Tag: pubmed

Microbiol Spectr. 2026 Aug 21:e0099126. doi: 10.1128/spectrum.00991-26. Online ahead of print.

ABSTRACT

Accurate O-serotyping of Escherichia coli remains essential for clinical surveillance, outbreak investigation, and evaluation of vaccines targeting invasive E. coli disease. Traditional agglutination-based serotyping is labor-intensive, low-throughput, and reliant on subjective visual interpretation. We developed a high-throughput (HTP) 96-well agglutination assay incorporating automated OD normalization (BioTek Epoch) and objective agglutination quantification using a CTL ImmunoSpot reader. A data-driven positivity cutoff (Total Intensity of Spots per Well < 11.65) was established via Youden’s index to optimize diagnostic discrimination. Validation was performed in a GCLP-compliant laboratory using clinical isolates representing the nine O-serogroups included in the ExPEC9V vaccine candidate. The assay demonstrated 100% sensitivity across all homologous O-serogroups (n = 9) and ≥95% specificity across heterologous O-serogroups, including five non-ExPEC9V clinical isolates. Robustness was confirmed for bacterial suspensions with OD₆₀₀ values of 0.6-1.2, the range recommended for clinical implementation. Long-term stability of boiled cultures stored at 2-8°C was inconsistent-particularly for O75 antisera-supporting same-day preparation of suspensions. Due to heat-associated interference observed with deep-well plastic blocks, glass 96-well tube systems were validated and adopted for clinical testing, demonstrating 100% specificity across all heterologous O-serogroups. This validated HTP agglutination assay provides a scalable, reproducible, and clinically actionable method for E. coli O-serotyping. By preserving the immunologic specificity of conventional agglutination while enabling automation and objective readouts, the assay is well suited for vaccine efficacy studies, reference laboratory workflows, and clinical microbiology programs requiring accurate phenotypic confirmation of O-antigen expression.IMPORTANCEAgglutination serotyping of bacterial isolates is labor-intensive, requires specialized laboratories and skilled personnel, and relies on subjective visual interpretation. Nevertheless, it remains essential for determining O-antigen expression, providing information that molecular methods-focused only on detecting serotype-specific genes-cannot. For this reason, agglutination O-serotyping continues to serve as the regulatory accepted gold standard. This study describes the development, optimization, and validation of a high-throughput agglutination O-serotyping assay designed to overcome the constraints of low throughput and operator-dependent variability. The validated assay demonstrated its scientific utility through the characterization of clinical isolates from a Phase 3 trial of a candidate Escherichia coli vaccine.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04899336.

PMID:42627174 | DOI:10.1128/spectrum.00991-26

Educ Prim Care. 2026 Aug 21:1-7. doi: 10.1080/14739879.2026.2714838. Online ahead of print.

ABSTRACT

INTRODUCTION: Combat Medical Technicians (CMTs) are central to military primary care but have limited opportunity for clinical exposure. Simulated patients offer a controlled method to maintain clinical currency. Advances in conversational artificial intelligence (AI) enable realistic and interactive simulated consultations. We present our evaluation of the feasibility, acceptability and educational impact of AI-simulated patients for CMT training.

METHODS: Five military primary care simulated patients were developed and hosted on the SimFlow.ai platform and delivered during a development course. Participants completed pre- and post-simulation surveys assessing confidence across 12 clinical domains alongside perceptions of realism, usability and educational value. Quantitative analysis used Wilcoxon signed-rank tests and Spearman rank correlations.

RESULTS: Twenty CMTs completed both simulations and surveys. Statistically significant improvements were observed in 10 of 12 clinical domains, including core consultation skills such as comprehensive history taking, identifying key symptoms, adapting questioning and formulating a management plan, and differential diagnoses (all p < 0.002). Evaluation of the simulations demonstrated positive perceptions of medical accuracy, patient narratives and overall educational value. Technical performance received mixed feedback, with response lags identified as the primary barrier. No associations were found between outcomes and CMT demographics which suggests equitable benefit across the cohort.

CONCLUSION: AI-simulated patients are feasible to implement and are associated with meaningful improvements in consultation confidence among CMTs. Despite technical constraints, AI-simulated patients represent a scalable, standardised adjunct to support clinical currency across the CMT workforce. Further research should evaluate objective competence outcomes and explore broader uses of this technology.

PMID:42627168 | DOI:10.1080/14739879.2026.2714838

Bioanalysis. 2026 Aug 21:1-13. doi: 10.1080/17576180.2026.2708544. Online ahead of print.

ABSTRACT

This white paper (Part 2 of a series on vaccine immunogenicity assay validation) addresses the development of Ligand Binding Assays (LBAs) to support vaccine immunogenicity studies. Developed through a collaborative effort by a working group of experts from 16 global vaccine manufacturers, national regulatory authorities, and a nonprofit global-health foundation convened under the Workshop on Recent Issues in Bioanalysis (WRIB), this manuscript provides practical guidance to complement existing regulatory frameworks for bioanalytical method validation.Part 2 details the iterative process of LBA development, with emphasis on defining the Analytical Target Profile (ATP) as a foundational tool for guiding decision-making across the assay life cycle. Key topics include assay purpose and analyte specificity, regulatory expectations, the use of statistical Design of Experiments (DOE) to systematically optimize assay conditions, and the selection of appropriate reagents, controls, and sample matrices. The paper also addresses the unique challenges posed by the structural diversity of vaccine antigens and the need for representative reference materials.The manuscript further highlights the importance of ongoing performance assessment and the adaptability of assays as they transition from early exploratory phases to pivotal clinical studies. Collectively, the recommendations presented aim to supplement existing regulatory guidance with vaccine-specific considerations, ultimately supporting the development of safe and effective vaccines. This paper is complemented by Part 1 (LBA Validation) and Part 3 (Assay Lifecycle Management, including Maintenance, Monitoring, and Transfers).

PMID:42627145 | DOI:10.1080/17576180.2026.2708544

J Rural Health. 2026 Jun;42(3):e70207. doi: 10.1111/jrh.70207.

ABSTRACT

PURPOSE: Given persistently low rates of lung cancer screening among eligible individuals, we examined racial and geographic differences in proximity to low-dose computed tomography (LDCT) screening facilities among American Indians and Alaska Natives (AIAN) and White adults in North Carolina.

METHODS: We used cancer registry data linked with health insurance claims (2016-2020) to examine a cohort of 18,154 AIAN and NHW lung cancer patients. We calculated straight-line distances between patient’s residential ZIP code and nearest LDCT facility available in the year prior to diagnosis, (within ZIP code, 1-10 miles, or ≥10 miles). Logistic regression models assessed associations between distance and stage at diagnosis (localized vs. non-localized and distant vs. non-distant), adjusting for race, age at diagnosis, and health insurance status.

FINDINGS: AIAN were more likely than NHW patients to live ≥10 miles from an LDCT facility (36% vs. 17%) and less often diagnosed at a localized stage (19% vs. 26%). Patients living ≥ 10 miles away had lower odds of localized stage diagnosis (adjusted OR = 0.89; 95% CI: 0.82-0.98) compared to those with access within their residential ZIP code.

CONCLUSIONS: Greater distance to LDCT facilities was associated with reduced odds of early-stage diagnosis. Strategies such as mobile screening units and culturally tailored outreach may improve access and outcomes in underserved AIAN communities.

PMID:42627130 | DOI:10.1111/jrh.70207

Spec Care Dentist. 2026 Jul-Aug;46(4):e70239. doi: 10.1111/scd.70239.

ABSTRACT

AIM: To assess the effect of an educational intervention on nursing professionals’ knowledge of hospital oral hygiene and associated factors.

METHODS: A single-group quasi-experimental study was conducted in a hospital in southern Brazil, including 138 nursing professionals (mean age: 35.46 ± 9.49 years). The intervention comprised three stages: a pre-test, a protocol-based educational session delivered by two dental surgeons, and a post-test. Data were analyzed using descriptive statistics, McNemar’s test, and Pearson’s chi-square test (α = 0.05).

RESULTS: Before the intervention, 19.6% of participants had never received academic instruction on oral hygiene, 59.4% had not received institutional training, and 37.7% were unaware of an institutional protocol. After the intervention, correct answers reached ≥95% in 15 of 19 items and 100% in four items (p < 0.001). The greatest improvements were observed for oral hygiene before bathing intubated patients (43.5% to 85.5%), and toothbrush use in hospital settings (52.9% to 85.5%). Higher baseline knowledge was associated with the presence of an institutional oral hygiene protocol (p < 0.05).

CONCLUSION: The educational intervention improved nursing professionals’ knowledge of hospital oral hygiene. Institutional protocols were associated with higher baseline knowledge, reinforcing the importance of continuing education and standardized protocols to support safe, evidence-based care.

PMID:42627123 | DOI:10.1111/scd.70239

Subst Use Misuse. 2026 Aug 21:1-11. doi: 10.1080/10826084.2026.2716304. Online ahead of print.

ABSTRACT

ABSTACTAlcohol consumption remains a major public health challenge and a leading preventable cause of morbidity and mortality worldwide. Although the Alcohol Use Disorders Identification Test (AUDIT) is widely used to identify hazardous alcohol use, reliance on total scores may obscure clinically meaningful heterogeneity in drinking behaviors. This study aimed to identify latent alcohol consumption typologies among Colombian adults using AUDIT response patterns and to examine their sociodemographic and psychosocial correlates. Latent class analysis (LCA) was conducted using ten dichotomized AUDIT items from 14,131 adults who reported alcohol consumption during the previous 30 days in the 2019 Colombian National Survey of Psychoactive Substance Use. Competing models were evaluated according to statistical fit, parsimony, classification accuracy, and interpretability. A three-class solution was selected, comprising Low Risk (50.7%), Hazardous Binge Drinking (38.5%), and Harmful/Dependence (10.8%) profiles. Although the two higher-risk classes showed similarly high probabilities of heavy episodic drinking, the Harmful/Dependence profile was characterized by substantially greater probabilities of dependence symptoms and alcohol-related consequences. Early alcohol initiation, peer heavy drinking, and depressive symptoms were associated with more severe profiles, whereas female sex and higher socioeconomic status were protective. These findings highlight the value of person-centered approaches for identifying heterogeneous alcohol use patterns and informing targeted prevention, screening, and intervention strategies.

PMID:42627088 | DOI:10.1080/10826084.2026.2716304

Genetics. 2026 Aug 21:iyag209. doi: 10.1093/genetics/iyag209. Online ahead of print.

ABSTRACT

Severe disease following infection with SARS-CoV or SARS-CoV-2 is driven in part by genetically regulated immune responses that promote lung injury. To study genetic mechanisms of immune-mediated coronavirus pathogenesis, we screened the Collaborative Cross (CC) panel for Mus musculus strains that are phenotypically divergent with respect to coronavirus susceptibility. We identified CC006/TauUnc and CC044/UncJ as susceptible and resistant, respectively, and crossed them in an intercross to produce a genetic mapping population. Previously, we mapped genetic loci associated with disease severity, including HrS43, which is both conserved across viruses and between mouse and human. Here, we incorporate immune cell data from flow cytometry and perform a systems genetics analysis to resolve immune pathways linking host genetic loci to disease outcomes. We identify: (1) immune predictors of disease severity, as revealed by Bayesian variable selection; (2) extensive genetic regulation of the immune system at homeostasis and in response to infection, as revealed by infection-stratified and combined genotype-by-treatment (GxT) QTL mapping; and (3) candidate causal pathways linking genetic loci, immune responses, and disease severity, as revealed by context-dependent Bayesian mediation analysis. Our analysis reveals distinct patterns of virus specificity across biological layers: immune effects on disease severity appear largely consistent across viruses; genetic architecture is both shared and virus-specific; and mediating immune traits are in most cases virus-dependent. Notably, HrS43 appears to influence disease severity through distinct immune mediators in SARS-CoV versus SARS-CoV-2, demonstrating that conserved genetic susceptibility can drive virus-specific immunopathology with translational relevance across species.

PMID:42627087 | DOI:10.1093/genetics/iyag209

J Neuroimaging. 2026 Jul-Aug;36(4):e70143. doi: 10.1111/jon.70143.

ABSTRACT

BACKGROUND AND PURPOSE: Brain magnetic resonance imaging (MRI) is an essential component for outpatient neurological evaluation, though access to timely imaging at the point of care is not feasible for most outpatient neurology practices. Portable ultra-low-field MRI systems offer a potential solution, but studies describing their clinical performance in routine outpatient neurology practice remain limited. This study evaluated clinical concordance and patient experience of portable MRI (pMRI) compared to standard-of-care MRI (sMRI) in independent neurology practices.

METHODS: In this prospective, multicenter study, adults presenting to outpatient neurology clinics and requiring clinically indicated brain MRI completed imaging with both pMRI (0.064 T) and sMRI (91% 3 T, 9% 1.5 T) in the neurology clinic. All examinations were independently reviewed by board-certified neuroradiologists in a blinded, randomized fashion without access to clinical history. The primary endpoint was patient-level concordance between modalities for the presence or absence of abnormal findings. Discordant cases underwent post hoc unblinded paired review with clinical history to assess clinical significance. Secondary endpoints included patient-reported experience, assessed using a structured questionnaire evaluating noise, comfort, claustrophobia, anxiety, and overall experience on 10-point Likert scales, as well as modality preference.

RESULTS: Among 125 participants imaged for common outpatient indications, including headache (40%), cognitive impairment or dementia (16%), multiple sclerosis follow-up (16%), and tumor surveillance (16%), portable and sMRI demonstrated 92% concordance on blinded review. Following clinically informed post hoc review, concordance increased to 98%. pMRI was rated more favorably across all patient experience domains (p < 0.001), and participants preferred pMRI (61%) over sMRI (14%) by a 4:1 ratio.

CONCLUSIONS: In outpatient neurology practices, pMRI images demonstrated high clinical concordance with sMRI for identifying the presence or absence of structural brain abnormalities and were strongly preferred by patients. These findings support the use of pMRI as a practical point-of-care imaging tool for neurology patients, enabling timely access to structural neuroimaging during the clinical encounter.

PMID:42627086 | DOI:10.1111/jon.70143

Cladistics. 2026 Aug 21. doi: 10.1111/cla.70065. Online ahead of print.

ABSTRACT

Oropouche virus (OROV) is a high-risk emerging arbovirus that causes recurrent febrile outbreaks across tropical Central and South America, posing persistent public health threats with expanding endemic ranges and rising zoonotic spillover risks. Limited comprehensive evidence regarding its genomic plasticity and multi-scale evolutionary dynamics hinders precise epidemic prevention. Herein, we performed systematic phylogenomic analyses of all available OROV sequences to elucidate its recombination profiles, adaptive evolution, cross-species transmission and spatial dispersal patterns. Phylogenetic reconstruction based on breakpoint-free regions revealed two major polyphyletic lineages characterized by extensive multi-host and transboundary circulation, with Brazilian strains dominating global OROV populations. Bayesian ancestral inference identified humans as the likely earliest detectable ancestral host, while all statistically robust host-switching events were closely associated with Callithrix spp., confirming their critical role as intermediate amplifying hosts. Phylogeographic analyses suggested Brazil and Peru as the primary ancestral origins, with neighbouring short-distance diffusion and frequent cross-border transmission forming a multi-path dissemination system concentrated in the Amazon Basin and southeastern coastal zone of Brazil. Pronounced topological incongruence among L, M and N genes demonstrated pervasive segmental reassortment, which has intensified temporally since 2010, especially during 2020-2024. Notably, the M gene undergoes intensive intra-segment recombination and prominent positive selection with relaxed functional constraints, representing the key adaptive hotspot, whereas L and N genes remain highly conserved under strong purifying selection. This study clarifies the synergistic evolutionary mechanisms of recombination, reassortment, host switching and differential selection, providing robust theoretical support for OROV surveillance and targeted intervention.

PMID:42627027 | DOI:10.1111/cla.70065

J Med Virol. 2026 Aug;98(8):e71113. doi: 10.1002/jmv.71113.

ABSTRACT

Immune reconstitution (IR) after allogeneic hematopoietic stem cell transplantation (HSCT) is crucial to prevent transplant-related complications. Plasma viral load of Torque teno virus (TTV-VL), considered apathogenic and the main component of human virome, may reflect immunosuppression state. In this single-center prospective study we recruited 32 children undergoing HSCT to explore the potential role of TTV-VL as an IR marker and predictor of clinical outcome. Blood samples were obtained prior to stem cell infusion, on the day of transplantation, and on days +15, +30, +90, +180, +270, and +360 post-transplant. TTV-VL diminished after conditioning, increased after engraftment, and correlated with lymphopenia since day +30, consistent with previous reports. In exploratory analyses, correlations with clinical outcomes were limited by small sample size: higher TTV-VL at day +15 correlated with accumulated bacterial infection episodes and mortality at 1 year; at pre-HSCT and at +180 days TTV-VL predicted viral reactivations at the subsequent study timepoint; at +30, TTV-VL anticipated graft versus host disease. Associations with NK cell function and HLA/KIR variables were also observed, although no mechanistic inference could be drawn. Overall, these results are hypothesis-generating and warrant validation in larger studies.

PMID:42627020 | DOI:10.1002/jmv.71113