Alzheimer's disease drug development in an evolving therapeutic landscape.

Unlabelled: The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA-approved amyloid plaque-lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape.

A standardized care pathway increases optimal dialysis starts.

Objective:  To determine whether an intensive value-based care educational program that includes a standardized end-stage renal disease (ESRD) transition pathway would improve the number of optimal starts within Kidney Contracting Entities (KCEs).

Study Design: Retrospective cohort study.

Methods:  We recorded optimal starts, defined as the initiation of dialysis without a central venous catheter, and the initial modality type (hemodialysis vs peritoneal dialysis [PD]) in adult Medicare patients in a Comprehensive Kidney Care Contracting program.

Long-Term Follow-Up and Overall Survival in NRG258, a Randomized Phase III Trial of Chemoradiation Versus Chemotherapy for Locally Advanced Endometrial Carcinoma.

This randomized phase III trial aimed to determine whether treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for four cycles (chemoradiotherapy [C-RT]) increased recurrence-free survival (RFS) and overall survival (OS) when compared with carboplatin and paclitaxel for six cycles (chemotherapy [CT]) in locally advanced endometrial cancer (UC). Previously reported results showed that C-RT did not improve RFS compared with CT. Here we report the final OS analysis.

Detecting gene expression in Caenorhabditis elegans.

Reliable methods for detecting and analyzing gene expression are necessary tools for understanding development and investigating biological responses to genetic and environmental perturbation. With its fully sequenced genome, invariant cell lineage, transparent body, wiring diagram, detailed anatomy, and wide array of genetic tools, Caenorhabditis elegans is an exceptionally useful model organism for linking gene expression to cellular phenotypes. The development of new techniques in recent years has greatly expanded our ability to detect gene expression at high resolution.

Intraplaque Hemorrhage and Plaque Ulceration Are More Likely in Patients with Symptomatic Mild-to-Moderate Carotid Artery Stenosis than in Symptomatic and Asymptomatic High-Grade Stenosis: A Retrospective Cohort Study.

Background: To compare a cohort of symptomatic patients with mild-to-moderate (<70%) carotid artery stenosis (CAS) with those patients with high-grade (≥70%) CAS (symptomatic and asymptomatic) to assess for markers that places them at a higher risk for stroke.

Methods: A propensity score-matched cohort study design for all patients who underwent carotid revascularization between 2015 and 2024 was utilized to compare the high-grade (≥70%) symptomatic and asymptomatic carotid stenosis groups against the mild to moderate (<70%) symptomatic carotid stenosis group. Matched variables included age, sex, and atrial fibrillation.

The development of children's gender stereotypes about STEM and verbal abilities: A preregistered meta-analytic review of 98 studies.

This meta-analysis studied the development of ability stereotypes that could limit girls' and women's participation in science, technology, engineering, and mathematics (STEM) fields, as well as contribute to boys' underachievement in reading and writing. We integrated findings from 98 studies measuring children's gender stereotypes about STEM and verbal abilities. The data comprised 145,204 children (ages 4-17) from 33 nations across more than 40 years (1977-2020).

Characteristics and Risks of Endophthalmitis Following 25-gauge Vitrectomy Surgery over a 14-year period.

Purpose: To analyze endophthalmitis characteristics and risks following a 25-gauge vitrectomy or microincision vitrectomy surgery (MIVS).

Design: Retrospective.

Subjects: Post-MIVS endophthalmitis patients.

Novel Macrocyclic NLRP3 Inhibitors.

Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later.

CATH v4.4: major expansion of CATH by experimental and predicted structural data.

CATH (https://www.cathdb.info) is a structural classification database that assigns domains to the structures in the Protein Data Bank (PDB) and AlphaFold Protein Structure Database (AFDB) and adds layers of biological information, including homology and functional annotation.

Barriers and Facilitators to Incorporating an Integrative Mind-Body Intervention in Youth With Type 2 Diabetes.

Objective: There has been little to no qualitative research done with adolescents and young adults (AYA) with type 2 diabetes (T2D) that can guide creation of interventions for this demographic. Using qualitative research methods, a novel mind-body intervention called Intervention for Early Onset Type 2 Diabetes (INTEND) has been developed for AYA aged 15 to 20 years, with the goal of improving self-management and coping skills, by enhancing routine care with augmented education coupled with mind-body skills.

Method: Qualitative interviews with AYA 15 to 20 years of age with T2D, their parents, and professionals caring specifically for this population were done through a focus group model.

Protocol for isolating specific C. elegans neuron types for bulk and single-cell RNA sequencing.

The C. elegans nervous system is compact and well described, ideal for identifying genetic programs that drive neuron-specific development, function, and connectivity. Here, we present a protocol for isolating specific neuron types for gene expression profiling by bulk or single-cell RNA sequencing.

Welfare and performance benefits of shade provision during summer for feedlot cattle in a temperate climatic zone.

There is increasing interest from cattle lot-feeders in the use of shade to mitigate the effects of a potential heat-stress event, though it is unclear whether the reported benefits of shade in previous studies conducted in more high-risk heat-stress zones are pertinent in cooler temperate zones. The objectives of this study were to measure the welfare and performance benefits of shade provision for lot-fed cattle at a commercial feedlot located in a mild heat-stress risk zone in Western Australia. Six blocks of black Angus (Bos taurus) steers were inducted into the feedlot over 6 time windows across a southern hemisphere summer, with 80 cattle per block housed in a partially shaded pen (providing 3.

Improving the integration of epidemiological data into human health risk assessment: What risk assessors told us they want.

One of the practical contributions of epidemiology studies is to inform risk assessment and management to protect public health. However, there is a perception among some that environmental and occupational epidemiology is falling short of satisfying the needs of risk assessors. The specific reasons for this are not clearly understood.

Implementation of a Standardized Process of Coude Catheter Insertion Decreases Traumatic Catheterizations.

Objective: To address the issue of traumatic foley catheterization, we developed and implemented a coude catheter education program for operating room nurses as well as standardize the usage of a coude catheter for male patients. Traumatic catheterization leads to patient morbidity and increased healthcare costs.

Methods: A retrospective review was conducted to identify all traumatic catherizations over a 6-month period for several surgical services at our institution.

Impact of Gene Expression Classifier Testing on Adjuvant Treatment Following Radical Prostatectomy: The G-MINOR Prospective Randomized Cluster-crossover Trial.

Background And Objective: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP.

Methods: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.

Evaluating Scholastic Achievement in Pediatric Brain Tumor Survivors Compared With Healthy Controls.

Purpose: Radiation therapy (RT) causes cognitive deficits in pediatric brain tumor survivors (PBTS). Traditionally, this is measured using neuropsychological testing, which lack prediagnosis baseline and do not necessarily trigger action. This pilot project investigated a novel patient-centered outcome of scholastic performance using state-collected educational data.

Benefits and risks of FDA-approved amyloid-targeting antibodies for treatment of early Alzheimer's disease: Navigating clinician-patient engagement.

The emergence of the United States Food and Drug Administration (FDA)-approved amyloid-targeting therapies for Alzheimer's disease challenges clinicians and healthcare providers with a transformative landscape. Effectively communicating the risks, benefits, burdens, costs, and available support associated with these novel disease-modifying treatments to patients, families, and other healthcare providers is essential but complex. In response, the Alzheimer's Association's Clinical Meaningfulness Workgroup has proposed language surrounding treatment eligibility, benefits, amyloid-related imaging abnormalities (ARIA), apolipoprotein E (APOE) genotyping, and treatment costs, serving as a resource to healthcare professionals in navigating discussions with patients and their families.

Measuring, processing, and generating partially coherent light with self-configuring optics.

Optical phenomena always display some degree of partial coherence between their respective degrees of freedom. Partial coherence is of particular interest in multimodal systems, where classical and quantum correlations between spatial, polarization, and spectral degrees of freedom can lead to fascinating phenomena (e.g.

Music in Care (MIC) by Nurses: Initial Validation of a Questionnaire to Characterize Nurses' Attitudes and Feasibility of Implementation on the Use of Music in Patient Care.

The purpose of this study was to characterize nurses' attitudes toward music and implementation of music into patient care and to characterize barriers and facilitators toward the implementation of music into patient care. A cross-sectional, quantitative, web-based questionnaire with minor qualitative elements. The questionnaire contained both open- and closed-ended questions.

FACTFINDERS for PATIENT SAFETY: Preventing procedure-related complications: Epidural lipomatosis and postpartum steroid exposure.

This series of FactFinders presents a brief summary of the evidence and outlines recommendations to improve our understanding and management of potential procedure-related complications. Evidence in support of the following facts is presented. (1) -- There is low-level evidence of an association between epidural steroid injections (ESIs) and the development and/or worsening of spinal epidural lipomatosis (SEL).