Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.

The WNK-OSR1/SPAK protein kinase pathway regulates ion homeostasis and cell volume, but its other functions are not well understood. To discover undefined signaling functions, we utilized experimentally-derived binding specificity to predict interactions and relative affinities with the conserved C-terminal (CCT) domains of OSR1 and SPAK, which bind short linear motifs. The upstream kinases WNKs 1-4 and their relatives, the pseudokinases NRBP1/2, also contain CCT-like domains which have conserved folds and motif binding pockets.

Physiology of gastroesophageal reflux in the neonate.

Gastroesophageal reflux is physiologically normal in infants but can become gastroesophageal reflux disease when it leads to significant symptoms (persistent vomiting, weight loss, feeding difficulties). Gastroesophageal reflux disease is highly prevalent among infants and contributes to increased health care utilization. There are several physiologic and lifestyle factors that predispose infants to a higher degree of gastroesophageal reflux and disease related to it.

The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.

The anti-inflammatory cholinergic pathway describes the interaction between cholinergic vagal nerves and splenic immune cells, yet the exact mechanisms underlying the anti-inflammatory cholinergic pathway remain disputed. Here, we mapped the expression of key molecular components of the anti-inflammatory cholinergic pathway in the adult mouse using RNAScope in situ hybridization (ISH) and quantitative PCR (qPCR). In C57BL/6J wild-type male mice, we observed the expression of choline acetyltransferase (Chat) and alpha 7 nicotinic acetylcholine receptor (Chrna7) in various autonomic neurons throughout the body, but not in the spleen, even after bacterial lipopolysaccharide (LPS) treatment.

The current state of paediatric publishing utilising high-fidelity physiologic data streaming with sickbay or etiometry: a systematic review.

Background: Physiologic data streaming and aggregation platforms such as Sickbay® and Etiometry are becoming increasingly used in the paediatric acute care setting. As these platforms gain popularity in clinical settings, there has been a parallel growth in scholarly interest. The primary aim of this study is to characterise research productivity utilising high-fidelity physiologic streaming data with Sickbay® or Etiometry in the acute care paediatric setting.

Targeting Methylglyoxal Metabolism to Enhance Ferroptosis Sensitivity in Tumor Therapy.

Ferroptosis, characterized by iron-dependent lipid peroxidation, is a form of oxidative cell death increasingly recognized for its role in cancer therapy. The susceptibility of cancer cells to ferroptosis varies, highlighting the need to elucidate its underlying metabolic mechanisms. This study identifies a novel pathway in which the E3 ubiquitin ligase, praja ring finger ubiquitin ligase 1 (PJA1), mediates the proteasomal degradation of glyoxalase I (GLO1) exclusively in ferroptosis-sensitive cancer cells.

Single cell map of the adult female mouse urethra reveals epithelial and stromal macrophages with distinct functional identities.

Epithelial linings at mucosal sites act in concert with resident immune cells to direct host defense. The epithelial lining of the urethra is an understudied mucosal barrier with emerging roles in antimicrobial defense during urinary tract infections. Here, we present a comprehensive cellular atlas of the adult female mouse urethra, focusing on epithelial and resident immune cells.

Anatomic Foundations of Surgery on the Female Perineum.

Although it is difficult to achieve expertise in surgical anatomy of the female perineum, this is essential for patient counseling, clinical decision making, and surgical safety. Education of female pelvic anatomy has often relied on historical illustrations that contain inaccuracies and omissions. Therefore, the Society of Gynecologic Surgeons Pelvic Anatomy Group was established to promote accuracy through standardization of terminology, to explore anatomy through three-dimensional magnetic resonance imaging (MRI) technology, and to disseminate knowledge through the development of a website that uses the human body as a primary source of education.

Temporal control of eating and body weight by GHSR-expressing suprachiasmatic nucleus neurons.

Food consumption impacts body weight differently depending on the time of day. Here, we investigated whether suprachiasmatic nucleus (SCN) neurons responsive to the hormone ghrelin temporally regulate eating and body weight in mice. The chemogenetic stimulation of GHSR (growth hormone secretagogue receptor)-expressing SCN neurons during the mid-rest phase-when mice are most sensitive to ghrelin's orexigenic effects-increased food intake.

Show Me the Money: A Movement Towards Transparency in Pediatric Emergency Medicine Compensation.

Background: National studies report sustained gender-based differences in physician compensation, even after adjustment for workplace factors such as academic rank, specialty type, and work hours. This study examines differences in compensation among pediatric emergency medicine (PEM) fellows' first job after training.

Methods: Between May 2023 and June 2023, we distributed an electronic survey to all United States PEM fellowship program directors (FPDs), requesting they forward it to their graduating fellows.

HNF1A-inactived Hepatocellular Adenomas in Fibropolycystic Kidney and Liver Disease Are Associated with Germline HNF1B Variant.

HNF1A-inactivated hepatocellular adenomas are rarely described in patients with hepatorenal fibrocystic disease, and their genetic relationship remains unexplored. This study reports a series of HNF1A-inactivated hepatocellular adenomas with molecular sequencing analysis in patients with fibrocystic kidney and/or liver disease. Cases were retrospectively identified from the pathology archives of three institutions.

Virtual radiotherapy plan quality education: Perspectives from a global setting.

Purpose: Evaluation of treatment plan quality is a critical element of training for radiotherapy professionals. With the increased adoption of intensity modulated radiotherapy internationally, this training is crucial to address patient care inequity. We aim to evaluate learning outcomes from a 14-session remote training course targeting critical elements of plan quality with advanced modalities.

Stu2 performs an essential kinetochore function independent of its microtubule polymerase activity.

ch-TOG family proteins, including the budding yeast Stu2, are essential for spindle formation and chromosome segregation. Such functions depend on an array of activities ranging from microtubule nucleation, polymerization, and depolymerization to conferring tension sensitivity to kinetochores. This functional diversity makes it challenging to dissect these various functions and understand their relative importance.

Strategies for Improving Access in Academic Neurology.

Neurologic disorders, now a leading cause of disease burden globally, have further added to the growing concerns of access to care, especially given the anticipated 19% shortfall of neurologists. There is a pressing need to improve access and decrease appointment wait times. We led a departmental initiative to bridge the access gap.

SMURF1/2 Are Novel Regulators of WNK1 Stability.

Angiogenesis is essential for remodeling and repairing existing vessels, and this process requires signaling pathways including those controlled by transforming growth factor beta (TGF-β). We have previously reported crosstalk between TGF-β and the protein kinase With No lysine (K) 1 (WNK1). Homozygous disruption of the gene encoding WNK1 results in lethality in mice near embryonic day E12 due to impaired angiogenesis, and this defect can be rescued by the endothelial-specific expression of an activated form of the WNK1 substrate kinase Oxidative Stress-Responsive 1 (OSR1).

Evaluating ChatGPT-4o and OpenEvidence for Structural Heart Disease Support: Insights From Tricuspid Valve Therapies.

•Evaluated ChatGPT-4o and OpenEvidence for structural heart disease decision support.•Among the first to assess the use of artificial intelligence amid rising adoption of TriClip and EVOQUE for transcatheter tricuspid valve interventions.•ChatGPT-4o delivered more accurate responses and proved more clinically reliable.

A novel circadian behavior rhythm in arrhythmic triple knockout mice revealed by constant light exposure.

The current model for autonomous circadian oscillation is based on the transcriptional-translational feedback loops of circadian genes. The deletion of one of the circadian genes and its paralogs leads to arrhythmicity. triple knockout ( KO) mice exhibit arrhythmic behavior in constant darkness.

Transcatheter vs. surgical aortic valve replacement in bicuspid aortic valve stenosis.

Aims: Patients with bicuspid aortic valve (BAV) stenosis were excluded from major TAVR trials, and data comparing TAVR and SAVR in this population remain limited. To compare real-world, risk-adjusted outcomes of TAVR vs. SAVR in patients with BAV stenosis.

Improved AAV9-based gene therapy design for -related Leigh syndrome with minimal toxicity.

Surfeit locus protein 1 (SURF1)-related Leigh syndrome is an early-onset neurodegenerative disorder characterized by a reduction in complex IV activity that disrupts mitochondrial function. Currently, there are no disease-modifying treatments available. Previously, we reported that a gene replacement therapy for -related Leigh syndrome was developed, which showed improved complex IV activity and restored exercise-induced lactate acidosis, as well as a high safety profile in wild-type (WT) mice.

Hospital Implementation of Endovascular Thrombectomy and Health Equity in Acute Stroke Outcomes.

Background: The introduction of novel therapeutics into clinical practice could impact equity in health outcomes.

Methods: This was a retrospective, observational cohort study based on the Get With The Guidelines-Stroke program of the American Heart Association. Two epochs were considered: January 2010 to December 2014 and January 2016 to December 2019.

Defining "Flares" in Atopic Dermatitis: A Narrative Review.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by fluctuating disease activity. Exacerbations of AD signs and/or symptoms, or flares, have a significant impact on patient quality of life and may require modification or escalation of treatment. However, research into preventing and managing flares may be hampered by the lack of consensus on a clear, clinically relevant, measurable definition of flare.

Real-world treatment patterns in patients with generalized pustular psoriasis (GPP).

Background: Generalized pustular psoriasis (GPP) is a chronic and life-threatening inflammatory skin disease, distinct from plaque psoriasis (PsO). There is a lack of GPP treatment guidelines.

Objective: To characterize treatment patterns among patients with GPP in the US during two 365-day periods (post-diagnosis and pre-diagnosis) between 2015 and 2020.

Ciprofloxacin Enhances RSL3-Induced Ferroptosis by Promoting Mitochondrial Zn Accumulation via the STING1-CAV2 Pathway.

Ciprofloxacin (CFX) is a broad-spectrum antibiotic belonging to the fluoroquinolone class, widely used to treat bacterial infections by inhibiting bacterial DNA replication. Ferroptosis, a form of regulated cell death, is characterized by lipid peroxidation on cellular and organelle membranes. Our previous studies demonstrated that ciprofloxacin inhibits erastin-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) protein stability.

Efficacy and Safety of Neuroendoscopy versus Craniotomy for Spontaneous Supratentorial Intracerebral Hemorrhage: An Updated Meta-Analysis of Randomized and Non-Randomized Studies.

Background: Spontaneous supratentorial intracerebral hemorrhage (ICH) is a critical condition with high morbidity and mortality rates warranting urgent surgical evacuation. This systematic review and meta-analysis compare the safety and efficacy of neuro-endoscopy (NE) versus traditional craniotomy (CR) for managing ICH.

Methods: From inception until July 2024, a comprehensive literature search was undertaken on PubMed, Cochrane Central, ScienceDirect, and Clinicaltrials.