Journal of Antimicrobial Chemotherapy最新文献

{"title":"Antibiotic stress affects the secretion and physicochemical features of extracellular vesicles produced by Helicobacter pylori.","authors":"Paweł Krzyżek, Agnieszka Opalińska, Paweł Migdał, Kaja Tusiewicz, Paweł Szpot, Marcin Zawadzki, Barbara Krzyżanowska, Michał Jerzy Kulus, Marzenna Podhorska-Okołów, Beata Sobieszczańska","doi":"10.1093/jac/dkaf172","DOIUrl":"https://doi.org/10.1093/jac/dkaf172","url":null,"abstract":"<p><strong>Background: </strong>Bacterial extracellular vesicles (EVs) may reduce the effectiveness of various antimicrobials; however, the impact of antibiotics on the secretion and properties of EVs produced by Helicobacter pylori has not been established.</p><p><strong>Methods: </strong>Using clinical H. pylori strains and culture in EV-depleted media, the influence of ¼ × MIC of clarithromycin, metronidazole and levofloxacin on EV features was determined. Physicochemical properties of EVs were measured using nanoparticle tracking analysis and dynamic light scattering. Determination of fatty acid profiles of EVs and bacterial cells was performed with GC triple-quadrupole tandem MS. Bacteria and EVs were observed by scanning and transmission electron microscopy, respectively.</p><p><strong>Results: </strong>Antibiotic stress induced in H. pylori affects the secretion intensity and physicochemical features of EVs secreted by this bacterium in a strain- and antibiotic-dependent manner. Exposure to ¼ × MIC of metronidazole or levofloxacin increased the secretion of EVs and contributed to significant changes in their fatty acid profile, whereas treatment with ¼ × MIC of clarithromycin did not induce such changes. Regardless of the culture conditions and the strain analysed, the existence of a conservative process of selective packaging of C17:0 fatty acids into EVs and a substantial limitation of this phenomenon for C14:0, C18:1 and C19c:0 was demonstrated.</p><p><strong>Conclusion: </strong>This is the first study showing the modulatory effect of antibiotic stress on the secretion and physicochemical features of EVs produced by H. pylori, as well as the first to suggest the involvement of EVs in maintaining the appropriate membrane fatty acid composition of this bacterium.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173849","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":"Posaconazole dosing of enteral formulations in infants and young children to achieve therapeutic concentrations.","authors":"Jeffrey Harrington, Gianni Scappaticci, Julia Brown, Madeleine King","doi":"10.1093/jac/dkaf151","DOIUrl":"https://doi.org/10.1093/jac/dkaf151","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159206","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":"Inner-mitochondrial membrane protein PfMPV17 is linked to P. falciparum in vitro resistance to the indoloquinolizidine alkaloid alstonine.","authors":"J R Macdonald, M S Arnold, M R Luth, D Cihalova, R J Quinn, E A Winzeler, M C Lee, G G van Dooren, A G Maier, T S Skinner-Adams, K T Andrews, G M Fisher","doi":"10.1093/jac/dkaf141","DOIUrl":"https://doi.org/10.1093/jac/dkaf141","url":null,"abstract":"<p><strong>Background: </strong>There are an estimated 260 million malaria cases and ∼600 000 deaths annually. Challenges to malaria eradication include the lack of highly effective and broadly applicable vaccines and parasite drug resistance. This is driving the need for new tools, including novel drugs and drug targets. The indoloquinolizidine alkaloid alstonine was previously shown to have in vitro activity against Plasmodium falciparum malaria parasites and a slow-action activity that is different from other slow-action antiplasmodial compounds such as clindamycin.</p><p><strong>Objectives: </strong>To investigate the action of the antiplasmodial compound alstonine by validating a putative resistance mutation and determining whether the activity of alstonine is linked to the mitochondrial electron transport chain.</p><p><strong>Materials and methods: </strong>In vitro evolution of resistance was used to generate alstonine-resistant P. falciparum, followed by whole-genome sequencing and CRISPR/Cas9 gene editing of wildtype parasites to validate a putative resistance-associated mutation. Links to mitochondrial function were assessed using oxygen consumption rate measurements and activity of alstonine in P. falciparum expressing the yeast dihydroorotate dehydrogenase.</p><p><strong>Results: </strong>P. falciparum parasites were selected with ∼20-fold reduced sensitivity to alstonine compared to wild-type parasites. Whole-genome sequencing of alstonine-resistant P. falciparum sub-clones identified several mutations including a copy number variation and point mutation (A318P) in a gene encoding a putative inner-mitochondrial membrane protein (PfMPV17). Introduction of the A318P mutation into the PfMPV17 gene in wild-type P. falciparum yielded parasites with reduced alstonine sensitivity. While a direct link between alstonine action and mitochondrial respiratory function was not found, a transgenic P. falciparum line resistant to the cytochrome bc1 inhibitor atovaquone and pyrimidine synthesis inhibitor DSM265 had reduced sensitivity to alstonine.</p><p><strong>Conclusions: </strong>These data demonstrate that PfMPV17 is linked to alstonine resistance and suggest that alstonine action is linked to the mitochondria and/or pyrimidine biosynthesis pathways.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159244","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":"Efficacy of linezolid in monotherapy q12h versus q8h versus combined with daptomycin in the treatment of experimental endocarditis caused by methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus strains.","authors":"María-Alexandra Cañas, Cristina García-de-la-Mària, Javier García-González, María Pilar Jiménez, Francesc Marco, María Sarasa, Marta Hernández-Meneses, Eduard Quintana, Carles Falces, José M Tolosana, Barbara Vidal, Andres Perissinotti, Jaume Llopis, Asunción Moreno, Guillermo Cuervo, José M Miró","doi":"10.1093/jac/dkaf149","DOIUrl":"10.1093/jac/dkaf149","url":null,"abstract":"<p><strong>Background: </strong>Daptomycin is a bactericidal antibiotic, highly effective against MRSA. Linezolid, though bacteriostatic, is effective in MRSA pneumonia and has excellent meningeal penetration. Therefore, the combination of both antibiotics can be required in some patients with disseminated MRSA infections.</p><p><strong>Objectives: </strong>This study aimed to evaluate the in vitro activity of linezolid plus daptomycin against MRSA and glycopeptide-intermediate Staphylococcus aureus (GISA) strains and to determine the efficacy of linezolid monotherapy administered every 12 h versus every 8 h versus the combination of linezolid-q12h plus daptomycin against MRSA and GISA experimental endocarditis (EE).</p><p><strong>Methods: </strong>In vitro time-kill studies were performed using standard (105 cfu/L) and high (109 cfu/mL) inoculum of six MRSA strains, including one GISA strain. MRSA-277 and GISA-700788 were selected for the EE model. Animals were treated with linezolid-q12h (600 mg/kg/12 h), linezolid-q8h (600 mg/kg/8 h), daptomycin (6 mg/kg/day) or daptomycin plus linezolid-q12h mimicking human-like serum levels.</p><p><strong>Results: </strong>Linezolid-q8h and linezolid-q12h showed similar activity in MRSA-277 EE (P = 0.15). Against GISA-700788 endocarditis, linezolid-q8h was more effective than linezolid-q12h (P < 0.001). Daptomycin monotherapy was very effective against MRSA-277 and GISA-700788 EE, sterilizing 70% and 60% of valvular vegetations, respectively. Daptomycin plus linezolid-q12h was similarly effective at 60% and 56%, respectively. This combination showed neither in vitro nor in vivo antagonism, and daptomycin-non-susceptible strains were not recovered.</p><p><strong>Conclusions: </strong>Increasing linezolid to 600 mg/8 h might be useful as initial treatment in clinical practice. If required, the combination of daptomycin plus linezolid-q12h could be a suitable option in MRSA/GISA bacteraemia/endocarditis.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159242","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":"World Health Organisation's Bacterial Pathogen Priority List (BPPL) 2017 and BPPL 2024 to combat global antimicrobial resistance crisis: 'challenges and opportunities'.","authors":"Vazhayil Hari Krishnaprasad, Vijayashree Nayak, Sanjay Kumar","doi":"10.1093/jac/dkaf167","DOIUrl":"https://doi.org/10.1093/jac/dkaf167","url":null,"abstract":"<p><p>Antibiotic resistance, in a broader perspective, antimicrobial resistance (AMR) presents a formidable global health challenge, threatening the effectiveness of antibiotics and other antimicrobial agents. As a result, AMR has become more challenging or even impossible to treat, leading to increased morbidity and mortality. The World Health Organisation (WHO) has been at the forefront of international efforts to combat AMR by sensitizing the world about the pressing need to tackle AMR to save the future of the human race. This article analyses WHO's efforts to combat AMR, including creating the Bacterial Pathogen Priority List (BPPL), developing a global action plan to address AMR and promoting surveillance and stewardship programmes. This article also examines the progress achieved by BPPL 2017 and the challenges ahead for BPPL 2024. Additionally, this article explores various efforts to combat AMR through two major approaches, like 'research and development' and 'the policy and regulation-based' approach. This article underscores various emerging strategies to tackle AMR, for example, biofilm disruption, nanotechnology, antibiotic resistance breakers, antibody-antibiotic conjugates, rapid detection tools and alternative therapies like phage therapy, antimicrobial peptides, CRISPR-Cas system, probiotics and microbiota modulations. This article also highlights the importance of coordinated actions and sustained commitment to safeguarding public health and ensuring the continued effectiveness of antimicrobial therapies.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159208","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":"Antibacterial activity of propylene glycol against Staphylococcus aureus and Staphylococcus epidermidis in neutral and mild acidic conditions.","authors":"Nadiia Mosiichuk, Gabriela Enggren, Zita Lopes Da Silva, Anna Karin Morén, Henri Hansson, Johan Engblom, Tautgirdas Ruzgas","doi":"10.1093/jac/dkaf153","DOIUrl":"https://doi.org/10.1093/jac/dkaf153","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus and Staphylococcus epidermidis normally coexist on the skin of healthy individuals. Their ratio and pathogenicity, however, change with different skin diseases and thus, the ability to control bacterial growth on the skin is important. Propylene glycol (PG), a widely used component in topical formulations, has been proved to have antimicrobial activity.</p><p><strong>Objectives: </strong>To investigate the concentration-dependent antimicrobial properties of PG against S. aureus and S. epidermidis skin isolates in mono- and co-culture at neutral (pH 7.4) and mildly acidic (pH 5) conditions.</p><p><strong>Results and discussion: </strong>The minimum inhibitory concentration of PG was 12.5% at both pH 5 and pH 7.4 for the selected bacterial strains. The viability of S. aureus exposed to 12.5% PG was lower at pH 5 than at pH 7.4, and post-treatment regrowth of S. aureus occurred slowly at acidic pH. When both bacterial strains were incubated in media containing 12.5% PG at pH 5 for 48 hours, S. epidermidis retained significantly higher viability, while at pH 7.4, the results were opposite.</p><p><strong>Conclusions: </strong>Under the acidic conditions of healthy skin, pathogenic S. aureus is more suppressed by 12.5% PG than commensal S. epidermidis.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142452","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":"Comparison of a modified broth microdilution Sensititre™ SLOMYCOI assay with the CLSI-recommended agar disk elution method for antimicrobial susceptibility testing of Mycobacterium haemophilum.","authors":"Doris Hillemann, Emmanuelle Cambau, Silke Polsfuß, Inna Friesen","doi":"10.1093/jac/dkaf162","DOIUrl":"https://doi.org/10.1093/jac/dkaf162","url":null,"abstract":"<p><strong>Objectives: </strong>Mycobacterium haemophilum is a fastidious nontuberculous mycobacterium that causes severe infections in immunocompromised patients. Due to its complex growth requirements, its detection and antimicrobial susceptibility testing (AST) remain challenging. This study aimed to compare the performance of a modified commercial broth microdilution method (Sensititre™ Myco susceptibility plates with added haemin) with the standard Clinical and Laboratory Standards Institute (CLSI) agar disk elution method for AST of M. haemophilum.</p><p><strong>Methods: </strong>We conducted 20 comparative AST tests on M. haemophilum ATCC 29548 and 10 clinical isolates, using the CLSI agar disk elution method as the reference. MICs were determined using both methods, and categorical concordance was assessed for multiple antibiotics.</p><p><strong>Results: </strong>The overall concordance between methods was 81.4%. High agreement was observed for clarithromycin, linezolid, trimethoprim-sulfamethoxazole and rifampicin (90%-100%), while lower concordance was noted for amikacin (40%), ciprofloxacin (75%) and doxycycline (65%). Sensititre™ microdilution plates demonstrated superior standardization, ease of use and reduced contamination risks compared to the agar disk method.</p><p><strong>Conclusions: </strong>The modified Sensititre™ microdilution method is a reliable alternative to the agar disk elution method for AST of M. haemophilum. It provides precise MIC values and is better suited for routine clinical use due to improved reproducibility and efficiency.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142557","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":"Is cefazolin an option for treatment of staphylococcal endogenous endophthalmitis?","authors":"Alexandra Morin, Julien Le Guen, Sihem Benaboud, Pauline Richebé, Léo Froelicher Bournaud, Daphné Dedieu, Antoine Brezin, Caroline Charlier, Etienne Canouï","doi":"10.1093/jac/dkaf165","DOIUrl":"https://doi.org/10.1093/jac/dkaf165","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142559","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":"Clinical characteristics and risk factors of tigecycline-induced acute pancreatitis in kidney transplant recipients: a retrospective study.","authors":"Lijuan Feng, Yuanyuan Hong, Jiawang Fan, Chunlan Yang, Yan Huang, Yuanbao Xu, Guiyi Liao, Yong Su","doi":"10.1093/jac/dkaf159","DOIUrl":"https://doi.org/10.1093/jac/dkaf159","url":null,"abstract":"<p><strong>Objective: </strong>Acute pancreatitis (AP) is a severe but insufficiently recognized adverse effect of tigecycline in kidney transplant (KT) recipients. This study aimed to identify the clinical characteristics and risk factors associated with tigecycline-induced AP in this population.</p><p><strong>Methods: </strong>A single-center retrospective study was conducted in KT recipients treated with tigecycline. The clinical characteristics of patients who developed AP were analyzed, and risk factors for tigecycline-induced AP were assessed using univariate analysis and multivariate logistic regression.</p><p><strong>Results: </strong>80 KT recipients were enrolled, of whom nine developed AP (incidence: 11.25%), and four died. The mean time from tigecycline administration to AP onset was 7.00 days, to symptomatic relief after discontinuation was 4.87 days, and to normalisation of pancreatic enzymes after discontinuation was 8.75 days. The analysis revealed that tacrolimus trough concentration (C0 Tac) and post-transplant acute kidney injury (AKI) were independent risk factors for tigecycline-induced AP in KT recipients. Logistic regression analysis produced a combined predictive expression: Ycombined = AKI + 0.064C0 Tac-2.789. Receiver operating characteristic curve analysis determined that the C0  Tac cut-off was 13.9 ng/mL. The area under the curve for C0  Tac and combined predictor were 0.802 and 0.853, respectively.</p><p><strong>Conclusion: </strong>The incidence of AP following tigecycline treatment was significantly higher in KT recipients than in non-transplant patients. Post-transplant AKI and elevated C0 Tac concentrations were identified as independent risk factors for the development of AP. Close monitoring of renal function and ensuring therapeutic monitoring of C0 Tac levels may help prevent AP.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127480","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":"An improved multiplex RT-quantitative PCR assay can reveal sex-specific activity of transmission-blocking drugs on ex vivo gametocytes from Plasmodium falciparum asymptomatic infections.","authors":"Mariagrazia Ciardo, Noëlie B Henry, Issiaka Soulama, Samuel S Sermé, Dante Rotili, Antonello Mai, Fabrizio Lombardo, Pietro Alano, Giulia Siciliano","doi":"10.1093/jac/dkaf146","DOIUrl":"https://doi.org/10.1093/jac/dkaf146","url":null,"abstract":"<p><strong>Objectives: </strong>To develop a multiplex RT-quantitative PCR (RT-qPCR) assay to quantify sex-specific Plasmodium falciparum gametocyte transcripts (pfCCp4, pfMGET), for evaluating the impact of drug treatments on gametocyte viability for malaria transmission-blocking drug development.</p><p><strong>Methods: </strong>We optimized an RT-qPCR assay incorporating a normalization transcript to use the ΔΔCt method (differences in Cycle threshold) to quantify gametocyte transcript levels. The assay was used on ex vivo gametocytes from P. falciparum natural infections exposed for 24 h to six drugs impairing mosquito transmission, as measured by the direct membrane feeding assay. Follow-up in vitro experiments showed that an additional 48 h incubation, following drug wash-out, was required to monitor decline in transcript levels and potential sex-specific effects.</p><p><strong>Results: </strong>The optimized assay revealed efficacy of drug treatment as a reduction in transcript levels for two of the six drugs tested: 30% for pfMGET and 80% for pfCCp4 in methylene blue (5 µM)-treated samples, and 75% for both sex-specific transcripts in samples treated with P218 (0.25 µM). In the remaining drugs, a 48 h incubation period post drug wash-out was required to measure a decline in transcript levels. Furthermore, a differential reduction in the levels of male versus female gametocyte transcripts suggested sex-specific effects for two of the drugs.</p><p><strong>Conclusions: </strong>The multiplex RT-qPCR assay provides a reliable method to assess the inhibitory effects of drug treatments on P. falciparum gametocytes, with the potential to evaluate both overall and sex-specific impacts on gametocyte viability. This assay represents a valuable tool in the development and evaluation of transmission-blocking drugs, particularly in distinguishing effects on male and female gametocytes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127466","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}