Search Results (61)

Background: We previously pioneered a multigene mRNA test, qMIDS^V2, validated through an international multicohort study with geographically and ethnically diverse oral squamous cell carcinoma (OSCC) patients from Europe and Asia. This study aimed to repurpose the qMIDS^V2 test for nasopharyngeal carcinoma (NPC). A molecular test independent of Epstein–Barr virus (EBV) status would be clinically useful for risk stratification in NPC patients with undetectable or low levels of EBV. Methods: This study investigated a Chinese cohort of 62 participants (18 donated normal nasopharyngeal mucosa (NPM) and 44 donated NPC tissue samples). Messenger RNA levels of 16 genes in each sample were quantified using the qPCR method, and an algorithm computed a malignancy index for cancer risk stratification. Results: We identified a unique 10-gene panel (containing eight target genes, namely NEK2, INHBA, FOXM1, TOP2A, BIRC5, CXCL8, NR3C1, and IVL, relative to two reference genes, YAP1 and POLR2A, collectively named qMIDS^NPC) that demonstrated the best overall diagnostic performance in segregating NPM from NPC, with AUC = 0.909 and positive/negative predictive values of 91% PPV and 78% NPV, respectively. Furthermore, we demonstrated prognostic value of qMIDS^NPC in segregating NPM from NPC stage III + IV, with AUC = 0.936, 92% PPV, and 84% NPV. Conclusions: Here, we present a simple qPCR-based 10-gene mRNA test, qMIDS^NPC, with potential clinical utilities for rapid (1 h) prognostic stratification of NPC. Further studies involving geographically and ethnically independent NPC cohorts would be needed to validate the clinical use of qMIDS^NPC in non-endemic NPC populations. Full article

Epstein–Barr virus is a globally disseminated oncovirus capable of causing various malignancies, including gastric cancer, Burkitt lymphoma, and Hodgkin’s lymphoma. The influence of recombination on the EBV genome revealed limitations in the current traditional EBV classification, and the extent of these recombination events across the EBV genome is not fully understood. The nuclear antigen 3C (EBNA3C) is an indispensable gene in the oncogenesis of the virus. Despite its critical role, little is known about EBNA3C sequence variability. We examined 988 EBNA3C gene sequences extracted from EBV genomes in this context. Among the protein motifs, the interaction sites with Nm23-H1, RBP-Jk, and nuclear localization signal (NLS) 2 and 3 were the most divergent between EBV types, while NLS-1 and the leucine zipper-like showed high conservation. In our study of the impact of recombination vs. point mutations in the EBNA3C gene, we found that recombination contributed five times more to substitutions than mutation. Notably, Asian populations exhibited the highest variability and recombination rates. Importantly, our analysis revealed geographical rather than disease-specific markers. Furthermore, filtering for recombination regions did not affect the classical classification of EBV-1 and EBV-2. This finding suggests that recombination is pivotal in the architecture of EBV genetic diversity of the EBNA3C gene. Full article

Viral presence in the brain may contribute to chronic neurologic diseases. However, investigating these associations is limited by the difficulty of directly sampling brain tissue in living individuals. Here, we evaluated whether peripheral viral detection using unbiased target-enrichment next-generation sequencing could inform viral presence in the brain across a diverse set of viral taxa. We applied ViroFind to matched brain, blood (peripheral blood mononuclear cells, spleen, and/or lymph node), and cerebrospinal fluid (CSF) to assess the predictive utility of viral detection in blood and CSF for identifying viral presence in brain samples obtained from the National NeuroAIDS Tissue Consortium, including both HIV-infected (HIV⁺) and HIV-uninfected (HIV⁻) individuals without known active viral infection of the brain. Blood negativity was generally more informative for predicting the absence of viruses in the brain than blood positivity for predicting viral presence. CSF viral detection demonstrated limited predictive utility for brain presence across most viral taxa examined. Among blood⁺ individuals, viral burden differed significantly between brain⁺ and brain⁻ cases for Epstein–Barr virus (EBV), parvovirus, and torque teno virus (TTV). Blood viral burden showed moderate ability to distinguish brain⁺ from brain⁻ cases for EBV and parvovirus, and strong discriminatory ability for TTV, with similar decision thresholds across HIV⁺ and HIV⁻ individuals. Full article

The Huang-huai sheep (Dorper × Small-tailed Han), certified in China in 2019, initially exhibited issues with genetic uniformity and meat quality. A six-year (2020–2025) breeding program was conducted at two core farms (collectively housing ~2400 breeding ewes representing 12 bloodlines) using the custom “Yuyang Muxin” 10 K SNP chip containing functional markers for reproduction (FecB), growth (CLPG, ACTC1), and meat quality (FABP3, CIDEa). Genotyping and marker-assisted selection were integrated with BLUP breeding values. After six years, favorable FecB genotype frequency increased from 68.97% to 82.58% (p < 0.05), while genetic diversity remained stable (F_IS < 0.05). Mixed model analysis accounting for farm and year random effects revealed significant genetic gains: 6-month ram body weight increased by 9.1% (58.50 to 63.80 kg, p < 0.05), dressing percentage improved from 56.02% to 57.8% (p < 0.05), and loin muscle area expanded by 9.4% (24.50 to 26.8 cm², p < 0.05). Meat quality was enhanced, with shear force decreasing by 14.1% (38.65 to 33.20 N, p < 0.05) and intramuscular fat increasing by 40.0% (2.0% to 2.8%, p < 0.05). Lambs weaned per ewe per year increased from 2.38 to 2.56 (p < 0.05). EBV trend analysis confirmed that improvements were primarily genetic. After Bonferroni correction, CIDEa expression was strongly correlated with intramuscular fat (r = 0.89, p < 0.001) and FABP3 expression with arachidonic acid (r = 0.70, p < 0.001). Nine months was identified as the optimal slaughter age. The “Yuyang Muxin” breeding chip effectively accelerated genetic improvement in Huang-huai sheep, enabling synergistic enhancement of multiple traits. Full article

The World Health Organization (WHO) and International Consensus Classification (ICC) systems have classified EBV-positive NK/T-cell neoplasms in adults and EBV-positive T/NK-cell lymphoid lymphoproliferative disorders (LPD) in children. Recent molecular profiling techniques have revealed the pathogenesis of these disorders, showing interactions among EBV-encoded proteins, host immune responses, and genetic alterations. Extranodal NK/T-cell lymphoma (ENKTL) shows molecular diversity, with various subtypes (TSIM, MB, and HEA) identified through a multiomics approach. Aggressive NK-cell leukemia (ANKL) has mutations in JAK/STAT, epigenetic regulators, and TP53 pathways. EBV-positive nodal T- and NK-cell lymphoma (ENTNKL) is a new entity, distinguished by primary nodal presentation and a unique molecular profile. Severe mosquito bite allergy (SMBA), hydroa vacciniforme lymphoproliferative disorder (HVLPD), and systemic chronic active EBV disease (CAEBV) are rare childhood EBV-driven LPDs defined by clinico-pathologic criteria, with largely unexplored genomic landscapes. Studies of CAEBV samples have found ENKTL-like driver mutations, including DDX3X and KMT2D, in EBV-infected NK/T cells, while KMT2D and chromatin modifier mutations were common in HVLPD. Comprehensive molecular sequencing of SMBA and Systemic EBV-positive T-cell lymphoma of childhood remains lacking. These findings suggest all EBV⁺ NK/T-cell LPDs exist on a biological continuum of viral oncogenesis. The integration of clinical, pathological, and molecular information aims to create a more accurate classification system, enabling better risk evaluation and tailored treatment strategies for patients with these complex disorders. Full article

Background: Epstein–Barr virus (EBV)-related primary splenic tumors are exceptionally rare and encompass a heterogeneous group of entities, including inflammatory pseudotumor (IPT), IPT-like follicular dendritic cell (FDC) tumors or sarcomas, and EBV-positive diffuse large B-cell lymphoma (DLBCL). Because clinical presentation and imaging findings are often nonspecific, establishing a definitive diagnosis remains challenging and frequently necessitates splenectomy for histopathologic confirmation. Methods: We retrospectively reviewed patients who underwent laparoscopic splenectomy for suspected primary splenic lesions at a single tertiary institution between June 2014 and August 2025. Among 67 patients, five consecutive patients were pathologically confirmed as EBV-related primary splenic tumors. Clinical characteristics, imaging features, histopathologic and immunophenotypic findings, EBV in situ hybridization results, treatment, and follow-up outcomes were analyzed. Results: This case series comprised four spindle cell–predominant EBV-related tumors (IPT or IPT-like FDC tumors/sarcomas) and one EBV-positive DLBCL. All patients presented with splenic masses that could not be definitively characterized by preoperative imaging alone and therefore required splenectomy. EBV in situ hybridization was positive in tumor cells in all cases. Patients with non-lymphomatous tumors achieved durable disease control following splenectomy alone, with disease-free survival of up to five years. In contrast, the patient with EBV-positive DLBCL required postoperative systemic immunochemotherapy. Conclusions: EBV-related primary splenic tumors represent a diagnostically challenging and clinically diverse disease spectrum. This case series highlights the pivotal role of splenectomy in establishing definitive diagnosis and guiding subsequent management, particularly for isolated splenic lesions with indeterminate imaging findings. Full article

Constructed wetlands (CWs) are nature-based solutions that integrate ecological processes for water purification, climate regulation, and biodiversity enhancement. However, biodiversity monitoring in CWs has often been underprioritized, limiting its recognition as a functional driver of ecosystem service performance. This study first developed the Biodiversity-based Ecosystem Service Index (BBESI), a hierarchical framework for evaluating biodiversity contributions to regulating services, and then systematically identified representative indicators from the literature to operationalize this framework. Following PRISMA 2020 guidelines, 39 studies spanning tropical, temperate, and arid climatic regions were reviewed across six ecosystem functions: pollutant removal, nutrient retention, biological uptake, carbon storage, greenhouse gas regulation, and microclimate control. Indicators were considered representative when they demonstrated clear functional relevance to CW ecosystem processes and were repeatedly supported across the reviewed studies. These included microbial diversity metrics, nutrient-cycling functional genes, plant–microbe functional complementarity, and vegetation structural attributes. Each indicator was mapped to the Essential Biodiversity Variables (EBV) framework, spanning Genetic Composition, Species Traits, Community Composition, Ecosystem Structure, and Ecosystem Function to provide a standardized basis for biodiversity assessment, using a rule-based assignment that prioritized the biological signal of each indicator rather than its functional category. Although all EBV classes were represented, this pattern reflects the available literature and is influenced by uneven reporting across microbial and plant indicators and across climatic regions, which limits broad generalization of indicator strength. The BBESI offers a transferable framework because its EBV-aligned structure and commonly measured indicators allow application across diverse CW designs and environmental contexts provided that multiple EBV co-signals are present rather than reliance on single-indicator measurements, with flexibility for future integration of various quantitative weighting approaches. Full article

Epstein–Barr virus (EBV) is distributed worldwide and shows a seroprevalence of over 90% in adults, while seroprevalence in children varies depending on geographic and socioeconomic factors. Although primary EBV infection (pEBV) is often asymptomatic in early childhood, infection later in life may present with a variety of symptoms, most commonly as infectious mononucleosis, though many other clinical manifestations may occur. We present four clinical cases to illustrate the diverse and uncommon manifestations of pEBV and to support diagnostic reasoning. The first case demonstrates a diagnostic challenge of pEBV in a patient with severe cholestatic hepatitis in the setting of a recent travel. The second case highlights bilateral eyelid swelling (Hoagland sign) as a potentially isolated early symptom of pEBV, which clinicians should consider within its broad differential diagnosis. In the third case, we emphasize the importance of clinical judgment in contrast to premature closure in the face of repeatedly negative EBV serologies and advocate for further diagnostic evaluation, such as PCR testing, when pEBV is strongly suspected. The fourth case describes a fatal outcome of pEBV late in life, complicated by hemophagocytic lymphohistiocytosis. Unusual presentations of pEBV may complicate the diagnostic process and may lead to unnecessary testing. Our case series underscores the broad clinical spectrum of pEBV and highlights key features that aid in distinguishing it from important differential diagnoses. Awareness of characteristic laboratory findings, including reactive lymphocytosis, elevated large unstained cells, persistent fever, and lymphadenopathy, splenomegaly, as well as mild-to-moderate hepatitis is essential for guiding a targeted diagnostic approach for pEBV. Full article

A systematic review was conducted to assess the effects of microgravity and space radiation on astronauts’ oral health. This review aimed to determine if these conditions increase the risk of dental and periodontal diseases, identify pre-mission dental care strategies, and specify relevant dental emergencies for astronauts to manage during missions. Following PRISMA guidelines, the review was registered on PROSPERO (CRD42023472765). Databases including PubMed, Scopus, Web of Science, Cochrane Library, and OVID Medline were searched. Of the 13 studies identified, 7 were eligible for qualitative synthesis. The included studies revealed that space conditions compromise oral health. Findings indicate changes in saliva composition, with a significant decline in salivary lysozyme levels during missions lasting 28 to 84 days. Salivary IgA levels also increased before and peaked after flights (microgravity alters fluid shear and protein folding). Viral reactivation was a key finding, with latent viruses such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) being reactivated during missions (immune suppression and gene expression shifts under spaceflight stress). Data from a study found that 50% of crew members shed viruses in their saliva or urine, and 38% tested positive for herpesviruses. The included studies also documented alterations in the oral microbiome, including increased gastrointestinal and decreased nasal microbial diversity. This suggests alterations in salivary biomarkers, viral shedding, and microbiome changes in astronauts during long-duration missions. These changes appear associated with immune dysregulation and stress, but causality remains uncertain due to observational designs, small heterogeneous samples, and confounding factors. Although current evidence is indicative rather than definitive, these findings highlight the need for preventive dental measures prior to missions and preparedness for managing oral emergencies in-flight. Future studies should address the mechanistic separation of microgravity and radiation effects, with implications for upcoming Moon and Mars missions. Full article

Lymphomas remain a significant cause of morbidity and mortality among patients living with HIV. Although the introduction of antiretroviral therapy has led to a reduction in the incidence of AIDS-related lymphomas (ARL) and an overall improvement in prognosis, these malignancies continue to pose a considerable clinical challenge. Beyond the inherent complexity of lymphoma treatment itself, the management of comorbidities, particularly infections, represents a therapeutic obstacle. Here, we review the published evidence on ARL complicated by COVID-19. Despite the fact that nearly 800 million confirmed cases of SARS-CoV-2 infection have been reported so far, only five cases of ARL and COVID-19 have been published, among whom most patients experienced a mild course of SARS-CoV-2 infection, with only one case progressing to severe COVID-19 that required oxygen therapy and prolonged hospitalization. Additionally, we present another case of a 49-year-old male patient with newly diagnosed ARL, Epstein–Barr virus (EBV)-positive, diffuse large B-cell lymphoma, not otherwise specified, complicated by prolonged SARS-CoV-2 infection. Although initially asymptomatic, the patient subsequently experienced transient respiratory failure. Despite administration of molnupiravir, both SARS-CoV-2 antigen and RT-qPCR tests remained positive for a minimum of 113 days. The prolonged SARS-CoV-2 infection, in conjunction with other opportunistic infections, impeded the delivery of adequate chemotherapy dose intensity and contributed to disease progression and ultimately the patient’s death. This case and review of the literature underscores the diversity of the clinical course of SARS-CoV-2 infection in patients with ARL and highlights the associated challenges in delivering optimal anti-lymphoma therapy in those patients. Full article

The Epstein–Barr virus (EBV) is a prevalent virus linked to various diseases, including infectious mononucleosis (IM), nasopharyngeal carcinoma, and Hodgkin’s lymphoma. Over the past few decades, EBV diagnostic strategies have evolved significantly—progressing from traditional serological assays and histopathology to more sensitive and specific molecular techniques such as nucleic acid amplification and high-throughput sequencing (HTS). While conventional methods remain valuable for their accessibility and established clinical use, they are often limited by sensitivity, speed, and multiplexing capability. In contrast, emerging technologies, including isothermal amplification, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based diagnostics, multi-omics integration, and AI-assisted analysis, have demonstrated great promise in improving diagnostic accuracy, speed, and applicability in diverse clinical settings, including point-of-care testing (POCT). This review systematically explores the historical development of EBV diagnostic technologies, highlighting key milestones and future trends in precision medicine and global health readiness. Full article

Mesenchymal dendritic cell neoplasms represent a distinct category of hematologic malignancies that challenge traditional classifications of histiocytic and classical dendritic/Langerhans cell neoplasms. Historically grouped under the broader umbrella of dendritic cell neoplasms, these entities differ significantly in their ontogeny, histopathologic features, molecular alterations, and clinical behavior. They are categorized into three main subtypes including follicular dendritic cell sarcoma, fibroblastic reticular cell tumor, and EBV-positive inflammatory follicular dendritic cell sarcoma/fibroblastic reticular cell tumor. They originate from mesenchymal stromal cells, and genetic alterations activating the NF- κβ pathway are frequent in follicular dendritic cell sarcomas. Immunophenotypic characterization is critical to distinguish these from other hematologic malignancies including histiocytic and classical dendritic/Langerhans cell neoplasms and other solid (non-hematopoietic) cancers. This review recapitulates current knowledge on existing classifications, details their diverse ontogeny from classical dendritic cell neoplasms, and provides insights into their clinicopathologic characteristics to improve diagnostic accuracy. We detail two case studies that demonstrate the challenges involved in the histopathologic diagnosis of these rare tumors, necessitating a comprehensive workup. Integrating developmental biology into practical diagnostic algorithms is essential to improve recognition and classification of these underdiagnosed neoplasms, ultimately guiding timely management. Full article

Diffuse large B-cell lymphoma (DLBCL), recognized as the most prevalent variant of adult non-Hodgkin lymphoma, presents considerable challenges in diagnosis owing to its diverse morphological features and frequent extranodal involvement, which may frequently mimic nonhematopoietic neoplasms. The 2022 WHO Classification of Lymphoid and Hematopoietic Tissues provides essential updates, highlighting the necessity of combining morphology, immunohistochemistry, cytogenetics, and molecular testing for precise subclassification. This review presents a practical method for differentiating DLBCL from other aggressive B-cell neoplasms, such as Burkitt lymphoma, B-lymphoblastic lymphoma, and mantle cell lymphoma. It highlights vital diagnostic tools, including CD45, B/T-cell markers, germinal center markers, and the Hans algorithm, as well as the role of FISH in identifying rearrangements of key genes MYC, BCL2, and BCL6, which are significant for recognizing double-hit and triple-hit lymphomas. Special focus is given to EBV-associated DLBCL and uncommon subtypes featuring plasmablastic or ALK-positive traits. This review aims to enhance diagnostic accuracy and ensure appropriate treatment strategies for patients with large B-cell lymphomas by emphasizing thorough morphological evaluation, specific adjunct testing, and adherence to the most recent classification standards. Full article

Most genomic studies on Epstein–Barr virus variability have focused on the geographic and pathological associations of EBV1 genomes. In contrast, the variability of EBV2 genomes has been less explored, mainly due to their restricted geographic circulation and the lesser number of sequenced EBV2 isolates. In this study, we sequenced and analyzed twenty-eight EBV1 and ten EBV2 genomes and a potential recombinant from Argentina, which were combined with two-hundred-and-thirty-nine downloaded complete genomes from other geographic regions, to produce an initial multi-sample.vcf file comprising 278 EBV genomes. In this context, we identified 1093/4541 positions in the viral genome that contribute to variability between viral types, mainly located in the EBNA2 and EBNA3 family of genes and the adjacent BZLF1, BZLF2, and BLLF1 genes. We further described that this variability exhibits distinct patterns across Africa, South America, and Southeast Asia. Compared to EBV1 genomes, EBV2 genomes showed fewer variable positions relative to their reference genome (Wilcoxon test, p = 0.0001). Principal component analysis revealed that EBV2 genomes from Southeast Asia segregate independently from those from South America (Wilcoxon test, Bonferroni correction; p = 1.1 × 10⁻⁷) and Africa (Wilcoxon test, Bonferroni correction; p = 2.6 × 10⁻⁹). Additionally, we identified those precise variable positions with geographic segregation strength: 1135/3666 in EBV1 and 380/3276 in EBV2. Furthermore, the distribution of variable positions along the genome disclosed a close relation for EBV2 isolates from Africa and South America as compared to isolates from Southeast Asia. Although our analysis is limited to EBV2 genomes isolated from three geographic regions, this was, to the best of our knowledge, the first study to comprehensively characterize the geographic variability of the complete EBV2 genome. These findings underscore the geographic and genetic diversity of EBV2 genomes and contribute to understanding the EBV’s evolutionary dynamics and potential regional adaptations. This research enhances our understanding of EBV2 genomic variability, supporting future epidemiological studies and advancing the knowledge base for targeted treatments and vaccine development for EBV-associated diseases. Full article

Development of any trait-directed selection strategy requires basic knowledge about some important population-specific parameters such as the effective population size $N_e$ and genetic connectedness among flocks. The $N_e$, as an indirect measure of genetic variability, is important for the conservation of the genome, while genetic connectedness is necessary for unbiased across-flock genetic evaluation. The average number of full generations (NFG) in the reference population of the Pag sheep under selection for dairy traits was 3.05. The $N_e$ estimated from individual coancestry rate $∆C_{ij}$ in the last generation was 127 animals, and the average prediction error variance of the difference in EBVs between animals belonging to different flocks ($\overline{{PEVD}_{i^{\prime },j^{\prime } }}$) was 0.81. Although conceptually different, these two population genetic parameters may be related in the populations under selection. Although it is difficult to prove this hypothesis, we decided to test it by regressing the partial (generational) estimates of $N_e$ on $\overline{{PEVD}_{i^{\prime },j^{\prime } }}$. It was estimated that $∆\overline{{PEVD}_{i^{\prime },j^{\prime } }}$ of −0.01 was accompanied by $∆N_e$ of +5.5 animals. The results suggest that strengthening genetic connectedness among flocks in populations might have a positive impact on genetic diversity; however, more research is needed before generalization. Full article