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).

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.

Enhancing Data Science and Genomics Capacity of a Historically Black Medical College Through Interdisciplinary Training and Research Collaborations.

As data grows exponentially across diverse fields, effectively leveraging big data has become increasingly crucial. In data science and computational genomics, however, minority groups, including African Americans, are significantly underrepresented, coupled with the lack of resources and infrastructure in minority-serving institutions. This paper summarizes the second phase of our funded project that aims to enhance the data science capacity of Meharry Medical College (MMC), a Historically Black College/University (HBCU), by providing training and fostering collaborations between data scientists and researchers in basic science and biomedical fields.

Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.

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.

Measuring food security in university students: A comparison of the USDA 10-item and six-item food security survey modules.

We examined discordant food security (FS) status classification between the USDA 10-item and six-item FS Survey Modules (FSSMs) among students at a U.S. university.

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.

Social Norms Regarding Alcohol Use, Perceptions of Alcohol Advertisement and Intent to Drink Alcohol among Youth in Uganda.

The objective of this paper is to address the scarcity of research on alcohol marketing exposure and underage drinking in sub-Saharan Africa. This study examines perceptions of alcohol advertisements and perceived peer, adult, and parental attitudes regarding alcohol use and intentions to drink among vulnerable youth. The Kampala Youth Survey is a cross-sectional study conducted in 2014 with service-seeking youth (ages 12-18 years) living in the slums of Kampala (n=1,134) who were participating in Uganda Youth Development Link drop-in centers.

Promoting braveness in children: A pilot study on the effects of a brief, intensive CBT-based anxiety prevention programme conducted in the South African context.

Background: Children within historically disadvantaged non-Western South African communities are considered as particularly vulnerable to the development of anxiety problems. Although the need for accessible mental health interventions is evident, this need has remained unmet in a country with extreme socio-economic disparities and a lack of mental health resources. Cognitive behavioural therapy-based (CBT-based) interventions that employ brief and intensive delivery methods may overcome existing barriers to access to mental health services faced by many South African children and may ameliorate the burden placed on under-resourced mental health care services.

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.

Macular patterns of neuronal and visual field loss in recovered optic neuritis identified by machine learning.

We used machine learning to investigate the residual visual field (VF) deficits and macula retinal ganglion cell (RGC) thickness loss patterns in recovered optic neuritis (ON). We applied archetypal analysis (AA) to 377 same-day pairings of 10-2 VF and optical coherence tomography (OCT) macula images from 93 ON eyes and 70 normal fellow eyes ≥ 90 days after acute ON. We correlated archetype (AT) weights (total weight = 100%) of VFs and total retinal thickness (TRT), inner retinal thickness (IRT), and macular ganglion cell-inner plexiform layer (GCIPL) thickness.