstract":"<p><strong>Aim: </strong>Enfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.</p><p><strong>Methods: </strong>Population pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to the approved body weight-based dosing regimen was defined as conservative equivalent boundaries of 90-111% for the calculated geometric mean ratios (GMRs) of area under the concentration-time curve and trough concentration.</p><p><strong>Results: </strong>A weight-band based dosing regimen for each dose level of enfortumab vedotin was developed. The GMRs for all pharmacokinetic outcomes were within the predefined equivalence boundaries. In addition, a more even exposure distribution was observed across the body weight quartiles. The average costs savings across all dose levels and per weight-band were approximately 15%.</p><p><strong>Conclusion: </strong>The proposed alternative dosing regimen shows that drug costs and spillage of enfortumab vedotin can be reduced while maintaining an equivalent and more evenly distributed exposure in treated patients.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"36"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymine as potential biomarker to predict 5-FU systemic exposure in patients with gastro-intestinal cancer: a prospective pharmacokinetic study (FUUT-trial).","authors":"Maarten A Hanrath, Evi Banken, Sebastian A H van den Wildenberg, Daan van de Kerkhof, Dirk Jan A R Moes, Michele Boisdron-Celle, Bianca J C van den Bosch, Ramon Bax, Pierre M Bet, Jan Gerard Maring, Geert-Jan M Creemers, Irene E G van Hellemond, Maarten J Deenen","doi":"10.1007/s00280-025-04759-8","DOIUrl":"10.1007/s00280-025-04759-8","url":null,"abstract":"<p><strong>Purpose: </strong>In 20-30% of the patients, fluoropyrimidines (5-FU) based chemotherapy leads to severe toxicity, which is associated with dihydropyridine dehydrogenase (DPD) deficiency. Therefore, DPYD genotyping became standard practice before treatment with fluoropyrimidines. Nevertheless, only 17% of the patients with severe toxicity have a DPYD variant. Therefore, an urgent need persists to investigate other strategies contributing to prediction and prevention of toxicity. Endogenous DPD substrates are considered as potential biomarkers to predict toxicity, yet contradictional data exist on demonstrating uracil as a reliable biomarker. Thymine as biomarker for toxicity has been investigated less. The aim of this study was to determine the association between the concentrations of uracil, thymine dihydrouracil (DHU) and dihydrothymine (DHT), with the systemic drug exposure of 5-FU and DPD enzyme activity in patients treated with 5-FU.</p><p><strong>Methods: </strong>We included 36 patients with gastrointestinal malignancy who received 5-FU infusion. DPYD genotyping was conducted before start of treatment. Blood samples for determining 5-FU, uracil and thymine concentrations during infusion and DPD enzyme activity were taken.</p><p><strong>Results: </strong>We found a significant correlation between the 5-FU systematic exposure and baseline thymine concentrations (R² = 0.1468; p = 0.0402). DPD enzyme activity was significantly correlated with baseline thymine concentrations but no correlation was found between DPD enzyme activity and 5-FU systemic drug exposure.</p><p><strong>Conclusion: </strong>5-FU dose individualization based on thymine concentrations could be a promising addition to DPYD genotyping to predict 5-FU-induced toxicity. Larger prospective trials are needed to examine thymine as predictor for toxicity in daily practice.</p><p><strong>Trial registration: </strong>Trial NL7539 at 'Overview of Medical Research in the Netherlands' (ID NL-OMON21471). Date of registration 19-02-2019.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"34"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}