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).

Parents' perspectives and behaviors regarding their child's access to alcohol: Variation by race/ethnicity, socioeconomic status, and neighborhood.

Background: Setting rules about alcohol use and minimizing its availability in the home are known effective parent-level strategies for reducing underage drinking risk. However, parents' restrictions and their perceptions of their child's alcohol access have rarely been considered in combination (e.g.

Transforming Agents: The Power of Structural Modifications in Glioblastoma Multiforme Therapy.

Glioblastoma (GBM) is a very deadly type of brain tumor with a poor prognosis and a short survival rate. Recent advancements in understanding GBM's molecular and genetic characteristics have led to the development of various therapeutic and diagnostic strategies. Key elements such as microRNAs, lncRNAs, exosomes, angiogenesis, and chromatin modifications are highlighted, alongside significant epigenetic alterations that impact therapy and diagnosis.

Reading the repertoire: Progress in adaptive immune receptor analysis using machine learning.

The adaptive immune system holds invaluable information on past and present immune responses in the form of B and T cell receptor sequences, but we are limited in our ability to decode this information. Machine learning approaches are under active investigation for a range of tasks relevant to understanding and manipulating the adaptive immune receptor repertoire, including matching receptors to the antigens they bind, generating antibodies or T cell receptors for use as therapeutics, and diagnosing disease based on patient repertoires. Progress on these tasks has the potential to substantially improve the development of vaccines, therapeutics, and diagnostics, as well as advance our understanding of fundamental immunological principles.

A cellulose synthase-like protein governs the biosynthesis of alkaloids.

Decades of research on the infamous antinutritional steroidal glycoalkaloids (SGAs) in Solanaceae plants have provided deep insights into their metabolism and roles. However, engineering SGAs in heterologous hosts has remained a challenge. We discovered that a protein evolved from the machinery involved in building plant cell walls is the crucial link in the biosynthesis of SGAs.

Measuring Phospholipid Flippase Activity by NBD-Lipid Uptake in Living Yeast Cells.

Phospholipid flippases in the P4-ATPase family are essential for establishing membrane asymmetry. These ATP-powered pumps translocate specific lipids from the exofacial leaflet to the cytosolic leaflet of the plasma membrane, thereby concentrating substrate lipids, such as phosphatidylserine, in the cytosolic leaflet while non-substrate lipids populate the exofacial leaflet. Here, we describe a method for measuring P4-ATPase transport activity in the yeast plasma membrane by using flow cytometry to quantify the uptake of lipids derivatized with a fluorescent [7-nitro-2-1,3-benzoxadiazol-4-yl)amino] (NBD) group on a short (C6) fatty acyl chain.

Thyroid hormone and the Liver.

It is known that thyroid hormone can regulate hepatic metabolic pathways including cholesterol, de novo lipogenesis, fatty acid oxidation, lipophagy, and carbohydrate metabolism. Thyroid hormone action is mediated by the thyroid hormone receptor (THR) isoforms and their coregulators, and THRβ is the main isoform expressed in the liver. Dysregulation of thyroid hormone levels, as seen in hypothyroidism, has been associated with dyslipidemia and metabolic dysfunction-associated fatty liver disease.

BLOOD FATTY ACID PROFILES IN CHILEAN () AND CARIBBEAN () FLAMINGOS IN MANAGED CARE.

Flamingos in managed care are vulnerable to inflammatory states, including pododermatitis, trauma, and capture myopathy. Fatty acids are an important component of well-balanced nutrition and crucial to endogenous immune responses associated with these conditions, yet fatty acids have not been assessed in flamingos. This study reported complete whole blood circulating fatty acid profiles in two flamingo species in managed care receiving different diets.

The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease.

Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.

Sex-specific mechanisms of cerebral microvascular BK dysfunction in a mouse model of Alzheimer's disease.

Introduction: Cerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca-activated K channels (BK) regulate cerebrovascular reactivity and are impaired in AD. BK activity depends on intracellular Ca (Ca sparks) and nitro-oxidative post-translational modifications.

Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study.

Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.

Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility.

The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition.

Strength of clinical evidence supporting the United States Food and Drug Administration Accelerated Approvals from 2015 to 2022.

Background: The Food and Drug Administration (FDA)'s Accelerated Approval (AA) pathway has increasingly used to authorize market approval of new drugs amid controversy. The present study aims to inform the most recent data on the strength of clinical evidence supporting such approvals.

Methods: Evidentiary characteristics of pre-approval pivotal clinical studies and regulator-required post-approval confirmatory studies supporting AAs between 2015 and 2022 were extracted from publicly available FDA documents.

Predicting emergence of crystals from amorphous precursors with deep learning potentials.

Crystallization of amorphous precursors into metastable crystals plays a fundamental role in the formation of new matter, from geological to biological processes in nature to the synthesis and development of new materials in the laboratory. Reliably predicting the outcome of such a process would enable new research directions in these areas, but has remained beyond the reach of molecular modeling or ab initio methods. Here we show that candidates for the crystallization products of amorphous precursors can be predicted in many inorganic systems by sampling the local structural motifs at the atomistic level using universal deep learning interatomic potentials.

Advancing digital sensing in mental health research.

Digital sensing tools, like smartphones and wearables, offer transformative potential for mental health research by enabling scalable, longitudinal data collection. Realizing this promise requires overcoming significant challenges including limited data standards, underpowered studies, and a disconnect between research aims and community needs. This report, based on the 2023 Workshop on Advancing Digital Sensing Tools for Mental Health, articulates strategies to address these challenges to ensure rigorous, equitable, and impactful research.

HRS Improves Active Surveillance for Prostate Cancer by Timely Identification of Progression.

Rationale And Objectives: Active surveillance (AS) is the preferred management strategy for low-risk prostate cancer. This study aimed to evaluate the impact of Habitat Risk Score (HRS), an automated approach for mpMRI analysis, for early detection of progressors in a prospective AS clinical trial (MAST NCT02242773).

Materials And Methods: The MAST protocol includes Confirmatory mpMRI ultrasound fusion (MRI-US) biopsy and yearly surveillance MRI-US biopsies for up to 3 years.

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Disparities in Access to Valganciclovir Cytomegalovirus Prophylaxis in High-Risk African American Kidney Transplant Patients.

Background: While access and outcomes disparities for African American (AA) kidney transplant recipients are documented, there are limited studies assessing medication access disparities in transplantation. Cytomegalovirus (CMV) causes severe complications for transplant recipients, and we aimed to understand differences in access to CMV prophylaxis valganciclovir and its impact on CMV infection rates in AA transplant recipients.

Methods: This single-center, retrospective longitudinal cohort study examined high-risk (CMV serostatus D+/R-) adult kidney transplant recipients between June 1, 2010, and May 31, 202, through EMR abstraction.

Early life exposure to structural sexism and late-life memory trajectories among black and white women and men in the United States.

Introduction: We investigated whether early life exposure to state-level structural sexism influenced late-life memory trajectories among United Staes (U.S.) -born women and men and determined whether associations differed between racialized groups.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice.

Inflammatory bowel disease is associated with several genetic risk loci. Loss-of-function mutation in the α1,2-fucosyltransferase (fut2) gene, which alters fucosylation on the surface of intestinal epithelial cells, is one example. However, whether bacterial fucosylation can contribute to gut inflammation is unclear.

Development of a natural rubber latex-based biodevice with mesenchymal stem cells as a potential treatment for skeletal muscle regeneration in gestational diabetes-induced myopathy.

Women with gestational diabetes mellitus show a high risk of developing Gestational Diabetes Induced Myopathy (GDiM). GDiM is characterized by significant pelvic floor skeletal muscle atrophy and urinary incontinence. This study aimed to develop a natural rubber latex (NRL) based biodevice with mesenchymal/stromal stem cells (MSCs) for skeletal muscle regeneration for women with GDiM.

Therapeutically-Induced Lymphangiogenesis is Ineffective in Resolving Established Kidney Disease in Mice.

Background: Chronic kidney disease (CKD) counts acute kidney injuries (AKI) as one of its many underlying causes. Lymphatic vessels are important in modulating inflammation post-injury. Manipulating lymphatic vessel expansion thus has the potential to alter CKD progression.