Biallelic null variants in C19orf44 cause a unique late onset retinal dystrophy phenotype characterized by patchy perifoveal chorioretinal atrophy.

Purpose: To identify the genetic cause for disease in individuals affected with inherited retinal disease (IRD), to characterize their retinal phenotype and the properties of the underlying gene.

Methods: Participants underwent a comprehensive ophthalmological evaluation, including best-corrected visual acuity, visual field testing, fundus autofluorescence, optical coherence tomography and electroretinography. Genetic analyses included exome, genome and Sanger sequencing.

Cardiac ischemia/reperfusion increases cardiomyocyte KLF5 in pigs and mice that aggravates tissue injury and remodeling.

Aims: Activation of the transcriptional factor Krüppel-like factor 5 (KLF5) is detrimental to chronic heart failure. We explored the involvement of KLF5 in myocardial ischemia/reperfusion injury.

Methods And Results: Yorkshire pigs underwent 75΄ of ischemia, followed by 3h or 24h of reperfusion.

Increased internal tibiofemoral rotation is associated with anterolateral ligament injury and high-grade pivot-shift in ACL-injured patients.

Purpose: To evaluate whether tibiofemoral rotation is associated with a concurrent anterolateral ligament (ALL) injury and pivot-shift grading in patients with a primary anterior cruciate ligament (ACL) tear.

Methods: In this multicenter cross-sectional study constituting a secondary analysis of previous studies, medical records and magnetic resonance imaging (MRI) scans of patients with unilateral primary ACL injury were reviewed. Demographics and pivot-shift grading were collected.

Soil and climate contribute to maintenance of a flower color polymorphism.

Premise: Floral pigments such as anthocyanins are well known to influence pollinator attraction, yet they also confer tolerance to abiotic stressors such as harsh soils, extreme temperatures, low precipitation, and UV radiation. In such cases, environmental variation in abiotic stressors over space or time could lead to the maintenance of flower color variation within species. Under this scenario, flower color in natural populations should covary with environmental stressors.

Dried Blood Spots to Assess Cardiovascular-Kidney-Metabolic Health.

Dried blood spot sampling offers a scalable strategy to close diagnostic gaps and improve global surveillance for cardiovascular-kidney-metabolic syndrome. However, assay performance and the extent of validity vary widely between biomarkers used in cardiovascular-kidney-metabolic health assessment under different settings and have not been well described. To fill this gap, we conducted a systematic search of the literature and a narrative synthesis through April 2024 and included reports with laboratory or field validation measuring biomarkers that can be used in cardiovascular-kidney-metabolic health assessment.

Correlating Left Atrial Enlargement and Left Ventricular Hypertrophy on ECG With Echocardiography and Cardiac Magnetic Resonance Imaging.

Background: ECGs are a primary assessment of cardiac structure and function. Alignment of their findings with cardiac imaging is not well defined. This study investigates the correlation of left atrial enlargement and left ventricular hypertrophy (LVH) found on ECG with transthoracic echocardiogram and cardiac magnetic resonance imaging (CMR) findings.

Identification of Long Noncoding RNA Candidate Disease Genes Associated With Clinically Reported Copy Number Variants in Congenital Heart Disease.

Background: Copy number variants (CNVs) contribute to 3% to 10% of isolated congenital heart disease (CHD) cases, yet their pathogenic roles remain unclear. Diagnostic efforts have focused on protein-coding genes, largely overlooking long noncoding RNAs (lncRNAs), which play key roles in development and disease.

Methods And Results: We systematically analyzed lncRNAs overlapping clinically validated CNVs in 743 patients with CHD from the Cytogenomics of Cardiovascular Malformations Consortium.

Posttraumatic Arthritis After Anterior Cruciate Ligament Injury: Machine Learning Comparison Between Surgery and Nonoperative Management.

Background: Nonoperative and operative management techniques after anterior cruciate ligament (ACL) injury are both appropriate treatment options for selected patients. However, the subsequent development of posttraumatic knee osteoarthritis (PTOA) remains an area of active study.

Purpose: To compare the risk of PTOA between patients treated without surgery and with ACL reconstruction (ACLR) after primary ACL disruption using a machine learning causal inference model.

Myocardial Proteome in Human Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF but has few effective therapies. Recent human myocardial transcriptomics and metabolomics have identified major differences between HFpEF and controls. How this translates at the protein level is unknown.

Impact of Lipoprotein(a) on Valvular and Cardiovascular Outcomes in Patients With Calcific Aortic Valve Stenosis.

Background: Lp(a) (lipoprotein(a)) is an independent risk factor for calcific aortic valve stenosis (CAVS). Whether patients with CAVS and high Lp(a) levels are at higher risk of valvular or cardiovascular events is unknown. The aim of this study is to determine whether higher Lp(a) levels are associated with valvular and cardiovascular outcomes in patients with CAVS.

Framework for Kidney Health Follow-Up Among Neonates With Critical Cardiac Disease: A Report From the Neonatal Kidney Health Consensus Workshop.

Acute kidney injury is common among neonates with critical cardiac disease. Risk factors and associations with kidney-related outcomes are heterogeneous and distinct from other neonates. As survival of children with critical cardiac disease increases to adulthood, the burden of chronic kidney disease is increasing.

Persistent Beta-Blocker Therapy Reduces Long-Term Mortality in Patients With Acute Ischemic Stroke With Elevated Heart Rates.

Background: Elevated heart rate in patients with acute ischemic stroke is associated with increased risk of mortality. Beta-blocker therapy is well known to reduce heart rate.

Methods And Results: This study was a post hoc analysis of patients with acute ischemic stroke with maximum heart rates ≥100 bpm.

Global sensitivity analyses for test planning with black-box models for Mars Sample Return.

This work describes sensitivity analyses performed on complex black-box models used to support experimental test planning under limited resources in the context of the Mars Sample Return program, which aims at bringing to Earth rock, regolith, and atmospheric samples from Mars. We develop a systematic workflow that allows the analysts to simultaneously obtain quantitative insights on key drivers of uncertainty, the direction of impact, and the presence of interactions. We apply optimal transport-based global sensitivity measures to tackle the multivariate nature of the output and we rely on sensitivity measures that do not require independence between the model inputs for the univariate output case.

Jean-Martin Charcot and Scandinavian literature: On the 200th anniversary of his birth.

French neurologist Jean-Martin Charcot, a towering figure familiar to late-19th-century physicians, became better known to the laity of different countries through periodicals, books, and plays. This article examines how Charcot influenced the works of four popular Scandinavian authors: Norwegians Bjørnstjerne Bjørnson, Hans Ernst Kinck, and Øvre Richter Frich, and a Swede, Axel Munthe. These popular novelists and playwrights, all having lived in Paris, provided pictures of different sides of the brilliant and innovative Parisian physician and researcher, who despite his renown was nonetheless criticized for his theories about the hysterias and hypnosis.

Transition in dynamic events: The 2020 lightning complex fires in Northern California as an adaptive system.

The transition from one level of operations to a next larger, more complex level while maintaining coherence as a system has stymied organizational theorists for decades. Drawing on systems theory, network analysis, and collaborative governance, we explore how networks adapt during rapidly escalating crises. Specifically, we investigate the emergence of a synthesizing intelligence function among networks to support coordinated action.

Multicenter Experience With a Novel Real-Time 3-Dimensional Intracardiac Echocardiography Catheter to Guide Interventional Cardiac Procedures.

Background: Recent technologies enable real-time 3-dimensional intracardiac echocardiography (ICE) with the advantages of 2-dimensional ICE and imaging capabilities of transesophageal echocardiography. The purpose of this study is to evaluate the real-world, multicenter safety and performance of a novel 3-dimensional ICE system in a variety of cardiac interventions used in standard clinical practice.

Methods: This prospective, multicenter, observational, single-arm study enrolled patients who were scheduled for an invasive cardiac procedure involving guidance with ICE and followed until discharge or ≤48 hours postprocedure.

Years of Potential Life Lost for Children and Adults With Congenital Heart Defects: United States, 2007 to 2017.

Background: Although most children with congenital heart defects (CHDs) live into adulthood, many have increased mortality risk across the lifespan. Little is known about years lost due to premature CHD-related deaths. We estimated the years of potential life lost (YPLL) among individuals with CHDs in the United States.

Outcomes After Noncardiac Surgery Performed Within 2 Years of Percutaneous Coronary Intervention.

Background: Limited data exist on noncardiac surgery patients with prior percutaneous coronary intervention (PCI) in the contemporary era. The objective was to examine rate, characteristics, and outcomes of patients who underwent noncardiac surgery within 2 years of PCI and develop a risk model of factors that predict long-term postoperative outcomes among patients with recent PCI.

Methods And Results: Patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent noncardiac surgery between October 1, 2017 and September 30, 2021 were included.

Racial and Ethnic Disparities in Referral to Outpatient Heart Failure Management at Hospital Discharge: A Get With The Guidelines Analysis.

Background: Black and Hispanic patients with heart failure (HF) have a higher risk of adverse clinical outcomes. Currently, it is unclear whether there are disparities in referral to outpatient HF management programs based on race and ethnicity.

Methods And Results: We used the American Heart Association GWTG-HF (Get With The Guidelines-Heart Failure) registry to examine 402 225 patients hospitalized for acute HF from January 1, 2010 to December 31, 2021.

GP or ChatGPT? Ability of large language models (LLMs) to support general practitioners when prescribing antibiotics.

Introduction: Large language models (LLMs) are becoming ubiquitous and widely implemented. LLMs could also be used for diagnosis and treatment. National antibiotic prescribing guidelines are customized and informed by local laboratory data on antimicrobial resistance.

mapping near metallic implants using turbo spin echo pulse sequences.

Purpose: To propose a B mapping technique for imaging of body parts containing metal hardware, based on magnitude images acquired with turbo spin echo (TSE) pulse sequences.

Theory And Methods: To encode the underlying B , multiple (two to four) TSE image sets with various excitation and refocusing flip angles were acquired. To this end, the acquired signal intensities were matched to a database of simulated signals which was generated by solving the Bloch equations taking into account the exact sequence parameters.

Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda.

A minimally invasive "continuous nicotine monitor" (CNM) would resolve the dynamic nicotine concentration, [nicotine]t, faced by high-sensitivity nicotinic acetylcholine receptors (nAChRs) during and after nicotine intake by individual subjects. Motivations: "Know the potential enemy at an individual level". Smoking or vaping produces an initial "bolus" of nicotine in the blood and brain, lasting ~5 min with a peak concentration of ~ 100-200 nM.

Pharmacodynamic assessment of apramycin against Mycobacterium abscessus in a hollow fibre infection model.

Background: Mycobacterium abscessus is an important cause of pulmonary infections, particularly among people with cystic fibrosis. Current treatment options for M. abscessus are suboptimal.