Global transcriptome modulation by xenobiotics: the role of alternative splicing in adaptive responses to chemical exposures.

Background: Xenobiotic exposures can extensively influence the expression and alternative splicing of drug-metabolizing enzymes, including cytochromes P450 (CYPs), though their transcriptome-wide impact on splicing remains underexplored. This study used a well-characterized splicing event in the Cyp2b2 gene to validate a sandwich-cultured primary rat hepatocyte model for studying global splicing in vitro. Using endpoint PCR, RNA sequencing, and bioinformatics tools (rSeqDiff, rMATs, IGV), we analyzed differential gene expression and splicing in CYP and nuclear receptor genes, as well as the entire transcriptome, to understand how xenobiotic exposures shape alternative splicing and activate xenosensors.

Voltage-Controlled Synthesis of Higher Harmonics in Hybrid Josephson Junction Circuits.

We report measurements of the current-phase relation of two voltage-controlled semiconductor-superconductor hybrid Josephson junctions (JJs) in series. The two hybrid junctions behave similar to a single-mode JJ with effective transparency determined by the ratio of Josephson coupling strengths of the two junctions. Gate-voltage control of Josephson coupling (measured from switching currents) allows tuning of the harmonic content from sinusoidal, for asymmetric tuning, to highly nonsinusoidal, for symmetric tuning.

Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes.

Objective: To assess 1) the association between metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk.

Research Design And Methods: A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999-2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals.

Family History of Diabetes and Clinical Characteristics in Children at Diagnosis of Type 1 Diabetes-A Swedish Population-Based Study.

Objective: To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes.

Research Design And Methods: Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA.

Optimizing care pathways: A study of the urgent dispatch program and its impact on emergency department visits.

Introduction: The use of acute hospital-level care at home (hospital-at-home) for patients who are chronically ill has led to decreased medical costs, amount of sedentary time, and hospital admissions. Our large integrated healthcare system identified the need to develop a mechanism through which to decrease emergency department (ED) visits in this patient population by creating a home acute care program called Urgent Dispatch. The primary objective of this study was to determine the medical condition for referral and seven and 30-day ED visit rates.