Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Preliminary effects of oral ANS-6637, an ALDH2 inhibitor, on cue-induced craving, safety and alcohol consumption among adults with alcohol use disorder: a proof-of-concept, randomized, human laboratory trial.

Aims: We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD).

Methods: A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200 mg and 600 mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session.

Daily associations between sleep and alcohol use among veterans: Acute and cumulative effects.

Background And Aims: Military veterans demonstrate high rates of heavy drinking and insomnia, but few if any studies have tested real-world, daily associations between sleep and alcohol use within this population. Moreover, although daily diary and experimental studies among civilians have found negative associations between alcohol use and sleep, these patterns change with consecutive days of drinking and may differ for those with insomnia. This study measured (a) acute and cumulative day-level associations between sleep and alcohol use among heavy-drinking US veterans and (b) the extent to which insomnia moderates these associations.

Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.

Exploring the Predictive Role of 11-Oxyandrogens in Diagnosing Polycystic Ovary Syndrome.

Context: Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS), yet the androgen(s) responsible remain ambiguous. Recent studies have suggested that 11-oxygenated C steroids (11-oxyandrogens), specifically 11-ketotestosterone, may be a good marker for hyperandrogenism in PCOS.

Objective: To investigate the utility of 11-oxyandrogens to differentiate women with and without PCOS relative to classical androgens.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Quantifying the Deficits of Body Water and Monovalent Cations in Hyperglycemic Emergencies.

Hyperglycemic emergencies cause significant losses of body water, sodium, and potassium. This report presents a method for computing the actual losses of water and monovalent cations in these emergencies. We developed formulas for computing the losses of water and monovalent cations as a function of the presenting serum sodium and glucose levels, the sum of the concentrations of sodium plus potassium in the lost fluids, and body water at the time of hyperglycemia presentation as measured by bioimpedance or in the initial euglycemic state as estimated by anthropometric formulas.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

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).

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.

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.

Neighborhood Factors related to Cancer Screening in Texas: a spatioecological study.

Introduction: To examine the associations of neighborhood socioeconomic status (nSES), ethnic enclaves, residential Black segregation with screening for breast, cervical and colorectal (CRC) cancers across the state of Texas (TX).

Methods: Using an ecologic study design, spatial clustering of low breast, cervical and CRC screening rates were identified across TX census tracts using local Moran's I statistics. Binomial spatial probit regression was used to estimate the associations between nSES, Hispanic/Latino and Asian American (AA) ethnic enclave neighborhoods and residential Black segregation with geospatial clusters of low screening, adjusting for behavioral characteristics.

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV.

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses).

Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis.

Background And Objective: The impact of menopause on the brain is not well understood. Hormonal changes, including puberty and pregnancy, influence the onset and course of multiple sclerosis (MS). After menopause, a worsening of MS disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some, but not all, studies.

Longitudinal cognitive performance of participants with sporadic early onset Alzheimer's disease from LEADS.

Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.

Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared.

Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms.

Introduction: Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.

Methods: We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).

Life's Essential 8 and midlife trajectories in cognition and brain health: The CARDIA study.

Introduction: Poor cardiovascular health (CVH) is linked to Alzheimer's disease and dementia; however, its association with neurocognitive trajectories earlier in life remains underexplored.

Methods: We included 3224 participants with information on CVH at early midlife (mean age 45.0 ± standard deviation 3.

Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.

Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.

Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts.

Sleep spindle variation in patients with Parkinson's disease on first nights of sub-optimal deep brain stimulation.

Objective: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a common treatment for motor symptoms of Parkinson's disease but its influence on non-motor symptoms is less clear. Sleep spindles are known to be reduced in patients with Parkinson's disease, but the effect of STN DBS is unknown. The objective of our study was to address this knowledge gap.

Retest reliability and reliable change of community-dwelling Black/African American older adults with and without mild cognitive impairment using NIH Toolbox-Cognition Battery and Cogstate Brief Battery for laptop.

Objective: With the increased use of computer-based tests in clinical and research settings, assessing retest reliability and reliable change of NIH Toolbox-Cognition Battery (NIHTB-CB) and Cogstate Brief Battery (Cogstate) is essential. Previous studies used mostly White samples, but Black/African Americans (B/AAs) must be included in this research to ensure reliability.

Method: Participants were B/AA consensus-confirmed healthy controls (HCs) (n = 49) or mild cognitive impairment (MCI) (n = 34) adults 60-85 years that completed NIHTB-CB and Cogstate for laptop at two timepoints within 4 months.

Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.

Background: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.

Methods: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment).