Antimicrobial Agents and Chemotherapy最新文献

{"title":"Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers.","authors":"Naoyuki Miyashita, Yasushi Nakamori, Makoto Ogata, Naoki Fukuda, Akihisa Yamura, Tomoki Ito","doi":"10.1128/aac.01064-24","DOIUrl":"https://doi.org/10.1128/aac.01064-24","url":null,"abstract":"<p><p>We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103773","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":"The fungal natural product fusidic acid demonstrates potent activity against <i>Mycoplasma genitalium</i>.","authors":"Gwendolyn E Wood, Jin Woo Lee, Thilini Peramuna, Karen L Wendt, Caroline M Kim, Laarni Kendra T Aguila, Claire L Calderon, Robert H Cichewicz","doi":"10.1128/aac.01006-24","DOIUrl":"https://doi.org/10.1128/aac.01006-24","url":null,"abstract":"<p><p>Antimicrobial resistance is extremely common in <i>Mycoplasma genitalium</i>, a frequent cause of urethritis in men and cervicitis, vaginitis, and pelvic inflammatory disease in women. Treatment of <i>M. genitalium</i> infections is difficult due to intrinsic and acquired resistance to many antibiotic classes. We undertook a program to identify novel antimicrobials with activity against <i>M. genitalium</i> from fungal natural products. Extracts of <i>Ramularia coccinea</i> contained a molecule with potent activity that was subsequently identified as fusidic acid, a fusidane-type antibiotic that has been in clinical use for decades outside the United States. We found that minimum inhibitory concentrations of fusidic acid ranged from 0.31 to 4 µg/mL among 17 <i>M</i>. <i>genitalium</i> strains including laboratory-passaged and low-passage clinical isolates. Time-kill data indicate that bactericidal killing occurs when <i>M. genitalium</i> is exposed to ≥10 µg/mL for 48 h, comparing favorably to serum concentrations obtained from typical loading dose regimens. Resistance to fusidic acid was associated with mutations in <i>fusA</i> consistent with the known mechanism of action in which fusidic acid inhibits protein synthesis by binding to elongation factor G. Interestingly, no mutants resistant to >10 µg/mL fusidic acid were obtained and a resistant strain containing a F435Y mutation in FusA was impaired for growth <i>in vitro</i>. These data suggest that fusidic acid may be a promising option for the treatment of <i>M. genitalium</i> infections.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103774","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":"Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular <i>S. aureus</i> infections in osteocytes.","authors":"Anja R Zelmer, Dongqing Yang, Nicholas J Gunn, L Bogdan Solomon, Renjy Nelson, Stephen P Kidd, Katharina Richter, Gerald J Atkins","doi":"10.1128/aac.00808-24","DOIUrl":"https://doi.org/10.1128/aac.00808-24","url":null,"abstract":"<p><p>Osteomyelitis caused by <i>Staphylococcus aureus</i> can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte <i>S. aureus</i> infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 <i>S. aureus</i> strains, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone estimated achievable concentration was commonly above their respective MIC for the strains tested were further assayed in a human osteocyte infection model under acute and chronic conditions. Osteocyte-like cells were treated at 1×, 4×, and 10× the MIC for 1 and 7 days following infection (acute model), or at 15 and 21 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of CFU reduction, small colony variant formation, and bacterial mRNA expression change. Only rifampicin, levofloxacin, and linezolid reduced intracellular CFU numbers significantly in the acute model. Consistent with the transition to a non-culturable state, few if any CFU could be recovered from the chronic model. However, no treatment in either model reduced the quantity of bacterial mRNA or prevented non-culturable bacteria from returning to a culturable state. These findings indicate that <i>S. aureus</i> adapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state that is protected against antibiotics, even at 10× their MIC. Thus, new therapeutic approaches are necessary to cure <i>S. aureus</i> intracellular infections in osteomyelitis.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078876","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":"Onametostat, a PfPRMT5 inhibitor, exhibits antimalarial activity to <i>Plasmodium falciparum</i>.","authors":"Hui Min, Amuza Byaruhanga Lucky, Jesper J Madsen, Anongruk Chim-Ong, Xiaolian Li, Liwang Cui, Jun Miao","doi":"10.1128/aac.00176-24","DOIUrl":"https://doi.org/10.1128/aac.00176-24","url":null,"abstract":"<p><p>Protein arginine methyltransferases (PRMTs) play critical roles in <i>Plasmodium falciparum</i>, a protozoan causing the deadliest form of malaria, making them potential targets for novel antimalarial drugs. Here, we screened 11 novel PRMT inhibitors against <i>P. falciparum</i> asexual growth and found that onametostat, an inhibitor for type II PRMTs, exhibited strong antimalarial activity with a half-maximal inhibitory concentration (IC₅₀) value of 1.69 ± 0.04 µM. <i>In vitro</i> methyltransferase activities of purified PfPRMT5 were inhibited by onametostat, and a shift of IC₅₀ to onametostat was found in the <i>PfPRTM5</i> disruptant parasite line, indicating that PfPRTM5 is the primary target of onametostat. Consistent with the function of PfPRMT5 in mediating symmetric dimethylation of histone H3R2 (H3R2me2s) and in regulating invasion-related genes, onametostat treatment led to the reduction of H3R2me2s level in <i>P. falciparum</i> and caused the defects on the parasite's invasion of red blood cells. This study provides a starting point for identifying specific PRMT inhibitors with the potential to serve as novel antimalarial drugs.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078852","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":"Pharmacokinetics and safety of TBAJ-876, a novel antimycobacterial diarylquinoline, in healthy subjects.","authors":"Antonio Lombardi, Fran Pappas, Jerry Nedelman, Dean Hickman, Sarah Jaw-Tsai, Morounfolu Olugbosi, Paul Bruinenberg, Maria Beumont, Eugene Sun","doi":"10.1128/aac.00613-24","DOIUrl":"https://doi.org/10.1128/aac.00613-24","url":null,"abstract":"<p><p>TBAJ-876, a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile compared with bedaquiline, is under development for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). A phase 1, first-in-human study of TBAJ-876, comprising a single-ascending dose (SAD) part including a food effect cohort, a multiple-ascending dose (MAD) part, and a relative bioavailability part of tablets versus oral suspension, was conducted on 137 healthy adults. A drug-drug interaction study was conducted on 28 healthy adults to evaluate the effects of TBAJ-876 on a cytochrome P450 3A4 substrate (midazolam) and a P-glycoprotein substrate (digoxin). TBAJ-876 was well-tolerated at single doses up to 800 mg and multiple doses up to 200 mg for 14 days. No deaths or serious adverse events occurred. No episodes of clinically significant prolongation of the QTc interval were observed. TBAJ-876 exposures were dose proportional in the SAD and MAD studies. TBAJ-876 exhibited multicompartmental pharmacokinetics (PK) with a long terminal half-life yielding quantifiable concentrations up to the longest follow-up of 10 weeks after a single dose and resulting in accumulation with multiple dosing. In the fed state, TBAJ-876 exposures approximately doubled with the tablet formulation, whereas M3 metabolite exposures decreased by approximately 20%. The relative bioavailability of TBAJ-876 was similar between tablets and the oral suspension at 100-mg doses. With co-administration of TBAJ-876, the AUC_0-inf of midazolam was unchanged and the C_max was reduced by 14%; the AUC_0-last of digoxin was increased by 51%, and the C_max was increased by 18%. These results support further investigation of TBAJ-876 for the treatment of tuberculosis.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078877","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":"Loss of glycerol catabolism confers carbon-source-dependent artemisinin resistance in <i>Mycobacterium tuberculosis</i>.","authors":"Maria Carla Martini, Maria Natalia Alonso, Juan Hilario Cafiero, Junpei Xiao, Scarlet S Shell","doi":"10.1128/aac.00645-24","DOIUrl":"https://doi.org/10.1128/aac.00645-24","url":null,"abstract":"<p><p>In view of the urgent need for new antibiotics to treat human infections caused by multidrug-resistant pathogens, drug repurposing is gaining strength due to the relatively low research costs and shorter clinical trials. Such is the case of artemisinin, an antimalarial drug that has recently been shown to display activity against <i>Mycobacterium tuberculosis</i> (Mtb), the causative agent of tuberculosis. To gain insight into how Mtb is affected by artemisinin, we used RNAseq to assess the impact of artemisinin on gene expression profiles, revealing the induction of several efflux pumps and the KstR2 regulon. To anticipate the artemisinin resistance-conferring mutations that could arise in clinical Mtb strains, we performed an <i>in vitro</i> evolution experiment in the presence of lethal concentrations of artemisinin. We obtained artemisinin-resistant isolates displaying different growth kinetics and drug phenotypes, suggesting that resistance evolved through different pathways. Whole-genome sequencing of nine isolates revealed alterations in the <i>glpK</i> and <i>glpQ1</i> genes, both involved in glycerol metabolism, in seven and one strains, respectively. We then constructed a <i>glpK</i> mutant and found that loss of <i>glpK</i> increases artemisinin resistance only when glycerol is present as a major carbon source. Our results suggest that mutations in glycerol catabolism genes could be selected during the evolution of resistance to artemisinin when glycerol is available as a carbon source. These results add to recent findings of mutations and phase variants that reduce drug efficacy in carbon-source-dependent ways.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078851","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":"Automated calculation and reporting of vancomycin area under the concentration-time curve: a simplified single-trough concentration-based equation approach.","authors":"Hyun-Ki Kim, Tae-Dong Jeong, Misuk Ji, Sollip Kim, Woochang Lee, Sail Chun","doi":"10.1128/aac.00699-24","DOIUrl":"https://doi.org/10.1128/aac.00699-24","url":null,"abstract":"<p><p>Vancomycin, a crucial antibiotic for Gram-positive bacterial infections, requires therapeutic drug monitoring (TDM). Contemporary guidelines advocate for AUC-based monitoring; however, using Bayesian programs for AUC estimation poses challenges. We aimed to develop and evaluate a simplified AUC estimation equation using a steady-state trough concentration (C_trough) value. Utilizing 1,034 TDM records from 580 general hospitalized patients at a university-affiliated hospital in Ulsan, we created an equation named SSTA that calculates the AUC by applying C_trough, body weight, and single dose as input variables. External validation included 326 records from 163 patients at a university-affiliated hospital in Seoul (EWUSH) and literature data from 20 patients at a university-affiliated hospital in Bangkok (MUSI). It was compared with other AUC estimation models based on the C_trough, including a linear regression model (LR), a sophisticated model based on the first-order equation (VancoPK), and a Bayesian model (BSCt). Evaluation metrics, such as median absolute percentage error (MdAPE) and the percentage of observations within ±20% error (P20), were calculated. External validation using the EWUSH data set showed that SSTA, LR, VancoPK, and BSCt had MdAPE values of 6.4, 10.1, 6.6, and 7.5% and P20 values of 87.1, 82.5, 87.7, and 83.4%, respectively. External validation using the MUSI data set showed that SSTA, LR, and VancoPK had MdAPEs of 5.2, 9.4, and 7.2%, and P20 of 95, 90, and 95%, respectively. Owing to its decent AUC prediction performance, simplicity, and convenience for automated calculation and reporting, SSTA could be used as an adjunctive tool for the AUC-based TDM.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078847","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":"Application of machine-learning models to predict the ganciclovir and valganciclovir exposure in children using a limited sampling strategy.","authors":"Laure Ponthier, Bénédicte Franck, Julie Autmizguine, Marc Labriffe, Philippe Ovetchkine, Pierre Marquet, Anders Åsberg, Jean-Baptiste Woillard","doi":"10.1128/aac.00860-24","DOIUrl":"https://doi.org/10.1128/aac.00860-24","url":null,"abstract":"<p><p>Intravenous ganciclovir and oral valganciclovir display significant variability in ganciclovir pharmacokinetics, particularly in children. Therapeutic drug monitoring currently relies on the area under the concentration-time (AUC). Machine-learning (ML) algorithms represent an interesting alternative to Maximum-a-Posteriori Bayesian-estimators for AUC estimation. The goal of our study was to develop and validate an ML-based limited sampling strategy (LSS) approach to determine ganciclovir AUC_0-24 after administration of either intravenous ganciclovir or oral valganciclovir in children. Pharmacokinetic parameters from four published population pharmacokinetic models, in addition to the World Health Organization growth curve for children, were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles of children. Different ML algorithms were trained to predict AUC_0-24 based on different combinations of two or three samples. Performances were evaluated in a simulated test set and in an external data set of real patients. The best estimation performances in the test set were obtained with the Xgboost algorithm using a 2 and 6 hours post dose LSS for oral valganciclovir (relative mean prediction error [rMPE] = 0.4% and relative root mean square error [rRMSE] = 5.7%) and 0 and 2 hours post dose LSS for intravenous ganciclovir (rMPE = 0.9% and rRMSE = 12.4%). In the external data set, the performance based on these two sample LSS was acceptable: rMPE = 0.2% and rRMSE = 16.5% for valganciclovir and rMPE = -9.7% and rRMSE = 17.2% for intravenous ganciclovir. The Xgboost algorithm developed resulted in a clinically relevant individual estimation using only two blood samples. This will improve the implementation of AUC-targeted ganciclovir therapeutic drug monitoring in children.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078846","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":"The novel MFS efflux pump SxtP, regulated by the LysR-type transcriptional activator SxtR, is involved in the susceptibility to sulfamethoxazole/trimethoprim (SXT) and the pathogenesis of <i>Acinetobacter baumannii</i>.","authors":"Marc Gaona, Jordi Corral, Susana Campoy, Jordi Barbé, María Pérez Varela, Jesús Aranda","doi":"10.1128/aac.00712-24","DOIUrl":"https://doi.org/10.1128/aac.00712-24","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a notorious opportunistic pathogen responsible for healthcare-associated infections worldwide. Efflux pumps play crucial roles in mediating antimicrobial resistance, motility, and virulence. In this study, we present the identification and characterization of the new <i>A. baumannii</i> efflux pump SxtP belonging to the MFS superfamily (<u>m</u>ajor <u>f</u>acilitator <u>s</u>uperfamily), along with its associated activator <u>L</u>ysR<u>-</u>type <u>t</u>ranscriptional <u>r</u>egulator (LTTR) SxtR, demonstrating their roles in sulfamethoxazole/trimethoprim (also known as co-trimoxazole or SXT) resistance, surface-associated motility and virulence.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078879","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":"Retrospective validation study of a machine learning-based software for empirical and organism-targeted antibiotic therapy selection.","authors":"Maria Isabel Tejeda, Javier Fernández, Pablo Valledor, Cristina Almirall, José Barberán, Santiago Romero-Brufau","doi":"10.1128/aac.00777-24","DOIUrl":"https://doi.org/10.1128/aac.00777-24","url":null,"abstract":"<p><p>Errors in antibiotic prescriptions are frequent, often resulting from the inadequate coverage of the infection-causative microorganism. The efficacy of iAST, a machine-learning-based software offering empirical and organism-targeted antibiotic recommendations, was assessed. The study was conducted in a 12-hospital Spanish institution. After model fine-tuning with 27,531 historical antibiograms, 325 consecutive patients with acute infections were selected for retrospective validation. The primary endpoint was comparing each of the top three of iAST's antibiotic recommendations' success rates (confirmed by antibiogram results) with the antibiotic prescribed by the physicians. Secondary endpoints included examining the same hypothesis within specific study population subgroups and assessing antibiotic stewardship by comparing the percentage of antibiotics recommended that belonged to different World Health Organization AWaRe groups within each arm of the study. All of iAST first three recommendations were non-inferior to doctor prescription in the primary endpoint analysis population as well as the secondary endpoint. The overall success rate of doctors' empirical treatment was 68.93%, while that of the first three iAST options was 91.06% (<i>P</i> < 0.001), 90.63% (<i>P</i> < 0.001), and 91.06% (<i>P</i> < 001), respectively. For organism-targeted therapy, the doctor's overall success rate was 84.16%, and that of the first three ranked iAST options was 97.83% (<i>P</i> < 0.001), 94.09% (<i>P</i> < 0.001), and 91.30% (<i>P</i> < 0.001), respectively. In empirical therapy, compared to physician prescriptions, iAST demonstrated a greater propensity to recommend access antibiotics, fewer watch antibiotics, and higher reserve antibiotics. In organism-targeted therapy, iAST advised a higher utilization of access antibiotics. The present study demonstrates iAST accuracy in predicting antibiotic susceptibility, showcasing its potential to promote effective antibiotic stewardship.</p><p><strong>Clinical trials: </strong>This study is registered with ClinicalTrials.gov as NCT06174519.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078878","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}