Patient-derived response estimates from zero-passage organoids of luminal breast cancer.

Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.

Unsymmetric hydroxylamine and hydrazine BAM15 derivatives as potent mitochondrial uncouplers.

Chemical mitochondrial uncouplers are protonophoric, lipophilic small molecules that transport protons from the mitochondrial intermembrane space into the matrix independent of ATP synthase, thus uncoupling nutrient oxidation from ATP production. Our previous work identified BAM15 (IC 0.27 μM) as a potent and efficacious mitochondrial uncoupler with potential for obesity treatment.

Associations of prenatal urinary melamine, melamine analogues, and aromatic amines with gestational duration and fetal growth in the ECHO Cohort.

Melamine, its analogues, and aromatic amines (AAs) were commonly detected in a previous study of pregnant women in the Environmental influences on Child Health Outcomes (ECHO) Cohort. While these chemicals have identified toxicities, little is known about their influences on fetal development. We measured these chemicals in gestational urine samples in 3 ECHO cohort sites to assess associations with birth outcomes (n = 1,231).

Rapid identification and phenotyping of nonalcoholic fatty liver disease patients using a machine-based approach in diverse healthcare systems.

Nonalcoholic fatty liver disease (NAFLD) is the most common global cause of chronic liver disease and remains under-recognized within healthcare systems. Therapeutic interventions are rapidly advancing for its inflammatory phenotype, nonalcoholic steatohepatitis (NASH) at all stages of disease. Diagnosis codes alone fail to recognize and stratify at-risk patients accurately.

US mortality trends from alcohol-associated hepatitis by sex, age, race, and ethnicity, 1999-2020.

Background: Alcohol-associated hepatitis (AH) is a subtype of alcohol-associated liver disease (ALD) resulting in severe acute liver inflammation. This study aims to examine longitudinal trends in mortality from AH in the United States (US) from 1999 to 2020, stratifying the data by sex, age, and racial/ethnic groups.

Methods: We performed a cross-sectional study using data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) to determine annual AH-related mortality rates (MR) in adults ≥21 years between 1999 and 2020.

Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury.

E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5).

Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.

The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

Examining social attention as a predictor of problem drinking behavior: A longitudinal study using eye-tracking.

Background: Researchers have long been interested in identifying objective markers for problem drinking susceptibility informed by the environments in which individuals drink. However, little is known of objective cognitive-behavioral indices relevant to the social contexts in which alcohol is typically consumed. Combining group-based alcohol administration, eye-tracking technology, and longitudinal follow-up over a 2-year span, the current study examined the role of social attention in predicting patterns of problem drinking over time.

Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.

Introduction: Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest without considering the underlying fiber geometry.

Methods: We propose a novel macrostructure-informed normative tractometry (MINT) framework to investigate how white matter (WM) microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia.

Sex differences in the relationships between 24-h rest-activity patterns and plasma markers of Alzheimer's disease pathology.

Background: Although separate lines of research indicated a moderating role of sex in both sleep-wake disruption and in the interindividual vulnerability to Alzheimer's disease (AD)-related processes, the quantification of sex differences in the interplay between sleep-wake dysregulation and AD pathology remains critically overlooked. Here, we examined sex-specific associations between circadian rest-activity patterns and AD-related pathophysiological processes across the adult lifespan.

Methods: Ninety-two cognitively unimpaired adults (mean age = 59.

GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis.

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated at 32.4%, reflecting its growing clinical significance. MASLD, which includes MASLD and metabolic dysfunction-associated steatohepatitis (MASH) has been linked to increased metabolic, cardiovascular, and malignant morbidity.

Need for and update on clinical trials for uncomplicated type B aortic dissection.

The mainstay of management for uncomplicated type B aortic dissection is currently optimal medical therapy, targeting blood pressure and heart rate, along with serial imaging. There is a paucity of data that informs whether early intervention with thoracic endografting in this group of patients will promote aortic remodeling and better long-term outcomes. Investigations to date, including the Investigation of Stent Grafts in Aortic Dissection (INSTEAD), INSTEAD-XL, and Acute Dissection: Stent Graft or Best Medical Therapy (ADSORB) studies, have compared thoracic endovascular aortic repair (TEVAR) with optimal medical therapy in patients with uncomplicated type B aortic dissection but have not shown a benefit for TEVAR conclusively.

LGBTQ+ youth policy and mental health: Indirect effects through school experiences.

The link between state policies and LGBTQ+ youth mental health is well-established, yet less well-understood are the mechanisms that drive these associations. We used a sample from the LGBTQ+ National Teen Survey (n = 8368) collected in 2022 to examine whether and to what degree LGBTQ+ inclusive school strategies, student perceptions of school safety, and experiences with bias-based bullying and peer victimization explain the association between state LGBTQ+ youth-focused policies and LGBTQ+ youth mental health symptomology. We observed significant indirect effects between policy and LGBTQ+ youth mental health through all four constructs, suggesting that each of these more proximal school experiences was independently implicated in this association.

Ghana's water safety journey: A review of efforts toward a risked-based water quality management.

In 2015, Ghana launched the National Drinking Water Quality Management Framework (NDWQMF) to promote a risk-based approach to water quality through water safety plans (WSPs). This study uses a narrative review to synthesize WSP implementation progress in Ghana, identify gaps in practice, and provide recommendations for enhanced effectiveness and scale-up. Findings show limited uptake: only three of 88 urban water supply systems have adopted WSPs, while in the rural sector, the Community Water and Sanitation Agency has implemented WSPs in 177 of 1,022 small-town systems, and the safe water network in 46 systems.

Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET).

Risk perception and mpox vaccine acceptability among people living with HIV in northern Nigeria.

Background: There is a dearth of information regarding mpox risk perception and vaccine acceptance among people living with human immunodeficiency virus (HIV), especially in countries with a dual burden of HIV and mpox, such as Nigeria.

Methods: We used an explanatory mixed methods design and structured questionnaires administered to a clinic-based sample of people living with HIV (n=430), followed by in-depth interviews with a purposive subsample (n=20). Data were analysed using binary logistic regression and the framework approach.

Partial microglial depletion and repopulation exert subtle but differential effects on amyloid pathology at different disease stages.

Colony-stimulating factor-1-receptor (CSF1R) inhibitors have been widely used to rapidly deplete microglia from the brain, allowing the remaining microglia population to self-renew and repopulate. These new-born microglia are thought to be "rejuvenated" and have been shown to be beneficial in several disease contexts and in normal aging. Their role in Alzheimer's disease (AD) is thus of great interest as they represent a potential disease-modifying therapy.

Impact of race and ethnicity on glaucoma progression detection by perimetry and optical coherence tomography.

This study assessed the impact of race and ethnicity on longitudinal test variability and time to detect glaucoma progression using standard automated perimetry (SAP) and optical coherence tomography (OCT). The sample consisted of 47,003 SAP tests from 5402 eyes and 25,480 OCT tests from 4125 eyes, with 20% of participants self-identifying as Black or African American and 80% as White; 29% as Hispanic or Latino and 71% as Not Hispanic or Latino. Variability was measured using standard deviations of residuals from linear regression models for SAP mean deviation (MD) and OCT retinal nerve fiber layer (RNFL) thickness over time.

Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure.

Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.

Nutritional composition, nitrogen-corrected true metabolizable energy, and standardized amino acid digestibility of palm kernel meal from several countries.

Extensive nutritional analyses were conducted for palm kernel meal (PKM) sourced from 5 countries. Two precision-fed rooster trials were conducted to evaluate the nitrogen-corrected true metabolizable energy (TME) and standardized amino acid (AA) digestibility of 10 PKM samples (PKM 1 to 10). The TME was determined using conventional Single Comb White Leghorn roosters, and standardized AA digestibility was determined using cecectomized roosters.

Changes in Medication Complexity and Post-Hospitalization Outcomes in Older Adults Hospitalized for Heart Failure.

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes.