Plural molecular and cellular mechanisms of pore domain encephalopathy.

variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path.

Glucarpidase for Treatment of High-Dose Methotrexate Toxicity.

High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.

Mucin5AC promotes breast cancer brain metastasis through cMET/CD44v6.

Purpose: Breast cancer (BC) brain metastasis (BrM) remains a significant clinical problem. Mucins have been implicated in metastasis; however, if they are also involved in BCBrM remains unknown. We queried BrM patient databases and found Mucin 5AC (MUC5AC) to be upregulated and therefore sought to define the role of MUC5AC in BCBrM.

Burn-induced mitochondrial dysfunction in hepatocytes: The role of methylation-controlled J protein silencing.

Background: Burn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model.

Comparing peer relationship ratings among adolescents with sport and Non-sport Related Concussions.

Objective: To evaluate if peer relationship ratings differ among adolescents who sustain a sport-related concussion compared to those who sustain a non-sport-related concussion.

Study Design: We conducted a cross-sectional investigation of 123 adolescents who sustained a concussion within 21 days before their initial post-injury evaluation (mean = 9.2 ± 3.

Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation.

Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited.

Screening pediatric patients to determine need for child life services using the pediatric emotional safety screener.

There can be adverse psychosocial outcomes for children who have negative healthcare experiences. Identifying children's risk for experiencing elevated distress early on when entering the healthcare setting would allow targeted, proactive support to help mitigate negative psychological sequelae. The aim of this retrospective study was to evaluate the psychometric properties of the Pediatric Emotional Safety Screener (PESS), designed to screen for psychosocial distress for pediatric patients.

Editorial: Climate change is a children's health hazard.

As temperatures defy heat records, it is difficult to ignore the implications of climate change for public health, including impacts on population health more specifically. In short, climate change is happening now and presents an immediate hazard to human health on a global scale. Age-related health effects are an inalienable truth; physiology is relatively universal, and so are the ways in which our bodies respond to different types and levels of exposures to environmental stressors at different lifestages.

Consensus on the lung cancer management after third-generation EGFR-TKI resistance.

Lung cancer is the most prevalent malignant tumour in the Asia-Pacific region. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers. Among these, the rate of mutations in Asian patients with lung adenocarcinoma is 40-60%.

Medical mistrust and COVID-19 vaccine attitudes and behavior: Findings from a population-based cohort study in Michigan.

Background: Uptake of COVID-19 vaccines has stalled in the U.S. Some studies suggest that medical mistrust may be a barrier, but evidence is limited due to cross-sectional designs or convenience sampling.

The Colorado Heart Failure Acuity Risk Model: A Mortality Model for Waitlisted Cardiac Transplant Patients.

Background: Currently, there is no mathematical model used nationally to determine the medical urgency of patients on the heart transplant waitlist in the United States. While the current organ distribution system accounts for many patient factors, a truly objective model is needed to more reliably stratify patients by their medical acuity.

Objectives: The aim of the study was to develop risk scores (Colorado Heart failure Acuity Risk Model [CHARM] score) to predict mortality in adults waitlisted for heart transplant.

Evolutionary mismatch in emotional support during childbirth: Lessons from the COVID-19 pandemic.

Background And Objectives: Selective pressures on human childbirth have led to the evolution of cooperative birth practices, with birth attendants playing a crucial role in providing emotional support during labor.

Methodology: We leveraged COVID-19-related healthcare disruptions to investigate the impact of the evolutionary mismatch in the availability of emotional support persons on perceived birth stress among a US-based convenience sample ( = 1082).

Results: Individuals who stated during pregnancy that they desired support from their partner or a doula but who did not receive this support had significantly higher perceived childbirth stress ( = 12.

Employer Perspective on Pain Fellowship Education: A Survey to Understand the Current State of Pain Medicine Training.

Background: Pain medicine care has expanded to encompass a wider range of conditions, necessitating updated education and training for pain specialists to utilize emerging technologies effectively. A national survey was conducted through several verified Pain organizations regarding pain physician employers' perspectives on pain medicine fellowship training and education. The survey aimed to gather insights from a diverse range of geographic locations, practice types (academic and private practice), and practice settings.

Nicotine and cannabis vaping among early high school adolescents: Disparities of use across sociodemographic characteristics and associations with psychosocial factors.

This study examines whether adolescent nicotine and cannabis vaping types (i.e., nicotine-only, cannabis-only, and dual use) differ across sociodemographic and school characteristics (e.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Brief Report: Precision Language and Deletion of the "S" Word.

Introduction: In 2021, the International Association for the Study of Lung Cancer (IASLC) published the IASLC Language Guide as guidance on preferred language and phrasing in oral and written communications, including presentations at conferences. This study analyzed presentations from the 2022 IASLC World Conference on Lung Cancer (WCLC) one year after implementation of the Language Guide to identify adoption rates of non-stigmatizing language and to determine correlations with presenter characteristics.

Methods: We downloaded 522 slide presentations from the IASLC WCLC 2022 conference attendee portal.

Curriculum as Change Agent: Promoting Inclusivity through an Advanced Feedback Curriculum.

Feedback curricula in medical education typically cover only the uncontextualized basics of feedback. We created a self-paced, online course that covered advanced feedback techniques with intentional inclusion of social dynamics that can influence feedback processes. Results revealed significant improvements in participant feedback orientation, feedback-seeking behaviors, and perceptions of feedback environment.

Mindfulness in the Medical Learning Environment: An Opportunity for the Struggling Learner?

Unlabelled: Mindfulness is defined as nonjudgmentally and purposefully paying attention in the present moment. Mindfulness may be a valuable tool in the remediation armamentarium, useful in bringing attention to an individual's struggles. However, such application has largely been unexplored.

Sex and genetic background influence intravenous oxycodone self-administration in the hybrid rat diversity panel.

Opioid Use Disorder (OUD) is an ongoing worldwide public health concern. Genetic factors contribute to multiple OUD-related phenotypes, such as opioid-induced analgesia, initiation of opioid use, and opioid dependence. Here, we present findings from a behavioral phenotyping protocol using male and female rats from 15 genetically diverse inbred strains from the Hybrid Rat Diversity Panel (HRDP).

Long-term Complications From Peripheral Nerve Blocks After Pediatric Orthopaedic Lower Extremity Procedures: A Systematic Review.

Background: Peripheral nerve blocks (PNBs) are frequently utilized as a regional anesthetic in pediatric orthopaedic surgery for postoperative pain control and reduced time to discharge; however, short- and long-term complications after these procedures are variably reported.

Purpose: To identify the frequency of long-term complications in pediatric patients who received regional anesthesia for a lower extremity orthopaedic procedure.

Study Design: Systematic review; Level of evidence, 4.

Biofabrication of anisotropic articular cartilage based on decellularized extracellular matrix.

Tissue-engineered grafts that mimic articular cartilage show promise for treating cartilage injuries. However, engineering cartilage cell-based therapies to match zonal architecture and biochemical composition remains challenging. Decellularized articular cartilage extracellular matrix (dECM) has gained attention for its chondro-inductive properties, yet dECM-based bioinks have limitations in mechanical stability and printability.

A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice.

Background: Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides.

Vanzacaftor-tezacaftor-deutivacaftor for children aged 6-11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial.

Background: In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor-tezacaftor-deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor-tezacaftor-deutivacaftor in children with cystic fibrosis aged 6-11 years.