Lancet Microbe最新文献

{"title":"State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus.","authors":"Julie Rodriguez, Zahra Hassani, Carolina Alves Costa Silva, Fay Betsou, Federica Carraturo, Alessio Fasano, Mads Israelsen, Anandhi Iyappan, Aleksander Krag, Amira Metwaly, Robert Schierwagen, Jonel Trebicka, Hub Zwart, Joel Doré, Magali Cordaillat-Simmons, Celine Druart","doi":"10.1016/j.lanmic.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.07.011","url":null,"abstract":"<p><p>Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First self-test for hepatitis C virus.","authors":"Priya Venkatesan","doi":"10.1016/j.lanmic.2024.100979","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100979","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cases of avian influenza A(H5) in the USA.","authors":"Priya Venkatesan","doi":"10.1016/j.lanmic.2024.100978","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100978","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study.","authors":"Daniel Mukadi-Bamuleka, François Edidi-Atani, Maria E Morales-Betoulle, Anaïs Legand, Antoine Nkuba-Ndaye, Junior Bulabula-Penge, Placide Mbala-Kingebeni, Ian Crozier, Fabrice Mambu-Mbika, Shannon Whitmer, Olivier Tshiani Mbaya, Lisa E Hensley, Richard Kitenge-Omasumbu, Richard Davey, Sabue Mulangu, Peter N Fonjungo, Michael R Wiley, John D Klena, Martine Peeters, Eric Delaporte, Johan van Griensven, Kevin K Ariën, Catherine Pratt, Joel M Montgomery, Pierre Formenty, Jean-Jacques Muyembe-Tamfum, Steve Ahuka-Mundeke","doi":"10.1016/S2666-5247(24)00137-X","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00137-X","url":null,"abstract":"<p><strong>Background: </strong>During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence.</p><p><strong>Methods: </strong>In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques.</p><p><strong>Findings: </strong>The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2.</p><p><strong>Interpretation: </strong>We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence.</p><p><strong>Funding: </strong>Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study","authors":"","doi":"10.1016/S2666-5247(24)00101-0","DOIUrl":"10.1016/S2666-5247(24)00101-0","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The emerging fungal pathogen &lt;em&gt;Candida auris&lt;/em&gt; poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual &lt;em&gt;C auris&lt;/em&gt; isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known &lt;em&gt;C auris&lt;/em&gt; clades (I–V).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this genotypic and phenotypic study, we characterised three &lt;em&gt;C auris&lt;/em&gt; clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these &lt;em&gt;C auris&lt;/em&gt; isolates. The complete genomes were compared with representative genomes of all known &lt;em&gt;C auris&lt;/em&gt; clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;The three investigated isolates were separated by at least 37 000 SNPs (range 37 000–236 900) from all existing &lt;em&gt;C auris&lt;/em&gt; clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of &lt;em&gt;C auris,&lt;/em&gt; clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;p&gt;The discovery of a new &lt;em&gt;C auris&lt;/em&gt; clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of &lt;em&gt;C auris&lt;/em&gt;, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of &lt;em&gt;C auris&lt;/em&gt; infections.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Funding&lt;/h3&gt;&lt;p&gt;Duke-NUS Academic Medical Center Nurturing Cl","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724001010/pdfft?md5=0066d8cd1c31db4feb85fd8b229654f1&pid=1-s2.0-S2666524724001010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To vaccinate or not against highly pathogenic avian influenza?","authors":"","doi":"10.1016/S2666-5247(24)00107-1","DOIUrl":"10.1016/S2666-5247(24)00107-1","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724001071/pdfft?md5=0460eae2fc132680c775001d030173bc&pid=1-s2.0-S2666524724001071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candida auris: new clade, same challenges","authors":"","doi":"10.1016/j.lanmic.2024.100977","DOIUrl":"10.1016/j.lanmic.2024.100977","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724002386/pdfft?md5=60b4b15fe34e21b7499564e96d19ae1c&pid=1-s2.0-S2666524724002386-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonising the measurement of neutralising antibodies against chikungunya virus: a path forward for licensing of new vaccines?","authors":"","doi":"10.1016/S2666-5247(24)00097-1","DOIUrl":"10.1016/S2666-5247(24)00097-1","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000971/pdfft?md5=6c1c52597c47530e515792ccb5212867&pid=1-s2.0-S2666524724000971-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MERS-CoV exposure and risk factors for MERS-CoV ELISA seropositivity among members of livestock-owning households in southern Jordan: a population based cross-sectional study","authors":"","doi":"10.1016/S2666-5247(24)00082-X","DOIUrl":"10.1016/S2666-5247(24)00082-X","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Although dromedary camels (&lt;em&gt;Camelus dromedarius&lt;/em&gt;) are known to be the host reservoir for MERS-CoV, the virus causing Middle East respiratory syndrome (MERS), zoonotic transmission pathways and camel subpopulations posing highest transmission risk are poorly understood. Extensively managed herds, ubiquitous across the Arabian Peninsula, present a major potential source of primary infection. In this study we aimed to address key knowledge gaps regarding MERS epidemiology among high-risk communities associated with such herds, which is essential information for effective control strategies.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We did a cross-sectional study between Sept 27, 2017, and Oct 11, 2018, among members of livestock-owning households in southern Jordan (Aqaba East, Aqaba West, Ma’an East, and Ma’an West regions), with random selection of households (house and tent dwellings) from Ministry of Agriculture lists via computer-generated randomisation lists. Household visits were done, with questionnaires administered to household members regarding potential risk factors for MERS-CoV exposure in the past 6 months and blood samples and nasal and oral swabs collected, alongside physical examination data including blood pressure and blood glucose. Children younger than 5 years and individuals without capacity to provide informed consent were excluded. Serum was tested for IgG antibodies to MERS-CoV spike protein (S1 subunit) and nucleocapsid (N) protein with in-house indirect ELISAs, and viral RNA was detected in nasal and oral samples by RT-PCR. The primary outcome was evidence of MERS-CoV exposure (ascertained by seropositive status on S1 or N ELISAs, or a positive swab sample on RT-PCR); secondary outcomes were potential associations between possible risk factors and seropositive status. RT-PCR data were to be presented descriptively. Seroprevalence estimates were obtained at the individual and household levels, and associations between hypothetical risk factors and seropositive status were assessed with use of mixed-effects logistic regression.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;We sampled 879 household members (median age 27 years [IQR 16–44]; 471 [54%] males and 408 [46%] females) from 204 households. 72 (8%) household members were seropositive on S1 ELISA (n=25, 3%) or N ELISA (n=52, 6%). No positive nasal or oral swab samples were identified on RT-PCR. Within-household clustering was identified for seropositivity on S1 ELISA (intraclass correlation coefficient 0·88 [0·35–0·96]) but not N ELISA (0·00 [0·00–0·27]). On multivariable analysis, S1 ELISA seropositivity was associated with frequently (≥weekly) interacting with young (age &lt;1 year) camels (adjusted odds ratio [OR&lt;sub&gt;adj&lt;/sub&gt;] 3·85 [95% CI 1·41–11·61], p=0·011), with frequent kissing and petting (OR&lt;sub&gt;adj&lt;/sub&gt; 4·56 [1·55–15·42], p=0·0074), and frequent feeding and watering (OR&lt;sub&gt;adj&lt;/sub&gt; 4·97 [1·80–15·29], p=0·0027) of young camels identified as ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266652472400082X/pdfft?md5=4e23a680a4d80620594bd79b719e967b&pid=1-s2.0-S266652472400082X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies","authors":"","doi":"10.1016/S2666-5247(24)00079-X","DOIUrl":"10.1016/S2666-5247(24)00079-X","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18–70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25–74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5–7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60–0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77–0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;p&gt;Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266652472400079X/pdfft?md5=fd2df1ffc0f7c117acb299cdf1ceffdd&pid=1-s2.0-S266652472400079X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}