We study one of the simplest scenarios of polygenic selection that can be imagined: a subdivided population of diploid individuals expressing an additive trait under spatially homogeneous stabilizing selection. We are interested in the amounts of variation that can be maintained at mutation-selection-migration-drift equilibrium, at individual loci and at the level of the trait, within and among subpopulations. We derive analytical approximations for variance components and summary statistics such as FST and QST under the assumptions of the infinite-island model and compare these with individual-based simulations. We find that: (i) There is a critical migration threshold (which depends on effect sizes of trait loci) below which population structure strongly inflates genic variance in the subdivided population to levels well above those in a panmictic population. Variation within each subpopulation is maximized close to the critical migration rate. (ii) The genetic basis of trait variation across subpopulations is most similar close to this migration threshold and (counter-intuitively) becomes less similar for higher migration rates. This has consequences for the `portability' of Genome-Wide Association Studies (GWAS) between subpopulations, i.e, the extent to which loci with large contributions to variance in one subpopulation explain variance in other subpopulations. (iii) An analytical mean-field approach based on the single-locus diffusion approximation, together with effective migration and selection parameters (to account for associations between loci), very accurately predicts various quantities.
Variant calling in paralogous genes using short-read sequencing is problematic due to mapping ambiguity between highly similar sequences. Aggregate variant calling, which treats paralogous loci as a single locus by realigning reads to a masked reference genome, can enable variant detection in paralogous genes. We used our informatics tool Parascopy to assess the accuracy of aggregate variant calling in paralogous genes using short-read data. Parascopy achieved significantly higher recall compared to standard variant calling without sacrificing precision. We identified 158 paralogous genes with over 25 percentage points improvement in recall using simulated data, and 118 genes with at least 10 percentage points improvement in recall across GIAB reference samples. Across 1000 Genomes samples, aggregate genotypes in paralogous genes were highly concordant between whole-genome and whole-exome data (r2=0.9998). Using sequence data from population and disease cohorts, we utilized aggregate variant calls to perform population-genetic analysis, case-control association analysis, and haplotype phasing in specific disease-relevant paralogous genes that are inaccessible to standard diploid variant calling. Specifically, in the SMN1 gene, we identified tag-SNPs for two-copy SMN1 haplotypes and showed that specific low-frequency missense variants in African populations occurred exclusively on such haplotypes. For the CFC1 gene-previously implicated in heterotaxy syndrome-association analysis using exome data indicated that loss-of-function variants are unlikely to be associated with heterotaxy in individuals with congenital heart disease. Finally, we utilized aggregate genotypes to perform haplotype phasing for the X-linked gene IKBKG, achieving 99.2% concordance between trio-based and statistical phasing approaches.
Carotid artery intima-media thickness (cIMT) is a highly heritable measure of subclinical atherosclerosis and a predictor of cardiovascular diseases. However, knowledge about its shared genetic basis remains limited. The majority of genome-wide association studies have been conducted in individuals of European ancestry, leaving the genetic determinants of cIMT in non-European ancestry populations largely understudied. A single-trait genome-wide association study was performed in 22 370 participants from the China Kadoorie Biobank to identify new genetic variants associated with cIMT. We then leveraged cIMT and cardiometabolic disease and trait data from populations of European and East Asian ancestries, to conduct linkage disequilibrium score regression and genome-wide cross-trait analysis, followed by gene-based analysis and Mendelian randomization. We identified 2 genome-wide significant loci for cIMT in the overall China Kadoorie Biobank analysis, including the known APOE locus and a novel locus at GGT5. In addition, a female-specific analysis identified a further novel locus at LINC02732. cIMT showed significant positive genetic correlations with coronary artery disease, type 2 diabetes, body mass index, and systolic blood pressure in both European and East Asian populations. Pleiotropic analysis found 110 and 699 significant pleiotropic variants in 4 trait pairs for East Asian and European populations, respectively, with 27 and 186 colocalized loci detected. Gene-based analysis highlighted important biological pathways involving lipid metabolism and carbohydrate metabolism. Mendelian randomization estimates indicated that higher systolic blood pressure and body mass index, and coronary artery disease and type 2 diabetes, were causal for cIMT, and a reverse effect was observed between cIMT and systolic blood pressure. Our large-scale genome-wide association study of cIMT identified novel loci in the Chinese population and shared genetic underpinnings and causal relationships with cardiometabolic diseases and traits. These findings potentially provide targets for intervention that may allow the development of new strategies targeting this aspect of atherosclerosis.
Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are central strategies for HIV prevention; however, a comprehensive understanding of how knowledge about these strategies is measured across different contexts remains limited. This scoping review aimed to map the instruments used to assess knowledge of PrEP and/or PEP. The study followed the recommendations of the JBI Reviewer's Manual, with a systematic search conducted on August 27, 2024, in PubMed, Embase, Web of Science, the Virtual Health Library, and grey literature. Original studies assessing knowledge of PrEP and/or PEP were included. Two reviewers independently conducted study selection through title and abstract screening, followed by full-text assessment. Data extraction was performed by a single researcher, and the findings were presented descriptively. A total of 1,922 records were retrieved, of which 49 studies were included. Cross-sectional studies predominated (n = 45; 91.8%), as did publications from 2020 to 2024 (n = 25; 51.0%). The instruments focused mainly on PEP (n = 27; 55.1%), followed by PrEP (n = 20; 40.8%), and were administered primarily to healthcare professionals or healthcare students (n = 35; 71.4%). The instruments varied in terms of the number of items, response formats, and scoring criteria, and showed limited reporting of their development and psychometric properties. The findings highlight substantial variability in the characteristics of instruments used to assess population knowledge of PrEP and/or PEP. Important gaps were identified in the reporting of instrument development and validation processes, reinforcing the need for methodologically robust instruments to assess population knowledge of PrEP and PEP. La profilaxis preexposición (PrEP) y la profilaxis posexposición (PEP) son estrategias centrales para la prevención del VIH; sin embargo, aún no existe una comprensión integral de cómo se ha medido el conocimiento sobre estas estrategias en diferentes contextos. Esta revisión de alcance tuvo como objetivo mapear los instrumentos utilizados para evaluar el conocimiento sobre la PrEP y/o la PEP. El estudio siguió las recomendaciones del Manual del Revisor del JBI, con una búsqueda sistemática realizada el 27 de agosto de 2024 en PubMed, Embase, Web of Science, la Biblioteca Virtual en Salud y la literatura gris. Se incluyeron estudios originales que evaluaron el conocimiento sobre la PrEP y/o la PEP. Dos revisores llevaron a cabo, de forma independiente, la selección de los estudios mediante el cribado de títulos y resúmenes, seguido de la evaluación del texto completo. La extracción de datos fue realizada por un único investigador, y los hallazgos se presentaron de forma descriptiva. Se recuperaron 1.922 registros en total, de los cuales se incluyeron 49 estudios. Predominaron los estudios transversales (n = 45; 91,8%), así como las publicaciones realizadas entre 2020 y 2024 (n = 25; 51,0%). Los instrumentos se centraron principalmente en la PEP (n = 27; 55,1%), seguida por la PrEP (n = 20; 40,8%), y se aplicaron principalmente a profesionales de la salud o estudiantes del área de la salud (n = 35; 71,4%). Los instrumentos variaron en cuanto al número de ítems, los formatos de respuesta y los criterios de puntuación, y mostraron una notificación limitada de su desarrollo y de sus propiedades psicométricas. Los hallazgos destacan una variabilidad sustancial en las características de los instrumentos utilizados para evaluar el conocimiento de la población sobre la PrEP y/o la PEP. Se identificaron brechas importantes en la notificación de los procesos de desarrollo y validación de los instrumentos, lo que refuerza la necesidad de contar con instrumentos metodológicamente robustos para evaluar el conocimiento de la población sobre la PrEP y la PEP.
People with Young Onset Dementia (YOD) are recognised as having a higher risk of being marginalised within society and in the care and support they receive. The consequences of stigma on people with YOD must be better understood to help reduce experiences of discrimination and increase awareness for this population. This qualitative systematic review aimed to synthesis the data on the experience of stigma within the YOD population globally. Five electronic databases (Scopus, MEDLINE, PubMed, Web of Science, and PsycINFO) were searched in December 2025. The quality of the studies was assessed using the Critical Appraisal Skills Programme Tool. Data were analysed using thematic synthesis. One researcher assessed the title and abstracts of the articles retrieved against the inclusion criteria. Included articles were then read in full by the same researcher. A second researcher reviewed 10% of these articles at both stages. 2994 articles were screened, and 17 studies were included in this review. Four themes were identified: Public perception and beliefs about YOD, Structural stigma and barriers to service access, The role of stigma in social isolation, and Overcoming stigma. This review highlights the pervasive and multifaceted nature of YOD, offering insights into individual and service level strategies needed to mitigate the negative consequences of stigma. The findings highlight the need for specialist age-appropriate support services alongside public and professional education on YOD to address misconceptions about dementia in younger adults. Community and government-led initiatives are recommended to help reduce negative stereotypes, social isolation and improve access to early diagnosis and tailored support for our YOD communities. Not applicable.
Epilepsy is characterized by recurrent seizures due to abnormal neuronal activity originating from a population of neurons. Seizures are often associated with abnormal glial cell function at the seizure focus. Studies have shown that each glial type, such as astrocytes, displays a significant degree of heterogeneity in their development, molecular signatures, and function depending on the brain region in which they are located. It is unknown, however, if such heterogeneity differentially influences or causes seizures. Previous studies in Drosophila have shown that aberrant Cortex glia (CG) function led to light-inducible (LI) seizures in Ceramide phosphoethanolamine synthase (cpes) and temperature-sensitive (TS) seizures in zydeco (zyd1) mutants. Here, we have optimized Gal4/Split-Gal4/Gal80/LexA drivers to specifically express a gene of interest throughout development in CG subpopulations in different parts of the brain including optic lobe (OL), central brain (CB), and ventral nerve cord (VNC). Using these tools, we performed brain region-specific CG rescue experiments in cpes and zyd1 mutants. We found that OL- and CB-specific, but not VNC-specific CG expression of CPES significantly suppressed LI seizures in cpes mutants. In contrast, VNC- but not OL- or CB-specific CG expression of ZYD suppressed TS seizures. In a third model, expression and activation of transient receptor potential, dTRPA1, exclusively in the VNC-specific CG was sufficient to induce TS seizures in wild-type flies. Our findings suggest that regionally specialized CG subtypes differentially regulate seizure susceptibility in seizure models.
The relationship between sex differences and clinical outcomes following coronary artery bypass grafting (CABG) has been highlighted in several studies. However, these studies were mostly based on single- or multi-center data, and only a few meta-analyses examined long-term outcomes. To address this limitation, we conducted a nationwide population-based cohort study in Korea. A total of 48,206 adult patients who underwent first-time isolated CABG between January 2005 and December 2021 were enrolled. To address potential confounding, propensity score (PS) matching was conducted. The primary outcome was overall mortality. Among the enrolled patients, 12,270 (25.5%) were female. The median age of the overall cohort was 66.0 years (interquartile range [IQR], 59.0-72.0), with female patients (median, 69.0; IQR, 63.0-75.0) being significantly older than male patients (P < 0.001). In the PS-matched cohort, in-hospital mortality did not differ significantly between female and male groups (odds ratio, 1.13; 95% confidence interval [CI], 0.78-1.64). However, the female group was a significant predictor of better overall survival (hazard ratio [HR], 0.83; 95% CI, 0.77-0.90) compared to the male group. Cardiac-related mortality was comparable between the two groups (HR, 0.89; 95% CI, 0.65-1.22). The median duration of the follow-up period was 7.8 (IQR, 4.0-12.6) years. In this nationwide population-based PS-matched cohort study, female patients who underwent isolated CABG exhibited significantly lower overall mortality compared to male patients during long-term follow-up, whereas no significant difference was observed in cardiac-related mortality.
ObjectivesCancer screening uptake in the United States remains below national targets despite established screening recommendations. Patient portals may support preventive care delivery, but their association with cancer screening uptake and population-level contribution remains unclear. We evaluated the association between patient portal use and breast, cervical, and colorectal cancer screening among screening-eligible U.S. adults.MethodsWe conducted a cross-sectional study using pooled data from the nationally representative Health Information National Trends Survey. Screening-eligible adults were defined according to U.S. Preventive Services Task Force criteria for breast, cervical, and colorectal cancer screening. The primary exposure was self-reported patient portal use within the prior 12 months. Outcomes included receipt of breast, cervical, and colorectal cancer screening. Survey-weighted modified Poisson regression was used to estimate adjusted prevalence ratios (aPRs), adjusting for sociodemographic and clinical characteristics. Adjusted absolute differences were estimated using marginal standardization, and population attributable risk percent (PARP) was calculated to estimate the population-level contribution of portal use.ResultsAmong 23,920 respondents, 13,210 (55.2%) reported patient portal use. Portal users had higher screening uptake than non-users for breast cancer screening (85.7% vs 75.1%; p<0.001), cervical cancer screening (83.8% vs 73.7%; p<0.001), and colorectal cancer screening (84.0% vs 72.5%; p=0.002). After adjustment, portal use was associated with higher prevalence of breast cancer screening (aPR 1.15, 95% CI 1.05-1.27; p=0.004) and cervical cancer screening (aPR 1.12, 95% CI 1.04-1.20; p=0.002), with a more modest association for colorectal cancer screening (aPR 1.08, 95% CI 0.99-1.17; p=0.07). Adjusted absolute differences associated with portal use were +14.3%, +12.9%, and +9.0% for breast, cervical, and colorectal cancer screening, respectively. PARP estimates were 7.7%, 6.9%, and 3.6%, respectively.ConclusionPatient portal use was associated with higher uptake of breast and cervical cancer screening, with a more modest and not statistically significant association for colorectal cancer screening after adjustment. Although portal engagement may support preventive care delivery, its population-level contribution to screening uptake was modest, suggesting that portal-based strategies should be paired with broader interventions addressing access, digital literacy, and structural barriers to cancer screening.
Allostatic load (AL) is an emerging framework quantifying physiological dysregulation from cumulative exposure to stressors over an individual's life. We evaluated the relationship between AL and malignant breast biopsy results in women across sociodemographic subgroups. Women 18 years and older who underwent at least one image-guided breast biopsy at a safety-net hospital between April 2016 and December 2023 were identified. Consistent with prior studies, AL was defined as a score based on eight values: resting pulse rate, systolic blood pressure, diastolic blood pressure, body-mass index, serum albumin, creatinine, estimated glomerular filtration rate, and white blood cell count. Multivariable logistic regression models were used to assess the association between AL and malignant breast biopsy results among different sociodemographic groups. Effect modification by racial/ethnic category was then examined using stratified models. 668 participants had data available for all eight biomarkers. Most participants were Hispanic (n = 376, 54.5%), reported English as their primary language (n = 423, 63.3%), and had Medicaid for insurance (n = 300, 44.9%). In stratified analyses, the association between AL and malignant breast biopsy result was significant in White, non-Hispanic patients. In White, non-Hispanic patients, after adjusting for age, every one-unit increase in AL was associated with a 46% increased likelihood of malignant breast biopsy result (OR 1.46, P = 0.03). AL was associated with malignant breast biopsy results in specific sociodemographic subgroups, potentially representing a modifiable risk factor for breast cancer prevention. Further research with large, diverse populations is required to evaluate additional factors impacting breast cancer outcomes across sociodemographic groups.
The coexistence of obesity and asthma is increasingly common and associated with poorer asthma outcomes. Weight loss has been shown to improve asthma outcomes. Although several effective weight-loss medications are available, evidence regarding their respiratory effects remains limited. To conduct a systematic review of the respiratory adverse events (AEs) associated with weight-loss medications in general populations and specifically among individuals with asthma. We searched Medline, Embase, Cochrane, and CINAHL, as well as trial registries, without date or language restrictions. We included randomized controlled trials, nonrandomized comparative studies, and large, single-group studies assessing the respiratory AEs of liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, phentermine-topiramate, and setmelanotide. We assessed the risk of bias in each study using design-specific, validated tools. We conducted random-effects model-based meta-analyses of risk differences for respiratory AEs, comparing active interventions and placebo. Our searches yielded 9,086 unique records. We included 123 studies, of which 122 studies evaluated general populations and one study specifically evaluated individuals with asthma. Overall, the randomized trials had low risk of bias. Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared with placebo. Insufficient data limited comparisons for other drugs. Respiratory events, such as upper respiratory tract infections and nasopharyngitis, were common, with nasopharyngitis incidence ranging from 4.1% (95% CI: 0.7%, 9.3%; tirzepatide, 0-6 months) to over 23.7% (95% CI: 19.6%, 28.1%; liraglutide, 13-24 months), although these were not clearly associated with doses or indications. Evidence specifically addressing individuals with asthma was sparse. There was no evidence of increased respiratory harm associated with weight-loss drugs compared with placebo, suggesting a reassuring respiratory safety profile in the general population. However, evidence specifically focused on individuals with asthma remains limited.
Evidence from multiple studies shows that the appendix may play a significant role in the pathogenesis of ulcerative colitis (UC). These findings have sparked interest in the possibility of appendicectomy as a potential adjunctive strategy in UC. This narrative review was conducted by synthesizing data from meta-analyses, immunological research, surgical case studies, population data reports, and prospective trials published since 2000. The evidence was appraised with a focus on appendicectomy and its clinical outcomes in UC, risks and limitations, as well as possible future directions. Observational studies show a reduced risk of colectomy and UC-related hospital admissions when appendicectomy is performed before UC diagnosis. On the other hand, appendicectomy post UC diagnosis in the presence of appendiceal inflammation has shown increased risk of colectomy. But if an appendicectomy is performed in the absence of inflammation, it might not correlate to the risk or reduce the risk of relapse and complications. Evidence also shows that patients with refractory UC may benefit from appendicectomy and may show longer periods of remission. However, some studies show appendicectomy might increase the colorectal cancer risk due to alterations in immunity and microbiota. While medical management remains the first line, appendicectomy may act as an adjunct surgical option in carefully selected cases before escalating to a colectomy. Large multicenter studies and randomized clinical trials are required to identify strategies for patient selection, potential complications, durability of response, and long-term outcomes. The appendix plays a major role in the pathogenesis of ulcerative colitis. Studies show appendicectomy could benefit selected patients with this disease and may be considered as an adjunct treatment to delay or avoid colectomy.
Since genome-wide association studies (GWAS) of sleep phenotypes have been conducted in differing populations and definitions of sleep phenotypes vary across studies, we investigated associations between several polygenic risk scores (PRSs) and potential sleep definitions among multiethnic cohorts. Using data from four cohorts (HCHS/SOL, ARIC, MESA, BHS, N = 16 895), we considered multiple definitions of short and long sleep, insomnia, and excessive daytime sleepiness (EDS). PRSs were developed based on summary statistics from GWAS in European ancestry individuals from the UK Biobank (UKB) and from GWAS conducted in a multiethnic population from the Million Veteran Program (MVP). Study-specific analyses estimated associations between sleep PRSs and corresponding sleep measures per 1 standard deviation increase in the PRS. Models were adjusted for age, sex, ancestral principal components, and center and race as appropriate. Results were meta-analyzed across studies. PRSs based on European ancestry UKB GWAS had statistically significant associations with multiple definitions of the corresponding sleep phenotypes. Associations that were most consistent across studies included: short sleep PRS with ≤6 hours (OR = 1.23,p = 1.80x10-7,phet = 0.97); long sleep PRS with ≥9 hours (OR = 1.09,p = 6.76x10-4,phet = 0.77); insomnia PRS with the Women's Health Initiative Insomnia Rating Scale (WHIIRS) ≥10 or a subset of three questions ≥6 in ARIC (OR = 1.17,p = 5.51x10-10,phet = 0.69); and EDS PRS with Epworth Sleepiness Scale (ESS) ≥11 (OR = 1.23,p = 1.83x10-13,phet = 0.83). PRSs based on multi-ancestry MVP GWAS had weaker associations compared to those based on European ancestry only. By evaluating several types of sleep PRSs and sleep phenotypes, we were able to highlight which sleep PRS performed well across diverse populations and which sleep definitions better captured genetic underpinnings.
Bipolar disorder (BD) is a complex and heterogeneous psychiatric condition, characterized by fluctuating clinical courses that affect approximately 1%-2% of the global population in their lifetime. Despite pharmacological advances, treatment response varies significantly among patients, making the identification of individualized treatment strategies a major challenge. Artificial Intelligence (AI), through its classical approaches, has emerged as a powerful tool in precision psychiatry to identify subtle patterns in complex data and inform personalized clinical decisions. The present systematic review aimed to examine the current evidence on classical AI-supported treatment optimization in the BD spectrum. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Four databases (PubMed, Web of Science, Scopus, and Embase) were searched for original studies published after 2015 on the application of classical AI in the treatment of BD in adult patients. Publication bias was evaluated by visual inspection of a funnel plot. The methodological quality, risk of bias, and clinical applicability of the predictive models were assessed using the Prediction Model Risk Of Bias Assessment Tool for prediction models using regression or AI methods (PROBAST+AI; PROBAST+AI Working Group) tool. A total of 35 studies were included and classified into 5 outcome-based categories, including acute symptomatic response, long-term maintenance response, relapse and readmission risk, safety and dose optimization, and brain aging and phenotyping. Acute symptomatic response models performed modestly (pooled area under the curve [AUC] 0.68), while imaging improved accuracy (74%-77%). Long-term maintenance response models showed moderate-to-high performance (pooled AUC 0.80), with biomarker- and cellular-based models reaching 96%-99% accuracy. Relapse and readmission prediction achieved a pooled AUC of 0.71, with digital phenotyping and rule-based methods performing best (AUC 0.85-0.88). Safety and dose optimization models achieved 85%-97% accuracy. Brain aging and phenotyping studies highlighted accelerated brain aging in BD, partially mitigated by lithium, and revealed novel data-driven subgroups. However, 3 studies were considered at high risk of bias due to small sample sizes associated with disproportionately high-performance estimates. An additional study was identified as potentially biased because it lay markedly distant from the funnel plot's confidence line. Finally, the PROBAST+AI assessment revealed a high risk of bias in most studies, primarily due to data analysis limitations, small sample sizes, and lack of external validation. The adoption of classical AI tools in BD serves as a driver for therapeutic optimization, although current AI tools in BD should still be considered exploratory rather than ready for clinical use. Effective implementation in real-world clinical scenarios requires more robust, transparent, and externally validated models to ensure reliability and generalizability.
To investigate the similarity and symmetry of biometric measures between eyes in a large dataset of measurements of both eyes taken with the LenStar optical biometer. Cross-sectional non-randomised study evaluating a dataset containing 13,420 bilateral LenStar 900 biometric measurements on patients without history of eye surgery or ocular pathology taken before cataract surgery, consisting of scalar parameters axial length AL, corneal thickness CCT, anterior chamber depth ACD, lens thickness LT and corneal diameter WTW. The keratometric power vector components equivalent power KEQ were assessed for similarity, and the projections of corneal astigmatism vector KC0 and KC45 were analysed for direct and mirror symmetry with respect to the vertical (sagittal) plane. Mean / standard deviation (squared correlation coefficient) difference between right and left eye measures was 0.02 ± 0.31(0.95) / 0.00 ± 0.01(0.93) / 0.00 ± 0.14(0.88) / -0.01 ± 0.22(0.78) / -0.02 ± 0.17(0.87) mm for AL / CCT / ACD / LT / WTW and -0.06 ± 0.48(0.92) dioptres for KEQ. Keratometric astigmatism showed a high degree of mirror symmetry (KC45 of left eyes inverted in sign) which outperforms direct symmetry. The median deviation of the keratometric axes of both eyes considering mirror symmetry was 15 degrees compared to 29 degrees for direct symmetry. In most cases, biometric measures match between eyes of a subject, but there are rare situations with large deviations between eyes. Keratometric astigmatism exhibits mirror symmetry. In most cases the biometric measures from the contralateral eye could be used where biometry is unavailable or to double-check before cataract surgery.
Lung cancer is a major global health issue, especially among men. While smoking and occupational or environmental exposures are known risks, the role of benzene remains under investigation. We aimed to conduct a systematic review and meta-analysis to evaluate the association between occupational benzene exposure and lung cancer incidence and mortality. We included cohort and case-control studies mentioned in the 2018 IARC Monograph on benzene and performed a systematic literature review to identify studies published up to 2024 by using PubMed, SCOPUS, and EMBASE databases. We constructed forest plots of relative risk (RR) to visualize and analyze the data. A random-effects model was used to address heterogeneity between studies. Stratified analyses were conducted to explore effect modification. We included 44 independent studies in our meta-analysis. The findings didn't reveal an association between total occupational benzene exposure and lung cancer overall (RR = 1.00, 95% CI 0.93-1.07, p-het ≤ 0.001, 45 risk estimates) or in major industries. Stratified analyses suggested an association in case controls studies (RR = 1.16, 95% CI 1.10-1.22: 7 risk estimates, p-het = 0.001), and in studies with results adjusted for smoking (RR = 1.17, 95% CI 1.11-1.24: 6 risk estimates, p-het = 0.001). There was also an association between high-level benzene exposure and lung cancer (p-trend = 0.03). Publication bias was excluded (p = 0.16). The increased risk after adjustment for smoking and the suggestion of a dose-response, are consistent with the hypothesis of an association between benzene exposure and lung cancer risk.
The intersection of HIV, aging, mental illness, and dementia presents a critical global health challenge, especially in resource-limited settings like Vietnam. This study examines the interconnected stigmas held by healthcare professionals toward older adults living with HIV/AIDS (OALWH), focusing on stigma toward HIV, aging, mental illness, and dementia, as well as knowledge gaps related to dementia. Using a cross-sectional online survey developed in collaboration with Hanoi Medical University in Vietnam and Michigan State University in the United States, data were collected from 81 healthcare professionals working with OALWH in Hanoi, Vietnam. Results indicated that stigma across these domains is highly interrelated, with stigma related to mental illness and dementia emerging as the most central factors. Additionally, participants reported moderate levels of dementia knowledge, but no significant relationship was found between knowledge and attitudes, suggesting that increasing factual knowledge alone may not reduce dementia stigma. These findings underscore the urgent need for coordinated treatment and interventions that span infectious disease, geriatrics, neurology, and psychiatry. Intervention efforts should address multiple intersecting stigmas and deliver culturally relevant content in hybrid formats to enhance accessibility and effectiveness. La intersección del VIH, el envejecimiento, las enfermedades mentales y la demencia representa un desafío crítico para la salud global, especialmente en contextos con recursos limitados como Vietnam. Este estudio examina los estigmas interrelacionados que mantienen los profesionales de la salud hacia los adultos mayores que viven con VIH/SIDA (OALWH, por sus siglas en inglés), centrándose en el estigma asociado al VIH, el envejecimiento, las enfermedades mentales y la demencia, así como en las brechas de conocimiento relacionadas con esta última. Utilizando una encuesta transversal en línea desarrollada en colaboración entre la Universidad Médica de Hanói en Vietnam y la Universidad Estatal de Michigan en Estados Unidos, se recopilaron datos de 81 profesionales de la salud que trabajan con OALWH en Hanói. Los resultados indican que el estigma en estos ámbitos está altamente interrelacionado, siendo los estigmas relacionados con las enfermedades mentales y la demencia los factores más centrales. Además, los participantes reportaron niveles moderados de conocimiento sobre la demencia, pero no se encontró una relación significativa entre el conocimiento y las actitudes, lo que sugiere que aumentar únicamente el conocimiento factual puede no ser suficiente para reducir el estigma hacia la demencia. Estos hallazgos subrayan la necesidad urgente de tratamientos e intervenciones coordinadas que abarquen enfermedades infecciosas, geriatría, neurología y psiquiatría, y sugieren que los esfuerzos de intervención deben abordar múltiples estigmas interseccionales y ofrecer contenidos culturalmente relevantes en formatos híbridos para mejorar la accesibilidad y la eficacia.
Mild cognitive impairment (MCI) represents a transitional state between normal cognitive aging and dementia, with significant implications for public health. The objective of our study was to estimate the pooled prevalence of MCI among Indian elderly individuals (≥60 years). We conducted a systematic review and meta-analysis in accordance with PRISMA-2020 guidelines. Four databases (PubMed, Scopus, Embase, Web of Science) were searched up to January 2025. Twenty-six studies met the eligibility criteria. Random-effects models were used to calculate pooled prevalence with 95% confidence intervals (CIs), stratified by community- and hospital-based settings. Heterogeneity was assessed using I² and τ² statistics. Subgroup and meta-regression analyses examined potential sources of heterogeneity. Publication bias was evaluated using funnel plots, Egger's regression test. The methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. The pooled prevalence of MCI was 21% (95% CI: 13%-29%) in community settings and 44% (95% CI: 31%-57%) in hospital-based populations. Higher prevalence was observed among individuals with type 2 diabetes (53%), hypertension (57%), and those undergoing hemodialysis (38%). Diagnostic tool choice significantly influenced prevalence, with MoCA-based assessments yielding higher estimates than MMSE or Petersen criteria. Substantial heterogeneity was present across studies (I² >96%). Publication bias was minimal. MCI is prevalent among India's elderly population, particularly in individuals with chronic conditions. These findings underscore the need to integrate cognitive screening into national noncommunicable disease programs and to adopt standardized, context-appropriate diagnostic protocols for early identification and intervention.
While endovascular thrombectomy (EVT) is the standard treatment for large vessel occlusion, its role in distal medium vessel occlusion (DMVO) remains uncertain. This systematic review and meta-analysis aim to evaluate the efficacy and safety of EVT in patients with acute ischemic stroke (AIS) due to DMVO. We systematically searched PubMed, Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception up to February, 2025 reporting the efficacy and safety of EVT for DMVO, compared with best medical management (BMM). Study risk of bias was assessed using the Newcastle Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2 (RoB 2) for randomized controlled studies. Random-effects meta-analyses were performed to pool data. Outcomes of interest included the proportion of excellent functional outcomes (mRS 0-1 at 90 days), the proportion of favorable functional outcome (mRS 0-2 at 90 days), 90-day mortality, and symptomatic intracranial hemorrhage (sICH). We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the certainty of the evidence. The study protocol was registered on PROSPERO (CRD420250656493). A total of thirty-seven studies with 12742 patients were included in our meta-analysis. Overall, no significant differences were observed between the EVT and BMM group regarding excellent functional outcome (OR: 1.02, 95% CI: 0.86-1.21) and favorable functional outcome (OR: 1.02, 95% CI: 0.87-1.19). However, the EVT group demonstrated significantly higher odds of mortality (OR: 1.28, 95% CI: 1.07-1.54) and sICH (OR: 1.44, 95% CI: 1.04-1.98) compared with the BMM group. Subgroup analyses indicated EVT was associated with a higher proportion of favorable functional outcome (OR: 1.52, 95% CI: 1.07-2.16) in patients with M2 occlusion (GRADE = Very low). In addition, EVT was associated with lower proportion of favorable functional outcome (OR: 0.61, 95% CI: 0.37-0.98) in patients with ACA occlusion (GRADE = Low). EVT achieved higher proportion of excellent functional outcome (OR: 1.20, 95% CI: 1.02-1.40) (GRADE = Low), but higher risk of mortality (OR: 1.65, 95% CI: 1.17-2.31) and sICH (OR: 2.53, 95% CI: 1.48-4.33) in patients with PCA occlusion (GRADE = Low, GRADE = Moderate, respectively). Our meta-analysis revealed that, for the broad population of DMVO-AIS, EVT is not associated with improved 90-day functional outcomes and may increase mortality and sICH risks. However, subgroup analyses suggest that effects are not uniform and may be favorable for selected patients, particularly those with M2 occlusions. Notably, these aggregate findings are limited by observational studies with inherent selection bias, so the generalizability may be affected.
This study aimed to examine the effects of nursing interventions on poststroke fatigue and analyze their characteristics. This systematic review was conducted in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were based on the Population, Intervention, Comparisons, Outcomes, Study Design (PICO-SD) framework, which focuses on adults with stroke, nurse-led interventions aimed at alleviating poststroke fatigue, and comparisons with usual care. The review included experimental and quasi-experimental studies. The protocol was registered in PROSPERO. We included 10 studies that met the inclusion criteria. The Cochrane Risk of Bias 2.0 and ROBINS-I tools were used for study quality assessment. Methodological concerns were noted across several studies, particularly regarding blinding and study design. Most interventions were administered individually and included psychosocial interventions, physical activities, and self-management strategies. Poststroke fatigue assessment and nursing interventions are relevant considerations in rehabilitation nursing practice. Nursing interventions designed to alleviate poststroke fatigue in stroke patients were reported to have beneficial effects. These findings highlight the importance of proactive attention and involvement of nurses and multidisciplinary professionals in addressing poststroke fatigue among stroke survivors.
Melanoma and non-melanoma skin cancers (NMSCs) represent significant sources of morbidity among military personnel. Aviation personnel experience unique occupational exposures, including increased ultraviolet (UV) radiation at altitude and potential cockpit-related UV transmission, which may elevate skin cancer risk. Prior civilian and military studies have demonstrated increased melanoma incidence among airline and military pilots; however, contemporary data comparing U.S. Navy and Marine Corps aviation personnel with non-aviation officers within the same service branch remain limited. This study evaluated melanoma and NMSC incidence among active duty Navy and Marine Corps aviators compared with non-aviation commissioned officers from 2016 to 2024. A retrospective cohort study was conducted using de-identified outpatient medical encounter data from the Defense Medical Epidemiology Database (DMED). Incident melanoma (ICD-10 C43) and NMSC (ICD-10 C44) diagnoses were identified using first ambulatory encounters. The analytic cohort was restricted to active duty commissioned officers in the Navy and Marine Corps (pay grades O1-O9). Aviation personnel included fixed-wing fighter/bomber pilots, other fixed-wing pilots, and helicopter pilots; the comparison group comprised non-aviation line officers. Annual and pooled incidence rates per 100,000 personnel were calculated using corresponding population denominators. Poisson regression models with log-population offsets were used to estimate crude and age-adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Statistical significance was defined as P < .05. The use of de-identified administrative data was determined to be exempt from institutional review board oversight. A total of 467,174 commissioned officers were included, including 185,616 aviators and 281,558 non-aviators. During the study period, 242 incident melanoma cases and 1,430 NMSC cases were identified. Pooled melanoma incidence was 56.0 per 100,000 among aviators and 49.0 per 100,000 among non-aviators (crude IRR = 1.14; 95% CI, 0.89-1.47) and remained non-significant after age adjustment (adjusted IRR = 1.18; 95% CI, 0.91-1.52). In contrast, NMSC incidence was significantly elevated among aviators (357.7 vs. 272.1 per 100,000; crude IRR = 1.32; 95% CI, 1.19-1.46), with persistent elevation after age adjustment (adjusted IRR = 1.42; 95% CI, 1.28-1.57). Absolute incidence increased with age, while the most pronounced relative elevation in melanoma risk was observed among personnel aged 35-39 years. Aviation personnel demonstrated a statistically significant elevation in NMSC incidence compared with non-aviation officers, while melanoma incidence was elevated but not statistically significant after age adjustment. These findings suggest a potential occupational contribution to keratinocyte carcinoma risk among military aviators. Strengths of this study include the use of population-level denominators and regression modeling with appropriate exposure offsets; limitations include reliance on administrative diagnostic coding and the absence of detailed exposure metrics such as cumulative flight hours or ultraviolet radiation dose. These results support consideration of targeted occupational risk mitigation strategies and enhanced dermatologic surveillance within military aviation communities. Further longitudinal research incorporating detailed exposure characterization is warranted to clarify potential dose-response relationships and guide force health protection policy.