Expert opinion on drug metabolism & toxicology最新文献_第6页

Physiologically based pharmacokinetic modeling in obesity: applications and challenges. 基于生理学的肥胖症药物动力学模型：应用与挑战。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-08-12 DOI: 10.1080/17425255.2024.2388690

Ruwei Yang, Qin Ding, Junjie Ding, Liyong Zhu, Qi Pei

{"title":"Physiologically based pharmacokinetic modeling in obesity: applications and challenges.","authors":"Ruwei Yang, Qin Ding, Junjie Ding, Liyong Zhu, Qi Pei","doi":"10.1080/17425255.2024.2388690","DOIUrl":"10.1080/17425255.2024.2388690","url":null,"abstract":"Introduction: Rising global obesity rates pose a threat to people's health. Obesity causes a series of pathophysiologic changes, making the response of patients with obesity to drugs different from that of nonobese, thus affecting the treatment efficacy and even leading to adverse events. Therefore, understanding obesity's effects on pharmacokinetics is essential for the rational use of drugs in patients with obesity.Areas covered: Articles related to physiologically based pharmacokinetic (PBPK) modeling in patients with obesity from inception to October 2023 were searched in PubMed, Embase, Web of Science and the Cochrane Library. This review outlines PBPK modeling applications in exploring factors influencing obesity's effects on pharmacokinetics, guiding clinical drug development and evaluating and optimizing clinical use of drugs in patients with obesity.Expert opinion: Obesity-induced pathophysiologic alterations impact drug pharmacokinetics and drug-drug interactions (DDIs), altering drug exposure. However, there is a lack of universal body size indices or quantitative pharmacology models to predict the optimal for the patients with obesity. Therefore, dosage regimens for patients with obesity must consider individual physiological and biochemical information, and clinically individualize therapeutic drug monitoring for highly variable drugs to ensure effective drug dosing and avoid adverse effects.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"805-816"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An update on oral antiplatelet drug interactions with proton pump inhibitors: what are the risks? 口服抗血小板药物与质子泵抑制剂相互作用的最新进展：有哪些风险？

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-07-15 DOI: 10.1080/17425255.2024.2378888

Georges Jourdi, Jean-Sébastien Hulot, Pascale Gaussem

{"title":"An update on oral antiplatelet drug interactions with proton pump inhibitors: what are the risks?","authors":"Georges Jourdi, Jean-Sébastien Hulot, Pascale Gaussem","doi":"10.1080/17425255.2024.2378888","DOIUrl":"10.1080/17425255.2024.2378888","url":null,"abstract":"Introduction: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel.Areas covered: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes. Therefore, we aimed to summarize the evidence for the widespread combined use of oral antiplatelet drugs and PPIs, to outline the current evidence supporting or opposing drug-drug interaction, and to discuss the clinical implications of such interactions.Expert opinion: A large body of evidence describes the PK/PD interaction of antiplatelet drugs with PPIs and its potential role in increasing clinical cardiovascular adverse events, but no solid clinical data have confirmed these effects. In the light of the published studies, there seems to be no restriction on the choice of PPI with aspirin, prasugrel, and/or ticagrelor. The choice of a PPI with no (or minimal) interference with the hepatic cytochrome P450 2C19 is preferred in patients receiving clopidogrel.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"749-764"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics of aspirin: evaluating shortcomings in the literature. 阿司匹林的药代动力学：评估文献中的不足之处。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-08-02 DOI: 10.1080/17425255.2024.2386368

Jacobus Lukas Visagie, Gabriel Sanjo Aruwajoye, Rencia van der Sluis

{"title":"Pharmacokinetics of aspirin: evaluating shortcomings in the literature.","authors":"Jacobus Lukas Visagie, Gabriel Sanjo Aruwajoye, Rencia van der Sluis","doi":"10.1080/17425255.2024.2386368","DOIUrl":"10.1080/17425255.2024.2386368","url":null,"abstract":"Introduction: Aspirin is known for its therapeutic benefits in preventing strokes and relieving pain. However, it is toxic to some individuals, and the biological mechanisms causing toxicity are unknown. Limited literature is available on the role of glycine conjugation as the principal pathway in aspirin detoxification. Previous studies have quantified this two-step enzyme reaction as a singular enzymatic process. Consequently, the individual contributions of these enzymes to the kinetics remain unclear.Areas covered: This review summarized the available information on the pharmacokinetics and detoxification of aspirin by the glycine conjugation pathway. Literature searches were conducted using Google Scholar and the academic journal databases accessible through the North-West University Library. Furthermore, the factors affecting interindividual variation in aspirin metabolism and what is known regarding aspirin toxicity were discussed.Expert opinion: The greatest drawback in understanding the pharmacokinetics of aspirin is the limited information available on the substrate preference of the xenobiotic ligase (ACSM) responsible for activating salicylate to salicyl-CoA. Furthermore, previous pharmacokinetic studies did not consider the contribution of other substrates from the diet or genetic variants, to the detoxification rate of glycine conjugation. Impaired glycine conjugation might contribute to adverse health effects seen in Reye's syndrome and cancer.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"727-740"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. 调查帕塞呋尼尔药代动力学和药物间相互作用的临床前和临床研究概述。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-07-09 DOI: 10.1080/17425255.2024.2373108

Hugues Chanteux, Merran MacPherson, Hester Kramer, Christian Otoul, Takuya Okagaki, Chiara Rospo, Steven De Bruyn, Mark Watling, Massimo Bani, David Sciberras

{"title":"Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil.","authors":"Hugues Chanteux, Merran MacPherson, Hester Kramer, Christian Otoul, Takuya Okagaki, Chiara Rospo, Steven De Bruyn, Mark Watling, Massimo Bani, David Sciberras","doi":"10.1080/17425255.2024.2373108","DOIUrl":"10.1080/17425255.2024.2373108","url":null,"abstract":"Background: Padsevonil is an antiseizure medication candidate intended to benefit patients with drug-resistant epilepsy. Our investigations aimed at characterizing pharmacokinetics and drug-drug interaction (DDI) profile of padsevonil.Research design and methods: An overview of preclinical and clinical pharmacology studies conducted during padsevonil development is provided.Results: In preclinical studies, cytochrome (CYP) 3A4 was identified as the main P450 isoform involved in padsevonil metabolism, with potential minor contribution from CYP2C19. Padsevonil was shown to be a time-dependent CYP2C19-inhibitor, weak CYP3A4-inducer, weak inhibitor of P-gp/OCT1/MATE2-K, and potent OCT2-inhibitor. Initial clinical pharmacology studies in healthy participants showed that padsevonil had (i) good absorption, (ii) clearance mediated mainly by metabolism, and (iii) time-dependent kinetics. A study in genotyped participants confirmed the role of CYP2C19 in clearance and time-dependent kinetics; the major contribution of CYP3A4 was confirmed in DDI studies with CYP3A4-inducers (carbamazepine, oxcarbazepine) and -inhibitor (erythromycin). Padsevonil did not affect pharmacokinetics of valproate/lamotrigine/levetiracetam/oxcarbazepine or oral contraceptives. In a cocktail clinical study, padsevonil showed moderate CYP2C19 inhibition (omeprazole) and weak CYP3A4 induction (oral midazolam). No specific effects on CYP1A2 (caffeine), CYP2C9 (S-warfarin), and CYP2D6 (dextromethorphan) were observed.Conclusions: The studies presented helped in understanding padsevonil disposition and risks of DDIs, which would inform dosing and prescribing.Clinical trial registration: https://www.clinicaltrials.gov identifiers are NCT04131517, NCT03480243, NCT03695094, NCT04075409.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"841-855"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating in VigiBase over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia. 根据文献资料，在 VigiBase® 中调查了 6000 多例氯氮平治疗患者的肺炎病例：重点关注高致死率以及与吸入性肺炎的关联。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1080/17425255.2024.2373111

Jose de Leon, Can-Jun Ruan, Georgios Schoretsanitis, Alejandro G Villasante-Tezanos, Edoardo Spina, Emilio J Sanz, Moisés Betancort, Carlos De Las Cuevas

{"title":"Investigating in VigiBase over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia.","authors":"Jose de Leon, Can-Jun Ruan, Georgios Schoretsanitis, Alejandro G Villasante-Tezanos, Edoardo Spina, Emilio J Sanz, Moisés Betancort, Carlos De Las Cuevas","doi":"10.1080/17425255.2024.2373111","DOIUrl":"10.1080/17425255.2024.2373111","url":null,"abstract":"Background: The literature associates clozapine with pneumonia/aspiration pneumonia.Research design and methods: The international pharmacovigilance database (VigiBase™) uses the information component (IC) as statistical signal. VigiBase clozapine reports were analyzed for pneumonia/aspiration pneumonia from introduction to 10 May 2023.Results: There were 6392 cases of all types of pneumonia (5572 cases of pneumonia, 775 of aspiration pneumonia, and 45 combined). The IC was 3.52 for aspiration pneumonia, introduced as a VigiBase label in 2003, and 1.91 for pneumonia. Patients were reclassified as 3628 with no signs of aspiration and 1533 with signs. Signs of aspiration were strongly associated with some co-medications: olanzapine, odds ratio (OR) = 23.8, 95% confidence interval (CI), 14.9-38.0; risperidone OR = 18.6, CI, 11.4-30.4; valproic acid, OR = 5.5, CI, 4.5-6.6; and benzodiazepines OR = 5.5, CI, 4.5-6.6. In 2415 cases with completed data, fatal outcomes made up 45% (signs of aspiration made no difference), but there was wide variability from 0% (females <45 years of age; duration ≤30 days) to 76% (males >64 years of age; duration >1 year). During the first week, pneumonia was associated with 1) very high titration doses, 2) very small doses in Parkinson's disease, and 3) Japan vs other countries.Conclusions: In clozapine-treated patients: 1) at least 30% of pneumonia cases may be aspiration pneumonia, 2) stopping some co-medications may decrease the risk of aspiration pneumonia, 3) average lethality in pneumonia was 45% but may be around 75% in geriatric patients with long-term treatment, and 4) safer titrations may sometimes require 5-mg tablets.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"857-871"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proposing a novel approach for the long-term use of monthly paliperidone palmitate: adjusting injection dose versus adjusting injection interval. 提出一种长期每月使用帕潘立酮棕榈酸酯的新方法：调整注射剂量与调整注射间隔。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-08-01 Epub Date: 2024-07-12 DOI: 10.1080/17425255.2024.2378896

Sergio Sánchez-Alonso, Enrique Baca-García, Santiago Ovejero, Jose de Leon, Georgios Schoretsanitis

引用次数: 0

In-depth mechanistic analysis including high-throughput RNA sequencing in the prediction of functional and structural cardiotoxicants using hiPSC cardiomyocytes. 深入的机制分析，包括使用hiPSC心肌细胞预测功能和结构心脏毒物的高通量RNA测序。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-07-01 Epub Date: 2023-11-23 DOI: 10.1080/17425255.2023.2273378

Alicia Rosell-Hidalgo, Christopher Bruhn, Emma Shardlow, Ryan Barton, Stephanie Ryder, Timur Samatov, Alexandra Hackmann, Gerald Ryan Aquino, Micael Fernandes Dos Reis, Vladimir Galatenko, Ruediger Fritsch, Cord Dohrmann, Paul A Walker

{"title":"In-depth mechanistic analysis including high-throughput RNA sequencing in the prediction of functional and structural cardiotoxicants using hiPSC cardiomyocytes.","authors":"Alicia Rosell-Hidalgo, Christopher Bruhn, Emma Shardlow, Ryan Barton, Stephanie Ryder, Timur Samatov, Alexandra Hackmann, Gerald Ryan Aquino, Micael Fernandes Dos Reis, Vladimir Galatenko, Ruediger Fritsch, Cord Dohrmann, Paul A Walker","doi":"10.1080/17425255.2023.2273378","DOIUrl":"10.1080/17425255.2023.2273378","url":null,"abstract":"Background: Cardiotoxicity remains one of the most reported adverse drug reactions that lead to drug attrition during pre-clinical and clinical drug development. Drug-induced cardiotoxicity may develop as a functional change in cardiac electrophysiology (acute alteration of the mechanical function of the myocardium) and/or as a structural change, resulting in loss of viability and morphological damage to cardiac tissue.Research design and methods: Non-clinical models with better predictive value need to be established to improve cardiac safety pharmacology. To this end, high-throughput RNA sequencing (ScreenSeq) was combined with high-content imaging (HCI) and Ca2+ transience (CaT) to analyze compound-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).Results: Analysis of hiPSC-CMs treated with 33 cardiotoxicants and 9 non-cardiotoxicants of mixed therapeutic indications facilitated compound clustering by mechanism of action, scoring of pathway activities related to cardiomyocyte contractility, mitochondrial integrity, metabolic state, diverse stress responses and the prediction of cardiotoxicity risk. The combination of ScreenSeq, HCI and CaT provided a high cardiotoxicity prediction performance with 89% specificity, 91% sensitivity and 90% accuracy.Conclusions: Overall, this study introduces mechanism-driven risk assessment approach combining structural, functional and molecular high-throughput methods for pre-clinical risk assessment of novel compounds.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"685-707"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioactivity descriptors for in vivo toxicity prediction: now and the future. 用于体内毒性预测的生物活性描述符：现在与未来。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-07-01 Epub Date: 2024-04-04 DOI: 10.1080/17425255.2024.2334308

Palle Helmke, Barbara Füzi, Gerhard F Ecker

引用次数: 0

Investigative analysis of blood-brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models. 利用预测性计算模型对电子尼古丁给药系统（电子烟）化学品的血脑屏障穿透潜力进行调查分析。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-07-01 Epub Date: 2024-06-21 DOI: 10.1080/17425255.2024.2366385

Kimberly Stratford, Jueichuan Connie Kang, Sheila M Healy, Zheng Tu, Luis G Valerio

{"title":"Investigative analysis of blood-brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models.","authors":"Kimberly Stratford, Jueichuan Connie Kang, Sheila M Healy, Zheng Tu, Luis G Valerio","doi":"10.1080/17425255.2024.2366385","DOIUrl":"10.1080/17425255.2024.2366385","url":null,"abstract":"Introduction: Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults.Areas covered: Using chemoinformatic computational models, chemicals (including flavors) documented to be present in ENDS were compared to known neuroactive compounds to predict the blood-brain barrier (BBB) penetration potential, central nervous system (CNS) activity, and their structural similarities. The literature search used PubMed/Google Scholar, through September 2023, to identify individual chemicals in ENDS and neuroactive compounds.The results show that ENDS chemicals in this study contain >60% structural similarity to neuroactive compounds based on chemical fingerprint similarity analyses. The majority of ENDS chemicals we studied were predicted to cross the BBB, with approximately 60% confidence, and were also predicted to have CNS activity; those not predicted to passively diffuse through the BBB may be actively transported through the BBB to elicit CNS impacts, although it is currently unknown.Expert opinion: In lieu of in vitro and in vivo testing, this study screens ENDS chemicals for potential CNS activity and predicts BBB penetration potential using computer-based models, allowing for prioritization for further study and potential early identification of CNS toxicity.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"647-663"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning and deep learning approaches for enhanced prediction of hERG blockade: a comprehensive QSAR modeling study. 增强 hERG 阻断预测的机器学习和深度学习方法：一项全面的 QSAR 建模研究。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-07-01 Epub Date: 2024-07-10 DOI: 10.1080/17425255.2024.2377593

Jie Liu, Md Kamrul Hasan Khan, Wenjing Guo, Fan Dong, Weigong Ge, Chaoyang Zhang, Ping Gong, Tucker A Patterson, Huixiao Hong

{"title":"Machine learning and deep learning approaches for enhanced prediction of hERG blockade: a comprehensive QSAR modeling study.","authors":"Jie Liu, Md Kamrul Hasan Khan, Wenjing Guo, Fan Dong, Weigong Ge, Chaoyang Zhang, Ping Gong, Tucker A Patterson, Huixiao Hong","doi":"10.1080/17425255.2024.2377593","DOIUrl":"10.1080/17425255.2024.2377593","url":null,"abstract":"Background: Cardiotoxicity is a major cause of drug withdrawal. The hERG channel, regulating ion flow, is pivotal for heart and nervous system function. Its blockade is a concern in drug development. Predicting hERG blockade is essential for identifying cardiac safety issues. Various QSAR models exist, but their performance varies. Ongoing improvements show promise, necessitating continued efforts to enhance accuracy using emerging deep learning algorithms in predicting potential hERG blockade.Study design and method: Using a large training dataset, six individual QSAR models were developed. Additionally, three ensemble models were constructed. All models were evaluated using 10-fold cross-validations and two external datasets.Results: The 10-fold cross-validations resulted in Mathews correlation coefficient (MCC) values from 0.682 to 0.730, surpassing the best-reported model on the same dataset (0.689). External validations yielded MCC values from 0.520 to 0.715 for the first dataset, exceeding those of previously reported models (0-0.599). For the second dataset, MCC values fell between 0.025 and 0.215, aligning with those of reported models (0.112-0.220).Conclusions: The developed models can assist the pharmaceutical industry and regulatory agencies in predicting hERG blockage activity, thereby enhancing safety assessments and reducing the risk of adverse cardiac events associated with new drug candidates.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"665-684"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141539123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0