Integrating RNA-Seq With GWAS Reveals a Novel SNP in Immune-Related HLA-DQB1 Gene Associated With Occupational Pulmonary Fibrosis Risk: A Multi-Stage Study

ObjectiveTo evaluate the association between single-nucleotide polymorphisms (SNPs) in RNA-seq identified mRNAs and silicosis susceptibility.MethodsA comprehensive RNA-seq was performed to screen for differently expressed mRNAs in the peripheral blood lymphocytes of eight subjects exposed to silica dust (four silicosis cases and four healthy controls). Following this, the SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility, were screened through silicosis-related genome-wide association studies (GWAS) (155 silicosis cases and 141 healthy controls), whereas functional expression quantitative trait locus (eQTL)-SNPs were identified using the GTEx database. Finally, the association between functional eQTL-SNPs and silicosis susceptibility (194 silicosis cases and 235 healthy controls) was validated.ResultsA total of 70 differentially expressed mRNAs (fold change > 2 or fold change < 0.5, P < 0.05) was obtained using RNA-seq. Furthermore, 476 SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility (P < 0.05) were obtained using GWAS, whereas subsequent six functional eQTL-SNPs were identified. The mutant A allele of rs9273410 in HLA-DQB1 indicated a potential increase in silicosis susceptibility in the validation stage (additive model: odds ratio (OR)= 1.31, 95% confidence interval (CI) = 0.99–1.74, P = 0.061), whereas the combination of GWAS and the validation results indicated that the mutant A allele of rs9273410 was associated with increased silicosis susceptibility (additive model: OR = 1.35, 95% CI =1.09–1.68, P = 0.006).ConclusionThe mutant A allele of rs9273410 was associated with increased silicosis susceptibility by modulating the expression of HLA-DQB1.

Dose-response relationship of reported lifetime meditation practice with mental-health and wellbeing: A cross sectional study

Objectives: Experimental studies of meditation practice predominantly examine short-term programs and reveal modest benefits. Thus it is not clear to what degree these results represent how contemporary meditators practice nor the dose-response relationship between amount of practice and outcome. This study sought to characterize how contemporary meditators practice; examine any possible dose-response relationships between historical practice and measures of psychological wellbeing; and explore which characteristics of practice most strongly predict positive psychological outcomes.Methods: 1,668 meditators completed demographic and practice characteristics, and outcome measures assessing positive and negative affect, psychological distress, and life satisfaction.Results: We observed a positive relationship between historical meditation practice (accumulated lifetime hours) and improvements in psychological outcomes. Model fit was optimized with a generalized additive model, indicating non-linear effects. The strength of the relationship between practice time and outcomes was generally strongest for the first ~500 hours, before plateauing to some degree. Several practice types, including Vipassana (as taught by S.N. Goenka) and cultivating practices (e.g. compassion, lovingkindness) were more strongly associated with favorable psychological outcomes.Conclusions: Benefits of meditation accrue over time in a non-linear manner, and show variation based on the context within which the meditator practices. These results highlight the importance of understanding how the benefits of meditation accrue over longer time durations than typical standardized programs that have been subject to most empirical investigations in the field.

A structured additive modeling of diabetes and hypertension in Northeast India

Background Multiple factors are associated with the risk of diabetes and hypertension. In India, they vary widely even from one district to another. Therefore, strategies for controlling diabetes and hypertension should appropriately address local risk factors and take into account the specific causes of the prevalence of diabetes and hypertension at sub-population levels and in specific settings. This paper examines the demographic and socioeconomic risk factors as well as the spatial disparity of diabetes and hypertension among adults aged 15–49 years in Northeast India. Methods The study used data from the Indian Demographic Health Survey, which was conducted across the country between 2015 and 2016. All men and women between the ages of 15 and 49 years were tested for diabetes and hypertension as part of the survey. A Bayesian geo-additive model was used to determine the risk factors of diabetes and hypertension. Results The prevalence rates of diabetes and hypertension in Northeast India were, respectively, 6.38% and 16.21%. The prevalence was higher among males, urban residents, and those who were widowed/divorced/separated. The functional relationship between household wealth index and diabetes and hypertension was found to be an inverted U-shape. As the household wealth status increased, its effect on diabetes also increased. However, interestingly, the inverse was observed in the case of hypertension, that is, as the household wealth status increased, its effect on hypertension decreased. The unstructured spatial variation in diabetes was mainly due to the unobserved risk factors present within a district that were not related to the nearby districts, while for hypertension, the structured spatial variation was due to the unobserved factors that were related to the nearby districts. Conclusion Diabetes and hypertension control measures should consider both local and non-local factors that contribute to the spatial heterogeneity. More importance should be given to efforts aimed at evaluating district-specific factors in the prevalence of diabetes within a region.

Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy

The mechanism of environmental factors in Kashin–Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin–responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin–responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

Association between the plasma-to-red blood cell ratio and survival in geriatric and non-geriatric trauma patients undergoing massive transfusion: a retrospective cohort study

Background The benefits of a high plasma-to-red blood cell (RBC) ratio on the survival of injured patients who receive massive transfusions remain unclear, especially in older patients. We aimed to investigate the interaction of age with the plasma-to-RBC ratio and clinical outcomes of trauma patients. Methods In this retrospective study conducted from 2013 to 2016, trauma patients who received massive transfusions were included. Using a generalized additive model (GAM),we assessed how the plasma-to-RBC ratio and age affected the in-hospital mortality rates. The association of the plasma-to-RBC ratio [low (< 0.5), medium (0.5–1.0), and high (≥ 1.0)] with in-hospital mortality and the incidence of adverse events were assessed for the overall cohort and for patients stratified into non-geriatric (16–64 years) and geriatric (≥ 65 years) groups using logistic regression analyses. Results In total, 13,894 patients were included. The GAM plot of the plasma-to-RBC ratio for in-hospital mortality demonstrated a downward convex unimodal curve for the entire cohort. The low-transfusion ratio group was associated with increased odds of in-hospital mortality in the non-geriatric cohort [odds ratio 1.38, 95% confidence interval (CI) 1.22–1.56]; no association was observed in the geriatric group (odds ratio 0.84, 95% CI 0.62–1.12). An increase in the transfusion ratio was associated with a higher incidence of adverse events in the non-geriatric and geriatric groups. Conclusion The association of the non-geriatric age category and plasma-to-RBC ratio for in-hospital mortality was clearly demonstrated. However, the relationship between the plasma-to-RBC ratio with mortality among geriatric patients remains inconclusive.

Sampling Designs for Monitoring Ichthyoplankton in the Estuary Area: A Case Study on Coilia mystus in the Yangtze Estuary

A fishery-independent survey can provide detailed information for fishery assessment and management. However, the sampling design for the survey on ichthyoplankton in the estuary area is still poorly understood. In this study, we developed six stratified schemes with various sample sizes, attempting to find cost-efficient sampling designs for monitoring Coilia mystus ichthyoplankton in the Yangtze Estuary. The generalized additive model (GAM) with the Tweedie distribution was used to quantify the “true” distribution of C. mystus eggs and larvae, based on the data from the fishery-independent survey in 2019–2020. The performances of different sampling designs were evaluated by relative estimation error (REE), relative bias (RB), and coefficient of variation (CV). The results indicated that appropriate stratifications with intra-stratum homogeneity and inter-stratum heterogeneity could improve precision. The stratified schemes should be divided not only between the North Branch and South Branch but between river and sea. No less than two stratifications in the South Branch could also get better performance. The sample sizes of 45–55 were considered as the cost-efficient range. Compared to other monitoring programs, monitoring ichthyoplankton in the estuary area required a more complex stratification and a higher resolution sampling. The design ideology and optimization methodology in our study would provide references to sampling designs for ichthyoplankton in the estuary area.

Neutralization Assessments Reveal High Cardiothoracic Ratio and Old Age as Independent Predictors of Low Neutralizing Antibody Titers in Hemodialysis Patients Receiving a Single Dose of COVID-19 Vaccine

Background: Data are lacking regarding predictors of quantification of neutralizing antibodies (nAbs) based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 50% neutralization titer (NT50) after a single dose of COVID-19 vaccine in hemodialysis (HD) patients. Methods: This prospective single-center study enrolled 200 HD patients and 82 healthy subjects to estimate antibodies against the SARS-CoV-2 viral spike protein 1 and receptor-binding domain after a first dose of a COVID-19 vaccine (ChAdOx1 or mRNA-1273), measured by enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict NT50 converted to international units. Results: After the first dose of ChAdOx1, multiple linear regression showed that age (p = 0.011) and cardiothoracic ratio (p = 0.002) were negatively associated with NT50. Older age (OR = 0.958, p = 0.052) and higher cardiothoracic ratio (OR < 0.001, p = 0.037) could predict negative humoral response (NT50 < 35.13 IU/mL). NT50 was lower in HD patients compared with healthy controls receiving ChAdOx1 (10.68 vs. 43.01 IU/m, p < 0.001) or mRNA-1273 (36.39 vs. 262.2 IU/mL, p < 0.001). ChAdOx1 elicited lower GMTs than mRNA-1273 in the HD cohort (10.68 vs. 36.39 IU/mL, p < 0.001) and in healthy controls (43.01 vs. 262.22 IU/mL, p < 0.001). Conclusion: High cardiothoracic ratio and old age could independently predict a decline in nAb titers in an HD cohort vaccinated with a single dose of ChAdOx1.

Long-Term Exposure to Ambient PM2.5, Sunlight, and Obesity: A Nationwide Study in China

BackgroundAccumulated researches revealed that both fine particulate matter (PM2.5) and sunlight exposure may be a risk factor for obesity, while researches regarding the potential effect modification by sunlight exposure on the relationship between PM2.5 and obesity are limited. We aim to investigate whether the effect of PM2.5 on obesity is affected by sunlight exposure among the general population in China.MethodsA sample of 47,204 adults in China was included. Obesity and abdominal obesity were assessed based on body mass index, waist circumference and waist-to-hip ratio, respectively. The five-year exposure to PM2.5 and sunlight were accessed using the multi-source satellite products and a geochemical transport model. The relationship between PM2.5, sunshine duration, and the obesity or abdominal obesity risk was evaluated using the general additive model.ResultsThe proportion of obesity and abdominal obesity was 12.6% and 26.8%, respectively. Levels of long-term PM2.5 ranged from 13.2 to 72.1 μg/m3 with the mean of 46.6 μg/m3. Each 10 μg/m3 rise in PM2.5 was related to a higher obesity risk [OR 1.12 (95% CI 1.09-1.14)] and abdominal obesity [OR 1.10 (95% CI 1.07-1.13)]. The association between PM2.5 and obesity varied according to sunshine duration, with the highest ORs of 1.56 (95% CI 1.28-1.91) for obesity and 1.66 (95% CI 1.34-2.07) for abdominal obesity in the bottom quartile of sunlight exposure (3.21-5.34 hours/day).ConclusionLong-term PM2.5 effect on obesity risk among the general Chinese population are influenced by sunlight exposure. More attention might be paid to reduce the adverse impacts of exposure to air pollution under short sunshine duration conditions.

Controlling factors on the global distribution of a representative marine heterotrophic diazotroph phylotype (Gamma A)

Heterotrophic diazotrophs emerge as a potentially important contributor to the global marine N2 fixation, while the factors controlling their distribution are unclear. Here, we explored what controls the distribution of the most sampled heterotrophic diazotroph phylotype, Gamma A, in the global ocean. First, we analyzed the relationship between nifH-based Gamma A abundance and climatological biological and environmental conditions. The carrying capacity of Gamma A abundance increased with net primary production (NPP) and saturated when NPP reached ~400 mg C m−2 d−1. The reduction in Gamma A abundance from its carrying capacity was mostly related to low temperature, which possibly slowed the decomposition of organic matter, and high concentration of dissolved iron, to which the explanation was elusive but could result from the competition with autotrophic diazotrophs. Using a generalized additive model, these climatological factors together explained 41 % of the variance in the Gamma A abundance. Second, in additional to the climatological background, we found that mesoscale cyclonic eddies can substantially elevate Gamma A abundance, implying that Gamma A can respond to short-term features and benefit from stimulated primary production by nutrient inputs. Overall, our results suggest that the distribution of Gamma A is most likely determined by the supply of organic matters, not by those factors controlling autotrophic diazotrophs, and therefore insight a niche differentiation between the heterotrophic and autotrophic N2 fixation. More samplings on Gamma A and other heterotrophic diazotroph phylotypes are needed to better reveal the controlling mechanisms of heterotrophic N2 fixation in the ocean.