Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Defining multiple layers of intratumor heterogeneity based on variations of perturbations in multi-omics profiling.

BACKGROUND: Intratumor heterogeneity (ITH) plays a crucial role in tumor progression, relapse, immune evasion, and drug resistance. Existing ITH quantification methods based on a single molecular level are inadequate to capture ITH evolving from genotype to phenotype. METHODS: We designed a set of information entropy (IE)-based algorithms for quantifying ITH at the genome (somatic copy number alterations and mutations), mRNA, microRNA (miRNA), long non-coding RNA (lncRNA), protein, and epigenome level, respectively. We evaluated the performance of these algorithms by analyzing the correlations between their ITH scores and ITH-associated molecular and clinical features in 33 TCGA cancer types. Moreover, we evaluated the correlations between the ITH measures at different molecular levels by Spearman correlation and clustering analysis. RESULTS: The IE-based ITH measures had significant correlations with unfavorable prognosis, tumor progression, genomic instability, antitumor immunosuppression, and drug resistance. The mRNA ITH showed stronger correlations with the miRNA, lncRNA, and epigenome ITH than with the genome ITH, supporting the regulatory relationships of miRNA, lncRNA, and DNA methylation towards mRNA. The protein-level ITH displayed stronger correlations with the transcriptome-level ITH than with the genome-level ITH, supporting the central dogma of molecular biology. Clustering analysis based on the ITH scores identified four subtypes of pan-cancer showing significantly different prognosis. Finally, the ITH integrating the seven ITH measures displayed more prominent properties of ITH than that at a single level. CONCLUSIONS: This analysis provides landscapes of ITH at various molecular levels. Combining the ITH observation from different molecule levels will improve personalized management for cancer patients.

Evaluation of the effects of meteorological factors on COVID-19 prevalence by the distributed lag nonlinear model.

BACKGROUND: Although numerous studies have explored the impact of meteorological factors on the epidemic of COVID-19, their relationship remains controversial and needs to be clarified. METHODS: We assessed the risk effect of various meteorological factors on COVID-19 infection using the distributed lag nonlinear model, based on related data from July 1, 2020, to June 30, 2021, in eight countries, including Portugal, Greece, Egypt, South Africa, Paraguay, Uruguay, South Korea, and Japan, which are in Europe, Africa, South America, and Asia, respectively. We also explored associations between COVID-19 prevalence and individual meteorological factors by the Spearman's rank correlation test. RESULTS: There were significant non-linear relationships between both temperature and relative humidity and COVID-19 prevalence. In the countries located in the Northern Hemisphere with similar latitudes, the risk of COVID-19 infection was the highest at temperature below 5 â„ƒ. In the countries located in the Southern Hemisphere with similar latitudes, their highest infection risk occurred at around 15 â„ƒ. Nevertheless, in most countries, high temperature showed no significant association with reduced risk of COVID-19 infection. The effect pattern of relative humidity on COVID-19 depended on the range of its variation in countries. Overall, low relative humidity was correlated with increased risk of COVID-19 infection, while the high risk of infection at extremely high relative humidity could occur in some countries. In addition, relative humidity had a longer lag effect on COVID-19 than temperature. CONCLUSIONS: The effects of meteorological factors on COVID-19 prevalence are nonlinear and hysteretic. Although low temperature and relative humidity may lower the risk of COVID-19, high temperature or relative humidity could also be associated with a high prevalence of COVID-19 in some regions.

Fast determination of tetrafluoroborate by high-performance liquid chromatography using a monolithic column.

Fast determination of tetrafluoroborate by high-performance liquid chromatography using a silica-based monolithic column and direct conductivity detection was carried out. Chromatographic separation was performed on a Chromolith Speed ROD RP-18e column (50 mm x 4.6 mm i.d.) with tetrabutylammonium hydroxide (TBA-OH)+ phthalic acid as eluent. The effects of eluent concentration, eluent pH, column temperature and flow rate on retention time of tetrafluoroborate were investigated. The optimized chromatographic conditions for determination of tetrafluoroborate were using 0.5mM TBA-OH + 0.31 mM phthalic acid (pH 5.5) as eluent, column temperature of 30 degrees C and flow rate of 6.0 mL/min. Retention time of tetrafluoroborate was less than 1min under the conditions. Common anions (Cl(-), Br(-), NO3(-) and SO4(2-)) did not interfere with the determination of tetrafluoroborate. Detection limit (S/N = 2) for tetrafluoroborate was 1.4 mg/L. The linear range of calibration curve between peak area and the concentration of tetrafluoroborate was from 1.4 to 100.0 mg/L. The reproducibility was 0.09% and 1.8% (n = 5) relative standard deviation (RSD) for retention time and peak area, respectively. The method has been applied to the determination of tetrafluoroborate in ionic liquids. Recoveries of tetrafluoroborate after spiking were 98.2-101.5%.