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Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanine aminotransferase, 190 aspartate aminotransferase, and 199 alkaline phosphatase genome-wide significant associations, with some affecting multiple different enzymes. Associated variants implicate genes that demonstrate diverse liver cell type expression and promote a range of metabolic and liver diseases. These findings provide insight into the pathophysiology of liver and other metabolic diseases that are associated with serum liver enzyme concentrations. Serum liver enzymes are used as markers of liver disease, their concentration influenced in part by genetic factors. Here the authors meta-analyse genome-wide association studies on the UK Biobank and BioBank Japan to evaluate the association of three liver enzymes with liver and other metabolic diseases.

Objective To apply SyMRI to quantify whole brain volume changes in patients with varying degrees of obstructive sleep apnea (OSA). Methods A total of 49 untreated adult patients diagnosed with OSA via polysomnography (PSG) at our hospital were included in this study. Among these patients, 21 were categorized into the mild-to‐moderate OSA group, and 28 into the severe OSA group. Additionally, 31 healthy adults were recruited as the healthy control (HC) group. SyMRI post‐processing software was used to obtain whole brain volume segmentation values. Results In terms of the STOP-BANG questionnaire, the score of the severe OSA group was significantly higher than that of the mild‐to‐moderate OSA group ( P <  0.05). Compared with the HC group, the mild‐to‐moderate OSA group and the severe OSA group exhibited a reduction in N3‐stage sleep (both P <  0.05). Post‐hoc multiple comparisons showed that compared with the HC group, the severe OSA group had increased GMV, BPV, and ICV, while the mild‐to‐moderate OSA group showed an increase in CSFV ( P <  0.05). Additionally, compared with the HC group, the mild‐to‐moderate OSA group exhibited a decrease and the severe OSA group showed an increase in MYV ( P <  0.05). Multiple comparisons of normalized volume fractions revealed that GMF, WMF, CSFF, MYF and BPVF were significantly different between the HC group and OSA groups (all P  < 0.05). Conclusion The brain volume parameters generated from SyMRI can quantify the degree of brain injury in patients with OSA. Clinical trial number Not applicable.

With the growing of economic globalization and world economic integration, customer demands are becoming increasingly personalization and diversification. How to design a reasonable schedule scheme becomes the key point of industries. Flexible job shop scheduling problem (FJSP) is an extension of the classical job scheduling problem (JSP). It is an important problem in the modern manufacturing system, and constitutes to one of the most difficult combinatorial optimization problems. This paper defines an objective function, which aims at minimizing the makespan, under the conveyor constraints. Moreover, we present a genetic algorithm (GA)-based approach to optimizing the objective. Specifically, we firstly propose a method for solving conveyor-constrained FJSP (CDFJSP) by using a plug-in greedy algorithm and a binary search algorithm. Considering the unexpected events that usually occur in real-life applications, a real-time method with dispatching rules (RDRP) is proposed. Extensive experimental results demonstrate the efficacy of our proposed methods.

Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide. NAFLD is associated with elevated serum triglycerides (TG), low‐density lipoprotein cholesterol (LDL), and reduced high‐density lipoprotein cholesterol (HDL). Both NAFLD and blood lipid levels are genetically influenced and may share a common genetic etiology. We used genome‐wide association studies (GWAS)–ranked genes and gene‐set enrichment analysis to identify pathways that affect serum lipids and NAFLD. We identified credible genes in these pathways and characterized missense variants in these for effects on serum traits. We used MAGENTA to identify 58 enriched pathways from publicly available TG, LDL, and HDL GWAS (n = 99,000). Three of these pathways were also enriched for associations with European‐ancestry NAFLD GWAS (n = 7176). One pathway, farnesoid X receptor (FXR)/retinoid X receptor (RXR) activation, was replicated for association in an African‐ancestry NAFLD GWAS (n = 3214) and plays a role in serum lipids and NAFLD. Credible genes (proteins) in FXR/RXR activation include those associated with cholesterol/bile/bilirubin transport/absorption (ABCC2 (MRP2) [ATP binding cassette subfamily C member (multidrug resistance‐associated protein 2)], ABCG5, ABCG8 [ATP‐binding cassette (ABC) transporters G5 and G8], APOB (APOB) [apolipoprotein B], FABP6 (ILBP) [fatty acid binding protein 6 (ileal lipid‐binding protein)], MTTP (MTP) [microsomal triglyceride transfer protein], SLC4A2 (AE2) [solute carrier family 4 member 2 (anion exchange protein 2)]), nuclear hormone–mediated control of metabolism (NR0B2 (SHP) [nuclear receptor subfamily 0 group B member 2 (small heterodimer partner)], NR1H4 (FXR) [nuclear receptor subfamily 1 group H member 4 (FXR)], PPARA (PPAR) [peroxisome proliferator activated receptor alpha], FOXO1 (FOXO1A) [forkhead box O1]), or other pathways (FETUB (FETUB) [fetuin B]). Missense variants in ABCC2 (MRP2), ABCG5 (ABCG5), ABCG8 (ABCG8), APOB (APOB), MTTP (MTP), NR0B2 (SHP), NR1H4 (FXR), and PPARA (PPAR) that associate with serum LDL levels also associate with serum liver function tests in UK Biobank. Conclusion: Genetic variants in NR1H4 (FXR) that protect against liver steatosis increase serum LDL cholesterol while variants in other members of the family have congruent effects on these traits. Human genetic pathway enrichment analysis can help guide therapeutic development by identifying effective targets for NAFLD/serum lipid manipulation while minimizing side effects. In addition, missense variants could be used in companion diagnostics to determine their influence on drug effectiveness.

Data from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.

Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This study included two cohorts. The first included 2,249 participants from the Framingham Heart Study who underwent a computed tomography scan to evaluate hepatic steatosis, dual‐energy x‐ray absorptiometry testing to assess body composition, and clinical examination. Body composition parameters were normalized to total body weight. A subset of participants underwent genotyping with an Affymetrix 550K single‐nucleotide polymorphism array. The second cohort, Michigan Genomics Initiative, included 19,239 individuals with genotyping on the Illumina HumanCoreExome v.12.1 array and full electronic health record data. Using sex‐stratified multivariable linear regression, greater central body fat associated with increased hepatic steatosis while greater lower extremity body fat associated with decreased hepatic steatosis. Greater appendicular lean mass was associated with decreased hepatic steatosis in men but not in women. A polygenic risk score for lipodystrophy (regional or global loss of adipose tissue) was associated with increased hepatic steatosis, increased liver fibrosis, and decreased lower extremity fat mass. Conclusion: Greater central body fat associated with increased hepatic steatosis, while greater lower extremity body fat and, in men, greater appendicular lean mass were associated with decreased hepatic steatosis. A genetic risk score for lipodystrophy was associated with NAFLD and liver fibrosis. Our results suggest that buffering of excess energy by peripheral fat and muscle may protect against NAFLD and liver fibrosis in the general population. Body composition influenced liver fat: central fat and intramuscular fat were associated with increased liver fat, while lower extremity fat and peripheral muscle were associated with decreased liver fat. A lipodystrophy polygenic risk score associated with increased hepatic steatosis and fibrosis.

Purpose Impulse buying has been the focus of attention in the marketing. With the rise of online shopping, online impulse buying phenomenon becomes increasingly serious. Whereas, the impulse buying behavior in an online environment is rarely discussed in relevant literature. The purpose of this paper is to explore the impact of the type of product and time pressure on consumer online impulse buying intention; this is a relatively new issue of marketing academia in China. Design/methodology/approach In this paper, the experimental methodology was adopted to explore the impact of consumer online impulse buying tendencies, the departure from the type of product and the time pressure. Findings Results show that low-involvement feeling products stimulate consumer online impulse buying tendencies. Simultaneously, there is an interaction effect between time pressure and product type, which is, under the influence of time pressure, the enhancement of low-involvement feeling products on consumer online impulse buying tendency is more significant. Originality/value This study discusses the interaction between time pressure and product type on consumers’ online impulse buying tendency, which has not been studied before. While discussing the impact of product types on consumers’ impulse buying tendency on the internet, this paper considers the impact of time pressure on consumers’ impulsive buying tendency, and applies the term of time pressure, a psychological research term, to the field of marketing research, so as to make the cross-links between disciplines closer.

Diverticular disease is common and has a high morbidity. Treatments are limited owing to the poor understanding of its pathophysiology. Here, to elucidate its etiology, we performed a genome-wide association study of diverticular disease (27,444 cases; 382,284 controls) from the UK Biobank and tested for replication in the Michigan Genomics Initiative (2,572 cases; 28,649 controls). We identified 42 loci associated with diverticular disease; 39 of these loci are novel. Using data-driven expression-prioritized integration for complex traits (DEPICT), we show that genes in these associated regions are significantly enriched for expression in mesenchymal stem cells and multiple connective tissue cell types and are co-expressed with genes that have a role in vascular and mesenchymal biology. Genes in these associated loci have roles in immunity, extracellular matrix biology, cell adhesion, membrane transport and intestinal motility. Phenome-wide association analysis of the 42 variants shows a common etiology of diverticular disease with obesity and hernia. These analyses shed light on the genomic landscape of diverticular disease. Genome-wide analyses identify 42 risk loci for diverticular disease, 39 of which are new. Genes in associated regions are enriched for expression in connective tissue cell types and are coexpressed with genes involved in vascular and mesenchymal biology.