Clinical Pharmacology & Therapeutics最新文献

{"title":"Reply to \"Chat GPT and the Challenges to Detect Potential Drug-Drug Interactions Related to QT Prolongation\".","authors":"Thorsten Bischof, Valentin Al Jalali, Markus Zeitlinger, Anselm Jorda, Michelle Hana, Karla-Nikita Singeorzan, Nikolaus Riesenhuber, Gunar Stemer, Christian Schoergenhofer","doi":"10.1002/cpt.3662","DOIUrl":"https://doi.org/10.1002/cpt.3662","url":null,"abstract":"","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762751","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":"Identification and Clinical Evaluation of Potential Biomarkers for Breast Cancer Resistance Protein (BCRP/ABCG2).","authors":"Andrew M Riselli, Sook Wah Yee, Jia Yang, Claire M Brett, Kelsey Trumbach, Xujia Zhou, Renmeng Liu, Xiaomin Liang, Yurong Lai, Runlan Huo, Yongjun Xue, Hong Shen, Lei Zhang, Xinning Yang, Qi Liu, Shiew-Mei Huang, Kathleen M Giacomini","doi":"10.1002/cpt.3657","DOIUrl":"https://doi.org/10.1002/cpt.3657","url":null,"abstract":"<p><p>Clinical inhibition and genetic variation of the Breast Cancer Resistance Protein (BCRP/ABCG2) efflux transporter can significantly influence drug exposure, highlighting the need for reliable BCRP functional biomarkers. This study aimed to identify and evaluate biomarkers predictive of BCRP function in humans. A comprehensive analysis of metabolomic genome-wide association studies (mGWAS) was conducted to discover potential BCRP biomarkers, followed by evaluation in in vitro transporter assays and a clinical drug-drug interaction (DDI) study. Across multiple mGWAS datasets, plasma concentrations of three herbicide derivatives-4-hydroxychlorothalonil (4HC), 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (BCDBA), and 3,5-dichloro-2,6-dihydroxybenzoic acid (DCDBA)-were significantly elevated (P < 5E-8) in individuals carrying reduced function ABCG2 polymorphisms. These compounds were confirmed as novel BCRP substrates via transporter uptake assays and selected for clinical evaluation alongside riboflavin, a known BCRP substrate and potential BCRP biomarker. In a DDI study with 11 healthy subjects, eltrombopag, a BCRP inhibitor, increased rosuvastatin concentrations by approximately twofold (P = 0.002). No significant changes in the plasma concentrations of organic anion transporting polypeptide 1B (OATP1B) biomarkers (CP-I and CP-III) or potential BCRP biomarkers (4HC, BCDBA, DCDBA, or riboflavin) were observed. Notably, two subjects were heterozygous carriers for the ABCG2 p.Q141K variant and exhibited significantly higher baseline concentrations of 4HC (P = 0.004) and BCDBA (P = 0.0003), consistent with reduced BCRP function. These findings suggest that 4HC and BCDBA are promising biomarkers for baseline BCRP function in specific populations, such as those harboring reduced function genetic polymorphisms, but do not appear suitable for detecting acute BCRP inhibition.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762750","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":"Chat GPT and the Challenges to Detect Potential Drug-Drug Interactions Related to QT Prolongation.","authors":"Emanuel Raschi, Elisabetta Poluzzi, Fabrizio De Ponti","doi":"10.1002/cpt.3660","DOIUrl":"https://doi.org/10.1002/cpt.3660","url":null,"abstract":"","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750659","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":"Use of Real-World Claims Data to Assess the Prevalence of Concomitant Medications to Inform Drug-Drug Interaction Risk in Target Patient Populations.","authors":"Alice S Tang, Logan Brooks, Denise M Boudreau, Pascal Chanu, Amita Joshi, Bianca Vora, Rui Zhu","doi":"10.1002/cpt.3652","DOIUrl":"https://doi.org/10.1002/cpt.3652","url":null,"abstract":"<p><p>A common issue in clinical drug development involves drug-drug interactions (DDI) that may lead to altered drug exposure and subsequent altered safety and efficacy of an investigational drug or concomitant medications (conmeds) in the target patient population. The drug development pipeline therefore involves DDI risk assessment of the investigational drug based on in vitro studies, in silico modeling, and clinical trials. Real-world data (RWD), particularly claims databases with reliable information on pharmacy dispensing, provide an opportunity to understand conmeds usage in the target indication in a real-world setting as one approach to assess potential DDI risk. We describe two cases of characterizing DDI-related conmeds usage with a large closed US-based claims database, IQVIA PharMetrics® Plus, and identified potential DDI risk for multiple sclerosis and hormone receptor-positive breast cancer. For example, prevalent and chronic use of statins (atorvastatin and simvastatin), which are CYP3A4 substrates, were identified among both disease cases. Further examples, limitations, and future directions are also discussed. These insights can therefore help augment decision-making during clinical drug research and development.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762752","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":"First-in-Human Single and Multiple Ascending Dose Studies of Balinatunfib, a Small Molecule Inhibitor of TNFR1 Signaling in Healthy Participants.","authors":"Nassr Nassr, Faiza Rharbaoui, Dietmar Weitz, Johann Gassenhuber, Markus Rehberg, Markus Kohlmann, Fabienne Schumacher, Amel Lahmar, Andreas Kovar, Laurent Perrin, Frank-Dietrich Wagner, Maria Wiekowski, Mai Anh Nguyen","doi":"10.1002/cpt.3655","DOIUrl":"https://doi.org/10.1002/cpt.3655","url":null,"abstract":"<p><p>Oral small molecule inhibitors of tumor necrosis factor alpha (TNFα) are emerging as attractive therapeutic agents for the treatment of various autoimmune diseases. Balinatunfib (SAR441566), a novel oral inhibitor of tumor necrosis factor receptor 1 (TNFR1) signaling, changes the configuration of the soluble TNFα (sTNFα) trimer and prevents its heterotrimerization with TNFR1 but not TNFR2, thereby blocking TNFR1 signaling. Herein, we report the results from a first-in-human (FIH) study that evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) following single ascending doses (SAD) and multiple ascending doses (MAD) of balinatunfib in healthy male participants. Single (5-600 mg) and multiple (100-600 mg total daily dose for up to 14 days) oral doses of balinatunfib were well-tolerated in all participants. Consistent PK data were obtained across the studies, with a median t_max of 2.5-5 hours, a mean terminal half-life of 22-30 hours, and a time to steady state of 5-6 days. A supra-proportional exposure increase was observed in both SAD and MAD studies, which was less pronounced at doses ≥ 180 mg. Food had no relevant effects on the PK characteristics of balinatunfib. As the main PD read-out, complete TNFα occupancy was shown at all tested time points after the treatment started. Balinatunfib, as the first clinically tested oral TNFR1 signal inhibitor, demonstrated a good safety profile along with favorable PK/PD characteristics that allowed both once and twice daily dosing, confirming a successful preclinical-to-clinical translation and guiding dose selection for further clinical efficacy studies.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750661","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":"Frequency and Nature of Generic \"Design Around\" of Brand-Name Patents in the United States.","authors":"Janet Freilich, Aaron S Kesselheim","doi":"10.1002/cpt.3659","DOIUrl":"https://doi.org/10.1002/cpt.3659","url":null,"abstract":"<p><p>Brand-name drug manufacturers commonly receive numerous patents covering their products to try to block price-lowering competition from generic manufacturers. However, under US law, generic manufacturers can develop clinically interchangeable versions that avoid some brand-name drug patents by creating new formulations that \"design around\" existing patents or skinny labels that do not include patented methods of use. Since generics nearly always lead brand-name manufacturers to file lawsuits, we sought to characterize the types of generic design around strategies by examining patent infringement litigation from 2000 to 2023. We used Lex Machina to identify cases and manually reviewed them to determine the drug involved and how generics designed around the patent. The cohort consisted of 153 cases involving 114 products. Twenty-eight cases (18%, 95% CI: 13-25) involved changes to how the product was used, including skinny labeling. The other 125 cases (82%, 95% CI: 75-87) involved alterations to the physical product or packaging. The most common physical change was to the formulation of the product (73 cases (48%, 95% CI: 40-56)). Changes to the active ingredient (18 cases (12%, 95% CI: 8-18)) or manufacturing process (15 cases (10%, 95% CI: 6-16)) were also common. Tablets and capsules were overrepresented in our cohort as compared to all approved drugs (the June 2023 Orange Book had 41% tablets and capsules, 95% CI: 39%-42%, P < 0.001), as were extended or delayed-release formulations (making up 23/57 (40% [95% CI: 29-53]) of the tablet or capsule products in our cohort vs. 324/886 in the Orange Book, 15% [95% CI: 14-17], P < 0.001).</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727295","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":"Hepatic Impairment and the Differential Effects on Drug Clearance Mechanisms: Analysis of Pharmacokinetic Changes in Disease State.","authors":"Lloyd Wei Tat Tang, Manthena V S Varma","doi":"10.1002/cpt.3643","DOIUrl":"https://doi.org/10.1002/cpt.3643","url":null,"abstract":"<p><p>Liver dysfunction can impact drug disposition and may lead to altered pharmacokinetics (PK). Here, we characterized the modulation in the in vivo activity of drug metabolizing enzymes and membrane transporters in populations with varying degrees of hepatic impairment (HI). Analysis of a well-curated dataset of 357 drugs across a range of clearance mechanisms suggested that the PK of OATP1B substrates is markedly altered by HI, while changes associated with other clearance mechanisms are relatively small. Of the metabolizing enzymes, CYP1A2 and UGTs were found to be most sensitive to disease progression, while PK changes of CYP2C/CYP2D6/CYP3A substrates were relatively less impacted. The median estimated loss in OATP1B and CYP3A activities, after adjusting for alterations in plasma protein binding, was found to be about 90% (n = 18) and 57% (n = 53) in severe HI, compared to healthy control, respectively. Large variability of AUC change within each HI category was present for CYP3A substrates compared to OATP1B substrates. Interestingly, exposure of drugs secreted in bile was not affected, while a statistically significant (P < 0.001) increase in AUC was noted for renally cleared drugs in severe HI. For CYP3A substrates, linear relationships (P < 0.001) between disease-induced AUC changes and AUC changes perpetrated by CYP3A probe inhibitor (ketoconazole/itraconazole) and the hepatic extraction ratio were evident. Similarly, there was a significant correlation between AUC changes following OATP1B inhibitor (rifampicin) and in the disease state for OATP1B substrates. Collectively, this meta-analysis suggests differential modulation in various clearance mechanisms and provides quantitation of the progressive reduction in metabolic/transport activity in HI.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707912","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 Model-Informed Drug Development on Drug Development Cycle Times and Clinical Trial Cost.","authors":"Vaishali Sahasrabudhe, Timothy Nicholas, Gianluca Nucci, Cynthia J Musante, Brian Corrigan","doi":"10.1002/cpt.3636","DOIUrl":"https://doi.org/10.1002/cpt.3636","url":null,"abstract":"<p><p>Model-informed drug development (MIDD) integrates data to quantify benefit/risk informing objective drug discovery and development decisions. An additional critical benefit of MIDD is postulated to be improvement in trial and program efficiencies. While the application of MIDD has grown, there have been no clear examples across programs to demonstrate its value at the portfolio level. This manuscript offers a methodology and examples to demonstrate MIDD value in terms of time and cost savings. We utilized an algorithm to estimate savings based on MIDD-related activities at each stage of development across the entire drug development portfolio during a typical year between 2021 and 2023. This algorithm, although company-specific, demonstrated general applicability across several programs of the portfolio. Overall, the use of MIDD yielded annualized average savings of approximately 10 months of cycle time and $5 million per program. Systematic application of MIDD approaches yielded significant time and cost savings across the drug development portfolio in addition to informing data-driven decisions. Increased utilization of MIDD approaches is a driver for improving drug development efficiency.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707914","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 Age and Factor Xa Inhibitor Concentrations on Bleeding Risk in Patients with Atrial Fibrillation.","authors":"Shin-Yi Lin, Yen-Bing Liu, Li-Ting Ho, Ching-Hua Kuo, Yu-Fong Peng, Chih-Fen Huang, Sung-Chun Tang, Jiann-Shing Jeng","doi":"10.1002/cpt.3654","DOIUrl":"https://doi.org/10.1002/cpt.3654","url":null,"abstract":"<p><p>This study aimed to analyze differences in the exposure-response relationship for factor Xa inhibitors (FXaI) between patients aged ≥ 80 and < 80 years. Patients with atrial fibrillation (AF) taking rivaroxaban, apixaban, or edoxaban were enrolled, and a single steady-state trough concentration was measured. FXaI concentrations were compared with the expected range reported in clinical trials to define high or low drug levels. The primary outcome was major bleeding, and the secondary outcome was ischemic stroke or transient ischemic attack (IS/TIA). From 2016 to 2023, 1,037 patients aged from 30 to 105 years were enrolled (average, 75.4 ± 10.0 years; 33.8% were aged ≥ 80 years). During a median follow-up of 2.35 years, 48 major bleeding events and 32 IS/TIA events were observed. Although drug concentrations were similar between the two age groups, those aged ≥ 80 years with high FXaI levels experienced a greater increase in major bleeding risk compared to those aged < 80 years with high levels (aHR 6.47 [2.07, 20.28] vs. 3.45 [1.15, 10.30]). Additionally, patients aged ≥ 80 years without elevated FXaI levels also had a higher risk of major bleeding compared to those aged < 80 years without elevated levels (aHR 2.39 [1.20, 4.76]). While low FXaI concentrations were associated with IS/TIA, the risk was not significantly different across age groups. In conclusion, despite similar FXaI concentrations, patients aged ≥ 80 years have a higher baseline risk of major bleeding and experience a greater increase in bleeding risk at high drug levels compared to those aged < 80 years.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699260","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":"Bench to Budget: Integrated Evidence Generation for Medications","authors":"Sebastian Schneeweiss,&nbsp;Rebecca Miksad","doi":"10.1002/cpt.3603","DOIUrl":"10.1002/cpt.3603","url":null,"abstract":"&lt;p&gt;“Bench to bedside” research has long driven evidence generation for drug development. However, modern healthcare demands a similar innovation feedback loop between medical science and population-level evidence—what we term “Bench to Budget.”&lt;/p&gt;&lt;p&gt;Population-level healthcare delivery and budget considerations are often neglected in early research discussions. Yet, the ultimate impact and value of any medical intervention depends on access and real-world effectiveness. Clinical trial efficacy data may not always be available for critical medical scenarios such as safety in special populations (e.g., patients with renal failure). Over the past decade, pharmaceutical companies, regulators, and health technology assessment (HTA) agencies have increasingly considered real-world evidence (RWE) to fill these gaps. We advocate for explicit discussions on best practices, barriers to implementation, and methods for generating and integrating evidence along the full bench-to-bedside-to-budget drug development pathway.&lt;/p&gt;&lt;p&gt;Modern medications, and our understanding of how to maximize their benefits and minimize their harms, are remarkable achievements. From bench research to payer budget, decision-making that impacts human health is often required in settings of uncertainty. This &lt;i&gt;Clinical Pharmacology &amp; Therapeutics&lt;/i&gt; (&lt;i&gt;CPT&lt;/i&gt;; Figure 1) “Bench to Budget” special issue explores the promise and perils of leveraging multiple sources and types of evidence in a holistic approach to developing, using, and paying for new medications.&lt;/p&gt;&lt;p&gt;Grueger and Srikant&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; describe an evidence-planning process that considers the many evidence needs of the stakeholders along a drug's life cycle and how they can be satisfied by using adequate data sources and scientific approaches. The resulting integrated evidence plans help ensure that no unforeseen evidence gaps will appear during the development, launch, and post-marketing process and lead to delayed access to medications. Such plans will identify efficiencies by planning mutually supporting knowledge transfers between research programs and by building pipelines of research studies that build on each other and share resources (see Figure 2 as an illustrative example).&lt;/p&gt;&lt;p&gt;Within the appealing framework of a longitudinally integrated evidence generation, Chen &lt;i&gt;et al&lt;/i&gt;.,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Yavuz &lt;i&gt;et al&lt;/i&gt;.,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Jiang &lt;i&gt;et al&lt;/i&gt;.,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Baumfeld Andre &lt;i&gt;et al&lt;/i&gt;.,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; and Bhattacharya &lt;i&gt;et al&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; address various conceptual and statistical challenges in managing and synthesizing evidence across scientific approaches during the drug-development lifecycle. Kent &lt;i&gt;et al&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; focuses on orchestrating evidence generation after the approval of medications. Bischof &lt;i&gt;et al&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; and Wilczok and Zhavoronkov&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; explore th","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"117 4","pages":"869-871"},"PeriodicalIF":6.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.3603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}