The association of dimethylarginine dimethylaminohydrolase 1 gene polymorphism with type 2 diabetes: a cohort study

<p>Abstract</p> <p>Background</p> <p>Elevated plasma levels of asymmetric dimethylarginine (ADMA) has been reported to be associated with insulin resistance and micro/macrovascular diabetic complications, and may predict cardiovascular events in type 2 diabetic patients. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme eliminating ADMA in humans, but the effect of genetic variations in <it>DDAH1 </it>on type 2 diabetes and its long-term outcome are unknown.</p> <p>Methods</p> <p>From July 2006 to June 2009, we assessed the association between polymorphisms in <it>DDAH1 </it>and type 2 diabetes in 814 consecutive unrelated subjects, including 309 type 2 diabetic patients and 505 non-diabetic individuals. Six single nucleotide polymorphisms (SNPs) in <it>DDAH1</it>, rs233112, rs1498373, rs1498374, rs587843, rs1403956, and rs1241321 were analyzed. Plasma ADMA levels were determined by high performance liquid chromatography. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).</p> <p>Results</p> <p>Among the 6 SNPs, only rs1241321 was significantly associated with a decreased risk of type 2 diabetes (AA <it>vs </it>GG+AG, OR = 0.64, 95% CI 0.47-0.86, p = 0.004). The association remained unchanged after adjustment for plasma ADMA level. The fasting plasma glucose and log HOMA-IR tended to be lower in subjects carrying the homozygous AA genotype of rs1241321 compared with the GG+AG genotypes. Over a median follow-up period of 28.2 months, there were 44 all-cause mortality and 50 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction and stroke). Compared with the GG and AG genotypes, the AA genotype of rs1241321 was associated with reduced risk of MACE (HR = 0.31, 95% CI: 0.11-0.90, p = 0.03) and all-cause mortality (HR = 0.18, 95% CI: 0.04-0.80, p = 0.02) only in subgroup with type 2 diabetes. One common haplotype (GGCAGC) was found to be significantly associated with a decreased risk of type 2 diabetes (OR = 0.67, 95% CI = 0.46-0.98, p = 0.04).</p> <p>Conclusions</p> <p>Our results provide the first evidence that SNP rs1241321 in <it>DDAH1 </it>is associated with type 2 diabetes and its long-term outcome.</p

Self-supervised learning-based general laboratory progress pretrained model for cardiovascular event detection

The inherent nature of patient data poses several challenges. Prevalent cases amass substantial longitudinal data owing to their patient volume and consistent follow-ups, however, longitudinal laboratory data are renowned for their irregularity, temporality, absenteeism, and sparsity; In contrast, recruitment for rare or specific cases is often constrained due to their limited patient size and episodic observations. This study employed self-supervised learning (SSL) to pretrain a generalized laboratory progress (GLP) model that captures the overall progression of six common laboratory markers in prevalent cardiovascular cases, with the intention of transferring this knowledge to aid in the detection of specific cardiovascular event. GLP implemented a two-stage training approach, leveraging the information embedded within interpolated data and amplify the performance of SSL. After GLP pretraining, it is transferred for TVR detection. The proposed two-stage training improved the performance of pure SSL, and the transferability of GLP exhibited distinctiveness. After GLP processing, the classification exhibited a notable enhancement, with averaged accuracy rising from 0.63 to 0.90. All evaluated metrics demonstrated substantial superiority (p < 0.01) compared to prior GLP processing. Our study effectively engages in translational engineering by transferring patient progression of cardiovascular laboratory parameters from one patient group to another, transcending the limitations of data availability. The transferability of disease progression optimized the strategies of examinations and treatments, and improves patient prognosis while using commonly available laboratory parameters. The potential for expanding this approach to encompass other diseases holds great promise.Comment: published in IEEE Journal of Translational Engineering in Health & Medicin

Superconductivity above 30 K achieved in dense scandium

Superconductivity is one of most intriguing quantum phenomena, and the quest for elemental superconductors with high critical temperature (Tc) is of great scientific significance due to their relatively simple material composition and the underlying mechanism. Here we report the experimental discovery of densely compressed scandium (Sc) becoming the first elemental superconductor with Tc breaking into 30 K range, which is comparable to the Tc values of the classic La-Ba-Cu-O or LaFeAsO superconductors. Our results show that Tconset of Sc increases from ~3 K at around 43 GPa to ~32 K at about 283 GPa (Tczero ~ 31 K), which is well above liquid neon temperature. Interestingly measured Tc shows no sign of saturation up to the maximum pressure achieved in our experiments, indicating that Tc might be even higher upon further compression.Comment: 22 pages, 16 figure

Tunable Excitons in Biased Bilayer Graphene

Recent measurements have shown that a continuously tunable bandgap of up to 250 meV can be generated in biased bilayer graphene [Y. Zhang et al., Nature 459, 820 (2009)], opening up pathway for possible graphene-based nanoelectronic and nanophotonic devices operating at room temperature. Here, we show that the optical response of this system is dominated by bound excitons. The main feature of the optical absorbance spectrum is determined by a single symmetric peak arising from excitons, a profile that is markedly different from that of an interband transition picture. Under laboratory conditions, the binding energy of the excitons may be tuned with the external bias going from zero to several tens of meV's. These novel strong excitonic behaviors result from a peculiar, effective ``one-dimensional'' joint density of states and a continuously-tunable bandgap in biased bilayer graphene. Moreover, we show that the electronic structure (level degeneracy, optical selection rules, etc.) of the bound excitons in a biased bilayer graphene is markedly different from that of a two-dimensional hydrogen atom because of the pseudospin physics

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin