Structure-guided optimization of small molecules targeting the yeast casein kinase, Yck2, as a therapeutic strategy to combat Candida albicans.

is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2.

Development of Effective Connectome from Infancy to Adolescence.

Delineating the normative developmental profile of functional connectome is important for both standardized assessment of individual growth and early detection of diseases. However, functional connectome has been mostly studied using functional connectivity (FC), where undirected connectivity strengths are estimated from statistical correlation of resting-state functional MRI (rs-fMRI) signals. To address this limitation, we applied regression dynamic causal modeling (rDCM) to delineate the developmental trajectories of effective connectivity (EC), the directed causal influence among neuronal populations, in whole-brain networks from infancy to adolescence (0-22 years old) based on high-quality rs-fMRI data from Baby Connectome Project (BCP) and Human Connectome Project Development (HCP-D).

From isolation to detection, advancing insights into endothelial matrix-bound vesicles.

Matrix-bound vesicles (MBVs), an integral part of the extracellular matrix (ECM), are emerging as pivotal factors in ECM-driven molecular signaling. This study is the first to report the isolation of MBVs from porcine arterial endothelial cell basement membranes (A-MBVs) and thyroid cartilage (C-MBVs), the latter serving as a negative control due to its minimal vascular characteristics. Using Transmission Electron Microscopy (TEM), Nano-Tracking Analysis (NTA), Electrochemical Impedance Spectroscopy (EIS), and Atomic Force Microscopy (AFM), we orthogonally characterized the isolated MBVs.

Understanding the bidirectional association between obesity and risk of psychological distress and depression in young adults in the US: available evidence, knowledge gaps, and future directions.

While the physical health effects of obesity are well-characterized, an emerging branch of research has shown that obesity additionally plays a critical role in one's mental health. Young adults, in a pivotal transition phase in their lives, may be particularly prone to the concurrent effects of obesity and adverse mental health outcomes. The purpose of this review is to comprehensively examine existing data regarding the connection between obesity and two widely validated measures of mental health: psychological distress and depression.

Meta-omics reveals role of photosynthesis in microbially induced carbonate precipitation at a CO-rich geyser.

Microbially induced carbonate precipitation (MICP) is a natural process with potential biotechnological applications to address both carbon sequestration and sustainable construction needs. However, our understanding of the microbial processes involved in MICP is limited to a few well-researched pathways such as ureolytic hydrolysis. To expand our knowledge of MICP, we conducted an omics-based study on sedimentary communities from travertine around the CO-driven Crystal Geyser near Green River, Utah.

A nociceptor-specific RNAi screen in larvae identifies RNA-binding proteins that regulate thermal nociception.

Nociception is the process by which sensory neurons detect and encode potentially harmful environmental stimuli to generate behavioral responses. Nociceptor neurons exhibit plasticity in which their sensitivity to noxious stimuli and subsequent ability to drive behavior may be altered by environmental conditions, injury, infection, and inflammation. In some cases, nociceptor sensitization requires regulated changes in gene expression, and recent studies have indicated roles for post-transcriptional mechanisms in regulating these changes as an aspect of nociceptor plasticity.

Challenges of Engaging Primary Care Providers in Specialized Telementoring Education About Sickle Cell Disease for Sickle Cell Specialists: Results from the Sickle Cell Disease Training and Mentoring Program for Primary Care Providers (STAMP) Project ECHO.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 100,000 individuals in the U.S. A lack of knowledgeable providers, particularly for adult patients, has led to a significant number of adults without access to high-quality care.

Evaluation of a new technology for terminal sterilization of flexible endoscopes using hydrogen peroxide gas plasma.

In laboratory testing, a novel hydrogen peroxide gas plasma endoscope sterilizer consistently reduced vegetative organisms, but not bacterial spores, to undetectable levels in the presence of high organism load (≥6.5 log) and organic material and salts. These findings highlight the importance of meticulous cleaning of endoscopes prior to sterilization.

Bayesian design of clinical trials with multiple time-to-event outcomes subject to functional cure.

With the continuous advancement of medical treatments, there is an increasing demand for clinical trial designs and analyses using cure rate models to accommodate a plateau in the survival curve. This is especially pertinent in oncology, where high proportions of patients, such as those with melanoma, lung cancer, and endometrial cancer, exhibit usual life spans post-cancer detection. A Bayesian clinical trial design methodology for multivariate time-to-event outcomes with cured fractions is developed.

Understanding the opioid syndemic in North Carolina: A novel approach to modeling and identifying factors.

The opioid epidemic is a significant public health challenge in North Carolina, but limited data restrict our understanding of its complexity. Examining trends and relationships among different outcomes believed to reflect opioid misuse provides an alternative perspective to understand the opioid epidemic. We use a Bayesian dynamic spatial factor model to capture the interrelated dynamics within six different county-level outcomes, such as illicit opioid overdose deaths, emergency department visits related to drug overdose, treatment counts for opioid use disorder, patients receiving prescriptions for buprenorphine, and newly diagnosed cases of acute and chronic hepatitis C virus and human immunodeficiency virus.

Differences in brain volume in individuals with mild cognitive impairment and normal cognition across different anatomical regions: The Atherosclerosis Risk in Communities (ARIC) study.

Background: Mild cognitive impairment (MCI) represents a stage between cognitively normal and Alzheimer's disease. Despite much published research on MCI, there continues to be a knowledge gap of volumetric brain changes in MCI versus cognitively normal (CN) in racially diverse, community-based samples.

Objective: The study aimed to understand differences in volume of selected brain regions in individuals with MCI versus those who are cognitively normal.

Assessing plasma-activated water as an acidic and sanitizer solution in clean-in-place (CIP) and comparing efficacy with other traditional CIP chemicals.

Cleaning-in-place (CIP) is the most commonly used cleaning and sanitation procedure for removing fouling deposits. Traditional CIP includes a series of chemical cleaning cycles, including alkaline, acid, and sanitizer. However, these chemicals are hazardous to the environment and employees.

Clin-STAR Corner: Rehabilitation for Older Adults With Heart Failure.

Heart failure is a major contributor to morbidity, mortality, and healthcare costs, especially among older adults. Despite a large body of evidence supporting the benefits of cardiac rehabilitation, less than 30% of eligible Medicare beneficiaries participate in cardiac rehabilitation. Thus, it is essential to examine alternatives, such as physical rehabilitation, a rehabilitation approach that focuses on physical activity and function.

Deployment and transcriptional evaluation of nitisinone, an FDA-approved drug, to control bed bugs.

Background: Bed bugs are blood-feeders that rapidly proliferate into large indoor infestations. Their bites can cause allergies, secondary infections and psychological stress, among other problems. Although several tactics for their management have been used, bed bugs continue to spread worldwide wherever humans reside.

Sex-specific effects on the heart from combined exposure to simulated galactic cosmic radiation and hindlimb unloading.

Future long duration space missions will expose astronauts to higher doses of galactic cosmic radiation (GCR) than those experienced on the international space station. Recent studies have demonstrated astronauts may be at risk for cardiovascular complications due to increased radiation exposure and fluid shift from microgravity. However, there is a lack of direct evidence on how the cardiovascular system is affected by GCR and microgravity since no astronauts have been exposed to exploratory mission relevant GCR doses.

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.

Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.

Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.

Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.

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).

Perceived organizational support for the treatment of opioid use disorder and its association with primary care provider treatment willingness and medication prescribing.

Introduction: Buprenorphine is a highly effective medication for opioid use disorder (MOUD; OUD), which can be prescribed alongside naloxone in the primary care setting as part of a harm reduction approach to OUD. Despite this potential, implementation challenges have limited adoption of MOUD. To address barriers at the organizational level, we need better tools to measure perceived organizational support for the treatment of OUD and use of MOUD in the primary care setting.

Different forms of stigma and rural primary care professionals' willingness to prescribe buprenorphine.

Introduction: Buprenorphine and other medications for opioid use disorder (MOUD) are highly effective but substantially under prescribed in the rural United States. Among the most cited barriers to buprenorphine prescribing is stigma, yet little progress has been made in developing successful strategies to reduce stigma and increase access to life-saving medication. One of the key challenges to developing successful implementation strategies is understanding the different types of stigma that limit implementation.