Large-scale Population Research Articles

Association of remnant cholesterol with risk of dementia: a nationwide population-based cohort study in South Korea

The association between remnant cholesterol (remnant-C) and cardiovascular disease risk is well established, but its association with dementia remains unclear. We aimed to examine this association using a large-scale population dataset. We did a nationwide, population-based cohort study in which we identified participants aged 40 years and older who underwent the national health examination in 2009 from South Korea's National Health Insurance Service. We excluded people who were younger than 40 years and those with a triglyceride concentration of 400 mg/dL or higher due to concerns regarding the accuracy of calculated low-density lipoprotein cholesterol concentration in individuals with extremely high triglyceride concentrations. People who were previously diagnosed with dementia before the index date, and those who had any missing variables were also excluded. To minimise the influence of possible reverse causation, we excluded individuals who had developed any type of dementia within 1 year of the baseline measurements. We calculated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease, and vascular dementia in each quartile of remnant-C using the Cox proportional hazards model adjusted for age, sex, body-mass index, estimated glomerular filtration rate, income level, smoking status, alcohol consumption, regular exercise, diabetes, hypertension, statin and fibrate use, and total cholesterol concentrations. We also did subgroup analyses to investigate the association between remnant-C and the risk of dementia stratified by age, sex, obesity, glycaemic status (normoglycaemia, impaired fasting glucose, new-onset type 2 diabetes, type 2 diabetes with a duration of less than 5 years, and type 2 diabetes with a duration of 5 years or more), hypertension, chronic kidney disease, and dyslipidaemia, using likelihood ratio tests. 4 234 415 individuals who underwent the national health examination in 2009 were deemed eligible for inclusion. We excluded 1 612 819 individuals on the basis of age, triglyceride concentration, missing variables, or having dementia at baseline. We identified 2 621 596 participants aged 40 years and older (1 305 556 men and 1 316 040 women) who underwent the national health examination and followed them up until the date of any incident of dementia or the end of the study period of Dec 31, 2020. During a median follow-up of 10·3 years (IQR 10·1-10·6), 146 991 (5·6%) participants developed all-cause dementia, 117 739 (4·5%) developed Alzheimer's disease, and 14 536 (0·6%) developed vascular dementia. The risk of dementia increased progressively with higher remnant-C concentrations. Compared with the lowest quartile of remnant-C (quartile 1), HRs in the highest quartile (quartile 4) were 1·11 (95% CI 1·09-1·13) for all-cause dementia, 1·11 (1·08-1·13) for Alzheimer's disease, and 1·15 (1·09-1·21) for vascular dementia. Subgroup analyses revealed that the risk of dementia associated with high remnant-C concentrations was higher in middle-aged people aged 40-59 years than in older people. The risk of dementia associated with high concentrations of remnant-C was notably more pronounced in individuals with diabetes compared with those without diabetes, and the risk increased steeply with a longer duration of diabetes. Results showed that higher remnant-C concentrations were independently associated with increased risks of all-cause dementia, Alzheimer's disease, and vascular dementia. More research is needed to determine the mechanisms underlying this finding. Monitoring and managing higher concentrations of remnant-C might have important implications for reducing the risk of dementia. None.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (β = -0.051, SE = 0.004, p < .001, per 10 years, and β = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (β = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (β = 0.067, SE = 0.007, p < .001 and β = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Using the Forest Maturity Index to model understory regeneration of post-agricultural forest in the NE Carpathians

The regeneration dynamics of understory vegetation in recent forests, arising from extensive agricultural land abandonment, is closely related to soil properties and proximity to ancient forests. However, the role of topography in shaping this regeneration process, especially in mountainous regions, remains unclear.This study addresses this gap by investigating the regeneration rate of understory vegetation in mountainous recent forests within the NE Carpathians, a region profoundly shaped by large-scale population displacements in the 1940s, leading to widespread agricultural land abandonment and the subsequent development of new forests.We quantified the understory regeneration rate of recent forests through extensive phytosociological relevé surveys conducted in one vegetation season. Data were collected from 194 randomly selected plots of recent forests and 100 plots of ancient forests, each exhibiting diverse topographic characteristics. By calculating the Forest Maturity Index based on ancient forest species and employing a parametrized multiple regression model, we identified key factors influencing the understory regeneration process. We further used the obtained regression formula to model the forest regeneration rate across the entire study area (40,975 ha).Proximity to ancient forests positively influenced understory regeneration. Elevation and slope also emerged as significant determinants, with the understory regeneration rate decreasing with elevation and increasing with slope steepness. Furthermore, a higher cover of pine in the tree stand had a suppressive effect. The above-mentioned dependencies resulted in substantial variations in the modeled understory regeneration of post-agricultural forests.The utilization of the Forest Maturity Index offers invaluable insights into identifying and subsequently safeguarding well-regenerated forests. Given the prevalence of forest secondary succession in various regions, this index emerges as a key indicator for future assessments and management strategies.

MHQ: constructing an aggregate metric of population mental wellbeing

BackgroundAccording to the World Health Organization (WHO), mental health is ‘a state of wellbeing in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community’. Any population metric of mental health and wellbeing should therefore not only reflect the presence or absence of mental challenges but also a person’s broad mental capacity and functioning across a range of cognitive, social, emotional and physical dimensions. However, while existing metrics of mental health typically emphasize ill health, existing metrics of wellbeing typically focus on happiness or life satisfaction, indirectly infer wellbeing from a selection of social and economic factors, or do not reflect a read out of the full spectrum of mental functioning that impacts people’s everyday life and that spans the continuum from distress and the inability to function, through to the ability to function to one’s full potential.MethodsWe present the Mental Health Quotient, or MHQ, a population metric of mental wellbeing that comprehensively captures mental functioning, and examine how it relates to functional productivity. We describe the 47-item assessment and the life impact rating scale on which the MHQ metric is based, as well as the rationale behind each step of the nonlinear algorithm used to construct the MHQ metric.ResultsWe demonstrate a linear relationship between the MHQ metric and productive life function where movement on the scale from any point or in any direction relates to an equivalent shift in productive ability at the population level, a relationship that is not borne out using simple sum scores. We further show that this relationship is the same across all age groups. Finally, we demonstrate the potential for the types of insights arising from the MHQ metric, offering examples from the Global Mind Project, an initiative that aims to track and understand our evolving mental wellbeing, and since 2020 has collected responses from over 1 million individuals across 140 + countries.ConclusionThe MHQ is a metric of mental wellbeing that aligns with the WHO definition and is amenable to large scale population monitoring.

A novel method to monitor rheumatoid arthritis prevalence using hospital and medication databases

BackgroundMost estimates of rheumatoid arthritis (RA) prevalence, including all official figures in Australia and many other countries, are based on self-report. Self-report has been shown to overestimate RA, but the ‘gold standard’ of reviewing individual medical records is costly, time-consuming and impractical for large-scale research and population monitoring. This study provides an algorithm to estimate RA cases using administrative data that can be adjusted for use in multiple contexts to provide the first approximate RA cohort in Australia that does not rely on self-report.MethodsSurvey data on self-reported RA and medications from 25 467 respondents of the Australian Longitudinal Study on Women’s Health (ALSWH) were linked with data from the national medication reimbursement database, hospital and emergency department (ED) episodes, and Medicare Benefits codes. RA prevalence was calculated for self-reported RA, self-reported RA medications, dispensed RA medications, and hospital/ED RA presentations. Linked data were used to exclude individuals with confounding autoimmune conditions.ResultsOf 25 467 survey respondents, 1367 (5·4%) women self-reported disease. Of the 26 840 women with hospital or ED presentations, 292 (1·1%) received ICD-10 codes for RA. There were 1038 (2·8%) cases by the medication database definition, and 294 cases (1·5%) by the self-reported medication definition. After excluding individuals with other rheumatic conditions, prevalence was 3·9% for self-reported RA, 1·9% based on the medication database definition and 0·5% by self-reported medication definition. This confirms the overestimation of RA based on self-reporting.ConclusionsWe provide an algorithm for identifying individuals with RA, which could be used for population studies and monitoring RA in Australia and, with adjustments, internationally. Its balance of accuracy and practicality will be useful for health service planning using relatively easily accessible input data.

Intelligent optimization of inspection route based on multi-population integer coding particle swarm optimization algorithm

Aiming at the problems of premature convergence and slow convergence speed in the optimization process of single population particle swarm optimization algorithm, in order to improve the global convergence performance of particle swarm optimization algorithm, a hierarchical three-population integer coded particle swarm optimization algorithm based on grade evaluation with parallel structure is proposed and used to solve the traveling salesman problem (TSP). The algorithm imitates the form of biological aggregation in nature. In the initialization stage, three independent populations are generated according to different particle fitness, including an elite population composed of small-scale individuals with high fitness and two large-scale civilian populations composed of remaining individuals. The three populations apply the immigration strategy based on grade evaluation to exchange particles after a certain number of evolutionary generations. By applying the grade evaluation strategy, the natural law of the biological cluster is integrated into the particle swarm optimization algorithm, which effectively improves the optimization efficiency of the particle swarm optimization algorithm. The above algorithm is applied to the inspection route optimization of one of the traveling salesman problems. The results show that the improved algorithm is superior to the single population particle swarm optimization algorithm in terms of convergence speed, global optimization ability and stability.

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.

Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that RPS19 exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56-0.83, P = 1.12 × 10-6), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene RPS19 mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of RPS19 during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.

Elevated basophil count is associated with increased risk of endometriosis.

Immunological dysregulation plays a fundamental role in the inflammatory aspects of endometriosis. Circulating blood leukocytes, one of the most abundant immune cell populations in the human body, have been shown diagnostic significance in some diseases. Nevertheless, the association between peripheral blood leukocyte counts and endometriosis remains unexplored to date. We analysed two targeted study cohorts: a tertiary centre cohort (Endometriosis at Oxford University [ENDOX] study, 325 cases/177 controls) and a large-scale population study (UK Biobank [UKBB], 1537 cases/6331 controls). In both datasets, peripheral venous blood sample results were retrieved and counts of leukocyte subpopulations, including neutrophils, lymphocytes, monocytes, eosinophils and basophils analysed. Logistic regression models were used to investigate the association of leukocyte subtype alterations with endometriosis status, adjusting for confounding factors. We demonstrate that higher blood basophil level is associated with increased odds of endometriosis. This association was first discovered in the ENDOX cohort (basophils >0.04 x10^9/L: OR 1.65 [95%CI:1.06-2.57], P trend = 0.025) and replicated in the UKBB dataset (basophils >0.04 x10^9/L: OR 1.26 [95%CI:1.09-1.45], P trend = 0.001). Notably, women with basophil counts in the upper tercile had significantly increased odds of having stage III/IV endometriosis (ENDOX study: OR = 2.30, 95% CI [1.25 to 4.22], P trend = 0.007; UKBB study (OR = 1.40, 95% CI [1.07 to 1.85], P trend = 0.015). None of the other leukocyte subtypes showed an association. Our findings suggest an association between inflammatory responses and the pathogenesis of endometriosis; future studies are warranted to investigate whether the association is causal.

Prevalence of mass social media-induced illness presenting with Tourette-like behavior in Germany between 2019 and 2021

Starting in 2019, in Germany the first well documented outbreak of mass sociogenic illness induced by social media (mass social media-induced illness; MSMI) occurred presenting with functional Tourette-like behaviors (FTB). This study aimed to provide first data on the prevalence rate of MSMI-FTB in Germany between 2019 and 2021 in the general population. We conducted a large-scale representative population survey in cooperation with the USUMA market and social research institute. Between August and December 2021, n = 2.509 people (mean age: 49.5 years, range: 16–95 years, n = 1.276 females) were randomly selected, visited in their households, interviewed, and asked to answer for themselves, but also for close family members (n = 6.744). Thus, in total, we received answers for n = 9.253 people. Probable MSMI-FTB was found in n = 33 individuals (mean age at onset: 30.5 years, n = 8 females). Based on strict criteria, the diagnosis of MSMI-FTB was considered highly likely in 16/33 individuals (mean age at onset: 25.6 years, n = 2 females) corresponding to prevalence rates of 0.17% (CIlower = 0.10, CIupper = 0.28) and 0.36% (CIlower = 0.25, CIupper = 0.50), respectively. This is the first large-scale, population representative study investigating the prevalence of MSMI-FTB in the general population in Germany between 2019 and 2021. Based on the prevalence rates found, MSMI-FTB is highly relevant for health economy. Accordingly, we suggest educating healthcare professionals and the general public to avoid misdiagnosis and inefficient treatment.

Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery

BackgroundOne of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as “genetic constraint”. Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes.MethodsWe aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues.ResultsWe identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism.ConclusionsGrouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation.

Effect of Rabies Booster Vaccination on Antibody Levels in African Wild Dogs (Lycaon pictus).

Rabies is a highly virulent viral disease that has been associated with large-scale population declines of the endangered African wild dog (Lycaon pictus). Rabies vaccination may be a valuable conservation tool in this species, but studies indicate that a single dose does not always confer protective immunity. We examined 47 serum samples from 22 captive African wild dogs (sampled opportunistically for other purposes) to assess whether serum antibody levels after vaccination correlated with the number of doses received and whether other factors affected outcomes. Results of the fluorescent antibody virus neutralization test showed that median antibody titers were 0.085 IU/mL prevaccination, 0.660 IU/mL after a single vaccination, and 22.150 IU/mL after a booster vaccination. Antibody titers above 0.5 IU/mL, internationally accepted as the threshold for seroconversion, were found in none of the samples taken prevaccination, 66.67% of samples taken after primary vaccination, and 90.90% of samples collected after booster vaccination. This study illustrates the probable protective benefit a rabies booster vaccination may provide in African wild dogs and serves as a basis for future research to improve vaccination protocols contributing to the conservation of this endangered species.

Water canals may promote large-scale defaunation of the Gran Chaco

In the Gran Chaco, one of the most biodiverse, yet imperiled, arid biomes in the world, open-to-air concrete water canals may threaten wildlife via drowning and habitat fragmentation, although these effects are usually overlooked. We performed field surveys and local people interviews along 250 km of canals in the Gran Chaco ecoregion of Argentina during austral spring and summer (six months). We documented 207 drowned individuals of 35 wildlife species, but more realistic estimations could increase this number to the thousands. Six species of conservation concern drowned in the canal, and eight of the drowned species have decreasing population trends. Drownings in some mammal species decreased with time without any mitigation measures implemented at the canal yet, suggesting an ongoing, large-scale population reduction due to this high mortality rate. Since mitigation measures applied in other regions were not effective to stop drowning and population isolation, these infrastructures should be avoided in arid environments worldwide.

Potentials of artificial intelligence in familial hypercholesterolemia: Advances in screening, diagnosis, and risk stratification for early intervention and treatment

Familial hypercholesterolemia (FH) poses a global health challenge due to high incidence rates and underdiagnosis, leading to increased risks of early-onset atherosclerosis and cardiovascular diseases. Early detection and treatment of FH is critical in reducing the risk of cardiovascular events and improving the long-term outcomes and quality of life for affected individuals and their families. Traditional therapeutic approaches revolve around lipid-lowering interventions, yet challenges persist, particularly in accurate and timely diagnosis. The current diagnostic landscape heavily relies on genetic testing of specific LDL-C metabolism genes, often limited to specialized centers. This constraint has led to the adoption of alternative clinical scores for FH diagnosis. However, the rapid advancements in artificial intelligence (AI) and machine learning (ML) present promising solutions to these diagnostic challenges. This review explores the intricacies of FH, highlighting the challenges that are encountered in the diagnosis and management of the disorder. The revolutionary potential of ML, particularly in large-scale population screening, is highlighted. Applications of ML in FH screening, diagnosis, and risk stratification are discussed, showcasing its ability to outperform traditional criteria. However, challenges and ethical considerations, including algorithmic stability, data quality, privacy, and consent issues, are crucial areas that require attention. The review concludes by emphasizing the significant promise of AI and ML in FH management while underscoring the need for ethical and practical vigilance to ensure responsible and effective integration into healthcare practices.

Testosterone levels increase following bariatric surgery - validation of preceding literature in a large-scale population analysis.

The effects of bariatric surgery on testosterone levels in men with obesity and hypogonadism have not been thoroughly explored yet. To investigate the possible effects of bariatric surgery on T levels in obese hypogonadal men by comparing T levels before and after surgery using a comprehensive claims database. The TriNetX US Collaborative Network database was used to identify men ages 18-80 who underwent a bariatric procedure and had a serum T value of<350ng/dL prior to surgery. Men who received testosterone therapy before/or after surgery were excluded. We conducted a retrospective self-matched cohort analysis to examine the difference in serum T levels before and after bariatric surgery. A sub-analysis was carried out to explore differences between men who reached eugonadal status or maintained low T levels following surgery. Descriptive statistics detailed sociodemographic and clinical characteristics, with continuous and categorical data compared using unpaired t-tests and chi-square analysis, respectively. Changes in T levels and body mass index (BMI) before and after surgery were compared using an unpaired t-test with a<0.05 set for significance. All analyses were conducted using the TriNetX platform which utilizes both Python and R software. The study analyzed 69 hypogonadal men who underwent bariatric surgery and had T levels assessed before and after the procedure. The mean (standard deviation) pre-surgery serum T level was 208±79ng/dL, which post-surgery increased to 371±164ng/dL, marking an average increase of 163±164ng/dL. Likewise, the mean (standard deviation) body mass index decreased from 42.9±9.0 to 38.8±5.7kg/m2. Post-surgery, 45% (31 men) achieved eugonadal status, while 55% (38 men) continued to have low T levels. A comparison between the post-surgery eugonadal cohort and the persistent low T cohort revealed that the former had higher pre-surgery serum T levels (235±71ng/dL vs. 184±80.4ng/dL, p=0.007), a higher pre-surgery body mass index (45.5±4.5kg/m2 vs. 41.1±11.5kg/m2, p=0.041), and a significantly greater reduction in body mass index post-surgery (7.3±7.2kg/m2 vs. 2.0±12.8kg/m2, p=0.04). Notably, the increase in T was significantly higher in the eugonadal cohort compared to the persistent low testosterone cohort (257±143ng/dL vs. 95±178ng/dL, p<0.0001). This study provides evidence of bariatric surgery's positive effect on serum T levels in obese men with baseline low T. Almost one out of two men with low T reached normal T levels after bariatric surgery. As the most comprehensive study to date, it validates and substantiates previous work suggesting that weight loss can improve T levels physiologically.

Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study

BackgroundObstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.MethodsA total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.ResultsIncreasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425–2.017; OR = 2.371, 95% confidence interval (CI): 2.009–2.816; OR = 3.392, 95% CI: 2.853–4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.ConclusionsThis study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

Exploring the genetic association between immune cells and susceptibility to osteonecrosis using large-scale population data

ObjectivesResearch shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset. MethodsWe conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR <0.05). Resultsour findings suggested that specific immune cell signatures, such as CD20− % lymphocytes, CD62L-monocytes, and CD33br HLA DR+ CD14−cells were associated with increased odds of osteonecrosis. In contrast, EM CD4+ activated cells and DP (CD4+ CD8+) T cells were associated with decreased odds. Notably, osteonecrosis was associated with a potential decrease in CD45 on immature MDSC cell content. ConclusionFrom a genetic perspective, we demonstrated a close association between immune cells and osteonecrosis. These findings significantly enhance our understanding of the interplay between immune cell infiltration and the risk of osteonecrosis, contributing to the potential design of therapeutic strategies from an immunological standpoint.

Environmental factors have stronger effects than biotic processes in patterns of intertidal populations along the southeast coast of Brazil

Rocky shore communities are shaped by complex interactions among environmental drivers and a range of biological processes. Here, we investigated the importance of abiotic and biotic drivers on the population structure of key rocky intertidal species at 62 sites, spanning ∼50% of the Brazilian rocky shoreline (i.e., ∼500 km). Large-scale population patterns were generally explained by differences in ocean temperature and wave exposure. For the gastropod species Lottia subrugosa, differences at smaller scales (i.e., 0.1–1 km) were better explained by other abiotic influences such as freshwater discharge and substrate roughness. Based on the general population patterns of intertidal species identified, three main oceanographic groups were observed: a cold-oligotrophic grouping at northern sites (Lakes sub-region), a eutrophic group associated with large estuaries and urban zones (Santos and Guanabara bays); and a transitional warm-water group found between the two more productive areas. Larger individuals of Stramonita brasiliensis, L. subrugosa and Echinolittorina lineolata were generally found in the cold-oligotrophic system (i.e., upwelling region), while small suspension feeders dominate the warm-eutrophic systems. Evidence of bottom-up regulation was not observed, and top-down regulation effects were only observed between the whelk S. brasiliensis and its mussel prey Pernaperna. Environmental drivers as compared to biotic interactions, therefore, play a key role determining the population structure of multiple intertidal species, across a range of spatial scales along the SW Atlantic shores.

Left Ventricular Hypertrophy In Ischemic Stroke Patients Single Center Experience

OBJECTIVES To ascertain the prevalence of left ventricular hypertrophy in individuals diagnosed with ischemic stroke. METHODOLOGY A cross-sectional study was undertaken in the Department of Medicine, Hayatabad Medical Complex, Peshawar, from October 1, 2020, to April 30, 2021, after obtaining ethical approval. The study included 143 individuals who had evidence of ischemic stroke on a CT scan. These patients were assessed for the presence or absence of left ventricular hypertrophy using transthoracic echocardiography. RESULTSThe average age of the participants in the study was 57 years, with a standard deviation of 7.9 years. The sample consisted of 67.8% males and 32.2% females. The average BMI was calculated to be 25.3 + 3.3kg/m2, and 39.9% of the patients were from urban areas. Left ventricular hypertrophy was observed in 16.8% of patients who had experienced an ischemic stroke, with the greatest occurrence rate of 39.9% found in the age range of 50-60 years. There was no significant correlation observed between hypertension, diabetes, location of residence, age, and smoking. CONCLUSION Early and precise identification of the modifiable risk factors during the illness, followed by proper intervention, has the potential to decrease the incidence of debilitating stroke greatly. It is necessary to conduct large-scale population screening studies inside our local community. TTE should be carried out in all acute ischemic stroke patients to optimize the management of these patients.

Validation of an abbreviated Big Five personality inventory at large population scale: Psychometric structure and associations with common psychiatric and neurological disorders

BackgroundThe five-factor model of personality, as quantified using instruments such as the Big Five Inventory, consists of broad personality domains including Extraversion, Agreeableness, Conscientiousness, Neuroticism (emotional instability), and Openness. Such instruments typically include >40 items. However, instruments with many items can be unwieldly and a cause of measurement error in clinical and cohort studies where multiple scales are sequenced. Conversely, established 5- and 10-item versions of the Big Five Inventory have poor reliability. Here, we developed and validated an abbreviated 18-item Big Five Inventory that balances efficiency, reliability and sensitivity. MethodWe analysed three datasets (N = 59,797, N = 21,177, and N = 87,983) from individuals who participated in the online Great British Intelligence Test (GBIT) study, a collaborative citizen science project with BBC2 Horizon. We applied factor analyses (FA), predictive normative modelling, and one-sample t-tests to validate the 18-item version of the Big Five and to investigate its associations with psychiatric and neurological conditions. ResultsThe 18-item version of the Big Five Inventory had higher validity and retest reliability compared to the other previously shortened versions in the literature, with comparable demographic associations to the full Big Five Inventory. It exhibited strong (i.e. large effect size) associations with psychiatric conditions, and moderate (small-medium) associations with neurological conditions. Neuroticism (emotional instability) was substantially higher in all psychiatric conditions, whereas Conscientiousness, Openness and Extraversion showed differential associations across conditions. ConclusionThe newly validated 18-item version of the Big Five provides a convenient means of measuring personality traits that is suitable for deployment in a range of studies. It retains psychometric structure, retest reliability and clinical-group sensitivity, as compared to the full original scale.

Examining the Impact of Social Support on Psychological Well-Being Among Canadian Individuals With COPD: Implications for Government Policies.

Chronic obstructive pulmonary disease (COPD) is a significant respiratory disease and is globally ranked as the third leading cause of death. In Canada, the direct healthcare costs associated with COPD are estimated to be $1.5 billion annually. This study utilized quantitative analyses to examine the impact of specific dimensions of social support, namely, guidance, reliable alliance, reassurance of worth, attachment, and social integration within a clinically identified population of individuals with COPD who exhibit symptoms of depression and anxiety. The study was based on the Social Provisions Theory and stress-buffering hypothesis, utilizing large-scale population data from Statistics Canada's 2012 Canadian Community Health Survey (CCHS) Mental Health component. On a national scale, individuals were more likely to report a decreased sense of belonging to a group of friends (social integration) and struggle to depend on others in stressful times (reliable alliance) while experiencing symptoms of anxiety and depression. These findings underscore the potential benefits of integrating peer support, socialization initiatives, and caregiver training into clinical programs designed for individuals with COPD.