Battlemcmillan2359

Arachidonic acid (AA), a major long-chain n-6 polyunsaturated fatty acid in animal foods, has been linked to inflammation, coagulation, and testosterone, which might relate to atherosclerotic cardiovascular diseases (ASCVD). We assessed the associations of genetically predicted plasma phospholipid AA with ASCVD and other CVD overall and by sex using Mendelian randomization (MR).

We conducted two-sample MR, applying eight genetic variants, independent of a highly pleiotropic variant (rs174547), strongly (p<5×10

) predicting AA, primarily to summary statistics of genetic associations with ASCVD, including ischaemic heart disease (IHD), ischaemic stroke, and peripheral artery disease (PAD) from CARDIoGRAMplusC4D 1000 Genomes (60,801 IHD cases, 123,504 controls), MEGASTROKE (34,217 ischaemic stroke cases, 406,111 controls), and Pan-UK Biobank (n=~420,531), and secondarily to genetic associations with other CVD from Pan-UK Biobank, Atrial Fibrillation Consortium, HERMES consortium, and FinnGen. We also assessed sex differences.

Genetically predicted AA was associated with ASCVD (odds ratio (OR) per % of total fatty acids increase 1.03, 95% confidence interval (CI) 1.01 to 1.05) and its subtypes IHD (OR 1.03, 95% CI 1.004 to 1.05), ischaemic stroke (OR 1.03, 95% CI 1.004 to 1.06) and possibly PAD (OR 1.08, 95% CI 1.00 to 1.17), possibly more strongly in men than women. AA was also associated with venous thromboembolism (OR 1.12, 95% CI 1.05 to 1.19). A similar pattern was observed when using rs174547 to genetically predict AA.

Our study suggests positive associations of AA with ASCVD and venous thromboembolism, with possibly stronger associations in men than women.

No funding.

No funding.Cardiovascular diseases (CVDs) are the leading cause of death and a major cause of disability globally. Transcription factor EB (TFEB), as a member of the microphthalmia transcription factor (MITF) family, has been demonstrated to be a master regulator of autophagy and lysosomal biogenesis. Emerging studies suggest that TFEB regulates homeostasis in the cardiovascular system and shows beneficial effects on CVDs, including atherosclerosis, aortic aneurysm, postischemic angiogenesis, and cardiotoxicity, constituting a promising molecular target for the prevention and treatment of these diseases. Post-translational modifications regulate TFEB nuclear translocation and its transcriptional activity. Therapeutic strategies have been pursued to enhance TFEB activity and facilitate TFEB beneficial effects on CVDs. The elucidation of TFEB function and the precise underlying mechanisms will accelerate drug development and potential applications of TFEB drugs in the treatment of human diseases.

Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.

We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). DB05448 Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.

When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P=6.1×10

 ; METTL8, rs116951054, MAF 0.09%, P=4.5×10

 ; and MATK, rs539182790, MAF 0.05%, P=3.4×10

). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P=1.2×10

, nearest gene GATM, and rs71147340, MAF=0.34, P=3.3×10

, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants.

This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

Pancreaticcancer (PC) is one of the most lethal solid malignancies in the world due to its excessive cell proliferation and aggressive metastatic features. Emerging evidences revealed the importance of posttranscriptional modifications of RNAs in PCprogression. However, knowledge about the 5-methylcytosine (m5C) RNA modification in PC is still extremely limited. In this study, we attempted to explore the expression changes and clinical significances of 12 known m5C-related genes among PC patients.

A total of 362 normal and 382 tumor specimens from PC patients were examined for candidate m5C-related gene and protein expression by using quantitative PCR (qPCR) and immunohistochemistry (IHC). The proliferation rate of PC cells was detected by MTS assay. Xenograft mouse models were used to assess the role of NSUN6 in PC tumor formation.

Through analyzing the four Gene Expression Omnibus (GEO) databases, six m5C-related genes shown significant and consistent alterations were selected for further examination a (Grant Nos. 81803014, 81802424, and 81802911).

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81803014, 81802424, and 81802911).

The aim of this study was to determine sensitivity, specificity, and best cutoff point for adductor pollicis muscle thickness (APMT) for diagnosis of sarcopenia in elderly community centers.

This was a cross-sectional study comprising 321 elderly individuals from four community centers in Cuiabá, Central-West region of Brazil. The main outcome variables were calf circumference (CC; cm) and the APMT (mm). A receiver operating characteristic curve was built to assess the accuracy of APMT having CC as a golden pattern for sarcopenia. The best cutoff point was defined by Youden's J statistic.

The area under curve of APMT was 0.70 (95% confidence interval [CI], 0.63-0.76; P < 0.001) for all individuals, 0.74 (95% CI, 0.67-0.81; P < 0.001) for women, and 0.71 (95% CI, 0.58-0.85; P =.01) for men. The best cutoff point defined by Youden's J statistic was 17.63 mm for all individuals, the same for women. and 18.51 mm for men.

The APMT can be used for the diagnosis of sarcopenia. The optimal cutoff points for APMT are 17.