Molecular basis of proton sensing by G protein-coupled receptors.

Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues.

Estimating cardiovascular mortality in patients with hypertension using machine learning: The role of depression classification based on lifestyle and physical activity.

Purpose: This study aims to harness machine learning techniques, particularly the Random Survival Forest (RSF) model, to assess the impact of depression on cardiovascular disease (CVD) mortality among hypertensive patients. A key objective is to elucidate the interplay between mental health, lifestyle, and physical activity while comparing the effectiveness of the RSF model against the traditional Cox proportional hazards model in predicting CVD mortality.

Methods: Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2014 were used for comprehensive depression screening.

Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204.

Purpose: In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival.

Sex Differences, Menses-Related Symptoms and Menopause in Disorders of Gut-Brain Interaction.

Background: Disorders of gut-brain interaction (DGBI) predominate in women, but little is known about sex differences in menses-related or menopause symptoms.

Methods: Using data from the Rome Foundation Global Epidemiology Survey, we assessed Rome IV DGBI symptoms in individuals in 26 countries who met criteria for ≥ 1 of 5 DGBI: irritable bowel syndrome (IBS), functional dyspepsia (FD), functional constipation (FC), functional diarrhea (FDr), or functional bloating (FB). Participants included pre- and post-menopausal women with DGBI and age-matched men.

A scoping review and consensus recommendations for emergency medical services buprenorphine (EMS-Bupe) programs.

Objectives: Emergency Medical Services (EMS) agencies are beginning to provide low-barrier access to treatment for opioid use disorder (OUD) through the development of EMS buprenorphine (EMS-Bupe) programs. However, evidence-based practices for these programs are lacking. Our aim was to review the current literature on EMS and emergency department (ED) based buprenorphine treatment programs to provide consensus recommendations on the EMS-Bupe program development.

Provider Perspectives on Implementation of Adult Community-Based Palliative Care: A Scoping Review.

While community-based palliative care (CBPC) programs have been expanding, there remain important obstacles to widespread use. Since provider perspectives on CBPC remain underexplored, we conducted a scoping review to summarize provider perspectives regarding barriers and facilitators to implementation of adult CBPC in the United States. We systematically searched OVID, MEDLINE, and CINAHL for peer-reviewed qualitative research published from January 1, 2010 to January 9, 2024, then used PRISM framework synthesis to organize themes into provider, organization, and external environment levels.

Covariate-adaptive biased coin randomization for master protocols with multiple interventions and biomarker-stratified allocation.

In a multi-arm trial with predefined subgroups for each intervention to target, it is often desirable to enrich assignment to an intervention by enrolling more biomarker-positive participants to the intervention. We describe how to implement a biased coin design to achieve desired allocation ratios among interventions and between the number of biomarker-positive and biomarker-negative participants assigned to each intervention. We illustrate the proposed method with the randomization algorithm implemented in the Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) trial.

Like Father, Like Daughter: A Family With a Constitutional Thrombocytopenia Variant Due to a Novel Heterozygous Missense Mutation in GP1BA.

Constitutional platelet disorders have become better understood since Bernard and Soulier first described a case in 1948. Their diagnosis can also be challenging due to overlap in clinical presentation and lab findings with platelet type von Willebrand. Bernard-Soulier syndrome is a disorder caused by GPIb receptor mutations that decrease its affinity for von Willebrand factor resulting in reduced platelet function and macrothrombocytopenia.

Investigating context-specific sedentary behaviours and cardiometabolic health in college-based young adults (CONTEXT-SB): a protocol for a longitudinal observational study.

Background: Sedentary behaviour (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific SB (CS-SB) are most detrimental for CMD risk, the lifestyle behaviours that cluster with CS-SBs and the socioecological predictors of CS-SB.

Methods And Analysis: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals.

Exposure therapy consortium: Outcomes of the proof-of-principle study.

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) in students with elevated anxiety sensitivity.

Medicare Advantage and rural hospital profitability.

Purpose: This study compares 2018-2023 Medicare Advantage (MA) days as a percentage of total Medicare days in rural and urban hospitals, describes 2022-2023 operating profitability of rural and urban hospitals by quartiles of MA days as a percentage of total Medicare days, and explores hospital characteristics that may be important for understanding the relationship between MA and profitability of rural hospitals.

Methods: Financial and hospital data were obtained from the Centers for Medicare & Medicaid Services (CMS) Healthcare Cost Report Information System (HCRIS) for the years 2018 to 2023. Hospitals were assigned to quartiles based on MA days as a percentage of total Medicare days.

AnkleImage - An ultrafast ultrasound image dataset to understand the ankle joint muscle contractility.

The role of the human ankle joint in activities of daily living, including walking, maintaining balance, and participating in sports, is of paramount importance. Ankle joint dorsiflexion and plantarflexion functionalities mainly account for ground clearance and propulsion power generation during locomotion tasks, where those functionalities are driven by the contraction of ankle joint skeleton muscles. Studies of corresponding muscle contractility during ankle dynamic functions will facilitate us to better understand the joint torque/power generation mechanism, better diagnose potential muscular disorders on the ankle joint, or better develop wearable assistive/rehabilitative robotic devices that assist in community ambulation.

Race disparities in dental care use from adolescence to middle adulthood in the USA.

Background: This study examines the longitudinal patterns of dental care use from adolescence to middle adulthood (ages 11-43) and investigates racial and ethnic disparities in these patterns.

Methods: Data from Waves I through V of the National Longitudinal Study of Adolescent to Adult Health (1993-2018; ages 11-43). Semiparametric group-based trajectory model identified distinct dental care use trajectories.

Activation of the contact system and intrinsic pathway in peripheral and portal venous circulations in liver cirrhosis.

Background: Portal vein system-specific risk factors contributing to portal vein thrombosis in cirrhosis are poorly investigated.

Aims: To quantify contact system and intrinsic pathway activation in peripheral compared to portal venous blood in patients with decompensated cirrhosis.

Methods: Adult patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt underwent simultaneous blood sampling from a peripheral vein and the portal vein.

Ethanol self-administration targets GluA2-containing AMPA receptor expression and synaptic activity in the nucleus accumbens in a manner that drives the positive reinforcing properties of the drug.

Rationale: The positive reinforcing effects of alcohol (ethanol) drive repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanol's reinforcing properties is unclear.

Objective: This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanol's reinforcing effects in male C57BL/6 J mice.

DNA duplication-mediated activation of a two-component regulatory system serves as a bet-hedging strategy for .

strain E264 (E264) and close relatives stochastically duplicate a 208.6 kb region of chromosome I via RecA-dependent recombination between two nearly identical insertion sequence elements. Because homologous recombination occurs at a constant, low level, populations of E264 are always heterogeneous, but cells containing two or more copies of the region (Dup+) have an advantage, and hence predominate, during biofilm growth, while those with a single copy (Dup-) are favored during planktonic growth.

Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.

Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality.

Ocular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses.

Non-infectious uveitis (NIU) is a painful recurrent disease affecting 2%-5% of horses. Current treatments require frequent administration with associated adverse events. In a previous study, intravitreal (IVT) adeno-associated virus (AAV) harboring equine interleukin-10 (eqIL-10) cDNA inhibited experimental uveitis in rats.

Population-specific reference panel improves imputation quality for genome-wide association studies conducted on the Japanese population.

To improve imputation quality for genome-wide association studies (GWAS) conducted on the Japanese population, we developed and evaluated four Japanese population-specific reference panels. These panels were constructed through the augmentation of the 1000 Genomes Project (1KG) panel using Japanese whole genome sequencing (WGS) data, with sample sizes ranging from 1 K to 7 K individuals enrolled through the Biobank Japan (BBJ) project, and sequencing depths ranging from 3× to 30×. Among these panels, an augmented reference panel comprising 7472 WGS samples of mixed depth (1KG+7K) exhibit the greatest improvement in imputation quality relative to the Trans-Omics for Precision Medicine (TOPMed) reference panel.

Sox17 and Erg synergistically activate endothelial cell fate in reprogramming fibroblasts.

Sox17-Erg direct reprogramming is a potent tool for the in vitro and in vivo generation of arterial-like induced-endothelial cells from fibroblasts. In this study, we illustrate the pioneering roles of both Sox17 and Erg in the endothelial cell reprogramming process and demonstrate that emergent gene expression only occurs when both factors are co-expressed. Bioinformatic analyses and molecular validation reveal both Bach2 and Etv4 as integral mediators of Sox17-Erg reprogramming with different roles in lung and heart fibroblast reprogramming.

Validation and expansion of Baveno VII criteria for cACLD and CSPH based on liver stiffness and platelet count: Correlation with risk of hepatic decompensation and death.

Background And Aims: Recently proposed "Rule-of-Five" criteria define compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) using liver stiffness (LS) and platelet count. We aimed to validate these criteria by determining whether they are associated with risk of adverse outcomes.

Approach And Results: Patients without prior hepatic decompensation or HCC who underwent LS and platelet measurements (n = 17,076) were categorized as follows: no cACLD (LS: 2.

Intervention and Sampling Trends in Literacy Research for Young Augmentative and Alternative Communication Users: A Scoping Review.

Purpose: This scoping review aims to characterize the body of literature addressing literacy interventions involving young children (ages 2-8 years) who use or would benefit from aided augmentative and alternative communication (AAC).

Method: A systematic search was conducted in six databases. The search yielded 33 intervention studies.

Early Language, Social Communication, and Autism Characteristics of Young Toddlers at Elevated Likelihood for Autism Identified by the First Years Inventory-Lite.

Purpose: The purposes of this article were (a) to compare the developmental skills of toddlers whose scores on the First Years Inventory-Lite (FYI-Lite), an early screening tool, indicated an elevated likelihood of a later diagnosis of autism (ELA) to the developmental skills of toddlers at a lower likelihood of a later diagnosis of autism (LLA) and (b) to examine how autism characteristics are correlated with communication measures in toddlers at an ELA.

Method: We assessed the language, social communication (SC) skills, and characteristics of autism demonstrated by 45 toddlers at an ELA and 37 toddlers at an LLA between the ages of 11 and 18 months and compared group scores on these measures. We also examined the correlations between the characteristics of autism and language measures within the ELA group.

A US-Based Consensus on Diagnostic Overlap and Distinction for Pediatric Feeding Disorder and Avoidant/Restrictive Food Intake Disorder.

Objective: As diagnoses covering dysfunctional feeding and eating in pediatrics, avoidant/restrictive food intake disorder (ARFID) and pediatric feeding disorder (PFD) contain inherent areas of overlap in their diagnostic criteria. Areas of overlap include criteria regarding nutritional consequences associated with feeding/eating dysfunction and shared emphasis on possible psychosocial impairment associated with restricted food intake. Complicating the differential diagnosis process is a lack of guidance regarding when the two conditions occur independently, co-qualify, and/or transition into the other.