The Journal of Infectious Diseases最新文献

{"title":"Anelloviruses and Cancer","authors":"Jason Y Tang, Trevor B Chen, Valentina L Kouznetsova, Igor F Tsigelny","doi":"10.1093/infdis/jiae626","DOIUrl":"https://doi.org/10.1093/infdis/jiae626","url":null,"abstract":"Anelloviruses are among the most prevalent viruses within the human virome, detected in over 90% of healthy individuals. Despite their ubiquity, the role of anelloviruses in human health remains elusive. This review examines the potential associations of anelloviruses torque teno virus (TTV), torque teno midi virus (TTMDV), and torque teno mini virus (TTMV) with various cancers, highlighting the mixed conclusions from current epidemiological studies. Anelloviruses may modulate cancer development through abnormal gene fusion, immune response, and toll-like receptor 9 (TLR9) activation. On the other hand, anelloviruses might suppress tumor formation through TTV-derived apoptosis-inducing protein (TAIP) and NF-κB signaling inhibition. The high prevalence of anelloviruses in cancer patients could also be attributed to their immunocompromised status rather than a direct causative role of the viruses. This review underscores the need for more comprehensive studies, including in vitro and in vivo experiments, to clarify the role of anelloviruses in cancer development and progression.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decline of antibodies to major viral and bacterial respiratory pathogens during the COVID-19 pandemic","authors":"Natalie Lorenz, Alex James, Tiaan Van Rooyen, Aimee Paterson, Ciara Ramiah, Lauren Carlton, Prachi Sharma, Michael G Baker, Richard Charlewood, Reuben McGregor, Nicole J Moreland","doi":"10.1093/infdis/jiae611","DOIUrl":"https://doi.org/10.1093/infdis/jiae611","url":null,"abstract":"Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort","authors":"Jianping Jiang, Lauren Komarow, Carol Hill, Angelique E Boutzoukas, Blake Hanson, Cesar A Arias, Robert A Bonomo, Scott Evans, Yohei Doi, Michael J Satlin, Gregory Weston, Eric Cober, Sandra Liliana Valderrama-Beltran, Soraya Salcedo Mendoza, Zhengyin Liu, Bettina C Fries, Paul Ananth Tambyah, Henry F Chambers, Vance G Fowler, David van Duin, Barry N Kreiswirth, Liang Chen","doi":"10.1093/infdis/jiae616","DOIUrl":"https://doi.org/10.1093/infdis/jiae616","url":null,"abstract":"Background Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp. infections. Methods Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016-2018 with cultures positive for carbapenemase-producing Enterobacter spp. were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed. Results We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp. from 30 hospitals in 7 countries. Among the 136 isolates, eleven Enterobacter species were identified, with most isolates belonging to E. xiangfangensis (n=81, 60%) and E. hoffmannii (n=17, 13%), and carrying blaKPC (n=106, 78%) and blaNDM (n=12, 9%). Clinical characteristics and outcomes were similar among patients with E. xiangfangensis, E. hoffmannii or the other Enterobacter spp. 30-day mortality was 20% and older age at enrollment (adjusted odds ratio 1.42, 95% confidence interval 1.08-1.87) was associated with increased mortality. Sequence type (ST)171 E. xiangfangensis, ST78 E. hoffmannii, and ST93 E. xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination. Conclusions Our findings demonstrated that E. xiangfangensis and E. hoffmannii are common species among international carbapenemase-producing Enterobacter spp., potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue Resident CD8+T-cells as mediators of protective immunity in breastmilk transmission of HCMV","authors":"Shara Legg, David C Moylan, Neema Kamau, Misty P Latting, Dhruv Devdhara, Sunil K Pati, David K Crossman, Suresh B Boppana, Olaf Kutsch, Steffanie Sabbaj","doi":"10.1093/infdis/jiae618","DOIUrl":"https://doi.org/10.1093/infdis/jiae618","url":null,"abstract":"While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk. In addition, we describe tissue resident memory T-cells (Trm) in breastmilk and demonstrate most were Tem. We present data that non-transmitter moms have increased frequency of CD8+ Trm T-cells in their breastmilk when compared to transmitters and that Trm frequency is inversely correlated with breastmilk HCMV VL. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in non-transmitters and demonstrate that these cells comprise CD8+ Trm T-cells. These studies suggest that CD8+ Trm T-cells may play a role in preventing viral transmission via breastmilk to infants.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance are Infrequent and Impart a Major Fitness Cost","authors":"Laura M Hagenah, Tomas Yeo, Kyra A Schindler, Jin H Jeon, Talia S Bloxham, Jennifer L Small-Saunders, Sachel Mok, David A Fidock","doi":"10.1093/infdis/jiae617","DOIUrl":"https://doi.org/10.1093/infdis/jiae617","url":null,"abstract":"Background Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa. Methods We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P. falciparum asexual blood stage parasites expressing three prevalent African mutant PfCRT haplotypes. Gene-edited clones were profiled in antimalarial concentration-response and competitive fitness assays. Results pfcrt-edited parasites expressing the contemporary Southeast Asian T93S or I218F mutations added to the GB4 and Cam783 haplotypes common in Africa did not mediate piperaquine resistance, with partial survival only at low drug concentrations. In contrast, parasites expressing these mutations on the rare PfCRT FCB haplotype, observed mostly in North-East Africa, acquired a moderate level of piperaquine resistance. Dd2GB4, Dd2Cam783, and Dd2FCB lines edited to express the T93S or I218F mutations showed increased susceptibility to chloroquine. Piperaquine-resistant African PfCRT isoforms conferred a substantial fitness cost, manifesting as reduced asexual blood stage parasite growth rates. Conclusions These findings suggest that piperaquine-resistant PfCRT mutations that emerged in Southeast Asia mediate resistance only in a limited subset of African PfCRT haplotypes, with fitness costs that we suspect would likely preclude dissemination in high-transmission malaria-endemic African regions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmodium knowlesi Infection Is Associated With Elevated Circulating Biomarkers of Brain Injury and Endothelial Activation","authors":"Cesc Bertran-Cobo, Elin Dumont, Naqib Rafieqin Noordin, Meng-Yee Lai, William Stone, Kevin K A Tetteh, Chris Drakeley, Sanjeev Krishna, Yee-Ling Lau, Samuel C Wassmer","doi":"10.1093/infdis/jiae553","DOIUrl":"https://doi.org/10.1093/infdis/jiae553","url":null,"abstract":"Background Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains unexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls. Methods Archived plasma samples from 19 Malaysian patients with symptomatic knowlesi infection and 19 healthy, age-matched controls were analyzed. Fifty-two biomarkers of brain injury, inflammation, and vascular activation were measured. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis. Results Bonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (P < .0001), Tau (P = .0007), UCH-L1 (P < .0001), αSyn (P < .0001), Park7 (P = .0006), NRGN (P = .0022), and TDP-43 (P = .005). Compared to controls, levels were lower in the infected group for BDNF (P < .0001), CaBD (P < .0001), CNTN1 (P < .0001), NCAM-1 (P < .0001), GFAP (P = .0013), and KLK6 (P = .0126). Hierarchical clustering revealed distinct group profiles for brain injury and vascular activation biomarkers. Conclusions Our findings highlight for the first time a potential impact of P knowlesi infection on the brain, with specific changes in cerebral injury and endothelial activation biomarker profiles. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered markers, through neuroimaging and long-term neurocognitive assessments.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of laundry practices in eliminating monkeypox virus (MPXV) from fabrics","authors":"Ana K Pitol, Siobhan Richards, Patrick Mirindi, Hibak O Mahamed, April Baller, Grant L Hughes, Sara E Beck","doi":"10.1093/infdis/jiae606","DOIUrl":"https://doi.org/10.1093/infdis/jiae606","url":null,"abstract":"Background The declaration of mpox as a Public Health Emergency of International Concern highlights the need for interventions to interrupt virus transmission, including transmission via fabrics. Current World Health Organization guidance on clothes washing is based on a general consensus of virus inactivation; however, there is uncertainty about the efficacy of laundry detergents and disinfectants or the reduction of risk achieved by washing clothes for monkeypox virus (MPXV) specifically. Methods This study investigates the efficacy of manual washing for inactivating MPXV from clothes. Using a simulated washing method, we evaluated the efficacy of commonly-used laundry products and high temperature water for inactivating MPXV on fabrics. Cotton and polyester fabrics were inoculated with MPXV for 1 min, placed in a microcentrifuge tube containing water or water with test product for 20 minutes, with agitation every 5 min to simulate manual washing. Results Sodium hypochlorite, liquid sanitizer, and two powdered laundry detergents dissolved in room temperature water, as well as 70-degree water alone, completely inactivated MPXV (>3 log10reduction or >99.9% inactivation) on both cotton and polyester fabrics. Conclusion Given the expected concentrations of MPXV on fabrics, the low transfer rate of viruses from porous surfaces to skin, the effective inactivation of laundry processes, and the expected doses required for infection, we expect the risk of transmission after laundering contaminated fabrics to be low. This study provides evidence to support WHO guidance for MPXV inactivation, reducing the viral load on fabrics to prevent the spread of mpox in both healthcare and household settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neisseria meningitidis urethritis clade (NmUC) acts as a “chimeric pathogen” during infection of primary, human male, urethral epithelial cells","authors":"Yih-Ling Tzeng, Danillo L A Esposito, Andrew G Nederveld, Rachael L Hardison, Alexandria M Carter, David S Stephens, Abigail Norris Turner, Jose A Bazan, Jennifer L Edwards","doi":"10.1093/infdis/jiae604","DOIUrl":"https://doi.org/10.1093/infdis/jiae604","url":null,"abstract":"Background Clusters of male urethritis cases, caused by a novel clade of non-groupable Neisseria meningitidis (NmUC, “the clade”), have been reported globally. Genetic features unique to NmUC isolates include: the acquisition of the gonococcal denitrification loci, norB-aniA; a unique factor H binding protein (fHbp) variant; and loss of group C capsule and intrinsic lipooligosaccharide sialylation. We hypothesized that these characteristics might confer a colonization and survival advantage to NmUC during male urethral infection relative to non-clade group C Neisseria meningitidis. Methods NmUC, gonococcal, and non-clade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial cell (UEC) infection studies. Results NmUC strains were approximately six times more invasive in UECs than the gonococcal strains tested, which could not be attributed to loss of capsule expression alone. Whereas gonococci and NmUC strains survived and proliferated within UECs, negligible survival was observed for non-clade meningococcal strains. NmUC adherence to, invasion of, and survival within UECs was significantly decreased when host receptors known to mediate gonococcal or meningococcal interactions with epithelial cells were blocked. Infection studies indicated that fHbp contributes to clade survival independent of its ability to bind extracellular factor H, and the gonococcal denitrification pathway, particularly NorB, plays an important role in promoting clade intracellular survival. Conclusions Whereas mechanisms used by NmUC to infect UECs are shared with other neisserial strains, hybrid mechanisms unique to the clade also mediate infection and allow adaptation to the male urethra. Thus, NmUC is a “chimeric pathogen”, displaying facets of gonococcal and meningococcal pathogenesis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HHV-6B, HHV-7, and B19V Are Frequently Found DNA Viruses in the Human Thymus but Show No Definitive Link with Myasthenia Gravis","authors":"Kirsten Nowlan, Leo Hannolainen, Irini M Assimakopoulou, Pia Dürnsteiner, Joona Sarkkinen, Santeri Suokas, Lea Hedman, Pentti J Tienari, Klaus Hedman, Mikael Niku, Leena-Maija Aaltonen, Antti Huuskonen, Jari V Räsänen, Ilkka K Ilonen, Mikko I Mäyränpää, Johannes Dunkel, Sini M Laakso, Maria Söderlund-Venermo, Maria F Perdomo, Eliisa Kekäläinen","doi":"10.1093/infdis/jiae600","DOIUrl":"https://doi.org/10.1093/infdis/jiae600","url":null,"abstract":"Myasthenia gravis (MG) is a rare autoimmune disorder characterised by muscle weakness resulting from autoantibody-mediated disruption of the neuromuscular junction. Notably, it is also frequently associated with thymic pathology. This study explores the relationship between MG and DNA viruses in the thymus, employing targeted NGS and qPCR to analyse thymic tissue samples from both MG patients and healthy controls. We detected HHV-6B, HHV-7, EBV, and B19V across various tissue groups. However, no significant enrichment of these viruses was observed in the thymic tissue of MG patients. Additionally, we confirmed a dormant persistence of B19V within the thymus of seropositive individuals. These findings indicate that DNA viruses are unlikely to serve as primary environmental triggers for MG.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct acting antivirals eradicate HCV from the liver quickly in people with HIV but do not fully reverse immune activation","authors":"Jaiprasath Sachithanandham, Julia Leep-Lazar, Jeffrey Quinn, Kenneth Bowden, Prasanthy Balasubramaniam, Kathleen Ward, Ruy M Ribeiro, Mark S Sulkowski, Ashwin Balagopal","doi":"10.1093/infdis/jiae598","DOIUrl":"https://doi.org/10.1093/infdis/jiae598","url":null,"abstract":"Background Hepatitis C virus (HCV) infects nearly one-fourth of people with HIV (PWH). The role of direct-acting antivirals (DAAs) on immune activation in PWH and HCV is poorly understood. Methods We quantified plasma HCV RNA and CXCL10 in persons with HCV mono- versus HIV/HCV co-infection receiving Sofosbuvir-Velpatasvir. Single-cell laser capture was applied to liver biopsies obtained before and within 4-7 days of DAA initiation to estimate HCV clearance and changes in interferon stimulated genes (ISGs). Results We enrolled ten people with chronic genotype 1a HCV: five were PWH. Median (min-max) ages at enrollment were 55.5 (28-66) years, five were women, and eight were African American. At baseline, plasma HCV RNA levels were 6.36 (5.68-7.93) log10 IU/mL; all had transient elastography liver stiffness < 9 kPa. CD4+ T cell counts in PWH were 768 (244-1136) cells/µL. All had suppressed HIV viremia on antiretrovirals. First and second phase plasma HCV RNA kinetics were not different between groups. Median (min-max) proportions of infected hepatocytes at biopsy 1 were 0.06 (0.01-0.59) in HCV mono- and 0.21 (0.04-0.87) in HIV/HCV co-infection and did not differ. Participants had lower intracellular HCV RNA levels at biopsy 2, but not differentially by HIV status. CXCL10 levels declined in both groups but was higher in co- than in mono-infection even at the end of treatment. Proportion of cells expressing ISGs diminished in mono- but increased in co-infection. Conclusion Whereas DAAs rapidly cleared intrahepatic HCV in both groups, immune activation was slower to diminish in PWH. Residual immune activation in PWH warrants further exploration.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"228 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}