Virus Research

Tuberculosis (TB) remains one of the deadliest infectious diseases, with over a million deaths annually and a growing threat from multidrug-resistant strains (MDR-TB). A major bottleneck in controlling TB is the lack of truly portable, rapid, and user-friendly diagnostic systems that can operate effectively in decentralized, resource-constrained settings. Here, we present a first-of-its-kind, portable nucleic-acid-based diagnostic platform that enables both primary TB screening and detection of drug resistance within the same unified framework, without any change in the operative embodiment. The system integrates loop-mediated isothermal amplification (LAMP) targeting dual Mycobacterium tuberculosis markers (IS6110 and IS1081) with a compact, AI-enabled device and smartphone-based readout, delivering rapid and reliable results at the point-of-care. Clinical evaluation across 105 samples demonstrated high sensitivity and specificity. Further validation through real-world deployment in a primary healthcare setting, using a single-gene (IS6110) configuration operated by minimally trained personnel, yielded 95.60% sensitivity and 100% specificity, benchmarked against GeneXpert. Critically, the same platform architecture, without modification, extends seamlessly to drug-resistance profiling, demonstrated here through a probe-free, allele-specific LAMP approach for identifying key mutations associated with rifampicin (rpoB) and isoniazid (katG) resistance. By combining robust molecular diagnostics with AI-driven automation in a compact and accessible format, this work represents a significant medical advancement toward democratizing TB care. The platform thus holds strong potential to enable early screening, guide timely treatment decisions, reduce transmission, and substantially strengthen global TB elimination efforts, particularly in high-burden, low-resource settings.

Successive dengue virus (DENV) outbreaks can progressively reshape population immunity influencing disease expression and diagnostic performance. Objectives The aim was to evaluate the impact of secondary infections across sequential outbreaks on clinical severity, serotype dynamics and diagnostic concordance. Methods This retrospective study analyzed 976 febrile-stage samples from three sequential outbreaks in Misiones, Argentina. For serotyping and clinical analyses, 869 viremic samples confirmed by at least one direct method were included (2016: n=512; 2019: n=148; 2024: n=209). Additionally, 318 samples, including 107 non-viremic cases, were used to compare NS1 rapid diagnostic tests (NS1 Ag) and RT-PCR. Viral serotyping and clinical and laboratory markers of disease severity were evaluated. Results Secondary infections increased from 31.05% (2016) to 43.24% (2019) and 53.87% (2024) (p<0.0010). Serotype distribution shifted from DENV-1 predominance in 2016 (95.12%), DENV-1/DENV-4 co-circulation in 2019 (60.71%/39.29%), and DENV-2 predominance in 2024 (97.60%). Secondary infections were associated with more severe disease manifestations, particularly in 2024, with higher hematocrit (p=0.0120) and hemoglobin (p=0.0080), lower white blood cells (p=0.020) and platelet counts (p=0.0030), and elevated AST (p=0.0007) and ALT (p=0.0130). Concordance between NS1 Ag and RT-PCR was lower in secondary infections (k=0.457 vs k=0.759, p=0.0013). Conclusions The rising frequency of secondary infections may affect both clinical severity and diagnostic performance during outbreaks. The clinical impact was more evident in 2024, likely associated with the introduction of a new serotype. These findings highlight the need for optimized surveillance and diagnostic strategies to improve case detection and patient management during epidemics.

This work focuses on the global and partial identification problem for fractional differential equations. We provide a general numerical procedure based on global and local optimization algorithms with two refinements for biological systems that ensure solution positivity and homogeneous parameter units. The method is applied to a new fractional model of Dengue outbreak called the Fractional Homogeneous Nishiura (FHN) model, calibrated using data of newly infected people in Cape Verde. We show that our identification method yields a better fit between data and model solutions than previous approaches and that our FHN model captures the dynamics of Dengue more closely than existing systems.

Currently, the genetic architecture of Middle Eastern populations is underrepresented in global genomic databases. This gap increases the rate of Variants of Uncertain Significance (VUSs) and clinical misinterpretations of genomic data especially in Middle Eastern populations. Whole exome sequencing was conducted on 90 healthy individuals from Jordan and the data were analysed using Principal Component Analysis (PCA) and multi-computational filtering. PCA revealed a double ancestry (EUR-AFR) admixture rather than a triple admixture (EUR-AFR-AMR). More than 3,500 populations-specific variants (PSVs) were identified, of which 72% were singletons. Additionally, 19 variants were significantly enriched compared to the maximum allele frequencies in public global databases (Fisher's exact test with Benjamini-Hochberg false discovery rate correction, p-value < 0.05). Consequently, the results suggest the reclassification of variants of Uncertain Significance (VUS) which reside in the ECE2 gene to likely benign and the variants of Conflicting Classification of Pathogenicity in the genes IL1RN and THPO to benign based on the significant allele frequency (AF=0.0389, p-value < 0.05). Furthermore, a pathogenic ClinVar variant was identified in a healthy individual, warranting careful interpretation. The findings underscore the importance of identifying PSVs in order to minimize or even prevent clinical misdiagnosis and highlight the unique genetic signature in Jordan. The study serves as a foundational resource for precision medicine in the region.

Background Oropouche virus (OROV) is an emerging vector-borne virus with rapidly expanding geographic range, increasing case counts, and growing evidence of severe outcomes including neuroinvasive disease and vertical transmission. Because OROV infection presents with nonspecific febrile illness that overlaps clinically with other viruses including dengue, zika, and chikungunya, accurate molecular diagnostics are essential for patient care and surveillance. Yet existing assays rely on single genomic targets and are vulnerable to detection failure as the virus evolves and reassorts. Methodology/Principal Findings To support diagnostic capacity, we developed and clinically validated a multiplexed qPCR assay targeting three regions of the OROV S segment, incorporating redundancy to preserve sensitivity across viral diversity while enabling robust clinical interpretation. The multiplex also includes an assay targeting RNaseP as an internal sample control to ensure adequate sample processing. We evaluated assay performance using both historical and contemporary OROV strains and validated the assay on contrived serum, plasma, and cerebrospinal fluid samples, assessing linearity, limit of detection (LOD), accuracy, specificity, precision, and sample stability. The assay met or exceeded all predefined acceptance criteria for clinical testing and achieved an LOD as low as 6 copies per reaction for contemporary outbreak strains. We further implemented a logic-based interpretation matrix that reduced false-positive risk while maintaining sensitivity near the analytical LOD. Conclusions/Significance Our assay sensitively and specifically detects OROV RNA in serum, plasma, and cerebrospinal fluid while incorporating safeguards against viral evolution and reassortment. The assay has been approved for use by CLIA at Nexus Medical Labs in 49 U.S. states, expanding access to timely OROV diagnostics in the United States and providing a durable framework for molecular detection of reassorting, rapidly evolving viruses as OROV continues to spread into new regions.

Andes orthohantavirus (ANDV), the primary etiological agent of hantavirus pulmonary syndrome (HPS) in South America, is uniquely capable of limited human-to-human transmission, posing a significant challenge for outbreak control. Recent events, including the 2018-2019 Epuyen outbreak and the 2026 MV Hondius incident, underscore the need for rapid, lineage-specific molecular diagnostics. In this study, we present an artificial intelligence (AI)-driven framework for the design of diagnostic primers targeting the S genomic segment of the Epuyen lineage. Using an evolutionary algorithm integrated with thermodynamic evaluation via Primer3Plus, candidate primers were optimized to maximize classification accuracy while satisfying stringent biochemical constraints. The resulting primer set enables amplification of lineage-specific regions suitable for molecular characterization and surveillance. In silico validation demonstrates that the proposed primers achieve perfect discrimination between 2026 outbreak sequences and other ANDV variants. Furthermore, in silico comparison with standard protocol-based primers reveals substantially reduced sensitivity and specificity in the latter, highlighting the limitations of static diagnostic designs when applied to evolving viral populations. Overall, this work demonstrates that AI-assisted primer design provides a robust and adaptable strategy to improve viral detection, enhance outbreak tracking, and support timely public health interventions. Integrating computational optimization into diagnostic development is essential for strengthening preparedness against emerging zoonotic threats.

Antibody-dependent enhancement (ADE) is a major concern across orthoflavivirus infections, yet how multiple viral exposures shape enhancement risk remains incompletely understood. Here, we integrated serosurveillance from Saude, Brazil with functional immunologic analyses to define how yellow fever virus (YFV)-associated orthoflavivirus immune histories influence ADE phenotypes. Using serocomplex-specific anti-premembrane antibody profiling validated by microneutralization assays, plasma samples were stratified into YFV-only, YFV+DENV, and YFV+DENV+ZIKV exposure groups. In Fc gamma receptor-bearing U937 cells, YFV-only plasma demonstrated minimal enhancement activity, whereas cumulative orthoflavivirus exposure generated broader ADE phenotypes across heterologous viruses. In IFNAR1-/- passive-transfer models, YFV-only plasma did not enhance ZIKV or DENV2 infection in vivo. In contrast, YFV+DENV plasma increased ZIKV viremia and accelerated mortality kinetics, while YFV+DENV+ZIKV plasma demonstrated concentration-dependent enhancement phenotypes. Collectively, these findings indicate that isolated YFV immunity does not predispose to ADE, whereas cumulative orthoflavivirus exposure generates antibody repertoires capable of producing concentration-dependent enhancement in vivo.

Background: Dengue is a major public health problem in Brazil, and Minas Gerais is one of the states with the highest burden. In January 2019, the Brumadinho dam collapse released about 12 million cubic meters of iron ore tailings into the Paraopeba River basin, causing environmental disturbance that could plausibly affect vector habitats and dengue transmission. We evaluated the spatiotemporal dynamics of dengue in Minas Gerais from 2014 to 2023 and tested whether the disaster was associated with changes in affected municipalities. Methods: We performed an ecological spatiotemporal analysis using dengue notifications from SINAN for all municipalities in Minas Gerais (2014-2023). Municipalities were classified as Paraopeba basin, regional controls, or state controls. Temporal similarity was assessed using Pearson correlation-based hierarchical clustering and non-metric multidimensional scaling (NMDS). Sources of variation were examined with PERMANOVA and principal component analysis (PCA). A linear mixed-effects model with municipality as a random effect was used to test changes after 2019, with pre/post contrasts estimated from marginal means. Results: Dengue showed strong temporal synchrony across the state, with major epidemic peaks in 2015-2016, 2019, and 2023. Health region explained 31.5% of the variation in temporal incidence profiles (p = 0.001), whereas Paraopeba basin status explained no significant variation (p = 0.998). No temporal cluster was enriched for municipalities in the Paraopeba basin. PCA identified 2023, 2019, and 2016 as the main years driving variability. In the mixed model, year was significant (p < 0.001), but Paraopeba basin status and its interaction with time were not. Incidence increased significantly after 2019 in non-exposed municipalities (p < 0.001), but not in basin municipalities (p = 0.088). Conclusions: Dengue dynamics in Minas Gerais were driven mainly by regional and state-wide epidemic processes, with no significant independent effect of the Brumadinho dam collapse on notified dengue patterns.

People living with HIV (PLWH) are known to maintain a degree of immune deficiency despite efficient antiretroviral therapy and may exhibit diminished responses to vaccines. In this study, we assessed the immune response to SARS-CoV-2 infection and vaccines in two geographically distinct PLWH populations. PLWH and HIV-negative (HIV-) participants were recruited from Qu&bec City (QC), Canada, and Bobo-Dioulasso (BD), Burkina Faso, for two visits at 24-week intervals during the predominance of the Omicron variant, from May 2022 to September 2023. Blood samples were collected at each visit for the detection of antibodies against spike (anti-S) and nucleocapsid (anti-N) proteins of SARS-CoV-2 in platelet-free plasma. A total of 360 participants were enrolled. We detected anti-S antibodies in 99% of participants, indicating that nearly all had prior exposure to the SARS-CoV-2 spike antigen, either through vaccination or prior infection. Anti-S titers showed no difference between PLWH and HIV& participants in each location, while significantly higher titers were observed in participants from QC compared to BD. In contrast, anti-N antibodies, indicative of prior infection, were detected in 39% and 86% of the participants in QC and BD, respectively, suggesting that the virus circulated largely in the latter population. No difference in anti-N levels was observed between PLWH and HIV& participants in BD. However, participants in QC had significantly lower titers compared to HIV participants. Overall, this study shows that PLWH develop robust antibody responses to SARS-CoV-2 vaccination, comparable to those observed in HIV& participants. Significant geographic differences were observed in anti-S titers, irrespective of HIV status, with participants from QC displaying higher titers. In contrast, participants from BD had higher anti-N antibody prevalence and titers, reflecting more SARS-CoV-2 infections in BD than in QC. Finally, analysis of anti-S antibody titers against several circulating variants revealed significantly lower levels in unvaccinated participants and in those vaccinated with monovalent vaccines in BD. No significant difference was observed between monovalent and bivalent vaccines administered in QC. All authors have seen and approved the manuscript.

Objective: To identify Dickkopf-1 (DKK1) as a prognostically relevant candidate in head and neck squamous cell carcinoma and to evaluate whether DKK1 and cytoskeleton-associated protein 4 (CKAP4) expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: DKK1 was screened using the Human Protein Atlas Pathology Atlas. Immunohistochemical expression of DKK1 and CKAP4 was examined in 54 patients with primary TSCC (cT1-4N0) treated surgically between 2015 and 2020. Nine cases were excluded because of insufficient tissue blocks or inadequate staining quality, leaving 45 evaluable cases. Associations with delayed cervical lymph node metastasis were assessed together with conventional clinicopathological factors, including infiltrative growth pattern (INF) and pathological depth of invasion (pDOI). Results: In public database analysis, high DKK1 expression was associated with poorer overall survival in head and neck squamous cell carcinoma. In the TSCC cohort, pDOI [&ge;]5 mm and INF pattern c were significantly associated with cervical lymph node metastasis. Positive DKK1 and CKAP4 expression were also significantly associated with cervical lymph node metastasis. Furthermore, combined DKK1/CKAP4 positivity, when incorporated with INF and pDOI, provided additional risk stratification, and cases with all 3 factors showed a markedly increased likelihood of cervical lymph node metastasis. Conclusions: Expression of DKK1 and CKAP4 was associated with cervical lymph node metastasis in TSCC. Combined assessment of DKK1/CKAP4 expression with INF and pDOI may improve pathological risk stratification and may help identify patients who require closer neck evaluation and postoperative management.

Background Cancer is a growing public health challenge in low- and middle-income countries, where urbanization, nutritional transition and lifestyle changes contribute to modifiable risk factors. In Mauritania, population-based data on cancer-related nutritional, behavioral and anthropometric risk factors remain limited. Objective To describe the frequency of the main nutritional, behavioral and anthropometric cancer-related risk factors among adults living in the three wilayas of Nouakchott. Methods A cross-sectional study was conducted among 1,000 adults aged 18 years and older in Nouakchott. Data were collected using a standardized questionnaire covering sociodemographic characteristics, dietary habits, physical activity and selected health behaviors. Anthropometric measurements were performed to assess body mass index and abdominal adiposity. Abdominal obesity was defined using sex-specific waist circumference cut-off points recommended by the World Health Organization: [&ge;] 88 cm in women and [&ge;] 102 cm in men. Results were presented as frequencies and proportions, with comparisons by sex, age group and wilaya of residence. Results Women represented 52.0% of participants, and 53.5% were aged 18-34 years. Excess body weight was frequent, with 38.6% overweight and 28.0% obese. Abdominal adiposity was also common, with 58.0% having increased or substantially increased waist circumference and 48.3% having an elevated waist-to-hip ratio. Physical inactivity was reported by 64.7% of participants, and 15.7% were current smokers. Dietary exposures included high red meat consumption in 66.8%, daily refined cereal intake in 67.5%, daily sugar-sweetened beverage consumption in 14.9%, and limited daily fresh fruit consumption in 13.8%. Significant differences were observed by sex for anthropometric indicators, by age for selected dietary habits, and by wilaya for physical activity, smoking and selected dietary behaviors. Conclusion This study shows a high frequency of modifiable cancer-related risk factors among adults in Nouakchott, particularly excess body weight, abdominal adiposity, physical inactivity and unfavorable dietary habits. These findings support the need to strengthen primary prevention strategies targeting nutrition, physical activity and tobacco control in Mauritania.

Background Rabies is a zoonotic neglected public health problem associated with animal bites, especially domestic carnivores claiming 59,000 deaths annually predominantly in developing countries of Africa and Asia. There is a high risk of exposure among rural communities endemic with animal rabies where adoption of prevention strategies is minimal. This study determined the prevalence of suspected rabies exposure, associated factors, and delayed post-exposure care-seeking among animal-bite human cases in Busia district, Uganda. Methods: This was a cross-sectional study that involved 332 consecutively sampled animal bite human cases that occurred within the period 2023 to 2024. Data for the bite cases from records were collected using a data abstraction tool. In addition, interviewer-administered semi-structured questionnaires were used to collect data on sociodemographic, animal-related and environmental characteristics. Approximate bite locations were collected using Global Positioning System (GPS) coordinates via Kobo collect. Analysis was carried out in STATA 17 using mixed effects modified Poisson regression for factors associated with suspected rabies exposure. Results: The median age of the bite cases was 18 (IQR: 9-36) with the male gender predominantly affected. The prevalence of suspected rabies exposure was 53.6% (95% Confidence interval - CI: 46.8-60.3). Factors associated were urban versus (vs) rural residence (adjusted prevalence ratio-aPR: 1.04, 95%CI: 1.00-1.08), being bitten by a stray animal (aPR: 1.28, 95% CI: 1.22-1.35) and wild animal (aPR: 1.22, 95% CI: 1.14-1.30) vs domestic animal, vaccination status of the biting animal i.e. vaccinated vs unvaccinated (aPR: 0.76, 95% CI: 0.69-0.85), provoked vs unprovoked bites (aPR: 0.82, 95% CI: 0.79-0.86), and distance to nearest river ([&ge;]5km) vs <5km (aPR: 0.93, 95% CI: 0.87-0.99). The prevalence of delayed post-exposure seeking was 23.0% (95% CI: 16.5-31.1) among the suspected rabies exposures. Conclusion: The study reveals a high prevalence of suspected rabies exposure. Factors associated are multidimensional i.e. are of human, animal and environmental origin. The one health paradigm should be emphasized during routine surveillance of rabies-related cases. The study observed that 1 in 5 bite cases delayed to seek care post bite exposure. We recommend collaborations between sectors, routine vaccination and awareness campaigns, and monitoring of wild carnivore populations and environmental dynamics in rabies-related surveillance.

Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of seasonal influenza vaccination against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand.Methods: We conducted a nationwide retrospective test-negative design study using administrative healthcare data from the National Health Security Office linked with laboratory-confirmed influenza surveillance data between June 1, 2013, and May 31, 2025, covering twelve influenza seasons (2013-2024). COPD-related clinical episodes among patients aged [&ge;]40 years who presented with pneumonia or acute exacerbation of COPD and underwent RT-PCR testing for influenza were included. Multilevel Poisson regression models were used to estimate adjusted risk ratios (RRs), and VE was calculated as (1 - adjusted RR) x 100.Results: A total of 606,072 COPD-related clinical episodes were included, of which 192,224 (31.7%) were influenza-positive. The overall adjusted VE against influenza-associated pneumonia was 63.2% (95% CI: 62.5-64.0), while VE against influenza-associated COPD exacerbations was 67.0% (95% CI: 48.8-78.8). VE estimates were broadly similar across age groups and remained substantial across COPD severity strata. Although point estimates were numerically higher in severe and very severe COPD, subgroup differences should be interpreted cautiously.Conclusions: Seasonal influenza vaccination was associated with substantial protection against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand.

Methicillin-resistant Staphylococcus (MRS) infections are a significant public health concern. Anterior nares serve as a major reservoir and source of spread of MRS ssp. People living with HIV (PLWHIV) tend to be at higher risk of colonisation with MRS organisms due to frequent healthcare exposure. We assessed the prevalence of MRS nasal carriage and associated factors among PLWHIV at the HIV clinic of Kiruddu National Referral Hospital, Kampala, Uganda, from May to July 2024. Nasal swabs from 256 PLWHIV were cultured, and microbiological isolation was performed at MBN Clinical Laboratories. Prevalence was calculated as proportions, and logistic regression identified associations with clinical and socio-demographic factors (p < 0.05). Of 256 participants, 163 (63.7%) carried Staphylococcus, with 82 (32%) identified as MRS carriers (8.9% MRSA, 23% MRCoNS). Frequent hospital visits ([&ge;]3) (adjusted incidence risk ratio [A-IRR] = 1.18 x 107, p < 0.001), second-line antiretroviral therapy (ART) (A-IRR = 3.82, p = 0.041), and unsuppressed viral load (>1000 copies/mL) (adjusted odds ratio [AOR] = 11.3, 95% CI: 2.11-60.58, p = 0.005) were significantly associated with MRS carriage. Mask-wearing was protective against MRCoNS (A-IRR = 1.66, 95% CI: 1.06-2.58, p = 0.026). MRS isolates exhibited high resistance to erythromycin (81.7%) and trimethoprim-sulfamethoxazole (79.3%), but susceptibility to linezolid (93.9%). MRS nasal carriage is prevalent among PLWHIV. Individuals with frequent health care contact and those on second-line ART regimens are more susceptible to MRS colonization, while individuals who wear face masks and those with an undetectable HIV viral load are less susceptible. Antimicrobial Resistance (AMR) surveillance within HIV programs, enhanced infection control, ART adherence, and targeted screening for high-risk groups are critical to mitigate colonization.

Abstract Schizophrenia (SCZ) and bipolar disorder (BPD) are highly heritable psychiatric disorders with complex polygenic architectures. Genome-wide association studies (GWASs) have identified numerous common variant associations, but rarer variants detectable through whole-genome sequencing (WGS) remain underexplored. We conducted rare variant association analysis using WGS data from the Portuguese Island Collection (PIC), including 28 families with SCZ (n = 53) and 41 families with BPD (n = 83) cases, and population controls (n = 62). Following ANNOVAR and CADD annotation, burden analysis of deleterious variants showed that both affected and unaffected family members from SCZ and BPD pedigrees had significantly higher burdens of rare deleterious variants compared to controls (p < 0.0001), with no significant differences observed between affected and unaffected relatives, consistent with shared familial genetic liability. Polygenic Risk Score (PRS) analysis confirmed significant genetic contributions to both disorders within PIC. Association analyses were subsequently performed using SAIGE-GENE+ identifying 483 and 583 nominally significant (suggestive associations) gene sets (p-value [&le;] 0.05; FDR > 0.05) for SCZ and BPD, respectively, including gene sets related to neurotransmission, synaptic function and structure, neurodevelopment, and neuroinflammation as well as major signaling pathways. Cross disorder overlaps also identified shared suggestive enrichment of GABA and glutamate signaling, synaptic signaling, and Wnt signaling gene sets in both SCZ and BPD. These findings support shared rare variant burden within multiplex psychiatric families and highlight the role of gene-set based rare variant analysis in identifying neurobiological pathways relevant to SCZ and BPD. Keywords: WGS, Rare Variants, Schizophrenia, Bipolar Disorder

Background: The ongoing Bundibugyo virus disease (BDBV) outbreak in Central Africa highlights the absence of approved vaccines specifically targeting BDBV. Whether licensed Zaire ebolavirus (EBOV) vaccines induce cross-reactive immunity against BDBV remains largely unknown. Methods: We performed an immunogenicity analysis using serum samples from participants enrolled in the PREVAC randomized clinical trial evaluating licensed Ebola vaccine strategies in West Africa. Samples collected at day 28 (D28) and month 3 (M3) following vaccination with rVSV{Delta}G-ZEBOV-GP or Ad26.ZEBOV/MVA-BN-Filo were assessed using a multiplex Luminex assay against glycoproteins from multiple filoviruses, including EBOV Kikwit, EBOV Mayinga, BDBV, Sudan virus, Reston virus, and Marburg virus. Results: A total of 179 samples were analysed. Detectable cross-reactive antibody responses against BDBV were observed across vaccine groups, timepoints, and age categories. However, BDBV responses remained substantially lower than homologous EBOV responses. In rVSV recipients, median BDBV responses (net MFI) reached 282 (IQR 164-644) at D28 compared with 1788 (832-3311) against the homologous Kikwit antigen. Similar patterns were observed following rVSV booster vaccination and Ad26.ZEBOV/MVA-BN-Filo vaccination. The heterologous Ad26/MVA regimen demonstrated increasing BDBV responses between D28 and M3. Conclusions: Licensed EBOV vaccines induced detectable but quantitatively reduced cross-reactive antibody responses against BDBV. Although no direct assessment of vaccine efficacy against BDBV disease was possible, these findings support the plausibility of partial heterologous immunity following EBOV vaccination. In the absence of approved BDBV-specific vaccines, these data support the urgent evaluation of currently available Ebola vaccines during BDBV outbreaks and reinforce the importance of developing broadly protective pan-filovirus vaccines.

Biological aging is heterogeneous across organ systems, yet whether CT-derived abdominal aging provides prognostic value beyond routine clinical data and whether organ decomposition adds beyond a unified estimate remains untested. We developed and evaluated organ-specific and ensemble biological age models from radiomic features across five abdominal organs in 68,675 CT scans from 32,883 subjects, evaluated on alignment with chronological age of healthy subjects (nested cross validation: MAE=3.68 years, R^2=0.90). In sequential analyses restricted to adults aged 20-60 years which is the stratum of strongest BAG-disease association, ensemble biological age gaps provided incremental prognostic value beyond demographic covariates for all-cause disease and mortality (Delta C-index=0.141, 0.051) and beyond routine blood biomarkers (Delta C-index=0.048), confirming CT-derived aging captures structural information beyond laboratory markers. Organ-specific biological age added incremental prognostic value beyond ensemble selectively for focal diseases: cardiovascular (aorta, Delta C-index=0.091) and hepato-pancreatic (pancreas, Delta C-index=0.096). These findings establish a hierarchical organization of CT-derived biological aging, positioning routine CT as a source that adds prognostic value to existing clinical biomarkers.

Background: Black and Latino adults in the United States experience a disproportionate burden of cardiometabolic conditions due to interacting behavioral, social, and structural drivers of health. Less is known about the impact of integrating digital health tools into CHW-led interventions to improve cardiometabolic health. This trial evaluates a multilevel community-digital health promotion model delivered by CHWs to improve service utilization, health behaviors and cardiometabolic health among Black and Latino adults. Methods: This community-partnered trial uses a randomized delayed-control group with a phased recruitment design. Four cohorts (N = 664) are enrolled through three community-based organizations (CBOs). Eligible participants are 18 years who self-identify as Black or Latino, and have prediabetes/diabetes, hypertension, or overweight/obesity. Participants are allocated to either (1) a multilevel intervention consisting of CBO and CHW capacity building combined with individualized CHW-led lifestyle coaching and group activities supported by digital tools, or (2) a delayed control group receiving SMS-only cardiometabolic health education. Data collected at baseline, 6, 9, and 18 months include surveys and health metrics. Qualitative data are collected from participants and community partners to assess intervention acceptability, implementation facilitators and barriers, and sustainability. Results: The primary outcome is health service utilization at 6 and 9 months. Secondary outcomes include health behaviors, health metrics, and social determinants of health. Sustainability of health behaviors and health metrics is assessed at 18 months. Conclusions: Findings will provide evidence to inform scalable, sustainable community-digital health models for CHW-supported cardiometabolic health interventions in underserved communities.

Background: Frontotemporal dementia (FTD) lacks widely accessible disease-specific biomarkers. Optical coherence tomography (OCT) and OCT angiography (OCTA) may provide non-invasive measures of retinal changes associated with neurodegeneration. We conducted a systematic review and meta-analysis evaluating retinal biomarkers in FTD compared with Alzheimer disease (AD) and controls. Methods: A systematic search of PubMed and Embase was conducted through April 25, 2026 according to PRISMA guidelines. Studies evaluating OCT/OCTA biomarkers in FTD with comparator groups were included. Inverse weighted random-effects models, publication bias assessments, and meta-regressions were performed. Results: Ten studies involving 139 individuals with FTD, 87 with AD, 29 with mild cognitive impairment, 14 with TDP-43 proteinopathy, 5 with tauopathy, and 255 controls were included in the systematic review; five studies were eligible for meta-analysis. Compared with AD, individuals with FTD demonstrated significantly thinner retinal nerve fiber layer (RNFL) thickness (SMD = -0.61, 95% CI -0.98, -0.24). Compared with controls, individuals with FTD exhibited significantly thinner ganglion cell layer-inner plexiform layer (GCL-IPL) thickness (SMD = -0.55, 95% CI -1.02, -0.08), whereas pooled analyses across multiple retinal biomarkers were non-significant (SMD = -0.19, 95% CI -0.52, 0.14). RNFL thickness correlated negatively with female % in FTD and positively with age in both AD and controls. Conclusions: Individuals with FTD exhibit lower RNFL thickness than AD and lower GCL-IPL thickness than controls, suggesting retinal alterations may reflect neurodegeneration. However, larger longitudinal studies with standardized OCT/OCTA protocols are needed to determine the diagnostic and prognostic utility of retinal biomarkers in FTD

ABSTRACT OBJECTIVE: We performed a systematic review and meta-analysis (SRMA) of post-surgical outcomes, comparing chlorhexidine gluconate (CHG) versus povidone iodine (PI) for vaginal antisepsis of major gynecologic procedures. DATA SOURCES: Ovid Medline, Embase, Scopus, Embase, Cochrane, and Clinicaltrials.gov were searched between 1986 and December 2023, for studies comparing CHG with PI for vaginal antisepsis of major gynecologic operations. STUDY ELIGIBILITY CRITERIA: We included Randomized Controlled Trials (RCTs) and non-RCTs comparing CHG to PI for vaginal antisepsis of major gynecologic operations. The primary outcome was surgical site infections (SSIs) and the secondary outcome was urinary tract infections (UTIs) and vaginal irritation. METHODS: Summary estimates were calculated by fixed effects models when I2 [&le;] 25% and by random effects models when I2 > 25%. Statistical analysis was performed using RevMan 5.4.1. The protocol for this systematic review was registered on PROSPERO (ID CRD42022378101). RESULTS: Nine studies met the inclusion criteria, four of which were randomized controlled trials (RCTs). 9538 patients were included, 4300 (45%) of whom were allocated to CHG and 5238 (55%) to PI. No statistically significant difference in SSI incidence was found for vaginal antisepsis with CHG versus PI in pooled analyses (n= 9538 patients; RR 1.20; 95% CI 0.92-1.57; I2 =0%). In contrast, a significantly higher risk of UTIs was observed for vaginal antisepsis with CHG than with PI (n=6061 patients; RR 1.48 95% CI 1.03-2.14; I2 = 0%). CONCLUSION: In our SRMA, there were no significant differences in SSI risk when either CHG or PI was utilized for antiseptic vaginal preparation. Interestingly, vaginal antisepsis with PI was associated with a lower incidence of post-operative UTIs following major gynecologic surgery. Our findings support current guidelines that form of vaginal antisepsis can be used for SSI prevention. They also suggest that PI may result in fewer postoperative UTIs but further randomized studies are needed to support these findings. Key words: surgical site infection, surgical wound infection, urinary tract infection, urogynecologic surgery, Chlorhexidine, Povidone Iodine, surgical antiseptic,