Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Background: The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases.

Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics.

An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)-a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene's spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power.

Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer.

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.

Gender differences in cognitive impairment among the elderly in rural West Texas counties.

Background: The prevalence of Alzheimer's disease or dementia in the elderly population has been increasing both nationally and globally. Males and females are impacted differently when it comes to cognitive health, and this can be influenced by various risk factors.

Objective: This study highlights the sociodemographic, chronic disease, and genetic biomarker risk factors associated with gender differences and cognitive impairments in the elderly population living in Cochran, Parmer, and Bailey counties of rural West Texas.

Subendocardial ischemia: does CMD really exist?

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress.

Galactic cosmic ray environment predictions for the NASA BioSentinel Mission, part 2:Post-mission validation.

The BioSentinel CubeSat was deployed on the Artemis-I mission in November 2022 and has been continuously transmitting physical measurements of the space radiation environment since that time. Just before mission launch, we published computational model predictions of the galactic cosmic ray exposure expected inside BioSentinel for multiple locations and configurations. The predictions utilized models for the ambient galactic cosmic ray environment, radiation physics and transport, and BioSentinel geometry.

Obsessive-compulsive symptoms in individuals with a history of eating disorders.

Background: OCD symptoms are well documented in anorexia nervosa (AN) and to a lesser extent in bulimia nervosa (BN), yet remain virtually unstudied in binge-eating disorder (BED).

Methods: In this cross-sectional observational study, 5927 participants with lifetime eating disorders (EDs) (i.e.

The Society of Thoracic Surgeons National Intermacs Database Risk Model for Durable Left Ventricular Assist Device Implantation.

Background: Statistical risk models for durable left ventricular assist device (LVAD) implantation inform candidate selection, quality improvement, and evaluation of provider performance. We developed a 90-day mortality risk model utilizing The Society of Thoracic Surgeons National Intermacs Database (STS Intermacs).

Methods: STS Intermacs was queried for primary durable LVAD implants from 1/ 2019 - 9/2023.

Patient Characteristics, Management and Long-term Outcomes of Patients with Cardiogenic Shock at a Large Safety Net Hospital.

Data regarding cardiogenic shock (CS) from safety-net hospitals serving socioeconomically-disadvantaged patients are limited. In addition, little is known regarding long-term outcomes and management of heart failure-related CS (HF-CS), a population potentially especially vulnerable to adverse social determinants of health (SDOH). A single-center retrospective cohort study of patients with Stage C, D, or E CS at a public safety-net hospital between 2017-2023 was performed.

Diffusion-weighted arterial spin labeling MRI to investigate mannitol-induced blood brain barrier disruption.

Purpose: Diffusion-weighted arterial spin labeling (DW-ASL) MRI has been proposed to determine the rate of water exchange (K) across the blood brain barrier (BBB). This study aims to further evaluate K MRI by comparing it with standard dynamic contrast-enhanced (DCE) MRI and histology in association with mannitol-induced disruption of the BBB.

Methods: DW-ASL was measured using a multiple b-value MRI protocol in normal rats at three post-labeling delays (N = 19), before and after intra-carotid injection of mannitol to disrupt BBB in one hemisphere (N = 13).

Impacto - A single-arm open-label pilot trial of a digital-based integrated smoking cessation program for Spanish-speaking Hispanic individuals who smoke: Development, feasibility, engagement, and clinical outcomes.

Introduction: Hispanic/Latinx (hereafter Hispanic) individuals who smoke have challenges in quitting and a disproportionate risk of smoking-related health problems when compared to the general population. The smoking inequalities among the Hispanic population are influenced by limited treatment access and chronic stress exposure (e.g.

Rhythm is essential: Unraveling the relation between the circadian clock and cancer.

Physiological processes such as the sleep-wake cycle, metabolism, hormone secretion, neurotransmitter release, sensory capabilities, and a variety of behaviors, including sleep, are controlled by a circadian rhythm adapted to 24-hour day-night periodicity. Disruption of circadian rhythm may lead to the risks of numerous diseases, including cancers. Several epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer.

Novel tertiary diarylethylamines as functionally selective agonists of the kappa opioid receptor.

Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC = 14 nM, 83 % E) that did not elicit a β-arrestin-2 recruitment functional response (E < 10 %).

The Full Range of Weight Status by Race and Ethnicity in Children with and without Autism: A Cross-sectional Study of US Children.

Objective: To identify and characterize how race and ethnicity influence the relationship between autism and weight status, across all categories of weight from underweight to severe obesity.

Study Design: We developed a propensity score-matched cross-sectional dataset of children with and without parent-reported autism in the National Survey of Children Health (NSCH, 2016-2022) and Adolescent Brain and Cognition Development Study (ABCD, 2016-2018). We included non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, and Hispanic children aged 6 to 17 years.

Mobilize the Troops! Military Involvement in the History of Testicular Cancer.

This review examines the historical evolution of testicular cancer (TCa) treatment, emphasizing the transformative impact of World War II. Prior to the war, cases of more than 50 testicular tumors were exceedingly rare. The mobilization of American troops, especially after the German Blitz, resulted in widespread military health screenings, leading to a surge in incidental TCa diagnoses during the 1940s.

Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.

Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration.

Characterizing the relationship between personality dimensions and psychosis-specific clinical characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included.

Effects of exercise and transient estradiol exposure in middle-aged female rats.

The benefits of estrogen treatment on cognition in middle-aged and older women are dependent on many factors, including the timing of treatment. Moreover, the potential interactive effects with other lifestyle factors, such as exercise, are poorly understood. In this study, we tested for lasting benefits of independent and combined treatment with estrogen and voluntary exercise initiated in midlife, using a rat model of menopause.

TiCT/Au NPs/PPy ternary heterostructure-based intra-capacitive self-powered sensor for DEHP detection.

Phthalate esters, particularly di(2-ethylhexyl) phthalate (DEHP), are widely used plasticizers found in various consumer products, posing significant environmental and health risks due to their endocrine-disrupting effects. In this study, a novel enzyme-free intra-capacitive biofuel cell self-powered sensor (ICBFC-SPS) was developed. The ICBFC-SPS integrated a ternary heterostructure-based capacitive anode and a cathode with a sensing interface into a single-chamber electrolytic cell.

The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.