The purpose of this study was to determine factors related to successful completion of peer support specialist training and certification. This study analyzed enrollment data to study graduation outcomes in 1,164 participants in the Certified Recovery Support Specialist (CRSS) Success Program, an intervention designed to scale up the number of peer specialists in the state by funding tuition and direct supports for students. Exploratory institutional-level binomial regression and grant funding data was used to understand the relationship between funding and graduation rate. Post-graduation survey data from 171 participants was also analyzed with logistic regression to understand factors associated with attempting and passing the peer specialist certification exam. Receiving financial support beyond tuition and receiving academic accommodations were strongly associated with an increased likelihood of graduation, while requiring service supports like counseling or legal assistance decreased this likelihood. Working as a peer specialist during training also significantly boosted the probability of graduation, whereas taking a leave of absence did the opposite. Among graduates, receiving tangible support during their training and having a smaller gap between graduation and attempting the exam were associated with attempting and passing the exam, respectively. Direct supports for students are associated with successful progression through the peer specialist training pipeline. Workforce development programs like the CRSS Success Program can further optimize outcomes by providing additional supports, especially to students at-risk of attrition.

Fairness is an important concern in statistical models, especially in clinical prediction models. Most fairness methods focus on model predictions, aiming for parity in model performance across relevant groups. However, this approach overlooks the broader implications of fairness when these models are used in clinical decision-making. We argue that prediction-based fairness frameworks, while valuable, are inherently limited when patient outcomes are equally, if not more, important concerning fairness. We analyze a deployed clinical prediction model, UTICalc, which was revised to improve fairness across racial groups and showed improved performance on a prediction-based fairness metric, namely, equal opportunity (equal true positive rate). We developed a decision-theoretic framework to assess the fairness of UTICalc by integrating patient outcome utilities with model predictions. To this end, we constructed a decision tree to model the clinical decision-making process for assessing and treating urinary tract infection (UTI) in young children, for which UTICalc was developed. Our results show that the revised UTICalc model did not improve an outcome-based fairness metric, namely, expected utility parity. This suggests that prediction-based and outcome-based fairness may diverge, with implications for clinical settings. Furthermore, we suggest that fairness in clinical prediction models should be evaluated based on patient outcomes as well as model predictions.

Northern Ireland's largest national population cohort over 50 years of age, with a focus on the collection of longitudinal data including computer-assisted personal interviews, self-completed questionnaires and in-person health assessments takes form as the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA). Data from 8,283 individuals over 50 years of age was collected from individuals within NICOLA's first wave of data collection for this cohort. Together, the data collected aims to help researchers explore how social, economic, health, lifestyle, and biological factors influence healthy ageing. NICOLA places a strong emphasis on molecular biomarkers, with a subset of 3,471 participants (44%) undergoing health assessments at wave 1, including the collection of blood samples specifically for this analysis. Objectives : Using blood-derived DNA collected from individuals within NICOLA, genetic data was generated to enable research projects associated with rich cross-sectional and longitudinal data within NICOLA to explore genetic connections to the health, lifestyle, environment and financial situations of people as they grow older. Data description: Genetic data was generated using the Illumina Infinium CoreExome-24 array (Illumina, USA) and is available for 2,978 NICOLA participants with 551,839 directly genotyped and 18,148,478 imputed single nucleotide polymorphisms following initial quality control.

Background and Methods: Point of care genetic testing has grown but cascade testing of At-Risk Relatives (ARR) remains underutilized. Between July and September 2023, we surveyed 912 individuals enrolled in the Cancer Prone Study, a registry of diverse high-risk families who received genetic counseling from cancer genetic experts. We analyzed correlates of familial disclosure and cascade testing among carriers of pathogenic/likely pathogenic variants (PV). Data on carrier status of PV in cancer-predisposing genes, penetrance level of variants, receipt of a family letter, familial disclosure, and follow up cascade testing of ARRs were collected. Results: Of 912 respondents, 39.4% were carriers of PV. Among these carriers, 78% had highly penetrant PVs (most common genes were BRCA1 : 39% and BRCA2 : 18%) and 17.5% had moderate penetrance PVs; Rate of disclosure of PV to at least one family member; receipt of family letter explaining genetic test results; and sharing of information with ARRs were 98%, 69% and 82% respectively. Cascade testing was more likely among carriers with highly penetrance PV (91.1%) compared to those with moderate penetrance PV (58.3%) (adjusted odds ratio [AOR], 5.70; 95% CI, 2.03-16.02), and among carriers who received a family letter than among those who did not receive (87.2% vs. 73.0%; AOR, 3.70; 95% CI, 1.42-9.61). These data suggest that access to family-based counseling facilitated by cancer genetic experts improves understanding of familial risks and improves cascade testing following results disclosure. Our data support family based clinical interventions to optimize precision prevention and cancer control in high-risk individuals.

Language lateralisation has long been viewed as a hallmark of left hemisphere specialisation. Yet the structural foundations of this asymmetry remain unclear. Using ultra-high-field 7T diffusion MRI from 172 Human Connectome Project participants, we reconstructed seven language-recruited white matter tracts and characterised the architecture of hemispheric asymmetry by combining a new Variability Index, Bayesian inference, and manifold learning. Joint analysis across tracts reveals that individuals vary along a continuous manifold of structural lateralisation rather than forming discrete left, right, or bilateral lateralisation phenotypes. Additionally, lateralisation is robust but tract-specific: the arcuate long segment, inferior longitudinal fasciculus, and frontal aslant tract show leftward asymmetry, while the anterior arcuate segment and uncinate fasciculus show rightward asymmetry. Despite these population-level results, microstructural variability is substantial, with certain tracts exhibiting greater dispersion in one hemisphere than the other. Bayesian evidence indicated that structural lateralisation is unrelated to handedness or language performance. Together, these results redefine hemispheric specialisation as a graded rather than distinctly distributed language connectome, balancing conserved structural scaffolds with individual flexibility.

Women face twice the lifetime risk of Alzheimer's disease (AD) compared with men. Inflammatory burden is widely implicated in AD, but whether sex-differentiated vulnerability is determined by cytokine levels or by the brain's sensitivity to those signals remains unclear. Here, we examined sex-specific associations between peripheral inflammatory markers, medial temporal lobe (MTL) white matter microstructure using NODDI diffusion MRI, and hippocampal-dependent memory in 121 cognitively unimpaired older adults. Women exhibited widespread alterations in MTL white matter microstructure relative to men. In women, peripheral cytokines (TNFα, IL-10) were associated with microstructural variation in hippocampal-prefrontal tracts, whereas these associations were absent in men. An indirect association between TNFα and memory through hippocampal cingulum neurite density was observed only in women. Despite these microstructural and coupling differences, cytokine levels were comparable between sexes, indicating that risk may be better captured by the coupling between peripheral immune signals and circuit integrity than by cytokine levels alone. These findings identify a sex-specific pattern of immune-brain coupling that reframes inflammatory risk in AD as a property of circuit-level sensitivity rather than overall inflammatory burden.

Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheal morbidity with no licensed vaccines. Role of gut microbiota in vaccine immunogenicity and protection was investigated using 16S rRNA sequencing from the stool samples of 27 volunteers receiving two doses of the live attenuated oral ETEC vaccine ACE527 followed by virulent ETEC H10407 challenge. Systemic and mucosal IgG and IgA responses to heat-labile toxin-B (LTB) and colonization-factor-antigen-I (CFA/I) were quantified by ELISA in serum and antibody-in-lymphocyte-supernatant (ALS). Microbiome α-diversity, β-diversity, and taxa–immune associations were evaluated using regression models, MiRKAT, and relaxed LASSO. Vaccination increased (~ 25–30%) Eubacterium_brachy_group, Family_XIII_AD3011 and Actinomyces. Higher α-diversity (inverse-Simpson) was associated with reduced ALS anti-LTB and CFA/I IgA responses, whereas β-diversity correlated with increased serum anti-CFA/I IgA. Members of Anaerovoraceae, Peptostreptococcaceae, Oscillospiraceae, and Veillonellaceae enhanced immune responses and protection against severe diarrhea and ETEC colonization, while Ruminococcaceae, Sutterellaceae, Coriobacteria, Clostridia, and Actinobacteria showed antagonistic associations.

Background: Hyperglycemia is one of the common complications in COVID-19 patients. Globally, hyperglycemia associated with COVID-19 was estimated to be 25%. Hyperglycemia results in increased morbidity and mortality yet proper screening and management protocols in developing countries. There is paucity of data in developing countries. Objectives: To determine the prevalence of hyperglycemia, clinical characteristics, and outcomes of COVID-19 admitted patients in Mbale and Soroti regional referral hospitals - Uganda. Methodology: Retrospective cross-sectional study was conducted on adult admitted COVID-19 patient's case files at two tertiary hospitals, in Eastern Uganda. 711 COVID-19 patient files with a capillary blood glucose test result during the study period from 1st March 2020 to 31st December 2021 were reviewed. Data was abstracted into a data collection tool specifically designed for this study. The variables included socio-demographics, clinical characteristics, and outcome status of the patients. Hyperglycaemia was defined based on the COVID-19 management algorithm as capillary blood glucose readings >11.1 mmol/l at or during admission, with the aid of the Glucometer One-Touch©. A primary outcome was hyperglycaemia in hospitalised patients. The Chi-Squared test was used for bivariate analysis, while the logistic regression model was applied for multivariate analysis. Results: Overall, hyperglycaemia was detected in 459 out of 711 (65%) patients. Living in rural areas (AOR 1.7, 95% CI: 1.1-2.7, P < 0.027), having a medical history of diabetes mellitus (AOR 4.8, 95% CI: 3.4-6.7, P < 0.001), and current use of steroids (AOR 2.9, 95% CI: 1.8-4.7, P < 0.001) immediately before admission were statistically significantly associated with hyperglycemia in COVID-19 patients. COVID-19 found to be an independent risk factor for Hyperglycaemia. Conclusion: The prevalence of hyperglycaemia among COVID-19 patients in eastern Uganda during the global epidemic was high, at 65%. Pre-admission conditions associated with hyperglycaemia included a medical history of diabetes mellitus, steroid use, living in rural area. Strengthening screening for hyperglycemia and specific management protocols during epidemics and pandemics is recommended.

SUMO E3 enzymes control the efficiency and specificity of protein SUMOylation, providing regulatory means for many cellular processes. While most SUMO E3s fulfill their roles as single proteins, the conserved Nse2 E3 is an obligatory subunit of the genome-protecting complex Smc5/6. How the Smc5/6 complex functions in SUMOylation and the roles of its non-SUMO E3 subunits in this process remain to be elucidated. Here we examine the budding yeast Smc5/6 in SUMOylation reactions and in cellular SUMOylation assays. Biochemical data show that DNA stimulates Smc5/6's E3 activity via fostering enzyme and substrate proximity. Mutational analyses reveal that four non-SUMO E3 subunits utilize their DNA binding abilities to support this stimulation. Moreover, ATP binding by SMC subunits favors SUMOylation by enhancing Smc5/6 association with DNA and chromatin and by enabling conformational changes. Our findings thus provide evidence for a specialized DNA- and ATP-stimulated composite SUMO E3 complex that uses inter-subunit collaboration to achieve efficient SUMOylation in genome regulation.

CD8+ NKG2D+ T cells mediate hair follicle (HF) damage in Alopecia Areata (AA); however, the mechanisms and targets of T cell attack are not yet known. Here, we showed that CD8+ T cells penetrate the dermal sheath and epithelial layers of HF in AA and stop abruptly upon reaching Henle's layer of the inner root sheath. CD8+ T cells assembled a cytolytic immune synapse (IS) with polarization of Lck kinase and convergence of granzyme B. The formation of IS and localization of caspase-8-dependent apoptosis in KRT71+ Henle's layer of IRS pinpointed these cells as T cell targets in AA. Using direct visualization of in situ activity of pathogenic CD8+ T cells within AA-affected mice skin, we elucidated the molecular mechanism and target of CD8+ T cell cytotoxicity within HF in AA.