Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

Background And Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).

Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.

Analysis of Line and Tube Detection Performance of a Chest X-ray Deep Learning Model to Evaluate Hidden Stratification.

This retrospective case-control study evaluated the diagnostic performance of a commercially available chest radiography deep convolutional neural network (DCNN) in identifying the presence and position of central venous catheters, enteric tubes, and endotracheal tubes, in addition to a subgroup analysis of different types of lines/tubes. A held-out test dataset of 2568 studies was sourced from community radiology clinics and hospitals in Australia and the USA, and was then ground-truth labelled for the presence, position, and type of line or tube from the consensus of a thoracic specialist radiologist and an intensive care clinician. DCNN model performance for identifying and assessing the positioning of central venous catheters, enteric tubes, and endotracheal tubes over the entire dataset, as well as within each subgroup, was evaluated.

A Critical Role for ERO1α in Arterial Thrombosis and Ischemic Stroke.

Background: Platelet adhesion and aggregation play a crucial role in arterial thrombosis and ischemic stroke. Here, we identify platelet ERO1α (endoplasmic reticulum oxidoreductase 1α) as a novel regulator of Ca signaling and a potential pharmacological target for treating thrombotic diseases.

Methods: Intravital microscopy, animal disease models, and a wide range of cell biological studies were utilized to demonstrate the pathophysiological role of ERO1α in arteriolar and arterial thrombosis and to prove the importance of platelet ERO1α in platelet activation and aggregation.

Resolution doubling in light-sheet microscopy via oblique plane structured illumination.

Structured illumination microscopy (SIM) doubles the spatial resolution of a fluorescence microscope without requiring high laser powers or specialized fluorophores. However, the excitation of out-of-focus fluorescence can accelerate photobleaching and phototoxicity. In contrast, light-sheet fluorescence microscopy (LSFM) largely avoids exciting out-of-focus fluorescence, thereby enabling volumetric imaging with low photobleaching and intrinsic optical sectioning.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

Association of -Independent Alzheimer Disease Polygenic Risk Score With Brain Amyloid Deposition in Asymptomatic Older Adults.

Background And Objectives: Brain amyloid deposition, a major risk factor for Alzheimer disease (AD), is currently estimated by measuring CSF or plasma amyloid peptide levels or by PET imaging. Assessing genetic risks relating to amyloid deposition before any accumulation has occurred would allow for earlier intervention in persons at increased risk for developing AD. Previous work linking amyloid burden and genetic risk relied almost exclusively on , a major AD genetic risk factor.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth.

Methods: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings.

Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment: DUNE Collaboration.

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM).

Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation.

Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose.

Community-Based Prevalence Estimates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Gay, Bisexual, and Other Men Who Have Sex With Men in Montréal, Canada.

Background: Reported cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are increasing among Canadian men. Estimates of community-based CT/NG prevalence are lacking among gay, bisexual, and other men who have sex with men (GBM).

Methods: Respondent driven sampling was used to recruit GBM in Montréal, Canada between February 2017 and June 2018.

Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor () mutations account for >90% of cases, apolipoprotein B () mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 () gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays.

Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease.

Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis.

Metoprolol for the Prevention of Acute Exacerbations of COPD.

Background: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.

Methods: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen.

Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Validation of Soluble Biomarkers in RA.

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.

Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years.

An Intravascular Tantalum Oxide-based CT Contrast Agent: Preclinical Evaluation Emulating Overweight and Obese Patient Size.

Purpose To compare the CT imaging performance of a carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle CT contrast agent with that of a conventional iodinated contrast agent in a swine model meant to simulate overweight and obese patients. Materials and Methods Four swine were evaluated inside three different-sized adipose-equivalent encasements emulating abdominal girths of 102, 119, and 137 cm. Imaging was performed with a 64-detector row CT scanner at six scan delays after intravenous injection of 240 mg element (Ta or I) per kilogram of body weight of TaCZ or iopromide.

Axogenic mechanism enhances retinal ganglion cell excitability during early progression in glaucoma.

Diseases of the brain involve early axon dysfunction that often precedes outright degeneration. Pruning of dendrites and their synapses represents a potential driver of axonopathy by reducing activity. Optic nerve degeneration in glaucoma, the world's leading cause of irreversible blindness, involves early stress to retinal ganglion cell (RGC) axons from sensitivity to intraocular pressure (IOP).

New algorithms for identifying the flavour of [Formula: see text] mesons using pions and protons.

Two new algorithms for use in the analysis of [Formula: see text] collision are developed to identify the flavour of [Formula: see text] mesons at production using pions and protons from the hadronization process. The algorithms are optimized and calibrated on data, using [Formula: see text] decays from [Formula: see text] collision data collected by LHCb at centre-of-mass energies of 7 and 8 TeV . The tagging power of the new pion algorithm is 60% greater than the previously available one; the algorithm using protons to identify the flavour of a [Formula: see text] meson is the first of its kind.