International Journal of Antimicrobial Agents最新文献

{"title":"Commentary on “Development and validation of a time-varying correction factor for QT interval assessment in drug-resistant tuberculosis patients”","authors":"Masoud Keikha","doi":"10.1016/j.ijantimicag.2025.107510","DOIUrl":"10.1016/j.ijantimicag.2025.107510","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107510"},"PeriodicalIF":4.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935609","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":"Cerebrospinal fluid concentrations of ceftaroline and ceftazidime/avibactam in healthy volunteers: Pharmacokinetics and probability of target attainment","authors":"Michael Wölfl-Duchek ,&nbsp;Wisse van Os ,&nbsp;Valentin al Jalali ,&nbsp;Ulrich Rabl ,&nbsp;Peter Wohlrab ,&nbsp;Martin Bauer ,&nbsp;Edith Lackner ,&nbsp;Beatrix Wulkersdorfer ,&nbsp;Peter Marhofer ,&nbsp;Felix Bergmann ,&nbsp;Anselm Jorda ,&nbsp;Birgit Reiter ,&nbsp;Thomas Stimpfl ,&nbsp;Markus Zeitlinger","doi":"10.1016/j.ijantimicag.2025.107512","DOIUrl":"10.1016/j.ijantimicag.2025.107512","url":null,"abstract":"<div><h3>Objectives</h3><div>This study measured the penetration of ceftaroline and ceftazidime/avibactam into cerebrospinal fluid (CSF) to evaluate the potential of both drugs for treatment of central nervous system (CNS) infections.</div></div><div><h3>Methods</h3><div>In this prospective, single-centre pharmacokinetic (PK) study, 24 healthy volunteers equally divided into two groups received four doses of either 600 mg ceftaroline fosamil or 2000/500 mg ceftazidime/avibactam as intravenous infusions over 2 h at 8 h intervals for 4 doses. Plasma samples were obtained on both study days and CSF was sampled once per subject at either 2 h, 4 h or 8 h after the start of the last infusion via lumbar puncture. PK data were analysed using non-compartmental analysis, as well as using a population PK modelling approach. Monte Carlo simulations were performed to calculate probability of PK-pharmacodynamic (PK-PD) target attainment.</div></div><div><h3>Results</h3><div>Two-compartment models described the plasma PK data for all three compounds. The ratios between the estimated distribution clearances into and out of the CSF were 0.021, 0.083 and 0.071 for ceftaroline, ceftazidime and avibactam, respectively, indicating limited CSF penetration. Ceftaroline and ceftazidime PK-PD targets were not attained in CSF for minimum inhibitory concentrations around commonly used susceptibility breakpoints, but exposure appears sufficient to treat several pathogens commonly causing CNS infections. Avibactam concentrations were well below reported threshold concentrations that are required for activity.</div></div><div><h3>Conclusion</h3><div>In healthy subjects, ceftaroline, ceftazidime and avibactam poorly distribute to CSF. Nonetheless, CSF exposure of both cephalosporins might be sufficient to cover certain, but not all, pathogens causative of CNS infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107512"},"PeriodicalIF":4.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935955","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107509","DOIUrl":"10.1016/j.ijantimicag.2025.107509","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107509"},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806860","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":"Procalcitonin-guided early cessation of antibiotics prevents gut inflammation and preserves gut microbiome: Data from the PROGRESS controlled trial","authors":"Evdoxia Kyriazopoulou ,&nbsp;Emmanouil Stylianakis ,&nbsp;Georgia Damoraki ,&nbsp;Panagiotis Koufargyris ,&nbsp;Ioannis Kollias ,&nbsp;Konstantina Katrini ,&nbsp;Elina Drakou ,&nbsp;Konstantinos Marousis ,&nbsp;Andronikos Spyrou ,&nbsp;Styliani Symbardi ,&nbsp;Nikolaos Alexiou ,&nbsp;Zoi Alexiou ,&nbsp;Malvina Lada ,&nbsp;Garyfallia Poulakou ,&nbsp;Georgios Chrysos ,&nbsp;George Adamis ,&nbsp;Evangelos J. Giamarellos-Bourboulis","doi":"10.1016/j.ijantimicag.2025.107507","DOIUrl":"10.1016/j.ijantimicag.2025.107507","url":null,"abstract":"<div><div>The PROGRESS randomised trial (ClinicalTrials.gov: NCT03333304) showed that early stopof antibiotics guided by procalcitonin (PCT) decreased the incidence of infections by multidrug-resistant organisms and/or <em>Clostridioides difficile</em> and was associated with survival benefit. This study was conducted to investigate whether this survival benefit is associated with microbiome dysbiosis. Patients with sepsis due to lung infection, acute pyelonephritis or primary bacteraemia were randomised to standard-of-care (SoC) duration of antibiotics or early stop using PCT. Faecal samples were collected before, and 7 and 28 days after randomisation and analysed using 16S rRNA Nanopore sequencing. Calprotectin was measured using an enzyme immunoassay. Median (Q₁-Q₃) antimicrobial duration was 5 (5-7.5) days in the PCT arm and 11 (8-15) days in the SoC arm (<em>P</em> &lt; 0.001). Faecal calprotectin levels were similar in the two treatment arms at baseline. By day 7, the levels of faecal calprotectin were significantly increased in the SoC arm (<em>P</em> = 0.002) but were unchanged in the PCT arm. Microbiome α- and β-diversity was similar at baseline in the PCT (n=81) and SoC (n=76) treatment arms. Shannon’s index was significantly lower in the SoC arm on day 7 compared with baseline (median [Q₁-Q₃], 2.88 [2.37-3.39] at day 1 vs. 2.24 [1.52-3.08] at day 7; <em>P</em>_t-test = 0.0013). This was not the case for the PCT arm (median [Q₁-Q₃], 2.73 [2.26-3.4] at day 1 vs. 2.43 [1.81-3.21] at day 7; <em>P</em>_t-test = 0.037, Bonferroni corrected α = 0.0125). The relative abundance of <em>Actinomycetota</em> and <em>Pseudomonadota</em> was decreased in the PCT arm by day 7 and that of <em>Bacillota</em> was increased. Early PCT-guided stop of antibiotics contributes to decreased microbiome dysbiosis by day 7.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107507"},"PeriodicalIF":4.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934620","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":"Bayesian evaluation of phage therapy efficacy against multidrug-resistant Acinetobacter baumannii","authors":"Momna Arooj Malik ,&nbsp;Sobia Manzoor ,&nbsp;Javed Ashraf","doi":"10.1016/j.ijantimicag.2025.107508","DOIUrl":"10.1016/j.ijantimicag.2025.107508","url":null,"abstract":"<div><h3>Purpose</h3><div>The objective of this study is to examine the efficacy of bacteriophage therapy in combating <em>Acinetobacter baumannii</em>, a pathogen known for its multidrug resistance, through the application of Bayesian statistical models. The research focuses on measuring survival outcomes in preclinical animal models that have been treated with bacteriophages, highlighting the promise of Bayesian methods in tackling the uncertainties present in biological data.</div></div><div><h3>Methodology</h3><div>We carried out a systematic review, focusing on identifying pertinent studies regarding phage therapy in animal models. Bayesian exploratory data analysis was utilized to evaluate survival rates among three species: rodents, <em>Galleria mellonella</em>, and zebrafish. Various prior distributions were utilized in sensitivity analyses to assess the reliability of the results.</div></div><div><h3>Results</h3><div>The study showed that groups that were treated with phage therapy had much higher survival rates across all experimental models. In untreated groups, survival rates for rodents ranged from 20% to 40%, while treated groups saw an increase to between 60% and 80%. Survival rates went up in the <em>G. mellonella</em> and zebrafish models. They went from 30% to 50% in the untreated groups to 70%–90% and 70%–80%, respectively, in the treated groups. The analysis demonstrated the reliability of these findings, showing consistent survival advantages across different prior assumptions.</div></div><div><h3>Practical implications</h3><div>The results support the clinical development of phage therapy as a possible way to treat infections that are resistant to multiple drugs. The use of Bayesian methods provides a strong foundation for assessing therapeutic effectiveness, especially in situations where conventional statistical approaches might fall short.</div></div><div><h3>Originality/value</h3><div>In this study, Bayesian methods are used in a new way to figure out how well phage therapy works. This shows that they can handle variation and uncertainty in preclinical studies. This research adds to the increasing body of evidence that highlights phage therapy as a viable alternative to traditional antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107508"},"PeriodicalIF":4.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922107","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 use of antimicrobial growth promoters linked to antimicrobial resistance in food-producing animals? A systematic review","authors":"Floriane Etienne ,&nbsp;Thibaut Lurier ,&nbsp;Javier Yugueros-Marcos ,&nbsp;Ana Luisa Pereira Mateus","doi":"10.1016/j.ijantimicag.2025.107505","DOIUrl":"10.1016/j.ijantimicag.2025.107505","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) poses a global threat to the health of humans, animals and plants, as well as the environment. In recent years, attention has increasingly focused on the role of antimicrobials as growth promoter (AGPs) in livestock. While the mechanism of action of AGPs is still poorly understood, mounting evidence suggests a link between AGP use and AMR. Consequently, several countries and regions have restricted/banned AGP use in livestock. However, such efforts encounter political, financial, social, and cultural challenges.</div><div>This systematic review aims to investigate the impact of AGP use on AMR in food-producing animals and focused on the emergence of phenotypic resistance in <em>Escherichia coli</em> isolated from livestock exposed to AGPs.</div><div>Overall, 7000 studies were screened at title, abstract and full text; from these, 10 were deemed eligible for inclusion in this review. Among the 10 selected studies, seven noted significant increase of AMR associated with AGP use. Significantly increased resistance levels to Highest Priority Critically Important Antimicrobials for human health such as ceftiofur, cefotaxime, ciprofloxacin, and nalidixic acid were observed among other antimicrobials. However, the studies revealed high risk of bias underscoring the need for further research.</div><div>This review provides a deeper understanding of the consequences of AGP use and occurrence of AMR. It highlights the need for implementing efficient surveillance systems and fostering research into suitable alternatives to AGPs. A shift to sustainable husbandry practices including responsible AMU while safeguarding animal health, productivity and farmers’ livelihoods are essential for successful policy implementation.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107505"},"PeriodicalIF":4.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794385","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 accurate amplification-free CRISPR/Cas12a-based assay for GES β-lactamase detection","authors":"Daniel Pablo-Marcos ,&nbsp;Leticia Fernández-Diego ,&nbsp;Jorge Rodríguez-Grande ,&nbsp;Nuria Fraile-Valcárcel ,&nbsp;Concha Ortiz-Cartagena ,&nbsp;Olga Pacios ,&nbsp;Samuel García-García ,&nbsp;Sergio García-Fernández ,&nbsp;Lucía Blasco ,&nbsp;Alain Ocampo-Sosa ,&nbsp;Jorge Calvo-Montes ,&nbsp;María Tomás","doi":"10.1016/j.ijantimicag.2025.107506","DOIUrl":"10.1016/j.ijantimicag.2025.107506","url":null,"abstract":"<div><h3>Objective</h3><div>Guiana-Extended-Spectrum (GES) β-lactamases belong to the minor class A β-lactamases and are probably underdiagnosed due to a lack of specific diagnostic tests. There is therefore an urgent need to develop new molecular diagnostic tools that will be able to fill the gap in the detection of rare β-lactamases. Here, we propose an optimized, amplification-free CRISPR/Cas12a-based assay for the accurate detection of GES β-lactamases and we validate its application with clinical isolates <strong>(Graphic abstract)</strong>. Based on the results of examination of 79 standard collection, the proposed assay exhibited 100% sensitivity and specificity, as well as 100% positive and negative predictive values in less than 1.5 hours.</div></div><div><h3>Methods</h3><div>We optimized the CRISPR/Cas12a method by harnessing a multiplex crRNA strategy, a highly efficient DNA reporter (TTATT-5C) and the Murine RNase Inhibitor to prevent crRNA degradation.</div></div><div><h3>Results</h3><div>Our yielded limits of detection of 1 ng/µL and 3 ng/µL in <em>Enterobacterales</em> and <em>Pseudomonas aeruginosa</em>, respectively. The observed difference is due to the location of the <em>bla</em>_GES gene. The gene occurs in a chromosomal integron present only in one to three copies in <em>P. aeruginosa</em>, whereas it occurs in plasmids present in multiple copies in <em>Enterobacterales</em>.</div></div><div><h3>Conclusions</h3><div>The proposed method could be established as a routine diagnostic tool in clinical microbiology laboratories to fill the gap in availability of commercial diagnostic tests for GES β-lactamases.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107506"},"PeriodicalIF":4.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788327","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":"Probiotic effects of Clostridium cellabutyricum against Pseudomonas aeruginosa infection in antibiotic-induced gut microbial dysbiosis mice model","authors":"Meng-Ling Wang ,&nbsp;Yuan-Jie Zhang ,&nbsp;Hong Xiao ,&nbsp;Xiao-Ling Lu,&nbsp;Li Chen,&nbsp;Zhi-Wen Ma,&nbsp;Anyi Chen,&nbsp;Qi Yin","doi":"10.1016/j.ijantimicag.2025.107503","DOIUrl":"10.1016/j.ijantimicag.2025.107503","url":null,"abstract":"<div><h3>Objective</h3><div>Gut microbiota dysbiosis induced by antibiotic use weakens its colonization resistance against opportunistic pathogens, increasing the risk of invasion and infection. While probiotics have the potential to restore the impaired gut microbial structure and prevent respiratory tract infections, the effectiveness of specific strains and the underlying mechanisms remain largely unexplored. In this study, the preventive effects of a novel butyrate-producing bacterium, <em>Clostridium cellabutyricum</em> YQ-FP-027^T against <em>Pseudomonas aeruginosa</em> infection after antibiotic exposure were investigated in antibiotic-pretreated mice model.</div></div><div><h3>Methods</h3><div>Phenotypic characterizations including the bacterial load in the lung, the assessment of gene expression of immune factors in lung tissue using qPCR, and detection of gut microbial composition using 16S rRNA sequencing were conducted. Pulmonary bacterial load and expression levels of immune factors of lung tissue, and gut microbial composition were evaluated.</div></div><div><h3>Results</h3><div>Our results demonstrated that YQ-FP-027^T ameliorated lung tissue integrity, significantly reduced pulmonary bacterial burden, and decreased the expression of interleukin-1β and TNF-α, while enhancing the expression of interleukin-10 and cathelicidin-related antimicrobial peptide. Furthermore, YQ-FP-027^T increased the abundance of <em>Lachnospiraceae</em> in the gut and reduced the abundance of opportunistic pathogens such as <em>Enterococcaceae</em> and <em>Helicobacteraceae</em>.</div></div><div><h3>Conclusions</h3><div>These results suggest YQ-FP-027^T exerts probiotic effects by restoring gut microbiota balance, enhancing intestinal barrier function, and positively influencing pulmonary immune responses through the gut-lung axis. This study reveals the preventive potential of YQ-FP-027^T against <em>P. aeruginosa</em> infection in the context of gut microbiota dysbiosis, offering a novel preventive strategy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107503"},"PeriodicalIF":4.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788330","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":"Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation","authors":"Alicia Moreno-Sabater ,&nbsp;Rachel Sintes ,&nbsp;Sandrine Truong ,&nbsp;Kimberly Lemoine ,&nbsp;Océane Camou ,&nbsp;Nathalie Kapel ,&nbsp;Denis Magne ,&nbsp;Anne-Christine Joly ,&nbsp;Isabelle Quelven-Bertin ,&nbsp;Laurent Alric ,&nbsp;Christophe Hennequin ,&nbsp;Harry Sokol ,&nbsp;the French Faecal Microbiota Transplant Group","doi":"10.1016/j.ijantimicag.2025.107504","DOIUrl":"10.1016/j.ijantimicag.2025.107504","url":null,"abstract":"<div><div>Fecal microbiota transplantation (FMT) for recurrent <em>Clostridioides difficile</em> infection (rCDI) requires careful selection of stool donors to avoid transmitting pathogens. <em>Dientamoeba fragilis</em> detection remains an exclusion criterion based on its uncertain pathogenicity. The aim of this study was to assess <em>D. fragilis</em> interhuman transmission by FMT and its impact on the clinical success of rCDI. A retrospective study was conducted in rCDI patients from the COSMIC cohort undergoing FMT to investigate the potential transfer of <em>D. fragilis</em> from donor to recipient. The impact of FMT involving <em>D. fragilis</em> was also evaluated in regard to the clinical outcomes of rCDI and adverse effects. This protist was found to be present in 15 of 86 healthy donors screened (18.7%) who voluntarily took part in an FMT program. Examination of <em>D. fragilis</em> presence in stool samples from 17 patients both before and after FMT with <em>D. fragilis</em>-positive donations revealed no evidence of interhuman transmission through this process. Analysis of clinical outcomes and adverse events in 124 rCDI patients who underwent FMT (with 45 receiving <em>D. fragilis</em>–positive donations) showed no significant differences in success rates between patients receiving positive or negative <em>D. fragilis</em> transplants (95.5% and 93.6%, respectively). No significant variances were observed in other side effects analyzed. These findings underscore the safety of using fecal transplant from <em>D. fragilis</em>–positive donors in the FMT process. <em>D. fragilis</em> should be removed from the donor screening, which will represent a major improvement in the donor selection process from financial and practical standpoints.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107504"},"PeriodicalIF":4.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788329","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00058-5","DOIUrl":"10.1016/S0924-8579(25)00058-5","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107501"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737835","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}