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Dose Individualisation of Antimicrobials from a Pharmacometric Standpoint: The Current Landscape. 从药物计量学角度看抗菌药物的剂量个体化:当前形势。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1007/s40265-024-02084-7
Tim Preijers, Anouk E Muller, Alan Abdulla, Brenda C M de Winter, Birgit C P Koch, Sebastiaan D T Sassen
{"title":"Dose Individualisation of Antimicrobials from a Pharmacometric Standpoint: The Current Landscape.","authors":"Tim Preijers, Anouk E Muller, Alan Abdulla, Brenda C M de Winter, Birgit C P Koch, Sebastiaan D T Sassen","doi":"10.1007/s40265-024-02084-7","DOIUrl":"10.1007/s40265-024-02084-7","url":null,"abstract":"<p><p>Successful antimicrobial therapy depends on achieving optimal drug concentrations within individual patients. Inter-patient variability in pharmacokinetics (PK) and differences in pathogen susceptibility (reflected in the minimum inhibitory concentration, [MIC]) necessitate personalised approaches. Dose individualisation strategies aim to address this challenge, improving treatment outcomes and minimising the risk of toxicity and antimicrobial resistance. Therapeutic drug monitoring (TDM), with the application of population pharmacokinetic (popPK) models, enables model-informed precision dosing (MIPD). PopPK models mathematically describe drug behaviour across populations and can be combined with patient-specific TDM data to optimise dosing regimens. The integration of machine learning (ML) techniques promises to further enhance dose individualisation by identifying complex patterns within extensive datasets. Implementing these approaches involves challenges, including rigorous model selection and validation to ensure suitability for target populations. Understanding the relationship between drug exposure and clinical outcomes is crucial, as is striking a balance between model complexity and clinical usability. Additionally, regulatory compliance, outcome measurement, and practical considerations for software implementation will be addressed. Emerging technologies, such as real-time biosensors, hold the potential for revolutionising TDM by enabling continuous monitoring, immediate and frequent dose adjustments, and near patient testing. The ongoing integration of TDM, advanced modelling techniques, and ML within the evolving digital health care landscape offers a potential for enhancing antimicrobial therapy. Careful attention to model development, validation, and ethical considerations of the applied techniques is paramount for successfully optimising antimicrobial treatment for the individual patient.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vorasidenib: First Approval. Vorasidenib:首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-10-08 DOI: 10.1007/s40265-024-02097-2
Yvette N Lamb
{"title":"Vorasidenib: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-024-02097-2","DOIUrl":"10.1007/s40265-024-02097-2","url":null,"abstract":"<p><p>Vorasidenib (VORANIGO<sup>®</sup>; Servier) is an orally administered, first-in-class, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes being developed for use in IDH-mutant diffuse glioma. Vorasidenib received its first approval on 6 August 2024, in the USA, for the treatment of adult and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection, or gross total resection. Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free survival and time to the next anticancer intervention relative to placebo. In the EU and other countries worldwide, regulatory review of vorasidenib in IDH-mutant glioma is currently underway. This article summarizes the milestones in the development of vorasidenib leading to this first approval for glioma.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy. 2 型糖尿病中的 GLP-1 受体激动剂和 SGLT2 抑制剂:多重心脏代谢效应和联合疗法的附加价值。
IF 13 1区 医学
Drugs Pub Date : 2024-09-28 DOI: 10.1007/s40265-024-02090-9
André J Scheen
{"title":"GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.","authors":"André J Scheen","doi":"10.1007/s40265-024-02090-9","DOIUrl":"https://doi.org/10.1007/s40265-024-02090-9","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven efficacy and safety in randomized clinical trials and observational real-life studies. Besides improving glucose control, reducing body weight, and lowering arterial blood pressure (surrogate endpoints), the breakthroughs were the demonstration of a significant reduction in cardiovascular and renal events in patients with type 2 diabetes at high risk. GLP-1RAs reduce events linked to atherogenic cardiovascular disease (especially ischemic stroke) and also renal outcomes (FLOW trial with semaglutide), with a limited effect on heart failure. The most striking protective effects of SGLT2is were a marked reduction in hospitalization for heart failure and a remarkable reduced progression of chronic kidney disease. These benefits have been attributed to numerous pleiotropic effects beyond glucose-lowering action. Underlying mechanisms contributing to cardiovascular and renal protection are at least partially different between GLP-1RAs (mainly anti-atherogenic and vascular effects) and SGLT2is (mainly systemic and intrarenal hemodynamic changes). Thus, patients at high risk may benefit from complementary actions when being treated with a GLP-1RA/SGLT2i combination. Such combination has proven its efficacy on surrogate endpoints. Furthermore, post hoc subgroup analyses of cardiovascular outcome trials have suggested a greater cardiorenal protection in patients treated with a combination versus either monotherapy. The benefits of a combined therapy have been confirmed in a few retrospective cohort studies. A dedicated prospective trial comparing a combined therapy versus either monotherapy is ongoing (PRECIDENTD); however, several challenges still remain, especially the higher cost of a combined therapy and the worldwide underuse of either GLP-1RAs or SGLT2is in clinical practice, even in patients at high cardiorenal risk.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials. 成人高血压患者的肾素-血管紧张素-醛固酮系统调节剂:随机对照试验的网络 Meta 分析》。
IF 13 1区 医学
Drugs Pub Date : 2024-09-23 DOI: 10.1007/s40265-024-02092-7
Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu
{"title":"Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu","doi":"10.1007/s40265-024-02092-7","DOIUrl":"https://doi.org/10.1007/s40265-024-02092-7","url":null,"abstract":"<p><strong>Background: </strong>Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.</p><p><strong>Results: </strong>We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74-0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68-0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61-13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06-1.91), hypotension (OR 2.10; 95% CI 1.02-4.34), and hyperkalemia (OR 1.99; 95% CI 1.17-3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99-3.62) when compared to placebo.</p><p><strong>Conclusions: </strong>MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.</p><p><strong>Registration: </strong>PROSPERO identifier number CRD42023405714.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Golidocitinib: First Approval 戈来西替尼首次批准
IF 11.5 1区 医学
Drugs Pub Date : 2024-09-19 DOI: 10.1007/s40265-024-02089-2
Susan J. Keam
{"title":"Golidocitinib: First Approval","authors":"Susan J. Keam","doi":"10.1007/s40265-024-02089-2","DOIUrl":"https://doi.org/10.1007/s40265-024-02089-2","url":null,"abstract":"<p>Golidocitinib (高瑞哲<sup>®</sup>) is an oral, potent, selective Janus kinase 1 (JAK1) inhibitor being developed by Dizal (Jiangsu) Pharmaceutical Co., Ltd for the treatment of cancer, including peripheral T cell lymphoma (PTCL). In June 2024, golidocitinib received conditional approval in China for the treatment of adult patients with relapsed or refractory (r/r) PTCL who have received at least one line of systemic treatment. This article summarizes the milestones in the development of golidocitinib leading to this first approval for the treatment of adults with PTCL.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now 利用四大支柱疗法减缓 2 型糖尿病患者慢性肾病的进展:行动就是现在
IF 11.5 1区 医学
Drugs Pub Date : 2024-09-11 DOI: 10.1007/s40265-024-02091-8
Panagiotis I. Georgianos, Vasilios Vaios, Theocharis Koufakis, Vassilios Liakopoulos
{"title":"Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now","authors":"Panagiotis I. Georgianos, Vasilios Vaios, Theocharis Koufakis, Vassilios Liakopoulos","doi":"10.1007/s40265-024-02091-8","DOIUrl":"https://doi.org/10.1007/s40265-024-02091-8","url":null,"abstract":"<p>Chronic kidney disease (CKD) is the most common co-morbidity in patients with type 2 diabetes (T2D) and its presence substantially amplifies the risk for premature death, adverse cardiovascular events, and faster progression of kidney injury to kidney failure. For nearly two decades, the pharmacological blockade of the renin-angiotensin-system (RAS) was the only pillar of therapy to afford cardiorenal protection in these patients. During the last 5 years, newer novel therapies have been added to our therapeutic armamentarium, offering promise for more effective management of diabetic kidney disease in the future. Large phase 3 clinical trials have demonstrated additive cardiorenal protective benefits of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors, the non-steroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, and glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide relative to placebo in patients with albuminuric CKD and T2D who are receiving standard-of-care treatment with a RAS-blocker. These therapies are likely much more effective when administered in a combined therapeutic algorithm, but the potential additive effects of combination therapy remain to be established in ongoing clinical trials. In this article, we assemble four pillars of therapy for the attenuation of residual cardiorenal risk in patients with CKD associated with T2D. We provide evidence from recent randomized trials and we discuss the concept of combined treatment for maximal cardiorenal protection in this high-risk patient population.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Elafibranor: First Approval. 更正:Elafibranor:首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-09-01 Epub Date: 2024-09-06 DOI: 10.1007/s40265-024-02088-3
Hannah A Blair
{"title":"Correction: Elafibranor: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-024-02088-3","DOIUrl":"10.1007/s40265-024-02088-3","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting DNA Damage Response Deficiency in Thoracic Cancers. 针对胸部癌症的 DNA 损伤反应缺陷。
IF 13 1区 医学
Drugs Pub Date : 2024-09-01 Epub Date: 2024-07-13 DOI: 10.1007/s40265-024-02066-9
Aleksandra Bzura, Jake B Spicer, Sean Dulloo, Timothy A Yap, Dean A Fennell
{"title":"Targeting DNA Damage Response Deficiency in Thoracic Cancers.","authors":"Aleksandra Bzura, Jake B Spicer, Sean Dulloo, Timothy A Yap, Dean A Fennell","doi":"10.1007/s40265-024-02066-9","DOIUrl":"10.1007/s40265-024-02066-9","url":null,"abstract":"<p><p>Thoracic cancers comprise non-small cell lung cancers (NSCLCs), small cell lung cancers (SCLCs) and malignant pleural mesotheliomas (MPM). Collectively, they account for the highest rate of death from malignancy worldwide. Genomic instability is a universal feature of cancer, which fuels mutations and tumour evolution. Deficiencies in DNA damage response (DDR) genes amplify genomic instability. Homologous recombination deficiency (HRD), resulting from BRCA1/BRCA2 inactivation, is exploited for therapeutic synthetic lethality with poly-ADP ribose polymerase (PARP) inhibitors in breast and ovarian cancers, as well as in prostate and pancreatic cancers. However, DDR deficiency and its therapeutic implications are less well established in thoracic cancers. Emerging evidence suggests that a subset of thoracic cancers may harbour DDR deficiency and may, thus, be effectively targeted with DDR agents. Here, we review the current evidence surrounding DDR in thoracic cancers and discuss the challenges and promise for achieving clinical benefit with such therapeutics.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imetelstat: First Approval. 伊美司他首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-09-01 Epub Date: 2024-08-20 DOI: 10.1007/s40265-024-02080-x
Susan J Keam
{"title":"Imetelstat: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-024-02080-x","DOIUrl":"10.1007/s40265-024-02080-x","url":null,"abstract":"<p><p>Imetelstat (RYTELO™), an oligonucleotide telomerase inhibitor, is being developed by Geron Corporation for the treatment of myeloid hematologic malignancies. In June 2024, imetelstat was approved in the USA for use in adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA). This article summarizes the milestones in the development of imetelstat leading to this first approval for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ivonescimab: First Approval. Ivonescimab:首次获批。
IF 13 1区 医学
Drugs Pub Date : 2024-09-01 Epub Date: 2024-07-29 DOI: 10.1007/s40265-024-02073-w
Sohita Dhillon
{"title":"Ivonescimab: First Approval.","authors":"Sohita Dhillon","doi":"10.1007/s40265-024-02073-w","DOIUrl":"10.1007/s40265-024-02073-w","url":null,"abstract":"<p><p>Ivonescimab (<sup>®</sup>) is a first-in-class, humanized, tetravalent bispecific monoclonal antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF)-A being developed by Akeso Biopharma for the treatment of non-small cell lung cancer (NSCLC) and other solid tumours, including breast cancer, liver cancer and gastric cancer. Ivonescimab simultaneously blocks the binding of PD-1 to its ligand (PD-L1), thereby relieving PD-1/PD-L1-mediated immunosuppression, and blocks the binding of VEGF-A to its receptor (VEGFR2), thus blocking tumour angiogenesis in the tumour microenvironment. In May 2024, ivonescimab, in combination with pemetrexed and carboplatin, received its first approval in China for the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed after tyrosine kinase inhibitor (TKI) therapy. Clinical studies of ivonescimab are underway in multiple countries worldwide. This article summarizes the milestones in the development of ivonescimab leading to this first approval for EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed after TKI therapy.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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