Inhibition of miR-92a normalizes vascular gene expression and prevents diastolic dysfunction in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) remains a major public health burden with increasing prevalence but only few effective therapies. Endothelial dysfunction and inflammation are identified as pathophysiological drivers of HFpEF disease progression. MicroRNAs are increasingly recognized as key regulators of these pathological processes, while antimiR-based therapies have been emerged as promising therapeutics in mice and humans.

Engineering of Impact Ionization Characteristics in GaAs/GaAsBi Multiple Quantum Well Avalanche Photodiodes.

The presence of large bismuth (Bi) atoms has been shown to increase the spin-orbit splitting energy in bulk GaAsBi, reducing the hole ionization coefficient (β) and thereby reducing the excess noise seen in avalanche photodiodes. In this study, we show that even very thin layers of GaAsBi introduced as quantum wells (QWs) in a GaAs matrix exhibit a significant reduction of β while leaving the electron ionization coefficient, α, largely unchanged. The optical and avalanche multiplication properties of a series of GaAsBi/GaAs multiple quantum well (MQW) p-i-n structures with nominally 5 nm thick, 4.

Cell-intrinsic effects of clonal hematopoiesis in heart failure.

Clonal hematopoiesis of indeterminate potential (CHIP) is caused by somatic mutations in hematopoietic stem cells and associates with worse prognosis in patients with heart failure. Patients harboring CHIP mutations show enhanced inflammation. However, whether these signatures are derived from the relatively low number of cells harboring mutations or are indicators of systemic pro-inflammatory activation that is associated with CHIP is unclear.

Surface-normal illuminated pseudo-planar Ge-on-Si avalanche photodiodes with high gain and low noise.

Germanium-on-Silicon (Ge-on-Si) avalanche photodiodes (APDs) are of considerable interest as low intensity light detectors for emerging applications. The Ge absorption layer detects light at wavelengths up to ≈ 1600 nm with the Si acting as an avalanche medium, providing high gain with low excess avalanche noise. Such APDs are typically used in waveguide configurations as growing a sufficiently thick Ge absorbing layer is challenging.

Diabetes, hypertension, and other cardiovascular disease risk factors among adults in an urban underprivileged community in Bangalore city, India.

Aim: Diabetes and hypertension are major risk factors of cardiovascular disease, which is known to be the leading cause of global mortality in the world today. Studies have shown that the prevalence of these risk factors is on the rise, with the burden of diabetes alone increasing by 80% in the last two decades. Complications of diabetes and hypertension result in huge public health challenges for the country and catastrophic medical expenditures for families among the urban poor.

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

Background: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value.

Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis.

Background: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown.

Methods: In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes.

DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role in driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes in patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential partners in interactions with CHIP-mutated monocytes.

Very low excess noise AlGaAsSb avalanche photodiode.

AlGaAsSb grown lattice-matched to InP has attracted significant research interest as a material for low noise, high sensitivity avalanche photodiodes (APDs) due to its very dissimilar electron and hole ionization coefficients, especially at low electric fields. All work reported to date has been on Al concentrations of x = 0.85 or higher.

Disrupted Binding of Cystathionine γ-Lyase to p53 Promotes Endothelial Senescence.

Background: Advanced age is unequivocally linked to the development of cardiovascular disease; however, the mechanisms resulting in reduced endothelial cell regeneration remain poorly understood. Here, we investigated novel mechanisms involved in endothelial cell senescence that impact endothelial cell transcription and vascular repair after injury.

Methods: Native endothelial cells were isolated from young (20±3.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

Aims: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients.

Aging impairs the neurovascular interface in the heart.

Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium is characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed the impact of aging on the cardiac neurovascular interface. We report that aging reduces nerve density in the ventricle and dysregulates vascular-derived neuroregulatory genes.

3Rs implementation in veterinary vaccine batch-release testing: Current state-of-the-art and future opportunities. A webinar and workshop report.

Regulatory authorities require veterinary batch-release testing to confirm vaccine potency and safety, but these tests have traditionally relied on large numbers of laboratory animals. Advances in vaccine research and development offer increasing opportunities to replace in vivo testing, and some stakeholders have made significant progress in incorporating 3Rs elements in quality control strategies. A three-part event series entitled "3Rs Implementation in Veterinary Vaccine Batch-Release Testing: Current state-of-the-art and future opportunities" was jointly organized by the Animal-Free Safety Assessment Collaboration, HealthforAnimals, and the International Alliance of Biological Standardization.

Circular RNA circPLOD2 regulates pericyte function by targeting the transcription factor KLF4.

Circular RNAs are generated by backsplicing and control cellular signaling and phenotypes. Pericytes stabilize capillary structures and play important roles in the formation and maintenance of blood vessels. Here, we characterize hypoxia-regulated circular RNAs (circRNAs) in human pericytes and show that the circular RNA of procollagen-lysine,2-oxoglutarate 5-dioxygenase-2 (circPLOD2) is induced by hypoxia and regulates pericyte functions.

Anomalous excess noise behavior in thick AlGaAsSb avalanche photodiodes.

AlGaAsSb has recently attracted significant research interest as a material for 1550 nm low-noise short-wave infrared (SWIR) avalanche photodiodes (APDs) due to the very wide ratio between its electron and hole ionization coefficients. This work reports new experimental excess noise data for thick AlGaAsSb PIN and NIP structures, measuring low noise at significantly higher multiplication values than previously reported (F = 2.2 at M = 38).

Cardiomyocyte hyperplasia and immaturity but not hypertrophy are characteristic features of patients with RASopathies.

Aims: RASopathies are caused by mutations in genes that alter the MAP kinase pathway and are marked by several malformations with cardiovascular disorders as the predominant cause of mortality. Mechanistic insights in the underlying pathogenesis in affected cardiac tissue are rare. The aim of the study was to assess the impact of RASopathy causing mutations on the human heart.

Acute injury to the mouse carotid artery provokes a distinct healing response.

Treatment of vascular stenosis with angioplasty results in acute vascular damage, which may lead to restenosis. Owing to the highly complex cellularity of blood vessels, the healing response following this damage is incompletely understood. To gain further insight into this process, scRNA-seq of mouse carotid tissue after wire injury was performed.

Retrospective Cohort Study of COVID-19 in Patients of the Brazilian Public Health System with SARS-CoV-2 Omicron Variant Infection.

Several vaccines against COVID-19 are now available, based on different techniques and made by different laboratories spread around the world. With the roll out of the vaccination process in an advanced stage in many countries, the reduced risk of hospitalization due to the Omicron variant relative to the Delta variant infection, despite the higher transmission risk of Omicron, may lead to a misinterpretation of the results, as infection by Omicron is associated with a significant reduction in severe outcomes and shorter hospitalization time than the Delta variant. We compared the in-hospital mortality due to the Omicron (Jan-Mar 2022) with Gamma (Jan 2021) and Delta (Oct-Dec 2021) variants of patients in the Brazilian public health system.

Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages.

MODELLING GLOBAL CARBON AND RADIOCARBON CYCLES.

Carbon cycle receives growing attention, in particular in connection with the climate change. Radiocarbon (14C) serves not only as the well-known basis of a dating technique but also as a tracer of the global carbon cycle, enabling one to assess the sizes of diverse compartments, fluxes between them and the related characteristic times. Mathematical modelling of the carbon cycle helps integrate the measurements, estimate the roles of underpinning processes and provide predictions, for instance on future CO2 concentrations in the atmosphere for various emission scenarios.

Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs.

Alterations of RNA editing that affect the secondary structure of RNAs can cause human diseases. We therefore studied RNA editing in failing human hearts. Transcriptome sequencing showed that adenosine-to-inosine (A-to-I) RNA editing was responsible for 80% of the editing events in the myocardium.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

Background: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP.

Methods: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP.

Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet.

Background: Recently, studies have suggested a role for the gut microbiota in epilepsy. Gut microbial changes during ketogenic diet (KD) treatment of drug-resistant epilepsy have been described. Inflammation is associated with certain types of epilepsy and specific inflammation markers decrease during KD.

The splicing-regulatory lncRNA NTRAS sustains vascular integrity.

Vascular integrity is essential for organ homeostasis to prevent edema formation and infiltration of inflammatory cells. Long non-coding RNAs (lncRNAs) are important regulators of gene expression and often expressed in a cell type-specific manner. By screening for endothelial-enriched lncRNAs, we identified the undescribed lncRNA NTRAS to control endothelial cell functions.

Impact of MRI/US fusion-guided prostate biopsy on biopsy-naïve patients: A single urologist's experience.

Objectives: To report our experience with imaging-guided targeted prostate biopsy (IGTpBx) for patients undergoing initial prostate biopsy in a clinical setting.

Materials And Methods: From July 2014 to February 2020, 305 men who had IGTpBx performed as their first prostate biopsy were enrolled. Two dedicated magnetic resonance imaging (MRI) radiologists segmented at least 1 region of interest (ROI) for each of these men using screening 1.