Virology Journal最新文献

{"title":"Editorial Expression of Concern: Development of an in vitro cleavage assay system to examine vaccinia virus I7L cysteine proteinase activity.","authors":"Chelsea M Byrd, Dennis E Hruby","doi":"10.1186/s12985-025-02894-5","DOIUrl":"https://doi.org/10.1186/s12985-025-02894-5","url":null,"abstract":"","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"296"},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970987","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":"Aptamer as a therapeutic agent for dengue infections.","authors":"Nur Aida Laili Mislan, Citartan Marimuthu, Amir Muhaimin Akmal Shukri, Jeyanthi Suppiah, Rozainanee Mohd Zain, Fadzilah Mohd Nor, Seok Mui Wang","doi":"10.1186/s12985-025-02893-6","DOIUrl":"https://doi.org/10.1186/s12985-025-02893-6","url":null,"abstract":"","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"295"},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970959","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":"From correlation to causation: unraveling the role of long non-coding RNAs in COVID-19 pathogenesis.","authors":"Tianfei Yu, Yunhan Zhang, Haolan Zhang, Ming Li","doi":"10.1186/s12985-025-02660-7","DOIUrl":"10.1186/s12985-025-02660-7","url":null,"abstract":"<p><p>Heydari et al. present an intriguing study examining the role of three long non-coding RNAs (lncRNAs)-H19, taurine upregulated gene 1 (TUG1), and colorectal neoplasia differentially expressed (CRNDE)-in the context of Coronavirus Disease 2019 (COVID-19), focusing on their diagnostic potential and biological significance. The authors argue that these lncRNAs play a role in inflammatory and fibrotic processes associated with COVID-19 and demonstrate their potential utility as biomarkers using machine learning-based predictive models. While the study offers significant contributions to the field, there are limitations in its methodology, interpretative depth, and generalizability that merit closer examination. This commentary critically evaluates the findings, suggesting avenues for refinement and further research.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"293"},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971007","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":"Respiratory viral infections in hospitalized adults: a comparative clinico-laboratory study of RSV, HMPV, and influenza.","authors":"Santhosha Devadiga, Prasad Varamballi, Ujwal Shetty, Chiranjay Mukhopadhyay, Anup Jayaram","doi":"10.1186/s12985-025-02924-2","DOIUrl":"https://doi.org/10.1186/s12985-025-02924-2","url":null,"abstract":"<p><strong>Background: </strong>Respiratory viral infections, including Human Metapneumovirus (HMPV), Influenza (Flu), and human Respiratory Syncytial Virus (hRSV), are major global health concerns. While their impact on vulnerable groups is known, their characteristics in healthy adults (18-65 years) are less clear. This study aimed to determine the incidence and clinical-laboratory features of RSV and HMPV in this population and compared them with those of Influenza A(H1N1) and influenza A(H3N2) for improved epidemiological and diagnostic understanding.</p><p><strong>Methodology: </strong>A retrospective analysis was conducted on data from an Acute Febrile Illness surveillance (2016-2018) in Manipal, India. The study included 96 HMPV, 68 hRSV, 75 Influenza A(H1N1), and 76 Influenza A(H3N2) positive hospitalized adults with fever (≥ 38 °C) and respiratory illness confirmed by RT‒PCR. Clinical and laboratory data collected within the first 8 days of illness were statistically analyzed.</p><p><strong>Results: </strong>The annual incidence rates of hRSV (0.33%-1.59%) and HMPV (0.14%-1.79%) varied. Coryza was common, but cough was most frequent in HMPV (97.9%). HMPV also resulted in increased rates of shortness of breath and chest pain. Leucopenia was most common in Influenza A(H1N1) patients, and thrombocytopenia was most common in hRSV patients. Significantly elevated leukocyte and platelet counts were observed in HMPV patients. Liver enzyme abnormalities are relatively common in hRSV and Influenza A(H1N1) patients. Symptom progression and laboratory trends revealed distinct patterns across the viruses.</p><p><strong>Conclusion: </strong>Despite overlapping initial symptoms, HMPV, hRSV, and influenza resulted in different clinical and laboratory profiles in adults. HMPV was associated with more prominent lower respiratory symptoms and a stronger inflammatory response. These distinctions can aid in the clinical differentiation and management of these common respiratory viruses in adults, highlighting the importance of timely diagnosis for improved patient care and public health strategies.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"294"},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970669","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":"Characterization and therapeutic evaluation of the lytic bacteriophage ENP2309 against vancomycin-resistant Enterococcus faecalis infections in a mice model.","authors":"Jiaqi Tian, Luyao Wang, Rui Gao, Wenwen Zhou, Shinan Zhang, Lingxia Li, Guoyuan Hu, Licheng Xiao, Yijuan Ma, Sang Ba, Daijiyongzang, Shengyi Han, Shengqing Li","doi":"10.1186/s12985-025-02917-1","DOIUrl":"https://doi.org/10.1186/s12985-025-02917-1","url":null,"abstract":"<p><strong>Background: </strong>The global emergence of vancomycin-resistant Enterococci (VRE) represents a growing threat to public health worldwide. To address this critical challenge, we isolated and characterized a novel lytic bacteriophage, ENP2309, from agricultural wastewater. Comprehensive analysis revealed distinct morphological features, biological properties, and genomic characteristics of ENP2309. Most notably, systematic evaluation in a mice infection model demonstrated significant in vivo therapeutic efficacy.</p><p><strong>Methods: </strong>Bacteriophage isolation was performed using the double-layer agar method with the Enterococcus faecalis strain. Phage morphology was characterized by transmission electron microscopy (TEM), The host range was determined via plaque assays and the plating efficiency of multiple bacterial isolates. was evaluated double-layer agar method was systematically employed to evaluate thermal stability, pH tolerance, one-step growth kinetics, and the optimal multiplicity of infection (MOI) through plaque-forming unit (PFU) enumeration. The genomic features were analysed using next-generation sequencing. Furthermore, the therapeutic efficacy of phage ENP2309 against Enterococcal infection in mice was systematically evaluated through a comprehensive assessment of multiple parameters including body weight dynamics, survival rates, histopathological analysis, peripheral blood cytokine profiles, and bacterial loads in the spleen and liver tissues, demonstrating its multidimensional therapeutic effects.</p><p><strong>Results: </strong>The phage ENP2309 showed broad-spectrum lytic capability, effectively targeting 13 distinct Enterococcus clinical isolates. TEM revealed the morphology of ENP2309, featuring an icosahedral capsid (70 ± 1 nm in diameter) and a contractile tail structure (145 ± 2 nm in length). Comprehensive biological characterization revealed optimal infection parameters including an exceptionally low multiplicity of infection (MOI = 0.001), a 40-minute latent period, and an extended 40-120 min burst period resulting in a burst size of 920 PFU/cell. The phage exhibited environmental stability, maintaining infectivity across broad temperature (10-60 °C) and pH (3-12) ranges, with optimal activity observed at 37 °C and neutral pH (7.0-7.5). Genomic analysis revealed a 148,806 bp linear dsDNA (35.9% GC content) containing 153 putative ORFs. Phylogenetic classification revealed that ENP2309 a member of the Kochikohdavirus genus, is closely related to the Enterococcus phage PBEF129. In vivo studies demonstrated exceptional therapeutic potential: a single dose (200 µL 2.0 × 10⁸ PFU/mL) of phage ENP2309 achieved 100% survival in mice models, completely clearing VRE from the spleen and liver while significantly improving physiological parameters, reducing organ damage, and attenuating systemic inflammation.</p><p><strong>Conclusions: </strong>These comprehensive findings establish ENP2309 as a highly promis","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"292"},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970947","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":"Neurological manifestations in HIV-infected patients: a retrospective cohort study in Northeastern Iran.","authors":"Zahra Sadat Mireskandari, Mahboubeh Haddad, Fereshte Sheybani, Amin Bojdi, Maliheh Dadgar Moghadam","doi":"10.1186/s12985-025-02911-7","DOIUrl":"https://doi.org/10.1186/s12985-025-02911-7","url":null,"abstract":"<p><strong>Background: </strong>Neurological complications are a severe aspect of HIV infection, impacting patient outcomes significantly. This study investigates the prevalence and types of neurological syndromes among HIV-infected patients and their outcomes in northeastern Iran.</p><p><strong>Objective: </strong>To evaluate the prevalence and types of neurological syndromes in HIV-infected patients, assess predictors of mortality, and compare survival rates between those with neurological versus non-neurological conditions.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted at major referral centers in northeastern Iran from 2011 to 2021. The study included adult HIV-infected patients admitted to the hospitals. Neurological diagnoses were categorized into central nervous system (CNS) involvement, peripheral nervous system involvement, and further categorized.</p><p><strong>Results: </strong>The cohort comprised 173 patients with a median age of 40 years (interquartile range, 33-46.8). Neurological syndromes were observed in 22.7% of admissions, with CNS involvement being predominant (93.3%). Neurological complications included primary HIV-associated syndromes (11.6%), infections (33.3%), autoimmune disorders (3.3%), vascular phenomena (3.3%), and neoplasms (1.7%). The in-hospital mortality rate was 22.9%, increasing to 35.6% among patients admitted with neurological syndromes as the primary cause of hospitalization. Significant mortality predictors included male sex (p < 0.001; OR: 3.95, 95% CI: 2.21-7.05), intravenous drug use (p: 0.018; OR: 2.22, 95% CI: 1.18-4.18), neurological syndromes (p = 0.023; OR = 2.07, 95% CI: 1.11-3.86), and altered consciousness (p = 0.004; OR = 3.31, 95% CI: 1.49-7.33). Kaplan-Meier survival curves demonstrate a continuous decline in survival rates since hospital admission, with a 36-month survival rate dropping to 36.3%. Survival rates for patients with neurological syndromes were significantly lower compared to those with other conditions (log-rank p = 0.008). 17.24% of deaths in those with neurological syndromes occurred within 24 h of admission.</p><p><strong>Conclusion: </strong>This study highlights the significant burden of neurological complications among HIV-infected patients, with a notable impact on mortality rates. Neurological infectious diseases accounted for one-third of neurological syndromes among HIV-infected patients. The identified predictors of mortality provide critical insights for healthcare providers, emphasizing the importance of early intervention strategies. Given the high rates of early in-hospital mortality associated with neurological syndromes, there is a need for enhanced monitoring and tailored therapeutic approaches for this vulnerable population.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"291"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970658","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":"Discovery of a novel broad-spectrum inhibitor against influenza virus A.","authors":"Ran Yu, Peng Li, Rong Shen, Wenting Fei","doi":"10.1186/s12985-025-02889-2","DOIUrl":"https://doi.org/10.1186/s12985-025-02889-2","url":null,"abstract":"<p><p>The pandemic of influenza A virus (IAV) is on the rise worldwide, however, drug resistance to anti-influenza drugs has been widely found. The viral mutation of IAV highlights the necessitate for discovery of new antiviral agents with broad-spectrum efficacy. Arbidol, an effective pharmaceutical against IAV and other viruses, inhibits viral fusion by targeting a conserved binding region across multiple virus types. The binding area of Arbidol is conserved towards many types of viruses, however, the structural characteristics of Arbidol make it possible human ether-α-go-go related gene (hERG) potassium channel inhibitory. The risk of arrhythmias by Arbidol will limit its further application. Therefore, developing new broad-spectrum antiviral drugs with reduced side effects based on Arbidol's scaffold is imperative. In this study, 50 natural products were screened for effective universal antiviral drug based on the structure-activity relationship between Arbidol and hemagglutinin (HA). Due to the structural characters of Arbidol related to hERG inhibition, the inhibitory activity of Arbidol on hERG channels were also analyzed by patch clamp technology and molecular docking for toxicity and safety evaluation of drug screening and development. The IC50 of Arbidol to hERG was 0.3030 µM. The results showed that Glycyrrhetinic acid has lower binding energy than Arbidol in the binding site. The molecular structure of Glycyrrhetinic acid is more flexible, which avoids significant interactions with hERG. These findings highlight glycyrrhetinic acid as a promising broad-spectrum anti-IAV candidate drug.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"290"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971035","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":"Molecular investigation on measles cases rise and variants co-circulation in the Lazio region, Italy.","authors":"Cesare Ernesto Maria Gruber, Silvia Gioacchini, Lavinia Fabeni, Martina Rueca, Licia Bordi, Eleonora Lalle, Melissa Baggieri, Paola Bucci, Raoul Fioravanti, Roberto Giuseppetti, Eliana Specchiarello, Pietro Giorgio Spezia, Giulia Berno, Fabrizio Carletti, Gabriella De Carli, Maria Concetta Fusco, Alessandra Barca, Paola Scognamiglio, Antonella Marchi, Emilio D'Ugo, Enrico Girardi, Francesco Vairo, Fabio Magurano, Fabrizio Maggi","doi":"10.1186/s12985-025-02910-8","DOIUrl":"https://doi.org/10.1186/s12985-025-02910-8","url":null,"abstract":"<p><strong>Purpose: </strong>In 2023-2024, measles cases progressively increased in Europe. Multiple outbreaks were reported and viral strains with three-nucleotide mutations potentially compromising diagnostic testing were identified. We analyzed the first cases of measles reported in Lazio (Central Italy) from September 2023 to March 2024, combining molecular characterization and phylogenetic analysis with epidemiological investigation to identify transmission chains and evaluate the sensitivity of PCR tests adopted on circulating viral strains.</p><p><strong>Methods: </strong>We tested samples collected through routine measles and rubella surveillance for IgM, IgG and Real-Time PCR. We sequenced positive samples with higher viral titers using an amplicon-based whole-genome next-generation sequencing (WG-NGS) approach and performed mutational and phylogenetic analysis. Furthermore, we tested the sensitivity of the PCR molecular diagnostic assay adopted in our laboratory to identify the mutated strains.</p><p><strong>Results: </strong>Of the 39 suspected cases, 28 were confirmed. Endemic cases were 82%; of these, 78% were sporadic at epidemiological investigation. From 21 high-titer samples, we obtained 14 strains belonging to the D8 genotype. Phylogenetic analysis identified four distinct clusters: three associating 50% of sporadic cases, and one confirming the epidemiological investigation. Several mutational patterns were identified, one of which had three nucleotide mutations potentially affecting the diagnostic test. However, our routine diagnostic PCR tests are able to detect mutated strains at different dilutions.</p><p><strong>Conclusion: </strong>Our results demonstrate that WG-NGS can be used to distinguish transmission chains and identify infection clusters to improve surveillance activity and enable the implementation of more targeted control measures, highlighting the importance of integrated epidemiological and genomic surveillance.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"288"},"PeriodicalIF":4.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971040","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":"Efficacy and safety of 3CL protease inhibitors in patients with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials.","authors":"Nicole Jean Lee, Eric Shih Katsuyama, Christian Ken Fukunaga, Wilson Falco Neto, Ana Carolina Covre Coan, Hilaria Saugo Faria, Eduardo Alexandrino Medeiros","doi":"10.1186/s12985-025-02899-0","DOIUrl":"https://doi.org/10.1186/s12985-025-02899-0","url":null,"abstract":"","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"286"},"PeriodicalIF":4.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970964","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":"Human herpes virus-7-related severe encephalitis diagnosed using mNGS in immunocompetent pediatric patients.","authors":"Xin Chen, Huan Zhao, Chunxue Jiang, Tingting Sun, Xuewen Xu, Kai You","doi":"10.1186/s12985-025-02841-4","DOIUrl":"https://doi.org/10.1186/s12985-025-02841-4","url":null,"abstract":"<p><strong>Background: </strong>This study sought to describe the clinical characteristics, examination results, and prognoses of immunocompetent children with human herpes virus 7 (HHV-7)-related severe encephalitis.</p><p><strong>Methods: </strong>Twelve immunocompetent children with severe HHV-7-related encephalitis were included, all of whom had HHV-7 DNA ( +) detected in the cerebrospinal fluid via metagenomic next-generation sequencing (mNGS) and were followed up for > 6 months.</p><p><strong>Results: </strong>The cohort comprised 75% males, with a median age of 4.5 years; all patients presented with fever and altered consciousness and required PICU admission for severe neurological symptoms. Two patients developed encephalitis sequelae and epilepsy. Abnormal electroencephalography and brain magnetic resonance imaging findings were observed in 90.9% (10/11) and 72.7% (8/11) of the patients, respectively. Five patients required ventilator support due to central respiratory failure (four invasive and one noninvasive). One patient underwent plasma exchange, while another received continuous renal replacement therapy. All patients were treated with acyclovir and immunomodulatory therapy. Four patients had poor prognoses, including one 9-year-old male who died and one 9-year-old female who was diagnosed with febrile infection-related epilepsy syndrome and remained in a coma with a Modified Rankin Scale score of 5 at the 6-month follow-up.</p><p><strong>Conclusions: </strong>Older immunocompetent children with severe HHV-7-related encephalitis have poor prognosis and low survival rates, both of which may be improved via empiric acyclovir administration combined with immunosuppressive therapy.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"287"},"PeriodicalIF":4.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970977","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}