Journal of Medical Virology最新文献

{"title":"Clinical Validation of the Venus HPV Full-Genotyping Assay for Cervical Cancer Screening in the VALGENT-4 Framework","authors":"Lan Xu,&nbsp;Chang Ma,&nbsp;Kate Cuschieri,&nbsp;Jesper Bonde,&nbsp;Marc Arbyn","doi":"10.1002/jmv.70527","DOIUrl":"https://doi.org/10.1002/jmv.70527","url":null,"abstract":"<div>\u0000 \u0000 <p>The Venus HPV assay (VenusHPV) is a real-time PCR-based human papillomavirus (HPV) test that is widely used in China but lacks extensive clinical validation. The VALidation of HPV GENotyping Tests (VALGENT) framework is an established protocol for evaluating HPV genotyping assays against a standard comparator test. This study aimed to assess the clinical accuracy and reproducibility of the VenusHPV assay following international validation criteria. The clinical performance of VenusHPV was evaluated against the GP5+/6+ PCR-based enzyme immunoassay (GP-EIA) using the VALGENT-4 panel, which included 998 consecutive routine screening samples enriched with 297 samples with abnormal cytology from the Danish cervical cancer screening program. Cases were defined as women diagnosed with histologically confirmed cervical intraepithelial neoplasia 2 or more (CIN2+), while two consecutive negative cytology results served as a proxy for nondisease. Intra- and interlaboratory reproducibility was assessed on 500 samples. Using the manufacturer-recommended cutoff, VenusHPV demonstrated noninferior sensitivity for detection of CIN2+, but its specificity for ≤ CIN1 was inferior to that of GP-EIA. Applying an optimized a posteriori cutoff improved the specificity, yielding relative specificity of 1.02 (95% CI [CI], 1.00–1.03; <i>p</i> noninferiority [<i>p</i>_n.inf] &lt; 0.0001), while maintaining a noninferior sensitivity (of 1.02; CI, 1.00–1.08; <i>p</i>_n.inf &lt; 0.0001). The intra- and interlaboratory reproducibility was excellent (95.2%, CI, 93.3–97.1%, Kappa [<i>κ</i>] = 0.87 and 94.0%, CI, 92.0%–96.0%, <i>κ</i> = 0.85, respectively). Notably, the reproducibility criteria were met consistently, regardless of whether the unadjusted or optimized cutoff was applied. The VenusHPV was as sensitive as the GP-EIA for detecting cervical precancer using the unadjusted cutoff but less specific. However, after cutoff optimization, VenusHPV met the international accuracy criteria for cervical cancer screening. Additionally, the assay demonstrated excellent reproducibility.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767472","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":"Single-Cell Omics Analysis Reveals Immunological Dysregulation in COVID-19 and HIV: Identifying a Shared Abnormality of B Cell Activation via the Unfolded Protein Response and Diagnostic Biomarkers Using Machine Learning Algorithms","authors":"Feng Li,&nbsp;Wei Zhao,&nbsp;Hong Liu,&nbsp;Yandie Niu,&nbsp;Jiahao Ma","doi":"10.1002/jmv.70538","DOIUrl":"https://doi.org/10.1002/jmv.70538","url":null,"abstract":"<div>\u0000 \u0000 <p>An increasing number of studies have demonstrated the exacerbation of disease progression of both COVID-19 and HIV when coexisting. However, the molecular mechanisms underlying the interplay between these two viruses are still poorly understood. In this study, we utilized a comprehensive analysis of single-cell transcriptomics to identify and characterize peripheral blood cell subsets in COVID-19 and HIV-infected patients. Our findings revealed that COVID-19 and HIV exhibit a partially similar cellular composition and cell cycle distribution. Additionally, we identified a common pathogenesis in B-cell subsets of COVID-19 and HIV patients, which showed abnormal activation states of the unfolded protein response (UPR) pathway. Based on B-cell signature genes and UPR-related genes, we developed a machine learning diagnostic model that can accurately diagnose both COVID-19 and HIV infections. Our model was validated using a large number of bulk transcriptome data sets and showed good clinical efficacy. Our study provides molecular insights into the single-cell level interplay between SARS-CoV-2 and HIV infections, suggesting a possible common disease mechanism that warrants further investigation.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767732","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":"Seroepidemiology of Human Non-Species A Rotavirus Infections in Valencia, Spain","authors":"Noemi Navarro-Lleó,&nbsp;Silvia Aznar-Córdoba,&nbsp;Dunia Asensio-Cob,&nbsp;Daniel Luque,&nbsp;Javier M. Rodríguez,&nbsp;Roberto Gozalbo-Rovira,&nbsp;María Jesús Alcaraz-Soriano,&nbsp;Roberto Cárcamo-Calvo,&nbsp;Jesús Rodríguez-Díaz,&nbsp;Javier Buesa","doi":"10.1002/jmv.70542","DOIUrl":"https://doi.org/10.1002/jmv.70542","url":null,"abstract":"<p>Species A rotavirus (RVA) is a major cause of acute gastroenteritis in children. However, three other rotavirus species (RVB, RVC, and RVH) are also able to infect humans. It has been suggested that vaccination against RVA could facilitate an increase of non-A rotavirus infections. We investigated the antibody prevalence against RVA, RVB, RVC, and RVH in 420 human sera collected between 2020 and 2022 from different age groups in Valencia (Spain). Antibody prevalence rates to RVA, RVB, RVC, and RVH were 79.3%, 17.9%, 18.8%, and 14.5%, respectively. Antibody titers against RVA remained consistent across the different age groups, and RVB showed low titers except in younger individuals. RVC-specific antibodies peaked in children 5–10 years of age, whereas RVH exhibited the highest titers in the elderly. The detection of antibodies against non-A rotaviruses in humans in Spain, for the first time against RVB and RVH, highlights the need for their surveillance.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758526","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":"Performance of Long-Read Single-Molecule Real-Time Sequencing for SARS-CoV-2 Genotyping in Clinical Samples","authors":"Pauline Trémeaux,&nbsp;Justine Latour,&nbsp;Camille Vellas,&nbsp;Sofia Demmou,&nbsp;Noémie Ranger,&nbsp;Antonin Bal,&nbsp;Jacques Izopet","doi":"10.1002/jmv.70539","DOIUrl":"https://doi.org/10.1002/jmv.70539","url":null,"abstract":"<p>Due to the continuous genetic evolution of SARS-CoV-2, numerous variants have emerged and different whole genome sequencing techniques, necessary for accurate virus typing, have been developed. In this study, we evaluated the performance of PacBio single-molecule real-time (SMRT) sequencing for SARS-CoV-2 typing. Reproducibility was assessed on two internal quality controls, whose median reading depths were 1154X and 1059X. The overall sensitivity on 1646 clinical samples collected between January 2023 and June 2024 was 83.6% and was correlated to the viral load. By comparison, the overall sensitivity of short-read illumina sequencing over the same period of time on 271 samples was 90.8%. Although less sensitive, SMRT sequencing was more efficient for the identification of the two lineages in a co-infection case due to the amplification of long fragments. Comparing the results obtained by the two techniques, 10 out of 50 samples were identified with the same clade but not the exact same lineage at the time of analysis, because of the very frequent updates of the Pango taxonomy. Nevertheless, we obtained very similar fasta consensus sequences with a maximum difference of 4 nucleotides, showing that both methods provide accurate typing of SARS-CoV-2, useful for epidemiological or clinical studies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758491","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":"Evaluating the Effectiveness of NOACs and LMWH in Reducing Mortality in Critically Ill Patients With COVID-19","authors":"Rubens Carmo Costa-Filho,&nbsp;Amarino Oliveira Jr.,&nbsp;Felipe Saddy,&nbsp;João Luiz Ferreira Costa,&nbsp;Marcela Santos Azevedo,&nbsp;Débora Fragoso Cerqueira,&nbsp;Víctor Hugo Amaral Gualberto,&nbsp;Maria Izabel Neves de Holanda Barbosa,&nbsp;Alda Maria Da-Cruz,&nbsp;Marco Aurélio Horta,&nbsp;José Paulo Gagliardi Leite,&nbsp;Hugo Castro-Faria-Neto","doi":"10.1002/jmv.70535","DOIUrl":"https://doi.org/10.1002/jmv.70535","url":null,"abstract":"<p>Severe COVID-19 is associated with increased prothrombotic and inflammatory responses, necessitating effective anticoagulation therapy. Novel oral anticoagulants (NOACs) are being explored as potential alternatives to low-molecular-weight heparin (LMWH). This retrospective observational cohort study compared the effectiveness and safety of NOACs and LMWH in reducing mortality among 76 critically ill, unvaccinated patients with confirmed SARS-CoV-2 infection. The cohort included 41 patients treated with LMWH and 35 with NOACs during their ICU stay. The primary outcomes was mortality, while secondary outcomes included deep vein thrombosis (DVT), bleeding episodes, and transfusion rates. Baseline characteristics, including demographic data and severity scores, were similar between the groups (mean age: LMWH, 74.5 ± 15.1 years [59% male]; NOAC, 71.6 ± 14.8 years [60% male]). Mortality was significantly higher in the LMWH group (51.21% [95% confidence interval (CI): 36.4–65.7]) compared to the NOAC group (20% [95% CI: 10.0–35.9]; <i>p</i> = 0.005), with standardized mortality ratios of 1.61 and 0.71, respectively (<i>p</i> = 0.004). Elevated <span>d</span>-dimer levels were strongly associated with an increased risk of mortality. Deep vein thrombosis (DVT) occurred in 9.76% of patients in the LMWH group and 5.71% of those in the NOAC group (<i>p</i> = 0.68). Bleeding and transfusion rates were comparable between the groups. The use of NOACs was associated with a significantly lower mortality rate compared to LMWH in critically ill COVID-19 patients, reflecting an 81% reduction in the risk of death. These findings highlight the potential benefits of NOACs in the management of severe COVID-19 and underscore the need for further research to optimize anticoagulation strategies and improve patient outcomes.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758490","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":"Heterogeneous Activation of Signaling Pathways and Therapeutic Vulnerabilities in KSHV-Associated Primary Effusion Lymphoma Cell Lines","authors":"Lianna Huang,&nbsp;Luping Chen,&nbsp;Yufei Huang,&nbsp;Shou-Jiang Gao","doi":"10.1002/jmv.70534","DOIUrl":"https://doi.org/10.1002/jmv.70534","url":null,"abstract":"<p>Primary effusion lymphoma (PEL) is a rare and aggressive B-cell malignancy caused by Kaposi's sarcoma-associated herpesvirus (KSHV), with limited treatment options and poor prognosis. KSHV-encoded proteins and miRNAs activate multiple signaling pathways that promote cell proliferation and survival. However, the heterogeneity in pathway activation and therapeutic responses among PEL cases remains poorly characterized. In this study, we investigated the activation status of key oncogenic and survival signaling pathways, including PI3K/AKT/mTOR, FOXOs and NF-κB, and assessed the efficacy of targeted inhibitors in three KSHV-positive EBV-negative PEL cell lines BC3, BCP1 and BCBL1, KSHV-negative BJAB cells, and KSHV-infected BJAB-KSHV cells. We observed heterogeneous activation of these pathways among PEL cell lines and differential sensitivity to pathway-specific inhibitors. All KSHV-infected cell lines exhibited constitutive AKT and mTORC1 activation and were sensitive to their respective inhibitors, though with varying efficacy. FOXO1 and FOXO3a, downstream targets of AKT, were frequently downregulated or inactivated by phosphorylation, consistent with AKT hyperactivation. Inhibition of FOXO1 suppressed proliferation and induced apoptosis in a cell line-specific manner. Canonical and noncanonical NF-κB pathways were differentially activated, and contributed to cell survival, as pathway-specific inhibition suppressed proliferation. Interestingly, responses to inhibitors did not always correlate with basal pathway activation levels, highlighting the complexity of PEL signaling networks. Importantly, dual PI3K/mTOR inhibitors BGT226 and Dactolisib demonstrated superior efficacy by potently inhibiting proliferation and inducing apoptosis and cell cycle arrest in all PEL cell lines, suggesting an advantage in overcoming compensatory feedback mechanisms. These findings underscore the heterogeneity of PEL and the need for personalized therapeutic strategies. Our results support the potential of combinatorial or multi-targeted approaches to improve treatment outcomes for PEL patients and warrant further preclinical and clinical investigations.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758605","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":"Causal Effects of Life-Course Adiposity and Metabolic Mediators on the Immune Response to COVID-19 Vaccination","authors":"Pu Liang,&nbsp;Chi Li,&nbsp;Yan Li,&nbsp;Jingfan Xiong,&nbsp;Jie Mi,&nbsp;Pei Xiao","doi":"10.1002/jmv.70540","DOIUrl":"https://doi.org/10.1002/jmv.70540","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Despite adiposity's potential role in modulating immune responses, the causal effects of adiposity at different life stages on immune responses to COVID-19 vaccines remain poorly understood. Thus, we aimed to investigate the causal association between life-course adiposity and the immune response to COVID-19 vaccination, and to explore the metabolic mechanisms underlying this association. We used a life-course Mendelian randomization (MR) analytic framework, starting with univariable MR, to estimate the total effects of body mass index (BMI) and obesity in childhood and adulthood on the immune response to COVID-19 vaccination. We then used multivariable MR to distinguish the direct and indirect effects of childhood adiposity, adjusting for adulthood adiposity and lifestyle confounders. Furthermore, we conducted a metabolome-wide mediation MR analysis to explore the potential links between adiposity at different life stages and immune responses to COVID-19 vaccination, mediated by 249 metabolic traits. The univariable MR results revealed that genetically predicted childhood and adulthood BMIs were significantly associated with an increased risk of anti-spike IgG seronegativity after both the first and second doses of the COVID-19 vaccine. The multivariable MR analyzes further revealed that childhood BMI had a direct causal effect on anti-spike IgG seronegativity after the first vaccine dose (OR 1.13, 95% CI 1.00–1.27), whereas adulthood BMI did not (OR 0.99, 95% CI 0.87–1.13). In contrast, adulthood BMI had a direct causal effect on anti-spike IgG seronegativity after the second vaccine dose (OR 1.29, 95% CI 1.14–1.46). Mediation analyzes identified 71 metabolic traits that mediated the effects of childhood and adulthood BMI on the immune response to COVID-19 vaccination. Notably, branched-chain amino acids (valine, leucine, and isoleucine) mediated over 20% of the causal effect between adulthood BMI and the vaccine-induced immune response. Furthermore, the triglycerides to total lipids ratio in medium LDL was identified as a significant mediator of the causal relationship between childhood BMI and anti-spike IgG seronegativity after the second vaccine dose, but not for adulthood BMI. The findings highlight the potential for targeted interventions to improve vaccine responses, particularly in individuals with a high childhood BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758492","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":"Prospective Evaluation of the FUJIFILM SILVAMP Dengue NS1 Ag for Early Dengue Detection: A Multicenter Study in Thailand","authors":"Umaporn Limothai,&nbsp;Sasipha Tachaboon,&nbsp;Janejira Dinhuzen,&nbsp;Mananya Wanpaisitkul,&nbsp;Chatchai Chulapornsiri,&nbsp;Anongrat Tiawilai,&nbsp;Thawat Tiawilai,&nbsp;Theerapon Sukmark,&nbsp;Chayomon Dokpong,&nbsp;Terapong Tantawichien,&nbsp;Usa Thisyakorn,&nbsp;Nattachai Srisawat","doi":"10.1002/jmv.70541","DOIUrl":"https://doi.org/10.1002/jmv.70541","url":null,"abstract":"<div>\u0000 \u0000 <p>Early detection of dengue is crucial to prevent severe outcomes. This multicenter prospective cohort study evaluated the performance of the FUJIFILM SILVAMP Dengue NS1 rapid test (SILVAMP NS1) compared to a commercially available rapid NS1 test (non-SILVAMP NS1) and NS1 enzyme-linked immunosorbent assay (ELISA), using real-time reverse transcription polymerase chain reaction (rRT-PCR) as the primary reference standard. A total of 402 patients with acute febrile illness were enrolled across four hospitals in Thailand between March 2023 and September 2024. Clinical features and baseline laboratory data were recorded at admission, and diagnostic testing was performed on both whole blood and serum samples. Among participants, 47.5% tested positive for dengue by rRT-PCR, with DENV-2 being the most prevalent serotype. Against rRT-PCR, SILVAMP NS1 demonstrated 73.5% sensitivity and 99.4% specificity. Its sensitivity and specificity were statistically comparable to those of NS1 ELISA (78.1% and 100%; <i>p</i> = 0.092 and 1.000, respectively). SILVAMP NS1 outperformed non-SILVAMP NS1 in sensitivity (66.9%; <i>p</i> &lt; 0.006) while maintaining equivalent specificity (100%; <i>p</i> = 1.000). Agreement between SILVAMP NS1 and NS1 ELISA was almost perfect, with a Cohen's <i>κ</i> of 0.90. The diagnostic performance of SILVAMP NS1 remained consistent across sample type, illness duration, serological status, and dengue serotype. In a subgroup analysis, finger-stick testing with SILVAMP NS1 maintained high specificity but exhibited reduced sensitivity. These findings demonstrate that SILVAMP NS1 provides reliable diagnostic performance with high specificity and strong concordance with NS1 ELISA. Its ease of use and applicability in point-of-care settings support its potential as a practical tool for early dengue diagnosis, particularly in resource-limited environments.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758489","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":"Diagnostic Machine Learning Models of Infectious Mononucleosis in Children Based on Clinical Data: A Retrospective Multicenter Study","authors":"Wenshen Gu,&nbsp;Shoufu He,&nbsp;Xiaohui Li,&nbsp;Weizhen Fang,&nbsp;Min Guo,&nbsp;Yonghong Wang,&nbsp;Chaohui Duan","doi":"10.1002/jmv.70529","DOIUrl":"https://doi.org/10.1002/jmv.70529","url":null,"abstract":"<div>\u0000 \u0000 <p>The clinical manifestations of infectious mononucleosis (IM) and acute respiratory tract infections (ARTI) exhibit significant similarities. We aim to develop cost-efficient models for IM in children utilizing the Shapley Additive explanation (SHAP) algorithm. We conducted a retrospective analysis of patients with the first diagnosis of IM from three medical centers. We employed four different machine learning techniques to develop new diagnostic models based on clinical features and serum inflammatory markers. The predictive accuracy of model was evaluated using the ROC curve and compared with traditional indicators. This study included a total of 853 patients with 49 clinical features. Through ten-fold cross-validation, the best-performing integrated learning models are GBM, XGBoost, and RSF. The models were interpreted using SHAP to derive the feature subsets Lymphocyte, PLR, LDH, SII, Age, these subsets comprised the final diagnostic prediction model. The results show that the models based on five indicators have the same IM diagnostic performance as the EBV-specific examination, and have a higher diagnostic value than the diagnosis based on atypical lymphocytes and EBV-DNA load. Meanwhile, our models are applicable to children with IM of different age groups. This study provides a new diagnostic tool for differentiating IM from ARTI in children. Our novel diagnostic models are independent of EBV-specific test results and exhibit superior diagnostic performance compared to traditional markers in the diagnosis of IM, particularly for primary healthcare units and institutions lacking EBV-specific detection capabilities.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751431","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":"Expression of Bovine Meat and Milk Factor in Hepatocellular Carcinoma and Colorectal Liver Metastasis Patients","authors":"Sumen Siqin,&nbsp;Mohammad Rahbari,&nbsp;Claudia Ernst,&nbsp;Imke Grewe,&nbsp;Karin Gunst,&nbsp;Michelle Neßling,&nbsp;Sylvia Kaden,&nbsp;Karsten Richter,&nbsp;Lisa Häfele,&nbsp;Lars Feuerbach,&nbsp;Damir Krunic,&nbsp;Claudia Tessmer,&nbsp;Ilse Hofmann,&nbsp;Emrullah Birgin,&nbsp;Alexander Brobeil,&nbsp;Nuh Rahbari,&nbsp;Mathias Heikenwälder,&nbsp;Timo Bund","doi":"10.1002/jmv.70507","DOIUrl":"https://doi.org/10.1002/jmv.70507","url":null,"abstract":"<p>Bovine meat and milk factors (BMMFs) are plasmid-like DNA molecules isolated from cow's milk, meat, and human cancer tissues proposed to contribute to the development of specific types of cancer including colorectal cancer (CRC) and breast cancer based on chronic inflammation-associated indirect carcinogenesis. Chronic necro-inflammation of the liver poses a strong risk factor for the induction of hepatocellular carcinoma (HCC), which is associated with high intake of meat. Whether BMMFs contribute to HCC carcinogenesis or the development of colorectal liver metastasis (CRLM) remains unknown. Therefore, in this study, the presence of BMMFs was assessed in the liver of patients with viral and nonviral hepatitis-related HCC (<i>n</i> = 25), CRLM (14) and in healthy liver tissue from autopsy specimens (18) using monoclonal antibodies against the conserved BMMF Rep protein for immunohistochemistry, immunofluorescence detection, and immunoblotting. Rep was expressed in all tumor-distant and peritumor tissue specimens of HCC and CRLM patients and associated with CD68⁺ macrophages around portal triads. The number of Rep⁺CD68⁺cells was increased in HCC and CRLM patients compared to healthy liver tissue, which may indicate a link between BMMFs and tumor-associated chronic inflammation in the liver. Exclusively in viral hepatitis-linked HCC, Rep expression was also detected in the tumor. In addition, specifically in the liver of healthy individuals, we observed a well-defined gradient Rep expression in hepatocytes around the central veins. Altogether, these observations may indicate that the presence of BMMFs in the liver is associated with chronic inflammation and may represent a novel risk factor or surrogate marker for liver cancer.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740216","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}