Antimicrobial Agents and Chemotherapy最新文献

{"title":"Genomics for antimicrobial resistance-progress and future directions.","authors":"Norelle L Sherry, Jean Y H Lee, Stefano G Giulieri, Christopher H Connor, Kristy Horan, Jake A Lacey, Courtney R Lane, Glen P Carter, Torsten Seemann, Adrian Egli, Timothy P Stinear, Benjamin P Howden","doi":"10.1128/aac.01082-24","DOIUrl":"https://doi.org/10.1128/aac.01082-24","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a critical global public health threat, with bacterial pathogens of primary concern. Pathogen genomics has revolutionized the study of bacterial pathogens and provided deep insights into the mechanisms and dissemination of AMR, with the precision of whole-genome sequencing informing better control strategies. However, generating actionable data from genomic surveillance and diagnostic efforts requires integration at the public health and clinical interface that goes beyond academic efforts to identify resistance mechanisms, undertake <i>post hoc</i> analyses of outbreaks, and share data after research publications. In addition to timely genomics data, consideration also needs to be given to epidemiological sampling frames, analysis, and reporting mechanisms that meet International Organization for Standardization (ISO) standards and generation of reports that are interpretable and actionable for public health and clinical \"end-users.\" Importantly, ensuring all countries have equitable access to data and technology is critical, through timely data sharing following the FAIR principles (findable, accessible, interoperable, and re-usable). In this review, we describe (i) advances in genomic approaches for AMR research and surveillance to understand emergence, evolution, and transmission of AMR and the key requirements to enable this work and (ii) discuss emerging and future applications of genomics at the clinical and public health interface, including barriers to implementation. Harnessing advances in genomics-enhanced AMR research and embedding robust and reproducible workflows within clinical and public health practice promises to maximize the impact of pathogen genomics for AMR globally in the coming decade.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":"69 5","pages":"e0108224"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966831","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}

{"title":"Impact of hepatic impairment and renal failure on the pharmacokinetics of linezolid and its metabolites: contribution of hepatic metabolism and renal excretion.","authors":"Jinyao Liu, Yingying Pang, Wenyan Li, Juanjuan Sun, Yujie He, Yonghong Guo, Jing Dong","doi":"10.1128/aac.01892-24","DOIUrl":"https://doi.org/10.1128/aac.01892-24","url":null,"abstract":"<p><p>Linezolid, an oxazolidinone antibiotic, is used in patients with liver or kidney disease. However, the effects and mechanisms of hepatic impairment or renal failure on the pharmacokinetics of linezolid and its metabolites (PNU-142586 and PNU-142300) remain unclear. We used carbon tetrachloride-induced impaired hepatic function and 5/6 nephrectomy-induced renal failure rat models to investigate linezolid and metabolite pharmacokinetics. Isolated primary rat hepatocytes were used to evaluate the impact of hepatic impairment or renal failure on linezolid metabolism. Uptake and efflux transport studies were also conducted. The influence of hepatic impairment or renal failure on the pharmacokinetics of linezolid and two metabolites did not differ between intragastric gavage and intravenous administration in rats. Linezolid did not accumulate in the brain, heart, lung, liver, kidney, and small intestinal tissues of the hepatic impairment or renal failure rats. And PNU-142300 did not accumulate in the liver or kidney tissue. Compared to the isolated normal rat hepatocytes, the <i>in vitro</i> hepatic clearance of linezolid in hepatic impairment and renal failure rat hepatocytes decreased by 61.3% and 44.1%, respectively. Organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, Na+-taurocholate co-transporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multidrug resistance-associated protein 2 (MRP2), or multidrug resistance protein 1 (MDR) did not mediate linezolid transport. Hepatic impairment primarily increases linezolid exposure through reduced hepatic metabolism, whereas renal failure increases both linezolid and two metabolites exposure through reduced hepatic metabolism and renal glomerular filtration. These findings guide adjusting the dose of linezolid in patients with hepatic and renal insufficiency.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":"69 5","pages":"e0189224"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967573","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}

{"title":"Combating yellow fever virus with 7-deaza-7-fluoro-2'-C-methyladenosine.","authors":"Julia C LeCher, Vivian Vasconcelos Costa, Lauren N Rust, Leda C Bassit, Dharmeshkumar Patel, Sahar Rezaei, Justin Moua, Felipe Rocha da Silva Santos, Matheus Rodrigues Goncalves, Celso Martins Queroz-Junior, Fernanda Martins Marim, Longhu Zhou, Sujin Lee, Tamara McBrayer, Ramyani De, Niloufar Azadi, Mohammad Salman, Keivan Zandi, Franck Amblard, Benjamin Burwitz, Mauro M Teixeira, Raymond F Schinazi","doi":"10.1128/aac.01889-24","DOIUrl":"https://doi.org/10.1128/aac.01889-24","url":null,"abstract":"<p><p>Yellow fever virus (YFV) is a deadly zoonotic flavivirus endemic in tropical/sub-tropical Africa and South America transmitted by mosquito vector (<i>Aedes aegypti</i>; <i>Haemagogus leucocelaenus</i>) to humans and non-human primates. There are no approved antiviral agents for YFV. We previously identified 7-deaza-7-fluoro-2'-C-methyladenosine (DFA) with anti-YFV activity. Interestingly, DFA exhibits pan-activity in vitro against flaviviruses, such as dengue, Japanese encephalitis, Zika, and hepatitis C. This study aimed to expand DFA's anti-flavivirus profile. DFA exhibited potent sub-micromolar anti-YFV activity <i>in vitro</i> against both the vaccine strain (YFV-17D) and a viscerotropic clinical YFV isolate (DakH1279) concomitantly with low cellular cytotoxicity and no notable mitochondrial toxicity. <i>In vivo</i>, efficacy was assessed against both YFV-17DD and a human clinical isolate in A129 and AG129 mouse flavivirus infection models, respectively. DFA significantly reduced virus replication in the livers of YFV-infected mice and the hallmarks of YFV-induced liver damage, including alanine transaminase levels and indocyanine green clearance. Collectively, this work identifies DFA as a potent YFV inhibitor and lays the groundwork for further therapeutic development as a YFV and, potentially, pan-flavivirus therapeutic.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":"69 5","pages":"e0188924"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952593","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}

{"title":"The newly identified <i>grdA</i> gene confers high-level plazomicin resistance in <i>Salmonella enterica</i> serovars.","authors":"Ahmed F Hikal, Shaohua Zhao, Steven Foley, Ashraf A Khan","doi":"10.1128/aac.01606-24","DOIUrl":"10.1128/aac.01606-24","url":null,"abstract":"<p><p>Plazomicin, a next-generation aminoglycoside, was recently approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant complicated urinary tract infections. It is highly effective against most aminoglycoside-modifying enzymes (AMEs). Here, we report that <i>Salmonella enterica</i> strains containing the newly identified gentamicin resistance gene (<i>grdA</i>) are highly resistant to plazomicin. Heterologous expression of <i>grdA</i> in <i>Escherichia coli</i> Δ<i>tolC</i> resulted in plazomicin resistance with minimum inhibitory concentration (MIC) > 256 µg/mL. These findings reveal that GrdA confers significantly higher resistance to plazomicin than the previously known plazomicin-resistant AMEs AA (2)-Ia and APH (2″)-Iva.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0160624"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770921","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}

{"title":"Inhibitory effect of copper chelators on the budding in <i>Candida albicans</i>.","authors":"Yushi Futamura, Kai Yamamoto, Rachael Uson-Lopez, Harumi Aono, Takeshi Shimizu, Yasuhiro Hori, Kuniki Kino, Hiroyuki Osada","doi":"10.1128/aac.00033-25","DOIUrl":"10.1128/aac.00033-25","url":null,"abstract":"<p><p><i>Candida albicans</i> exhibits a unique dimorphic behavior, allowing it to switch between unicellular budding yeast and filamentous hyphal growth. This dimorphism is crucial for its pathogenicity, influencing processes such as adhesion, invasion, immune evasion, and host response. A comprehensive understanding of the molecular mechanisms governing yeast and hyphal growth, as well as the switch between these forms, is crucial for the development of effective anticandidal therapies. In this study, we screened for small molecules that interfere with the dimorphism of <i>C. albicans</i> and identified the actinomycete metabolite RK-276A/SF2768 as a potent inhibitor of this process. Time-lapse microscopy revealed that SF2768 inhibited hyphal branching and lateral yeast budding during the hyphal-to-yeast transition. Interestingly, SF2768 also suppressed farnesol-induced yeast growth by inhibiting yeast bud formation. The effects of SF2768 were canceled with copper addition, and other copper chelators, such as trientine and d-penicillamine, induced similar phenotypes, indicating that the copper-chelating activity of SF2768 is crucial for its antifungal properties. Furthermore, copper ions induced both hyphal and yeast bud formation. These findings strongly suggest that copper ions play a role in <i>Candida</i> budding, and the copper chelators could be developed as novel antifungal agents against not only dimorphic <i>Candida</i> spp. but also non-dimorphic <i>Candida</i> spp.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0003325"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810331","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}

{"title":"Distribution of ganciclovir in the porcine central nervous system.","authors":"Johan Mikkel Guldbæk, Theis Mariager, Mikkel Dreyer Nielsen, Jacob Holmen Terkelsen, Roland Nau, Carsten Reidies Bjarkam, Henrik Nielsen, Jacob Bodilsen","doi":"10.1128/aac.01815-24","DOIUrl":"10.1128/aac.01815-24","url":null,"abstract":"<p><p>Ganciclovir is often used compassionately for encephalitis due to cytomegalovirus (CMV) and human herpes virus 6b (HHV-6b). Ganciclovir pharmacokinetic studies in the central nervous system (CNS) generally rely on single measurements in the cerebrospinal fluid (CSF) or homogenized brain tissue. Therefore the objective was to compare brain extracellular fluid (ECF) concentrations of ganciclovir with plasma and CSF concentrations in a porcine model, using microdialysis during a 24 h period. Six Danish landrace pigs (female, age 4 months, 31-37 kg) received two weight-adjusted intravenous doses of ganciclovir. Unbound ganciclovir concentrations were determined by microdialysis over 24 h in five compartments: CSF (lateral ventricle, cisterna magna, and lumbar) and brain ECF (cortical and subcortical). Data were compared with paired plasma samples. Ganciclovir concentrations >IC₅₀ for CMV (1.6 µg/mL) were achieved in all compartments. Concentrations >IC₉₀ for CMV (8.3 µg/mL) were only achieved in plasma and the lumbar CSF compartment. The concentration time curves indicated higher lumbar and cisternal CSF concentrations than ECF concentrations. The ECF compartments achieved greater maximum concentration (C_max), area under the concentration time curve (AUC), and time >IC₅₀ after the second dose, and an accumulation ratio (R_ac) >1. The greater C_max, AUC, time >IC₅₀, and R_ac >1 in the ECF compartments with repeated dosages suggest that therapeutic concentrations may be achieved during long-term treatment. A higher loading dose might be warranted to improve early viral inhibition.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0181524"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673233","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}

{"title":"Antibiotic killing of drug-induced bacteriostatic cells.","authors":"Teresa Gil-Gil, Brandon A Berryhill","doi":"10.1128/aac.00156-25","DOIUrl":"10.1128/aac.00156-25","url":null,"abstract":"<p><p>There is a long-standing belief that bacteriostatic drugs are inherently antagonistic to the action of bactericidal antibiotics. This belief is primarily because the action of most bactericidal antibiotics requires the target bacteria to be growing. Since bacteriostatic drugs stop the growth of treated bacteria, these drugs would necessarily work against one another. Our results question this long-standing belief by demonstrating conditions where sequential treatment with a bacteriostatic then bactericidal antibiotic is as or more effective than treatment with a bactericidal drug alone. These results raise the need to investigate the pharmacodynamics of the joint action of bacteriostatic and bactericidal antibiotics <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0015625"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708249","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}

{"title":"Impact of porin deletions on cefepime-taniborbactam activity against <i>Klebsiella pneumoniae</i>.","authors":"Tsuyoshi Uehara, Cassandra L Chatwin, Brittany Miller, Mitchell Edwards, Annie Stevenson, Jenna Colombo, Kyoko Uehara, Denis M Daigle","doi":"10.1128/aac.01672-24","DOIUrl":"10.1128/aac.01672-24","url":null,"abstract":"<p><p>We determined the frequency of resistance to cefepime-taniborbactam in NDM-1-producing <i>Klebsiella pneumoniae</i> at <10^-10. Isolated mutants that were less susceptible to cefepime-taniborbactam had an increased copy number of the <i>bla</i>_NDM-1 gene or disruption of major porins OmpK36 and OmpK35. Antibacterial susceptibility testing using <i>K. pneumoniae</i> isogenic strains indicated that while cefepime penetrates into the periplasm mainly through the major porins, taniborbactam does not have a strong dependence on OmpK35 or OmpK36 for periplasmic accumulation.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0167224"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12073839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762839","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}

{"title":"Repurposing drugs to advance the treatment of Buruli ulcer.","authors":"Sanjay Singh, Rie Yotsu, Eric Nuremberger, Shashikant Srivastava","doi":"10.1128/aac.00029-25","DOIUrl":"10.1128/aac.00029-25","url":null,"abstract":"<p><p>Aligned with the World Health Organization's Road Map, there is an unmet need for research to improve the treatment of Buruli ulcer caused by <i>Mycobacterium ulcerans</i>. The repurposing of drugs could speed up new regimen development to treat Buruli ulcer. Using a virulent reporter strain of <i>M. ulcerans</i> with intrinsic bioluminescence (MuAL), we compared the minimum inhibitory concentration (MIC) of moxifloxacin, bedaquiline, telacebec, tebipenem, omadacycline, and epetraborole with standard-of-care drugs-rifampin and clarithromycin. We also compared the efficacy (maximal kill or <i>E</i>_max) and potency (EC₅₀ or concentration associated with 50% of <i>E</i>_max) as single and two-drug combinations. The doubling time of MuAL was calculated as 3.66 (95% CI: 3.41-3.93) days. Telacebec had the lowest MIC (0.0000075 mg/L) among the eight drugs tested, followed by rifampicin (0.5 mg/L) and clarithromycin (0.5 mg/L). Epetraborole, telacebec, and moxifloxacin monotherapy at tested concentrations showed higher <i>E</i>_max compared to clarithromycin and rifampicin. In preclinical studies, telacebec combined with rifampicin or epetraborole and epetraborole combinations with moxifloxacin and omadacycline were superior to the rifampin-clarithromycin combination. The MuAL strain is useful in the rapid screening of drugs' efficacy and potency against <i>M. ulcerans</i>. We should leverage the progress made in the tuberculosis drug development pipeline to repurpose the drugs for the rapid development of new therapeutic modalities for Buruli ulcer.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0002925"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708257","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}

{"title":"Phenotypic and genotypic resistance to bedaquiline in patients with multi-drug-resistant tuberculosis-experiences from Armenia.","authors":"E Ardizzoni, W Mulders, M De Diego Fuertes, A Hayrapetyan, A Mirzoyan, J Faqirzai, N Khachatryan, I Oganezova, F Varaine, M Bastard, P Graulus, C J Meehan, L Rigouts, B C de Jong, T Decroo, C Hewison, A Van Rie","doi":"10.1128/aac.01839-24","DOIUrl":"10.1128/aac.01839-24","url":null,"abstract":"<p><p>Risk factors for baseline bedaquiline (BDQ) resistance, amplification during treatment, and correlations with treatment outcomes are not fully understood. This cohort included Armenian patients with multidrug-resistant TB predominantly fluoroquinolone-resistant enrolled between 2013 and 2015 in a BDQ compassionate use program. BDQ resistance at baseline and during treatment was assessed using MGIT (pDST_MGIT), minimal inhibitory concentration in 7H11 (MIC_7H11), and whole-genome sequencing. Risk factors, such as treatment effectiveness or stage of the disease, were analyzed for association with baseline BDQ resistance, acquired BDQ resistance, and treatment outcome. Among 39 patients, baseline BDQ resistance was 6% (2/33) by pDST_MGIT and 7% (2/29) by MIC_7H11. All four baseline isolates with an <i>Rv0678</i> mutation were phenotypically resistant. During treatment, 48% of the patients acquired BDQ resistance by pDST_MGIT, and 52% acquired mutations at various frequencies (97% in <i>Rv0678</i>). None of the factors significantly contributed to baseline or acquired BDQ resistance. Unfavorable treatment outcome (41%) was more frequent in the presence of acquired <i>Rv0678</i> mutations [odds ratio (OR) 132, 95% confidence interval (CI) 7.43, 2375], phenotypic BDQ resistance (OR 176, 95% CI 6.48, 2423), or MIC increase above or below the critical concentration (both OR 84.3, 95% CI 2.93, 2423) during treatment. For these highly treatment-experienced patients, low baseline prevalence but high incidence of acquired BDQ resistance was observed. Acquisition of mutations in BDQ candidate resistance genes, regardless of their frequency, or increased MICs during treatment, even below the critical concentration, should be seen as a warning sign of resistance amplification and increased risk of unfavorable treatment outcome.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0183924"},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810341","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}