Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Effect of hepatitis B virus on steatosis in hepatitis C virus co-infected subjects: A multi-centre study and systematic review.

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi-centre cohort of HBV-HCV subjects, and by performing a systematic review and meta-analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV-HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV-HCV subjects compared to HCV controls.

Review article: Sepsis in the emergency department - Part 2: Investigations and monitoring.

Sepsis is characterised by organ dysfunction resulting from infection, with no reliable single objective test and current diagnosis based on clinical features and results of investigations. In the ED, investigations may be conducted to diagnose infection as the cause of the presenting illness, identify the source, distinguish sepsis from uncomplicated infection (i.e.

Serum lactate cut-offs as risk stratification tool for in-hospital adverse outcomes in emergency department patients screened for suspected sepsis.

Objectives: We investigated specific lactate thresholds for adverse outcomes in patients presenting to emergency departments (EDs) with suspected sepsis identified based on the performance of a sepsis screening algorithm.

Design And Setting: A standardised sepsis bundle was implemented across public hospitals in New South Wales, Australia, as a quality improvement initiative. A register of all adult ED presentations (≥18 years) meeting predefined criteria for sepsis was created, using a combination of data linkage and direct reporting from 97 participating sites.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI.

VMG II transport medium stabilises oral microbiome samples for Next-Generation Sequencing.

Next-Generation Sequencing is providing insights into the critical role of the oral microbiome in dental diseases. Application of this method can require the collection of dental plaque from large cohorts in field-type conditions, which necessitates a transport medium to preserve the microbiome composition. We evaluated the use of two transport media, VMG II and RNAprotect® Bacteria Reagent (Qiagen), for room temperature storage of dental plaque.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study.

Background & Aims: The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings.

Review article: Sepsis in the emergency department - Part 1: Definitions and outcomes.

Sepsis has recently been redefined as acute organ dysfunction due to infection. The ED plays a critical role in identifying patients with sepsis. This is challenging due to the heterogeneity of the syndrome, and the lack of an objective standard diagnostic test.

NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection.

Thymocytes must pass both positive and negative selections to become mature T cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune diseases, while positive selection ensures the survival and maturation of thymocytes whose TCRs display intermediate affinity to self pMHCs for effective immunity, but whether transcriptional regulation helps conserve positively selected thymocytes from being purged by negative selection remains unclear. Here we show that the specific deletion of nuclear receptor co-repressor 1 (NCoR1) in T cells causes excessive negative selection to reduce mature thymocyte numbers.

Role of nutrition, gene polymorphism, and gut microbiota in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. The nutrients play important roles in the development and progression of NAFLD. High-calorie diet, especially the diet rich in saturated fatty acids and cholesterol, as well as sugary drinks with high fructose content, induces hepatic steatosis and triggers progression of steatohepatitis, fibrosis, and even hepatocellular carcinoma.

Motivators and barriers of tamoxifen use as risk-reducing medication amongst women at increased breast cancer risk: a systematic literature review.

Background: Selective estrogen receptor modulators, such as tamoxifen, reduce breast cancer risk by up to 50% in women at increased risk for breast cancer. Despite tamoxifen's well-established efficacy, many studies show that most women are not taking up tamoxifen. This systematic literature review aimed to identify the motivators and barriers to tamoxifen use 's amongst high-risk women.

Metabolomics of Diabetic Retinopathy.

Purpose Of Review: Metabolomics is the study of dysregulated metabolites in biological materials. We reviewed the use of the technique to elucidate the genetic and environmental factors that contribute to the development of diabetic retinopathy.

Recent Findings: With regard to metabolomic studies of diabetic retinopathy, the field remains in its infancy with few studies published to date and little replication of results.

Fundamental niche prediction of the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii in Europe.

Fundamental niche prediction of Cryptococcus neoformans and Cryptococcus gattii in Europe is an important tool to understand where these pathogenic yeasts have a high probability to survive in the environment and therefore to identify the areas with high risk of infection. In this study, occurrence data for C. neoformans and C.

Germline whole exome sequencing and large-scale replication identifies as a likely high grade serous ovarian cancer susceptibility gene.

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10).

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families.

Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families.

GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation.

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells.

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

Purpose: To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD.

Design: Systematic review and meta-analysis.

Methods: Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015.

Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered transcript splicing.

Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4-8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo.

tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer.

Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNA and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer.

Bacillus Calmette-Guerin alleviates airway inflammation and remodeling by preventing TGF-β induced epithelial-mesenchymal transition.

Bacillus Calmette-Guerin (BCG) is a potent agent for the prevention of tuberculosis. Current studies have regarded BCG as an immunomodulator. However, there is little information on whether it can be used to inhibit airway inflammation and airway remodeling caused by asthma.

DNA methylation landscape of ocular tissue relative to matched peripheral blood.

Epigenetic variation is implicated in a range of non-communicable diseases, including those of the eye. However, investigating the role of epigenetic variation in central tissues, such as eye or brain, remains problematic and peripheral tissues are often used as surrogates. In this study, matched human blood and eye tissue (n = 8) were obtained post-mortem and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform.

IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.

Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3.

Recombinant CC16 protein inhibits the production of pro-inflammatory cytokines via NF-κB and p38 MAPK pathways in LPS-activated RAW264.7 macrophages.

Accumulating evidence indicates that Clara cell protein-16 (CC16) has anti-inflammatory functions, although the involved molecular pathways have not been completely elucidated. Here, we evaluated the effect of recombinant rat CC16 (rCC16) on the expression of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8 in lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW264.7 cells) and explored the underlying molecular mechanisms.

Diagnostic Accuracy of Noninvasive Fibrosis Scores in a Population of Individuals With a Low Prevalence of Fibrosis.

Background & Aims: Noninvasive scoring systems for fibrosis are increasingly used in the clinic and in research because of their ease of use, accessibility, and low cost. However, test performance characteristics were established in groups of patients with a high prevalence of advanced fibrosis; little is known about diagnostic accuracy in low-risk populations.

Methods: In a cross-sectional study, 922 members of a general ambulatory population in Hong Kong (randomly selected; 18-70 years old) underwent clinical assessment from May 2008 through December 2010.