{"title":"Development of a HiFi-LAMP Assay for Detection of Human Pegivirus Type 1 RNA","authors":"Xiuli Zhao, Chuyue Lu, Ziyan Wang, Feng Qiao, Chiyu Zhang, Zhenzhou Wan","doi":"10.1002/jmv.70423","DOIUrl":"https://doi.org/10.1002/jmv.70423","url":null,"abstract":"<div>\u0000 \u0000 <p>Human pegivirus (HPgV) is a blood-borne RNA virus belonging to the family <i>Flaviviridae</i>, and contains two types HPgV-1 and HPgV-2. HPgV-1 infection does not cause acute diseases in healthy individuals but was demonstrated to play beneficial roles in individuals coinfected with HIV-1. HPgV-1 has a high prevalence in blood donors and the general population worldwide. The long-term consequence of HPgV-1 infection in healthy individuals remains unknown. High prevalence of HPgV-1 in blood donors raises concerns about the risk of transfusion transmission. Development of rapid and accurate point-of-care testing (POCT) of HPgV-1 will facilitate the screening of HPgV-1 infection among blood donors. Here, we reported a novel high-fidelity loop-mediated isothermal amplification (HiFi-LAMP) assay for detection of HPgV-1 and evaluated its performance in 175 healthy adults from Taizhou, China. The assay exhibits high specificity and sensitivity with limits of detection (LODs) of 122.6–135.7 copies of viral RNA/25 μL reaction for various HPgV-1 variants and can be completed within 30 min. Clinical validation showed that the assay had a 100% concordance with a previously described RT-qPCR assay for 175 sera from healthy adults, showing 100% sensitivity and specificity. Furthermore, we reported a 28.0% (111/397) prevalence of HPgV-1 in healthy adults in Taizhou, China, with no significant differences between genders and ages. The prevalence is obviously higher than a pooled HPgV-1 prevalence of 3.3% in blood donors in China. The novel HPgV-1 HiFi-LAMP assay offers a robust, rapid, and cost-effective tool for HPgV-1 surveillance to mitigate transfusion risk, especially in resource-limited areas. High prevalence of HPgV-1 in healthy adults underscores its potential public health relevance.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic Molecular Changes in Brain, Lung, and Heart of Hamsters Infected With SARS-CoV-2: Insights From a Severe and Recovery Phase Model","authors":"Wanjun Peng, Xiaohui Wei, Yue Wu, Chunmei Shi, Xiaoyan Liu, Jing Wu, Hekai Yang, Na Rong, Binbin Zhao, Gengxin Zhang, Wei Zhang, Jiangfeng Liu, Jiangning Liu, Juntao Yang","doi":"10.1002/jmv.70410","DOIUrl":"https://doi.org/10.1002/jmv.70410","url":null,"abstract":"<div>\u0000 \u0000 <p>The Global pandemic of coronavirus disease 2019 was initiated by the emergence of severe acute respiratory syndrome coronavirus 2. In addition to conventional pulmonary lesions, a range of neurological injury symptoms have been identified in clinical practice, but the aetiology of neurological disorders linked to SARS-CoV-2 infection remains poorly understood. Syrian hamsters, which are highly susceptible to SARS-CoV-2 infection, exhibit a disease phenotype similar to that observed in human COVID-19 patients. In this study, a hamster model of COVID-19 infection was used to analyze molecular changes in different tissues at various time points post infection with distinct strains using proteomic and phosphoproteomic approaches. Multi-omics analysis showed that SARS-COV-2 infection triggers sustained downregulation of the abundance and phosphorylation levels of neuronal and synapse-associated proteins in the brain, suggesting that neuronal damage persists even during the recovery period. Additionally, infections with SARS-CoV-2 may contribute to the onset of long-term symptoms of COVID-19 by impacting energy metabolism, neurotransmitter release, and synaptic transmission pathways. This study provides a comprehensive molecular profile of hamsters infected with different SARS-CoV-2 strains in different tissues, offering foundational insights into the pathogenic mechanisms of COVID-19.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Whole Genome Sequencing and Genetic Diversity of Respiratory Viruses Detected in Children With Acute Respiratory Infections: A One-Year Cross-Sectional Study in Senegal”","authors":"","doi":"10.1002/jmv.70419","DOIUrl":"https://doi.org/10.1002/jmv.70419","url":null,"abstract":"<p>A. J. S. Ndiaye, S. Cortaderona, L. Delorme, et al., “Whole Genome Sequencing and Genetic Diversity of Respiratory Viruses Detected in Children With Acute Respiratory Infections: A One-Year Cross-Sectional Study in Senegal,” <i>Journal of Medical Virology</i> 97, no. 4 (2025): e70342, https://doi.org/10.1002/jmv.70342.</p><p>In the list of authors, the last name of the second author, “Cortaderona”, is incorrect. The correct spelling is: “Cortaredona.”</p><p>We apologize for this error.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Hantaan Virus (HTNV) Human Infection on Jeju Island, South Korea: Unique Phylogeny and Epidemiology of HTNV”","authors":"","doi":"10.1002/jmv.70420","DOIUrl":"https://doi.org/10.1002/jmv.70420","url":null,"abstract":"<p>M. Kim, S. T. Heo, S. Y. Kang, et al., “Hantaan Virus (HTNV) Human Infection on Jeju Island, South Korea: Unique Phylogeny and Epidemiology of HTNV,” <i>Journal of Medical Virology</i> 97 (2025): e70305, https://doi.org/10.1002/jmv.70305.</p><p>In the original publication, the grant number was incorrect in both the Funding section and the Acknowledgments as “Grant 2024040FABA-00”. This should change to: “Grant 2024ER210200.”</p><p>We apologize for this error.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Étienne Racine, Jocelyne Piret, Rodica Gilca, Rachid Amini, Guy Boivin
{"title":"Viral Interference and Coinfections: A Perspective From Hospital Surveillance of Respiratory Viruses","authors":"Étienne Racine, Jocelyne Piret, Rodica Gilca, Rachid Amini, Guy Boivin","doi":"10.1002/jmv.70399","DOIUrl":"https://doi.org/10.1002/jmv.70399","url":null,"abstract":"<div>\u0000 \u0000 <p>Viral interference may influence pathogen transmission at the population level, potentially affecting seasonal epidemics of respiratory infections. A frequently employed association measure purported to reflect interference effects is the prevalence ratio, the proportion of individuals coinfected with two viruses divided by the product of the proportions of individuals infected by each virus separately. However, the prevalence ratio neglects three important factors relevant to coinfection detection in epidemiological surveillance programs: undetected mono-infections, duration of viral excretion or detectability and circulation patterns of both viruses. We propose a generalization of the prevalence ratio that accounts for these factors to better assess the presence or absence of viral interactions in epidemiological surveillance data. We applied this association measure to influenza—respiratory syncytial virus (RSV) coinfection data from a hospital-based surveillance program of respiratory infections in the province of Québec, Canada, from 2012–2013 to 2018–2019 (HospiVir program). Our analysis suggests that influenza-RSV interference may be important in children but less in adults. However, our results are sensitive to population-level seasonal attack rates; coinfection data could be compatible with interference in adults if assumed attack rates increased from 3% to 5% to over 10%.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maternal Vaccination and Protective Immunity Against SARS-CoV-2 Infection in Pups","authors":"Kunpeng Liu, Juhong Rao, Xue Hu, Huize Sun, Mingqing Lu, Xiaoyu Zhang, Fang Huang, Chao Shan","doi":"10.1002/jmv.70418","DOIUrl":"https://doi.org/10.1002/jmv.70418","url":null,"abstract":"<div>\u0000 \u0000 <p>The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact worldwide. Currently, several vaccines are approved for emergency use in humans, and these vaccines have played a large role in controlling COVID-19. Pregnant women and newborns constitute a special population for vaccine policy. Here, we established a maternal vaccination model by injecting pregnant mice with a SARS-CoV-2 receptor-binding domain (RBD) homodimer. Maternal immunization with the RBD dimer did not cause obvious adverse effects on pregnancy or fetal development. Moreover, two-shot immunization fully protected dams and fetuses from SARS-CoV-2 infection during pregnancy. Neutralizing antibodies can be transferred from immunized dams to pups, providing protection for both lactating and weaned pups against SARS-CoV-2 infection. Our results indicate that, in addition to being used to vaccinate nonpregnant individuals, the RBD dimer can also be considered for maternal vaccination.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lan Yang, Tingting Cai, Xiaoyi Wang, Qiong Ge, Likun Lv, Dajin Xiao, Yunting Zeng, Xiaozhen Ma, Xiaofang Zhou, Yong Zhang, Na Liu, Dongmei Yan, Shuangli Zhu, Qian Yang, Jinbo Xiao, Qiang Sun, Lei Zhou, Mengyi Xiao, Tianjiao Ji
{"title":"Multiple Transmission Pathways of Coxsackievirus A10 Leading to its Global Spread: A Phylogenetic and Spatiotemporal Analysis Based on Virological Surveillance","authors":"Lan Yang, Tingting Cai, Xiaoyi Wang, Qiong Ge, Likun Lv, Dajin Xiao, Yunting Zeng, Xiaozhen Ma, Xiaofang Zhou, Yong Zhang, Na Liu, Dongmei Yan, Shuangli Zhu, Qian Yang, Jinbo Xiao, Qiang Sun, Lei Zhou, Mengyi Xiao, Tianjiao Ji","doi":"10.1002/jmv.70416","DOIUrl":"https://doi.org/10.1002/jmv.70416","url":null,"abstract":"<div>\u0000 \u0000 <p>Coxsackievirus A10 (CVA10) has been reported frequently in many infectious diseases and cases associated with hand, foot, and mouth disease (HFMD) emerging increasingly in recent years. Based on the National HFMD System Surveillance, 180 CVA10 strains were isolated from the mainland of China between 2008 and 2023. These strains were analyzed alongside 103 representative full VP1 sequences obtained from GenBank, with a focus on global-scale phylogenetic analysis and spatiotemporal dynamics of CVA10. Eight genotypes (A–H) were defined, of which the genotype C was the dominant gene subtype in Chinese mainland. Bayesian analysis indicated that the most renascent common ancestor (tMRCA) of CVA10 originated in 1932 (95% HPD:1867-1958), with a high evolutionary rate of 3.32 × 10<sup>−3</sup> substitutions/site/year (95% HPD: 2.62 × 10<sup>−3</sup> to 3.40 × 10<sup>−3</sup>). By analyzing the spatial propagation paths, the global CVA10 exhibited distinct regional characteristics. Though the origin of CVA10 could be in the USA, regional dissemination was mainly located around the Asia-Europe region. The spatiotemporal dynamics of CVA10 exhibited frequent viral traffic among localities, and virus from East and South China have played a central role in spreading around the mainland of China. Our phylogenetic description and phylogeographic analyses indicate the importance of large spatial- and temporal-scale studies in understanding epidemiological dynamics of CVA10, particularly the diffusion routes will be of great importance to global control efforts.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Concetta Piazzese, Sophie Williams, Adam Brentall, Beatrix Kele, Jon Bible, Kathryn Harris, Teresa Cutino-Moguel
{"title":"Analysis of Variants' Dynamic Using the CLIMB Database in COVID-19 Patients Admitted to Hospitals of Barts Health NHS Trust","authors":"Concetta Piazzese, Sophie Williams, Adam Brentall, Beatrix Kele, Jon Bible, Kathryn Harris, Teresa Cutino-Moguel","doi":"10.1002/jmv.70402","DOIUrl":"https://doi.org/10.1002/jmv.70402","url":null,"abstract":"<p>The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant global health challenges. This study analyzes the dynamics of SARS-CoV-2 variants among patients admitted to Barts Health National Health Service (NHS) Trust hospitals using data from the CLIMB-COVID decentralized digital infrastructure allowing precise identification of SARS-CoV-2 variants. A total of 423 patients admitted between October 2020 and March 2021 were included in the study and divided into two groups: the alpha lineage group, which comprised the B.1.1.7 variant, and the other lineages group, which included all other variants. Whole-genome sequencing of SARS-CoV-2 genomes was conducted using the COVID-CLIMB pipelines. Clinical outcomes, such as mortality rates and deterioration within 28 days, were analyzed. To ensure robust findings, analyzes were adjusted for confounding factors, including age and comorbidities. Our findings revealed a significant increase in mortality with age for the alpha lineage and other lineages. The study underscores the importance of age adjustment in clinical studies to accurately assess the impact of different variants. Consistent genomic sequencing and data completeness are crucial for obtaining reliable results and guiding public health responses. These insights are vital for improving patient outcomes and providing a truthful picture of the pandemic, informing both current and future healthcare strategies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriella Zarkovic, Phillip Ziegler, Jennifer Hye-Rim Lee, Brooke Dresden, Amit Kumar, Masahiro Shuda, Alan Bäckerholm, Kathy Ho Yen Shair
{"title":"Disruption of ATR Signaling by Epstein–Barr Virus Latent Membrane Protein 1 Sensitizes Nasopharyngeal Carcinoma Cells to Cisplatin","authors":"Gabriella Zarkovic, Phillip Ziegler, Jennifer Hye-Rim Lee, Brooke Dresden, Amit Kumar, Masahiro Shuda, Alan Bäckerholm, Kathy Ho Yen Shair","doi":"10.1002/jmv.70407","DOIUrl":"https://doi.org/10.1002/jmv.70407","url":null,"abstract":"<p>Nasopharyngeal carcinoma (NPC) occurs with high incidence in Southeast Asia where almost all tumors are associated with Epstein–Barr virus (EBV) infection. Cisplatin is used in combination chemotherapy. In this study, we determined that the EBV oncoprotein, latent membrane protein 1 (LMP1), perturbs DNA damage response (DDR) signaling, activation of cell cycle checkpoints, and sensitivity to cisplatin in NPC cells (HK1). Hypersensitivity was validated by LMP1 knockdown and CRISPR/Cas9 targeting in HK1-EBV cells with latent EBV infection. The conserved PxQxT motif (in CTAR1) and Y384 residue (in CTAR2) were required for the hypersensitivity. Inhibition of ATR (VE821 or AZD6738), but not ATM (KU55933 or AZD0156), phenocopied the G1 arrest and hypersensitivity. Attenuation of DDR signaling and hypersensitivity by LMP1 or ATR inhibition was also observed in the C17 NPC cell line with restored stable LMP1 expression. LMP1 expression in NPC tumors is highly variable. Publicly available RNA-sequencing data from microdissected NPC tumors showed that LMP1 expression in the primary tumors was the lowest in cisplatin-treated patients that experienced recurrence. These findings could have clinical significance in stratifying NPC patients such that tumors with limited or variable LMP1 expression might benefit from ATR inhibitor therapy.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sérgio Santos-Silva, Marta Lois, Ana Machado, Adriano Bordalo, Andreia V. S. Cruz, Helena M. R. Gonçalves, Wim H. M. Van der Poel, Maria S. J. Nascimento, António Rivero-Juarez, Jesús L. Romalde, João R. Mesquita
{"title":"Environmental Surveillance of Hepatitis E Virus and Rat Hepatitis E Virus in Portugal and Spain, 2020–2022","authors":"Sérgio Santos-Silva, Marta Lois, Ana Machado, Adriano Bordalo, Andreia V. S. Cruz, Helena M. R. Gonçalves, Wim H. M. Van der Poel, Maria S. J. Nascimento, António Rivero-Juarez, Jesús L. Romalde, João R. Mesquita","doi":"10.1002/jmv.70414","DOIUrl":"https://doi.org/10.1002/jmv.70414","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis E virus (<i>Paslahepevirus balayani</i> [HEV]) is an important cause of acute viral hepatitis globally, with zoonotic genotypes linked to transmission through consumption of raw or undercooked swine meat or products. Recently, <i>Rocahepevirus ratti</i> (RHEV), member of <i>Hepeviridae</i> family, has emerged as a potential public health concern, with some human cases being reported. The present study aimed to investigate the presence of HEV, as well as RHEV in wastewaters from northern Portugal and Spain (nPS). Given the reported decline in HEV detection in swine from several regions of the world, we also aimed to explore HEV and RHEV in fattened swine fecal samples from the same region of the wastewaters. Between April 2020 and January 2022, a total of 44 wastewater samples were collected from wastewater treatment plants in nPS, alongside 400 fattened swine fecal samples from five farms of the same regions. Wastewater and swine fecal samples RNA extracts were screened for HEV using pangenotypic RT-qPCR and for RHEV using a RT-qPCR assay followed by characterization using nested RT-PCR. Regarding wastewaters, three tested positive for HEV, while 39 out of 44 tested positive for RHEV. Wastewater analysis in the Iberian Peninsula revealed a predominance of RHEV and a near absence of HEV. The absence of both viruses was observed in the swine fecal samples. This combined analysis showing near/total absence of HEV in wastewaters/fattened swine samples warrants further studies. High levels of RHEV in wastewater might also pose environmental transmission risks, particularly for individuals with occupational exposure, emphasizing the need for enhanced zoonotic virus surveillance in urban areas.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}