H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium.

Plasticity is needed during development and homeostasis to generate diverse cell types from stem and progenitor cells. Following differentiation, plasticity must be restricted in specialized cells to maintain tissue integrity and function. For this reason, specialized cell identity is stable under homeostatic conditions; however, cells in some tissues regain plasticity during injury-induced regeneration.

Inactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.

The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.

Examining clinicians' fatigue in a pediatric emergency department.

We examined fatigue among emergency department (ED) clinicians. ED clinicians are susceptible to burnout, because of fatigue. Fatigue represents a latent hazard in ED care, being associated with impaired clinician performance, poor patient outcomes, and a negative impact on patient safety.

Interaction between perfluoro-octanoic sulfonate and common antibiotics induces developmental anomalies and lethality in Xenopus laevis.

Background: Perfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non-stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. Perfluoroalkyl substances molecules are known to bioaccumulate in various organisms.

Dual ASXL1 and CSF3R mutations drive myeloid biased stem cell expansion and enhance neutrophil differentiation.

Mutations in the epigenetic regulator Additional Sex Combs-Like 1 (ASXL1) are frequently observed in chronic neutrophilic leukemia (CNL). CNL is a myeloproliferative neoplasm (MPN) driven by activating mutations in the Colony Stimulating Factor 3 Receptor (CSF3R), which cause excessive neutrophil production. Despite the high rates of co-occurrence, the interplay between ASXL1 and CSF3R mutations in hematopoiesis and leukemia remains poorly understood.

Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado.

Background: High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 products for weight loss in Colorado.

Prevalence of Depression in Older Adults and the Potential Protective Role of Volunteering: Findings From the LongROAD Study.

Background: As the US population continues to age, depression and other mental health issues have become a significant challenge for healthy aging. Few studies, however, have examined the prevalence of depression in community-dwelling older adults in the United States.

Methods: Baseline data from the Longitudinal Research on Aging Drivers study were analyzed to examine the prevalence and correlates of depression in a multisite sample of community-dwelling adults aged 65-79 years who were enrolled and assessed between July 2015 and March 2017.

Long-Term Trajectories of Older Adults Served by an Emergency Department/Hospital-Based Elder Mistreatment Response Program.

Background: An emergency department (ED) visit or hospitalization provides an opportunity to identify elder mistreatment and initiate intervention, but this seldom occurs. To address this, we developed the Vulnerable Elder Protection Team (VEPT), a novel interdisciplinary consultation service. We explored the long-term trajectories of patients receiving VEPT evaluation and intervention.

Malignant Cerebral Edema After Cranioplasty: A Case Report and Literature Insights.

BACKGROUND Decompressive craniectomy is a common life-saving intervention in the setting of elevated intracranial pressure. Cranioplasty restores the calvarium and intracranial physiology once swelling recedes. Cranioplasty is often thought of as a low-risk intervention.

Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment.

Background: Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.

Methods: Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.

The Trifecta of Industry, Academic, and Health System Partnership to Improve Mental Health Care Through Smartphone-Based Remote Patient Monitoring: Development and Usability Study.

Background: Mental health treatment is hindered by the limited number of mental health care providers and the infrequency of care. Digital mental health technology can help supplement treatment by remotely monitoring patient symptoms and predicting mental health crises in between clinical visits. However, the feasibility of digital mental health technologies has not yet been sufficiently explored.

The Circadian Response to Evening Light Spectra in Early Childhood: Preliminary Insights.

Although the sensitivity of the circadian system to the characteristics of light (e.g., biological timing, intensity, duration, spectrum) has been well studied in adults, data in early childhood remain limited.

Lung Endothelial Cell Heterogeneity in Health and Pulmonary Vascular Disease.

Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH).

Non-Genotoxic and Environmentally Relevant Lower Molecular Weight Polycyclic Aromatic Hydrocarbons Significantly Increase Tumorigenicity of Benzo[]pyrene in a Lung Two-Stage Mouse Model.

The World Health Organization has classified air pollution as a carcinogen, and polycyclic aromatic hydrocarbons (PAHs) are major components of air particulates of carcinogenic concern. Thus far, most studies focused on genotoxic high molecular weight PAHs; however, recent studies indicate potential carcinogenicity of the non-genotoxic lower molecular weight PAHs (LMW PAHs) that are found in indoor and outdoor air pollution as well as secondhand cigarette smoke. We hypothesize that LMW PAHs contribute to the promotion stage of cancer when combined with benzo[]pyrene (B[]P), a legacy PAH.

Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants.

Background: Tetrahydrocannabivarin (THCV) is a phytocannabinoid commonly found in cannabis with potential pharmacological properties; however, its post-acute pharmacokinetics (PK) in humans have not been studied yet. THCV has two isomers, Δ9- and Δ8-THCV, which seem to have different pharmacological properties. We investigated the PK of the Δ8-THCV isomer after oral administration as part of a two-phase, dose-ranging, placebo-controlled trial in healthy participants.

DEAD/H Box 5 (DDX5) Augments E2F1-Induced Cell Death Independent of the Tumor Suppressor p53.

In almost all cancers, the p53 pathway is disabled and cancer cells survive. Hence, it is crucially important to induce cell death independent of p53 in the treatment of cancers. The transcription factor E2F1 is controlled by binding of the tumor suppressor pRB, and induces apoptosis by activating the gene, an upstream activator of p53, when deregulated from pRB by loss of pRB function.

Evolutionary Adaptations in Biliverdin Reductase B: Insights into Coenzyme Dynamics and Catalytic Efficiency.

Biliverdin reductase B (BLVRB) is a redox regulator that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductions of multiple substrates, including flavins and biliverdin-β. BLVRB has emerging roles in redox regulation and post-translational modifications, highlighting its importance in various physiological contexts. In this study, we explore the structural and functional differences between human BLVRB and its hyrax homologue, focusing on evolutionary adaptations at the active site and allosteric regions.

Metoprolol vs diltiazem for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis of adverse events.

Background: Intravenous (IV) diltiazem and metoprolol are commonly used to achieve rate control for atrial fibrillation with RVR (Afib with RVR), and are both recommended as first-line by current guidelines. While prior studies investigated the efficacy of these medications, there is little evidence available regarding the risk of adverse events (AEs) with their use.

Methods: We identified randomized controlled trials (RCT) and observational studies reporting rates of AEs following administration of IV diltiazem and metoprolol for Afib with RVR by searching PubMed, SCOPUS, EMBASE, and Cochrane Library.

Metabolic Switch in Endocrine Resistant Estrogen Receptor Positive Breast Cancer.

Purpose: The development of endocrine resistance remains a significant challenge in the clinical management of estrogen receptor-positive () breast cancer. Metabolic reprogramming is a prominent component of endocrine resistance and a potential therapeutic intervention point. However, a limited understanding of which metabolic changes are conserved across the heterogeneous landscape of ER+ breast cancer or how metabolic changes factor into ER DNA binding patterns hinder our ability to target metabolic adaptation as a treatment strategy.

Novel interactions within the silent information regulator heterochromatin complex potentiate inter-subunit communication and gene repression.

Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. The Silent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner.

Genome sequencing reveals the impact of non-canonical exon inclusions in rare genetic disease.

Introduction: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging sequencing technologies are now being deployed in the clinical setting to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive clinical genetic testing.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts.

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems.

Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.

The effects of war-related experiences on mental health symptoms of individuals living in conflict zones: a longitudinal study.

On October 7, 2023, a large-scale attack in southern Israel and the subsequent war resulted in extensive loss of life and injuries, with many individuals experiencing traumatic losses, such as family members or close friends being killed or kidnapped. This study aims to longitudinally examine its effects on mental health, specifically, clinical symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD). We anticipated greater symptom severity among individuals who experienced traumatic loss, were forcibly displaced, or suffered income loss, as well as among women and members of ethnic minorities.