CPT: Pharmacometrics & Systems Pharmacology最新文献

{"title":"Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed/Refractory Multiple Myeloma","authors":"Fernando Carreño,&nbsp;Martijn van Noort,&nbsp;Adekemi Taylor,&nbsp;Stefan Zeiser,&nbsp;Theodoros Papathanasiou,&nbsp;Teun M. Post,&nbsp;Yi Ting (Kayla) Lien,&nbsp;Yu Liu Ho,&nbsp;Geraldine Ferron-Brady","doi":"10.1002/psp4.70276","DOIUrl":"10.1002/psp4.70276","url":null,"abstract":"<p>Quantitative modeling can guide drug development and regulatory decisions by providing insights into pharmacokinetics, pharmacodynamics, efficacy, and safety. Integrating models allows simulations that support dosing considerations. A simulation framework for belantamab mafodotin (B) in relapsed/refractory multiple myeloma was developed using data from monotherapy studies and combination studies with bortezomib/dexamethasone (BVd) and pomalidomide/dexamethasone (BPd). Individual changes from baseline in serum M-protein concentrations were modeled using a tumor growth inhibition model. Changes in ophthalmic exam findings (OEFs) grades per the Keratopathy and Visual Acuity (KVA) scale were modeled using a continuous-time Markov model. Belantamab mafodotin concentrations were modeled with a population pharmacokinetic model. All final models adequately described the clinical data. The M-protein/KVA/pharmacokinetic models were integrated in a simulation framework, and simulations of treatment outcomes were performed. Simulated regimens included dose modifications (holds/reductions) for OEFs. Simulations of protocol dosing and dose modifications from the phase 3 DREAMM-7 (BVd) and DREAMM-8 (BPd) trials predicted similar results to the respective trials (for BVd simulations/DREAMM-7 data: very good partial response rates [VGPR+] 62.0%/62.0%, median progression-free survival [mPFS] 39.4/36.6 months, and grade ≥ 3 OEFs 87.5%/76.5%; for BPd simulations/DREAMM-8 data: VGPR+ rates 60.2%/68.0%, mPFS not reached/not reached, and grade ≥ 3 OEFs 77.2%/82.5%). Simulations of alternative BVd regimens indicated that a 2.5 mg/kg starting dose produces the highest efficacy, and schedule extensions after the first BVd dose can improve tolerability while continuing to demonstrate efficacy. This framework adequately predicted outcomes from DREAMM-7/DREAMM-8, supporting its use to predict benefit–risk profiles of alternate belantamab mafodotin dosing strategies.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psp4.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Venous Thromboembolism Prophylaxis in Burn Patients Using Enoxaparin Through PBPK Modeling.","authors":"Sabiha Rahman Mim, Venkata K Yellepeddi, Francine J Azeredo","doi":"10.1002/psp4.70265","DOIUrl":"10.1002/psp4.70265","url":null,"abstract":"<p><p>Burn injuries cause physiological changes that alter enoxaparin pharmacokinetics, often leading to inadequate exposure and suboptimal venous thromboembolism (VTE) prophylaxis. Current weight-based dosing and anti-Xa monitoring provide limited guidance for dose optimization across burn severities. This study develops a physiologically based pharmacokinetic (PBPK) model of enoxaparin across burn phases to evaluate target attainment under standard dosing while accounting for burn severity, augmented renal clearance (ARC), and body weight, and to propose individualized dosing strategies to improve VTE prophylaxis. Real-world data of 1288 anti-Xa concentrations were collected from 408 burn patients receiving subcutaneous enoxaparin. A PBPK model was developed in healthy adults and extrapolated to burn patients by incorporating burn-specific changes, including reduced absorption and decreased antithrombin levels. This validated PBPK model for burn patients was used to simulate dosing regimens across burn severities and ARC, with model performance assessed using average fold error (AFE) and absolute average fold error (AAFE). Sub-therapeutic drug exposure was most prominent from 0 to 96 h post burn across all severities. In obese patients, dose escalation from 40 to 60 mg reduced subtherapeutic exposure from 27.3% to 16.9%. Although trough anti-Xa concentrations increased with higher doses, levels remained lower in patients with ARC compared to those with normal renal clearance (NRC), indicating the need for dose adjustment in ARC. Standard enoxaparin dosing is frequently inadequate in burn patients, particularly early after injury and in those with ARC. PBPK-informed precision dosing can improve VTE prophylaxis beyond weight-based dosing with anti-Xa monitoring alone.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70265"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the Weight-Tiered Q3W Regimen of Amivantamab in Combination With Carboplatin-Pemetrexed in EGFR-Mutated Non-Small Cell Lung Cancer.","authors":"Dongfen Yuan, Corey J Bishop, Jaydeep Mehta, Wangda Zhou, Lu Zhang, Jie Zhou, Raja Venkatasubramanian, Alex Yu, Trishala Agrawal, Sujay Shah, Mahadi Baig, Joshua M Bauml, Pritam Kambuj, Lahila-Carina Ojeda, Pamela L Clemens, Nahor Haddish-Berhane, Yaming Su, Mahesh Samtani","doi":"10.1002/psp4.70263","DOIUrl":"10.1002/psp4.70263","url":null,"abstract":"<p><p>Amivantamab, a bispecific antibody targeting epidermal growth factor and mesenchymal-epithelial transition receptors, was initially approved under accelerated approval as a monotherapy for second-line treatment of non-small cell lung cancer (NSCLC) with exon 20 insertion mutations. Subsequently, amivantamab in combination with carboplatin-pemetrexed demonstrated prolonged progression-free survival compared to chemotherapy alone in the first-line treatment of NSCLC with exon 20 insertion mutations and the second-line treatment of NSCLC with exon 19 deletion or exon 21 L858R substitution mutations. To enable the combination with chemotherapy, the amivantamab regimen was changed from every 2 weeks (Q2W) to every 3 weeks (Q3W); both are weight-tiered with a cutoff at 80 kg. Here we present the population pharmacokinetics (PK) and exposure-response (E-R) analysis supporting this dose regimen change. The population PK analysis demonstrated that the Q3W regimen achieved comparable trough concentrations as the approved Q2W regimen as well as between the two weight tiers. After accounting for confounding covariates, the E-R relationship for PFS was flat in both indications. The safety profile of the Q3W regimen was generally manageable, despite trends of a positive E-R relationship for adverse effects related to the mechanism of action. Besides weight, dose adjustment for other covariates was not warranted. These analyses supported the registration of the weight-tiered Q3W regimen for amivantamab in combination with carboplatin-pemetrexed in the new indications. This work demonstrates how the use of fit-for-purpose pharmacometrics analyses can support dose regimen changes without extensive dose selection clinical studies.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70263"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External Evaluation of Population Pharmacokinetic Models of Cabotegravir, During Its Oral and Intramuscular Administration in HIV-Infected Patients.","authors":"Quentin Renou, Nadège Néant, Alexandre Destere, Jennifer Lagoutte-Renosi, Matthieu Grégoire, François Parant, Sébastien Lalanne, Florian Lemaitre, Peggy Gandia, Nicolas Venisse, Stéphane Bouchet, Minh P Lê, Patrice Muret, Gilles Peytavin, Caroline Solas, Sihem Benaboud","doi":"10.1002/psp4.70180","DOIUrl":"10.1002/psp4.70180","url":null,"abstract":"<p><p>Cabotegravir (CAB), combined with rilpivirine, is the first long-acting injectable therapy approved for HIV-1 maintenance treatment. While adherence and patient satisfaction have been improved, pharmacokinetic (PK) variability remains a concern. Two population PK models have been developed: one based on data from phase I-III trials and the other on routine clinical data. However, neither model has undergone thorough external evaluation. The aim of this study was to evaluate the predictive performance of these models using an independent prospective dataset to evaluate their suitability to support model-informed precision dosing (MIPD). External validation was performed using data from the French observational and multicenter (n = 14) ANRS0255 CARLAPOP study (736 HIV-infected patients, representing 2192 concentrations). Models were implemented using MONOLIX software and evaluated using goodness-of-fit, prediction-based, and simulation-based diagnostics. For Han's model, regarding plasma concentrations following intramuscular administration, Median Prediction Error (MDPE) was -1.2% (PRED) and -4.4% (IPRED); Median Absolute Prediction Error (MDAPE) was 36.6% (PRED) and 17.9% (IPRED). For Thoueille's model, MDPE was -24.2% (PRED) and -9.2% (IPRED); MDAPE was 39.0% (PRED) and 15.3% (IPRED). However, < 70% of predictions were within a 20% error margin with both models. Graphical analyses of Thoueille's model showed systemic bias, particularly in women, nonsmokers, and patients with higher body mass index. Therefore, neither model was considered reliable enough for MIPD application in our population. Although Han et al.'s model demonstrated higher predictive performances, further improvements are required before it can be reliably applied for MIPD in daily routine.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70180"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically Based Pharmacokinetic Modeling of Elexacaftor/Tezacaftor/Ivacaftor in Infants With Cystic Fibrosis.","authors":"Ngoc Hoa Truong, Sihem Benaboud, Naïm Bouazza, Eric Deneuville, Anne Mornand, Philippe Reix, Mélanie Ribault, Pierre-Régis Burgel, Léo Froelicher-Bournaud, Steeve Rouillon, Mohammed Rohi Sanoufi, Gabrielle Lui, Saïk Urien, Jean-Marc Tréluyer, Isabelle Sermet-Gaudelus, Frantz Foissac","doi":"10.1002/psp4.70225","DOIUrl":"10.1002/psp4.70225","url":null,"abstract":"<p><p>Ivacaftor is the only cystic fibrosis transmembrane conductance regulator modulator approved for infants ≥ 1 month. The elexacaftor/tezacaftor/ivacaftor combination, approved for children aged ≥ 2 years, has been shown to significantly slow CF progression. Expanding elexacaftor/tezacaftor/ivacaftor use to infants may offer additional therapeutic benefits. This study aims to predict elexacaftor/tezacaftor/ivacaftor pharmacokinetics in infants aged 1 month to < 2 years using physiologically based pharmacokinetic modeling (PBPK) and to determine whether age- and weight elexacaftor/tezacaftor/ivacaftor doses, extrapolated from ivacaftor monotherapy, produce drug exposures comparable to adult levels. Adult elexacaftor/tezacaftor/ivacaftor PBPK published models were first reproduced using Simcyp. These models were scaled to children aged 2-18 years via the Simcyp Pediatric Simulator and the Uprety-Wahlström cytochrome-P450 3A4 ontogeny method to simulate the current elexacaftor/tezacaftor/ivacaftor dosing regimen. FDA-approved ivacaftor monotherapy dosing was evaluated in children 1 month to < 2 years and subsequently used to guide the extrapolation of elexacaftor/tezacaftor/ivacaftor combination dosing regimens. The overall workflow was validated using in vivo pharmacokinetic data or literature-based sources. Elexacaftor/tezacaftor/ivacaftor PBPK models for adults and children ≥ 2 years were validated against observed clinical pharmacokinetic data. Simulations of elexacaftor/tezacaftor/ivacaftor doses based on ivacaftor monotherapy in infants < 2 years matched adult-reported levels, except in infants 1-2 months, who showed lower exposures, and in those weighing ≥ 14 kg, who may experience higher exposures. Using PBPK modeling, supported by clinical pharmacokinetic data, this study explores elexacaftor/tezacaftor/ivacaftor dosing in children under 2 years. The findings offer preliminary dosing guidance, pending confirmation in larger clinical studies, with therapeutic drug monitoring recommended to guide treatment.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70225"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Barriers Between Species: Integrated Multi-Species PK Models Improve Human PK Predictions.","authors":"Miriam S R Happ, Jens M Borghardt, Charlotte Kloft, Hermann Rapp, Achim Sauer, Anneke Himstedt, Bettina Gerner","doi":"10.1002/psp4.70262","DOIUrl":"10.1002/psp4.70262","url":null,"abstract":"<p><p>The accurate prediction of human pharmacokinetics (PK) is critical for compound selection and determining the human efficacious dose in drug discovery. Besides predicting the key PK parameters clearance (CL) and steady-state distribution volume (V_ss), the prediction of exposure metrics, e.g., maximum and trough concentrations (C_max, C_trough), are essential to evaluate efficacy and toxicity. Still, methods for predicting further PK-shape-defining parameters like absorption rate constant (k_a), central and peripheral distribution volume (V_c, V_p), and intercompartmental clearance (Q) remain underexplored. Thus, this work aimed to improve the prediction of respective parameters, building up on a published PK-prediction-framework. The updated framework leveraged a multi-species PK model, enabling the joint prediction of shape-defining parameters by incorporating allometric scaling, while keeping established mechanism-based prediction methods for bioavailability (F) and CL. The performance of the multi-species model was tested for 40 small molecules with known human PK profiles and benchmarked against the literature framework, published alongside the data. The new predictions showed a reduction in geometric mean fold-error (GMFE) compared to the benchmark for both the predicted PK profile and its shape, associated with an improved prediction of Q and late concentrations (C_24h). The overall improvement was primarily driven by compounds, exhibiting inconsistent PK model structures across species when applying the benchmark method. Meanwhile, the prediction performance on other compounds remained comparable, making the integrated multi-species PK-model framework a promising approach for human PK prediction, especially in cases where difficulties in individual species model integration are faced or accurate trough concentration prediction is a priority.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70262"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OpenPMX Software for Nonlinear Mixed-Effect Models in Pharmacometrics: Precision Compared With NONMEM First-Order Conditional Estimation.","authors":"Douglas J Eleveld, Jeroen V Koomen, Jasper Stevens, Pieter J Colin, Michel M R F Struys","doi":"10.1002/psp4.70250","DOIUrl":"10.1002/psp4.70250","url":null,"abstract":"<p><p>Mixed effects models are a backbone of pharmacometrics, and NONMEM software, with the first-order conditional method with interaction having become the de facto industry standard for model estimation. Documentation exists for the general mathematical methodology for estimation, but many technical and implementation details are lacking. OpenPMX aims to enable nonlinear mixed-effects modeling and estimation in a transparent and efficient manner, with open source licensing allowing for broad application and development. Model parameter estimation bias and root mean squared error (RMSE) obtained using OpenPMX were compared to that using NONMEM for five population models and datasets with varying degrees of complexity. For each model and dataset, repeated simulation and estimation were performed, and the per-dataset difference in precision for parameter estimates was calculated for OpenPMX versus NONMEM. We found that the bias and RMSE of OpenPMX are comparable to the industry standard NONMEM, and in some cases slightly better. The project has low complexity, few dependencies, and is open source, with all technical details open for inspection, auditing, and scientific collaboration.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":"e70250"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Model Based Sensitivity Analysis to Lower Recruitment Burden for Young Children Requiring Intravenous Immunoglobulin G Replacement","authors":"Todd Dumas,&nbsp;Shahram Mehr,&nbsp;Rebecca Avila,&nbsp;Amy Doman,&nbsp;Kaitlin Kestenberg,&nbsp;Isaac Melamed","doi":"10.1002/psp4.70275","DOIUrl":"10.1002/psp4.70275","url":null,"abstract":"<p>To support a post-marketing requirement for pharmacokinetic (PK)-focused assessments in patients ages 2–16 years, a model-informed drug development approach was used to overcome enrollment barriers in recruiting pediatric subjects with primary immune deficiency (PID) disorders under Age 6 in a Phase 4 pediatric study. Models (1) characterized total immunoglobulin G (IgG) PK of Immune Globulin Intravenous [Human], 10% Liquid [IVIG] (BIVIGAM) in children and adolescents with PID; (2) quantified the impact of age and body weight; and (3) compared simulated exposure of IVIG between pediatric and adult subjects. Models were developed using pooled adult and pediatric data from 2 Phase 3/4 studies in 79 subjects (1243 IgG levels) with 3, 9, 13, and 54 subjects 2 to &lt; 6 years, 6 to &lt; 12 years, 12–16 years, and &gt; 16 years, respectively. Serum IgG PK of IVIG following intravenous infusion was characterized using a 2-compartment PK model with body weight on total IgG clearance and volumes of distribution. Model-based clearance values when estimating allometric exponents were comparable across age-group categories. Simulations predicted trough IgG levels for a virtual population of subjects for recommended IVIG 10% dosages of 300–800 mg/kg. Fixed and estimated allometric scaling allowed conservative extrapolation with simulations showing ≥ 90% of subjects would achieve trough levels ≥ 5 g/L (minimum recommended level) for a mid-range dose of 500 mg/kg. Modeling and simulation were integral in confirming achievement of clinically acceptable trough IgG levels (~7 g/L) to support supplemental PK, efficacy, and dosing recommendations for patients ≥ 2 years of age.<b>Trail Registration:</b> NCT00538915 and NCT03164967</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psp4.70275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148088442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":"15 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148086885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}