The association between salivary oxytocin, age, and puberty in children with and without OCD.

The oxytocin system has been thought to contribute to obsessive-compulsive disorder (OCD). Few studies, only involving adults, have investigated this hypothesis and have found inconsistent results regarding oxytocin system activity and OCD. We investigated whether salivary oxytocin concentrations differed between children and adolescents with and without OCD and qualified our comparative analysis by investigating the possible covariates age, pubertal stage, and sex.

A novel GFAP frameshift variant identified in a family with optico-retinal dysplasia and vision impairment.

Gain-of-function variants in GFAP leads to protein aggregation and is the cause of the severe neurodegenerative disorder Alexander Disease (AxD), while loss of GFAP function has been considered benign. Here, we investigated a six-generation family, where multiple individuals presented with gliosis of the optic nerve head and visual impairment. Whole genome sequencing (WGS) revealed a frameshift variant in GFAP (c.

Early experience with targeted and combination biopsies in prostate cancer work-up in Denmark from 2012 to 2016.

Purpose: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology.

Methods: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year.

Danish Prostate Registry (DanProst) - an Updated Version of the Danish Prostate Cancer Registry, Methodology, and Early Results.

In 2016, we introduced the Danish Prostate Cancer Registry (DaPCaR) which was built on the National Pathology Register from 1995 to 2011. DaPCaR was laborious to use as most data had to be manually imputed with no regular updates. In here we present a new comprehensive centralized prostate registry called the Danish Prostate Registry (DanProst), which includes all men having undergone any histological evaluation of prostate tissue merged with laboratory-, treatment-, prescription data as well as vital status.

An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate.

Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids.

Rare Catechol--methyltransferase Missense Variants Are Structurally Unstable Proteasome Targets.

Catechol--methyltransferase (COMT) is a key enzyme in the metabolism of catecholamines. Substrates of the enzyme include neurotransmitters such as dopamine and epinephrine, and therefore, COMT plays a central role in neurobiology. Since COMT also metabolizes catecholamine drugs such as L-DOPA, variation in COMT activity could affect pharmacokinetics and drug availability.

Alkalinity and diatom assemblages in lowland streams: How to separate alkalinity from inorganic phosphorus in ecological assessments?

Benthic algae are widely used as ecological indicators of the ecological status of streams because they are widely distributed, they show high species diversity and they respond rapidly to human pressures in particular eutrophication and organic pollution. Recent findings have highlighted that in addition to human pressures, alkalinity may also play a role for community composition as bicarbonate becomes an increasingly important carbon source for photosynthesis when alkalinity increases. With this study, we aimed to elucidate how alkalinity influences the distribution of diatoms in Danish lowland streams, and to explore ifdiatom assemblage patterns can be affected by alkalinity in a way that interferes with the ecological assessment using diatom-based indices.

Co-evolution of drug resistance and broadened substrate recognition in HIV protease variants isolated from an Escherichia coli genetic selection system.

A genetic selection system for activity of HIV protease is described that is based on a synthetic substrate constructed as a modified AraC regulatory protein that when cleaved stimulate l-arabinose metabolism in an Escherichia coli araC strain. Growth stimulation on selective plates was shown to depend on active HIV protease and the scissile bond in the substrate. In addition, the growth of cells correlated well with the established cleavage efficiency of the sites in the viral polyprotein, Gag, when these sites were individually introduced into the synthetic substrate of the selection system.

Towards a general application programming interface (API) for injection molding machines.

Injection molding is a complicated process, and the final part quality depends on many machine and process parameters settings. To increase controllability of the injection molding process, acquisition of the process data is necessary. This paper describes the architecture and development of a prototype of an open application programming interface (API) for injection molding machines (IMMs), which has the potential to be used with different IMMs to log and set the necessary process parameter values.

Associations of low-dose aspirin or other NSAID use with prostate cancer risk in the Danish Diet, Cancer and Health Study.

Purpose: Epidemiologic studies suggest that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. We examined these associations overall and according to clinical and lifestyle parameters.

Methods: We identified male participants in the Danish Diet, Cancer and Health Study (n = 26,339), holding information on anthropometric measures and lifestyle factors.

Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms.

Infants born to diabetic or obese mothers are at greater risk of heart disease at birth and throughout life, but prevention is hindered because underlying mechanisms remain poorly understood. Using a rat model, we showed that prenatal exposure to maternal diabetes and a high-fat diet caused diastolic and systolic dysfunction, myocardial lipid accumulation, decreased respiratory capacity, and oxidative stress in newborn offspring hearts. This study aimed to determine whether mitochondrial dynamism played a role.

Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer.

Background: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity.

Esc2 promotes telomere stability in response to DNA replication stress.

Telomeric regions of the genome are inherently difficult-to-replicate due to their propensity to generate DNA secondary structures and form nucleoprotein complexes that can impede DNA replication fork progression. Precisely how cells respond to DNA replication stalling within a telomere remains poorly characterized, largely due to the methodological difficulties in analysing defined stalling events in molecular detail. Here, we utilized a site-specific DNA replication barrier mediated by the 'Tus/Ter' system to define the consequences of DNA replication perturbation within a single telomeric locus.

The future of European water management: Demonstration of a new WFD compliant framework to support sustainable management under multiple stress.

The Water Framework Directive (WFD), which is the most comprehensive instrument of EU water policy, is more relevant than ever. Sixty percent of Europe's surface water bodies still fail to achieve good ecological status and a multitude of new stressors continue to emerge. A sustained and wholehearted water management effort is therefore of highest priority.

Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population.

Aims/hypothesis: In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes using a recessive genetic model, thereby increasing the power to detect variants with recessive effects.

Methods: We investigated three cohorts of Greenlanders (B99, n = 1401; IHIT, n = 3115; and BBH, n = 547), which were genotyped using Illumina MetaboChip.

Safety and feasibility of home-based chemotherapy.

Introduction: The purpose of this study was to evaluate the safety and feasibility of home-based chemotherapy and to compare chemotherapy given at home with chemotherapy given as an outpatient treatment in relation to toxicity, quality of life and patient's preference.

Methods: Patients who had undergone radical surgery for colon cancer and who were eligible to receive adjuvant treatment with capecitabine and oxaliplatin could be included. To ensure patient safety, the first infusion was given at an outpatient clinic.

YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.

Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state.

Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review.

Purpose: Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.

Heparan sulfate proteoglycans present PCSK9 to the LDL receptor.

Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation.

Gestational Protein Restriction in Wistar Rats; Effect of Taurine Supplementation on Properties of Newborn Skeletal Muscle.

Taurine ameliorates changes occurring in newborn skeletal muscle as a result of gestational protein restriction in C57BL/6 mice, but taurine supplementation effects may be exaggerated in C57BL/6 mice due to their inherent excessive taurinuria.We examined if maternal taurine supplementation could ameliorate changes in gene expression levels, properties of mitochondria, myogenesis, and nutrient transport and sensing, in male newborn skeletal muscle caused by a maternal low protein (LP) diet in Wistar rats.LP diet resulted in an 11% non-significant decrease in birth weight, which was not rescued by taurine supplementation (LP-Tau).

The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal.

Objective: Coding variants in the GBA gene have been identified as the numerically most important genetic risk factors for Parkinson's disease (PD). In addition, genome-wide association studies (GWAS) have identified associations with PD in the SYT11-GBA region on chromosome 1q22, but the relationship to GBA coding variants have remained unclear. The aim of this study was to sequence the complete GBA gene in a clinical cohort and to investigate whether coding variants within the GBA gene may be driving reported association signals.