Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.

GW170814: A Three-Detector Observation of Gravitational Waves from a Binary Black Hole Coalescence.

On August 14, 2017 at 10∶30:43 UTC, the Advanced Virgo detector and the two Advanced LIGO detectors coherently observed a transient gravitational-wave signal produced by the coalescence of two stellar mass black holes, with a false-alarm rate of ≲1 in 27 000 years. The signal was observed with a three-detector network matched-filter signal-to-noise ratio of 18. The inferred masses of the initial black holes are 30.

Plasmodium falciparum Infection Early in Pregnancy has Profound Consequences for Fetal Growth.

Malaria during pregnancy constitutes a large health problem in areas of endemicity. The World Health Organization recommends that interventions are initiated at the first antenatal visit, and these improve pregnancy outcomes. This study evaluated fetal growth by ultrasonography and birth outcomes in women who were infected prior to the first antenatal visit (gestational age, <120 days) and not later in pregnancy.

The sponge microbiome project.

Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching clade known for forming intimate partnerships with complex communities of microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised different extraction and amplification methodologies to target the microbial communities of a limited number of sponge species, severely limiting comparative analyses of sponge microbial diversity and structure. Here, we provide an extensive and standardised dataset that will facilitate sponge microbiome comparisons across large spatial, temporal, and environmental scales.

TRPC6 channels modulate the response of pancreatic stellate cells to hypoxia.

Pancreatic cancer is characterized by a massive fibrosis (desmoplasia), which is primarily caused by activated pancreatic stellate cells (PSCs). This leads to a hypoxic tumor microenvironment further reinforcing the activation of PSCs by stimulating their secretion of growth factors and chemokines. Since many of them elicit their effects via G-protein-coupled receptors (GPCRs), we tested whether TRPC6 channels, effector proteins of many G-protein-coupled receptor pathways, are required for the hypoxic activation of PSCs.

Drug-eluting stents versus bare-metal stents for acute coronary syndrome.

Background: Approximately 3.7 million people died from acute coronary syndrome worldwide in 2012. Acute coronary syndrome, also known as myocardial infarction or unstable angina pectoris, is caused by a sudden blockage of the blood supplied to the heart muscle.

The phylogeny of extant starfish (Asteroidea: Echinodermata) including Xyloplax, based on comparative transcriptomics.

Multi-locus phylogenetic studies of echinoderms based on Sanger and RNA-seq technologies and the fossil record have provided evidence for the Asterozoa-Echinozoa hypothesis. This hypothesis posits a sister relationship between asterozoan classes (Asteroidea and Ophiuroidea) and a similar relationship between echinozoan classes (Echinoidea and Holothuroidea). Despite this consensus around Asterozoa-Echinozoa, phylogenetic relationships within the class Asteroidea (sea stars or starfish) have been controversial for over a century.

The Association Between Maternal Chronic Inflammatory Bowel Disease and Long-term Health Outcomes in Children-A Nationwide Cohort Study.

Background: Very little is known about the long-term impact of maternal inflammatory bowel disease (IBD) on the offspring's future health. We aimed to examine whether children born to mothers with IBD had an increased risk of long-term morbidities.

Methods: In this nationwide register-based cohort study, including all children born alive in Denmark between 1989 and 2013, we investigated the association between maternal IBD and 15 selected disease categories of physical and mental conditions in the offspring.

S-25-hydroxyvitamin D and C3-epimers in pregnancy and infancy: An Odense Child Cohort study.

Background: Analysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated by the less active or in-active vitamin D metabolite C3-epi-25(OH)D (C3-epimer). We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other determinants and describe the longitudinal course of the C3-epimer fraction in paired mother-child samples.

Method: S-25(OH)D and s-C3-epimer were estimated by liquid chromatography mass spectrometry in 290 mother-infant pairs from the population-based Odense Child Cohort.

An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes.

This study investigates the challenge of comprehensively cataloging the complete human proteome from a single-cell type using mass spectrometry (MS)-based shotgun proteomics. We modify a classical two-dimensional high-resolution reversed-phase peptide fractionation scheme and optimize a protocol that provides sufficient peak capacity to saturate the sequencing speed of modern MS instruments. This strategy enables the deepest proteome of a human single-cell type to date, with the HeLa proteome sequenced to a depth of ∼584,000 unique peptide sequences and ∼14,200 protein isoforms (∼12,200 protein-coding genes).

Predicting the HMA-LMA Status in Marine Sponges by Machine Learning.

The dichotomy between high microbial abundance (HMA) and low microbial abundance (LMA) sponges has been observed in sponge-microbe symbiosis, although the extent of this pattern remains poorly unknown. We characterized the differences between the microbiomes of HMA ( = 19) and LMA ( = 17) sponges (575 specimens) present in the Sponge Microbiome Project. HMA sponges were associated with richer and more diverse microbiomes than LMA sponges, as indicated by the comparison of alpha diversity metrics.

Nutrition support in hospitalised adults at nutritional risk.

Background: The prevalence of disease-related malnutrition in Western European hospitals is estimated to be about 30%. There is no consensus whether poor nutritional status causes poorer clinical outcome or if it is merely associated with it. The intention with all forms of nutrition support is to increase uptake of essential nutrients and improve clinical outcome.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors).

Dyslipidemia and reference values for fasting plasma lipid concentrations in Danish/North-European White children and adolescents.

Background: Dyslipidemia is reported in 27 - 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity.

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction.

Directional Limits on Persistent Gravitational Waves from Advanced LIGO's First Observing Run.

We employ gravitational-wave radiometry to map the stochastic gravitational wave background expected from a variety of contributing mechanisms and test the assumption of isotropy using data from the Advanced Laser Interferometer Gravitational Wave Observatory's (aLIGO) first observing run. We also search for persistent gravitational waves from point sources with only minimal assumptions over the 20-1726 Hz frequency band. Finding no evidence of gravitational waves from either point sources or a stochastic background, we set limits at 90% confidence.

Upper Limits on the Stochastic Gravitational-Wave Background from Advanced LIGO's First Observing Run.

A wide variety of astrophysical and cosmological sources are expected to contribute to a stochastic gravitational-wave background. Following the observations of GW150914 and GW151226, the rate and mass of coalescing binary black holes appear to be greater than many previous expectations. As a result, the stochastic background from unresolved compact binary coalescences is expected to be particularly loud.

Ketone Body Infusion With 3-Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study.

Background: High levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and-most recently-treatment with sodium-glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans.

Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations.

Objective: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 () gene.

Methods: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives.

Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO and Advanced Virgo.

We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy.

The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients.

One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive.

Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms.

In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi.

Children in Greenland: disease patterns and contacts to the health care system.

Background: Previous studies of Greenlandic children's disease pattern and contacts to the health care system are sparse and have focused on the primary health care sector.

Objective: We aimed to identify the disease pattern and use of health care facilities of children aged 0-10 in two Greenlandic cohorts.

Methods And Design: In a retrospective, descriptive follow-up of the Ivaaq (The Greenland Child Cohort) and the CLEAR (climate changes, environmental contaminants and reproductive health) birth cohorts (total n=1,000), we reviewed medical records of children aged 6-10 in 2012 with residence in Nuuk or Ilulissat (n=332).