Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Enhancing Event Sequence Modeling with Contrastive Relational Inference

Neural temporal point processes(TPPs) have shown promise for modeling continuous-time event sequences. However, capturing the interactions between events is challenging yet critical for performing inference tasks like forecasting on event sequence data. Existing TPP models have focused on parameterizing the conditional distribution of future events but struggle to model event interactions. In this paper, we propose a novel approach that leverages Neural Relational Inference (NRI) to learn a relation graph that infers interactions while simultaneously learning the dynamics patterns from observational data. Our approach, the Contrastive Relational Inference-based Hawkes Process (CRIHP), reasons about event interactions under a variational inference framework. It utilizes intensity-based learning to search for prototype paths to contrast relationship constraints. Extensive experiments on three real-world datasets demonstrate the effectiveness of our model in capturing event interactions for event sequence modeling tasks.Comment: 6 pages, 2 figure

Fire-Needle Moxibustion for the Treatment of Knee Osteoarthritis: A Meta-Analysis

Objectives. The aim of this study was to evaluate the effectiveness of fire-needle moxibustion as an intervention in the treatment of knee osteoarthritis (KOA). Methods. An updated meta-analysis of randomized controlled trials (RCTs) on fire-needle moxibustion in treating KOA was conducted by searching PubMed, Embase, the Cochrane Library, Web of Science, Wanfang database, and the Chinese Medical Database (CNKI) since their inception through March 2016. The meta-analysis was performed using RevMan 5.3. Results. Thirteen RCTs were identified in the systematic study which consisted of 1179 participants. Fire-needle moxibustion treatment group had a statistical significance on recovery rate as well as recovery and marked-improvement rate compared with control group. Subgroup analysis indicated that there was significant difference between fire-needle moxibustion group and control group. However, GRADE analysis indicated that the quality of evidence for all outcomes was relatively low. Only two of 13 studies reported adverse reactions (difficulty in movement and intolerance of cold). Conclusion. This meta-analysis suggests that fire-needle moxibustion is more effective than control group in symptom management of KOA. Further high quality trials should be conducted to evaluate the effectiveness of fire-needle moxibustion on KOA

Faktor-Faktor Yang Mempengaruhi Pengungkapan Tanggung Jawab Sosial

Penelitian ini bertujuan untuk menentukan faktor-faktor yang mempengaruhi luasnya tingkat pengungkapan tanggung jawab sosial Perusahaan (Corporate Social Responsibility) dengan menguji pengaruh ukuran Perusahaan, profitabilitas, leverage, kepemilikan insti­tusional, ukuran dewan komisaris, ukuran dewan direksi, dan ukuran komite audit. Sampel yang digunakan adalah Perusahaan sektor pertambangan terdaftar di Bursa Efek Indonesia selama 2010-2012. Data diperoleh dari laporan keuangan auditan dan laporan tahunan serta laporan keberlanjutan (sustainability report) jika ada. Penelitian ini menggunakan pendekatan kuantitatif dengan analisis regresi linear berganda. Penelitian ini menunjukkan bahwa ukuran Perusahaan dan komite audit memiliki pengaruh positif terhadap peng­ungkapan tanggung jawab sosial. Tidak ditemukan bukti pengaruh profitabilitas, leverage, kepemilikan institusional, ukuran dewan komisaris, dan ukuran dewan direksi terhadap terhadap pengungkapan tanggung jawab sosial

A SU6668 pure nanoparticle-based eyedrops:toward its high drug Accumulation and Long-time treatment for corneal neovascularization

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics

The Last April

<p>Parameter settings of virtual datasets.</p

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью