Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related.

Sex-related incidence and survival differences in pediatric high-grade glioma subtypes: A population-based cohort study.

Not much is known on sex differences in incidence, survival, and treatment characteristics for midline and hemispheric pHGGs. This population-based study confirms previously reported study results that found worse survival outcomes for malignant diffuse gliomas in girls in the age group 0-9 years. Additionally, in our study we pinpoint this difference to girls with midline pHGGs aged 0-4 years.

Pediatric joint hypermobility: a diagnostic framework and narrative review.

Background: Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are debilitating conditions. Diagnosis is currently clinical in the absence of biomarkers, and criteria developed for adults are difficult to use in children and biologically immature adolescents. Generalized joint hypermobility (GJH) is a prerequisite for hEDS and generalized HSD.

Recurring Fatigue After Biologic Administration: Patient-Reported Data from the Dutch Biologic Monitor.

Background: Fatigue is a common problem in immune-mediated inflammatory disease (IMID) patients, significantly impacting their quality of life.

Objectives: In this study, we describe the pattern and characteristics of fatigue as a patient-reported adverse drug reaction (ADR) of biologics, and compared patient and treatment characteristics with patients reporting other ADRs or no ADRs.

Methods: In this cohort event monitoring study, the description and characteristics of fatigue reported as a possible ADR in the Dutch Biologic Monitor were assessed and analysed for commonly recurring themes or patterns.

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.

Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts.

Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints.

Registered prodromal symptoms of out-of-hospital cardiac arrest among patients calling the medical helpline services.

Background Early identification of warning symptoms among out-of-hospital cardiac arrest (OHCA) patients remains challenging. Thus, we examined the registered prodromal symptoms of patients who called medical helpline services within 30-days before OHCA. Methods Patients unwitnessed by emergency medical services (EMS) aged ≥18 years during their OHCA were identified from the Danish Cardiac Arrest Registry (2014-2018) and linked to phone records from the 24-h emergency helpline (1-1-2) and out-of-hours medical helpline (1813-Medical Helpline) in Copenhagen before the arrest.

HOXA1, a breast cancer oncogene.

More than 25 years ago, the first literature records mentioned HOXA1 expression in human breast cancer. A few years later, HOXA1 was confirmed as a proper oncogene in mammary tissue. In the following two decades, molecular data about the mode of action of the HOXA1 protein, the factors contributing to activate and maintain HOXA1 gene expression and the identity of its target genes have accumulated and provide a wider view on the association of this transcription factor to breast oncogenesis.

Brain Activation in Response to Low-Calorie Food Pictures: An Explorative Analysis of a Randomized Trial With Dapagliflozin and Exenatide.

Background And Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce less weight loss than expected. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, contributing to increased appetite and food intake. This hyperphagia may be specific to high-calorie foods.

Survival rates of children and young adolescents with CNS tumors improved in the Netherlands since 1990: A population-based study.

Introduction: Survival of children with central nervous system (CNS) tumors varies largely between countries. For the Netherlands, detailed population-based estimation of incidence, survival, and mortality of pediatric CNS tumors are lacking but are needed to evaluate progress.

Methods: All CNS tumors diagnosed in patients <18 years during 1990-2017 were selected from the Netherlands Cancer Registry.

Routine reporting of grey-white matter differentiation in early brain computed tomography in comatose patients after cardiac arrest: A substudy of the COACT trial.

Aim: A multimodal approach is advised for neurological prognostication in comatose patients after out-of-hospital cardiac arrest (OHCA). Grey-white matter differentiation (grey-white ratio, GWR) obtained from a brain CT scan performed < 24 hours after return of circulation can be part of this approach. The aims of this study were to investigate the frequency and method of reporting the GWR in brain CT scan reports and their association with outcome.

Mitochondrial Genome Study Identifies Association Between Primary Open-Angle Glaucoma and Variants in Genes and Haplogroups.

Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by death of retinal ganglion cells and atrophy of the optic nerve head. The susceptibility of the optic nerve to damage has been shown to be mediated by mitochondrial dysfunction. In this study, we aimed to determine a possible association between mitochondrial SNPs or haplogroups and POAG.

Epidemiology and risk factors of sudden cardiac arrest.

Purpose Of Review: Sudden cardiac arrest (SCA) remains a major health burden around the globe, most often occurring in the community (out-of-hospital cardiac arrest [OHCA]). SCA accounts for 15-20% of all natural deaths in adults in the USA and Western Europe, and up to 50% of all cardiovascular deaths. To reduce this burden, more knowledge is needed about its key facets such as its incidence in various geographies, its risk factors, and the populations that may be at risk.

Genome-wide CNV investigation suggests a role for cadherin, Wnt, and p53 pathways in primary open-angle glaucoma.

Background: To investigate whether copy number variations (CNVs) are implicated in molecular mechanisms underlying primary open-angle glaucoma (POAG), we used genotype data of POAG individuals and healthy controls from two case-control studies, AGS (n = 278) and GLGS-UGLI (n = 1292). PennCNV, QuantiSNP, and cnvPartition programs were used to detect CNV. Stringent quality controls at both sample and marker levels were applied.

Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles.

The aetiology of Kawasaki disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host 'omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple 'omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering, and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infections at the transcriptomic and proteomic levels through comparison of 'omic profiles from children with KD to those with bacterial and viral infections.

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impact of single phase CT angiography collateral status on functional outcome over time: results from the MR CLEAN Registry.

Background: Collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent.

Methods: We included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT.