Laramcculloch7390

The ability to generate multi-omics data coupled with deeply characterizing the clinical phenotype of individual patients promises to improve understanding of complex cardiovascular pathobiology. There remains an important disconnection between the magnitude and granularity of these data and our ability to improve phenotype-genotype correlations for complex cardiovascular diseases. This shortcoming may be due to limitations associated with traditional reductionist analytical methods, which tend to emphasize a single molecular event in the pathogenesis of diseases more aptly characterized by crosstalk between overlapping molecular pathways. Network medicine is a rapidly growing discipline that considers diseases as the consequences of perturbed interactions between multiple interconnected biological components. This powerful integrative approach has enabled a number of important discoveries in complex disease mechanisms. In this review, we introduce the basic concepts of network medicine and highlight specific examples by which this approach has accelerated cardiovascular research. We also review how network medicine is well-positioned to promote rational drug design for patients with cardiovascular diseases, with particular emphasis on advancing precision medicine.Bicarbonate (NaHCO3) present in soils is usually considered to be a mixed stress for plants, with salts and high pH. NaHCO3-specific signaling in plants has rarely been reported. In this study, transcriptome analyses were conducted in order to identify NaHCO3-specific signaling in Arabidopsis. Weighted correlation network analysis was performed to isolate NaHCO3-specific modules in comparison with acetate treatment. The genes in the NaHCO3-root-specific module, which exhibited opposite expression to that in sodium acetate treatments, were further examined with their corresponding knock-out mutants. The gene Exclusively Bicarbonate Sensitive 1 (EBS1) encoding an S-ribonuclease binding protein, was identified to be specifically involved in plant tolerance to NaHCO3, but not to the other two alkaline salts, acetate and phosphate. We also identified the genes that are commonly regulated by bicarbonate, acetate and phosphate. Multiple brassinosteroid-associated gene ontology terms were enriched in these genes. Genetic assays showed that brassinosteroid signaling positively regulated plant tolerance to NaHCO3 stress, but negatively regulated tolerance to acetate and phosphate. Overall, our data identified bicarbonate-specific genes, and confirmed that alkaline stress is mainly dependent on the specificities of the weak acid ions, rather than high pH.

Patients with Crohn disease (CD) often develop strictures that require surgery. Endoscopic balloon dilation (EBD) is an alternative treatment that can be safe and effective. The objective of this study was to assess factors associated with the need for repeat EBD and surgery after initial EBD for stricturing CD.

Patients with stricturing CD who underwent EBD from 2007 to 2017 were identified. Demographic and clinical information was obtained from the electronic medical record. A Cox proportional hazards regression model and Kaplan-Meier curves were generated for variables associated with repeat EBD and surgical resection.

Ninety-nine patients underwent a total of 240 EBD proedures; 35% had a history of perianal disease, and 63% were on a biologic at the time of initial EBD. Fifty-one percent of patients had obstructive symptoms at the time of initial EBD, and 75% of the EBDs were successful. selleck kinase inhibitor Complications occurred in 8 EBDs (3.3%). Repeat intervention after EBD was more likely in patients on biologics at baseline EBD (76% vs 54%; P = 0.029). Thirty-three percent of patients had surgical resection at a median of 5 months (interquartile ratio = 2.0-13.0 months) after initial EBD. The presence of obstructive symptoms at the time of EBD was associated with surgical resection (hazard ratio = 3.18; 95% confidence interval, 1.28-7.86). Conversely, a history of perianal disease was negatively associated with surgical resection (hazard ratio = 0.27; 95% confidence interval, 0.10-0.68).

Patients on biologic treatment at the time of EBD are more likely to need an intervention in the future. Patients with obstructive symptoms at the time of initial EBD and those without a history of perianal involvement are more likely to undergo surgical intervention.

Patients on biologic treatment at the time of EBD are more likely to need an intervention in the future. Patients with obstructive symptoms at the time of initial EBD and those without a history of perianal involvement are more likely to undergo surgical intervention.

Smoking among young adults is often associated with social contexts and alcohol use. Although many countries, including New Zealand, have prohibited smoking inside licensed premises, outdoor areas have enabled smoking and alcohol co-use to persist. We examined whether and how outdoor bar areas facilitate and normalize young adult smoking and explored potential policy implications.

We conducted in-depth interviews with 22 young adults who had recently smoked in a New Zealand bar or nightclub and investigated how physical design attributes (atmospherics) influenced experiences of smoking in outside bar settings. We used qualitative description to identify recurring accounts of the outdoor bar environment and thematic analysis to explore how participants experienced the bar in relation to smoking.

Participants valued outdoor smoking areas that were comfortable and relaxing, and saw attributes such as seating, tables, heating, protection from inclement weather, and minimal crowding, as important. We identifny stimuli that cue and reinforce smoking and integrate smoking into social experiences. Expanding smokefree bar settings to include outdoor areas would reduce exposure to these stimuli, decrease opportunities for casual smoking, help maintain young people's smokefree status, and support longer-term goals of sustained reductions in smoking prevalence.Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. As triglyceride-rich lipoprotein particles (TRLPs) have recently emerged as a casual factor for atherogenesis, the aim of this study was to evaluate the relationship between subclinical hypo- and hyperthyroidism and TRLP subfractions. We selected 5066 participants from the ELSA-Brasil cohort with available data of thyroid function and lipid profile measured by nuclear magnetic resonance (NMR) spectroscopy. Individuals were divided into 3 groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). Triglyceride-rich lipoprotein particle subfractions were analyzed through NMR spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted univariate and multivariate linear regression models adjusted for demographic characteristics, body mass index, diabetes, smoking status, and alcohol use. Of 3304 individuals, 54% were women, with a mean age of 50.6 ± 8.7 years, 51% white, and 53% with at least a college education. Of these individuals, 92% were euthyroid, whereas 6.8% had subclinical hypothyroidism and 1.2% had subclinical hyperthyroidism. The univariate linear regression showed that very small TRLPs (P = 0.026) and very large TRLPs (P = 0.008) were statistically increased in subclinical hypothyroidism when compared with euthyroidism. In subclinical hyperthyroidism, there was a reduction in total TRLPs (P = 0.003), seemingly driven by reduced very small TRLPs (P = 0.067). The findings were confirmed when adjusted for demographic characteristics, as well as comorbidities. This study suggests that subclinical hypothyroidism is associated with very small and very large TRLPs, which are related to an unfavorable atherogenic profile. Subclinical hyperthyroidism is associated to lower very small TRLPs.

Cancer somatic driver mutations associated with genes within a pathway often show a mutually exclusive pattern across a cohort of patients. This mutually exclusive mutational signal has been frequently used to distinguish driver from passenger mutations and to investigate relationships among driver mutations. Current methods for de novo discovery of mutually exclusive mutational patterns are limited because the heterogeneity in background mutation rate can confound mutational patterns, and the presence of highly mutated genes can lead to spurious patterns. In addition, most methods only focus on a limited number of pre-selected genes and are unable to perform genome-wide analysis due to computational inefficiency.

We introduce a statistical framework, MEScan, for accurate and efficient mutual exclusivity analysis at the genomic scale. Our framework contains a fast and powerful statistical test for mutual exclusivity with adjustment of the background mutation rate and impact of highly mutated genes, and a multi-step procedure for genome-wide screening with the control of false discovery rate. We demonstrate that MEScan more accurately identifies mutually exclusive gene sets than existing methods and is at least two orders of magnitude faster than most methods. By applying MEScan to data from four different cancer types and pan-cancer, we have identified several biologically meaningful mutually exclusive gene sets.

MEScan is available as an R package at https//github.com/MarkeyBBSRF/MEScan.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.The focus of this review is maternal nutrition during the periconceptual period and offspring developmental outcomes in beef cattle, with an emphasis on the first 50 d of gestation, which represents the embryonic period. Animal agriculture in general, and specifically the beef cattle industry, currently faces immense challenges. The world needs to significantly increase its output of animal food products by 2050 and beyond to meet the food security and agricultural sustainability needs of the rapidly growing human population. Consequently, efficient and sustainable approaches to livestock production are essential. Maternal nutritional status is a major factor that leads to developmental programming of offspring outcomes. Developmental programming refers to the influence of pre-and postnatal factors, such as inappropriate maternal nutrition, that affect growth and development and result in long-term consequences for health and productivity of the offspring. In this review, we discuss recent studies in which we and others have addressed the questions, "Is development programmed periconceptually?" and, if so, "Does it matter practically to the offspring in production settings?" The reviewed studies have demonstrated that the periconceptual period is important not only for pregnancy establishment but also may be a critical period during which fetal, placental, and potentially postnatal development and function are programmed. The evidence for fetal and placental programming during the periconceptual period is strong and implies that research efforts to mitigate the negative and foster the positive benefits of developmental programming need to include robust investigative efforts during the periconceptual period to better understand the implications for life-long health and productivity.