Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review.

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

Correlation between different boundaries used in upper airway assessment.

Background: The aim of this study was to evaluate the correlation of the volume and minimum axial area (MAA) measurements between different upper and lower boundaries used for oropharyngeal airway assessment.

Methods: Cone Beam Computed Tomography (CBCT) scans of 49 subjects taken for pre-orthognathic surgical planning were obtained retrospectively from the archives (n = 49; 32 females, 17 males; mean age = 20.9 ± 5.

Anomalous left pulmonary artery: case reports exploring anatomic variants.

Background: Pulmonary artery sling (PAS) is a rare congenital anomaly where the left pulmonary artery (LPA) branches from the right pulmonary artery, compressing the trachea and esophagus and frequently leading to respiratory distress in infants. Surgical intervention, such as LPA reimplantation or translocation, is crucial to relieve airway compression and restore normal pulmonary function.

Case Presentation: This report highlights varied LPA anatomies, including a unique case of an anomalous LPA without true sling formation but causing tracheal compression, alongside two typical PAS cases.

Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From TROPiCS-03.

Introduction: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).

Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study in solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one prior line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle.

Novel Use of Drug-eluting Stent in Otologic Surgery to Prevent Restenosis.

Objectives: The primary objective of this case series is to assess the effectiveness of the off-label use of the PROPEL drug-eluting stent, traditionally FDA-approved for sinus surgery, in preventing restenosis following canalplasty in patients with chronic otologic conditions or congenital anomalies. The stent provides both mechanical support to maintain canal patency and localized steroid delivery to reduce inflammation and scarring.

Methods: Four patients with various otologic conditions underwent canalplasty, followed by the placement of drug-eluting stents into the external auditory canal.

Histopathologic Features of Acral Skin Biopsies in Dermatomyositis Patients and Comparison to Histopathologic Features in Non-Acral Biopsies.

Background: Acral lesions may represent the best/only skin lesions to biopsy in patients suspected to have dermatomyositis (DM). However, histopathologic features of acral DM skin lesions are poorly characterized.

Methods: We reviewed 50 acral biopsies from 46 DM patients and assessed numerous histopathologic features.

Hair isoniazid levels predict TB sputum culture conversion.

Sputum culture is the gold standard for diagnosing TB disease and confirming treatment outcomes. However, the turnaround time is 6-8 weeks, which leads to delays in decision-making regarding the care of TB patients.To evaluate isoniazid hair drug levels as a predictor of sputum culture conversion at 8 weeks of TB treatment.

A little protein makes big news in translation initiation.

While most of the regulation of translation initiation occurs in the cytosol predominantly through phosphorylation, Ly et al. have discovered the first instance of regulation via protein concentration due to disruption of the nuclear membrane at mitosis. Only eIF1 appears to be involved in this regulation, and its release at mitosis enhances translational accuracy of start codon recognition.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Basic Science and Pathogenesis.

Background: Several viruses have been linked to Alzheimer disease (AD) by independent lines of evidence.

Method: Whole genome and whole exome sequences (WGS/WES) derived from brain (3,404 AD cases, 894 controls) and blood (15,612 AD cases, 24,544 controls) obtained from European ancestry (EU), African American (AA), Mexican (HMX), South Asian Indian (IND), and Caribbean Hispanic (CH) participants of the Alzheimer's Disease Sequencing Project (ADSP) and 276 AD cases 3,584 controls (all EU) from the Framingham Heart Study (FHS) that did not align to the human reference genome were aligned to viral reference genomes. A genome-wide association study (GWAS) for viral DNA load was conducted using PLINK software and regression models with covariates for sex, age, ancestry principal components, and tissue source.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.

Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) has both genetic and environmental risk factors. Gene-environment interaction may help explain some missing heritability. There is strong evidence for cigarette smoking as a risk factor for AD.

Basic Science and Pathogenesis.

Background: Apolipoprotein E (ApoE) is the primary cholesterol and lipid transporting apolipoprotein in the central nervous system (CNS) and is the greatest genetic risk factor for Alzheimer's Disease (AD). There are three main isoforms differing by single amino acid changes: ε3 is "neutral", ε4 is "risk" (Cys112Arg), and ε2 is "resilience" (Arg158Cys). Rare forms (Christchurch, Jacksonville) have also been proposed as resilience alleles, while an ε4-like allele (with Arg61Thr) is present in non-human primates without AD risk.

Basic Science and Pathogenesis.

Background: The Apolipoprotein E ε4 (APOE-ε4) allele is common in the population, but acts as the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Despite the strength of the association, there is notable heterogeneity in the population including a strong modifying effect of genetic ancestry, with the APOE-ε4 allele showing a stronger association among individuals of European ancestry (EUR) compared to individuals of African ancestry (AFR). Given this heterogeneity, we sought to identify genetic modifiers of APOE-ε4 related to cognitive decline leveraging APOE-ε4 stratified and interaction genome-wide association analyses (GWAS).

Basic Science and Pathogenesis.

Background: Microglia have been implicated as a key aspect of the pathology of Alzheimer's disease (AD). However, high microglial heterogeneities, including disease-associated microglia (DAM), tau microglia (tau-pathology related), and neuroinflammation-like microglia (NIM), hinder the development of microglia-targeted treatment.

Method: In this study, we integrated ∼0.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a severe neurodegenerative condition that affects millions of people worldwide. The TgF344 AD rat model, which exhibits early depression-like behavior followed by later cognitive impairment, is widely used to evaluate putative biomarkers and potential treatments for AD. The P7C3 neuroprotective compounds have shown protective efficacy for both brain pathology and neuropsychiatric impairment in this model.

Basic Science and Pathogenesis.

Background: Although high-throughput DNA/RNA sequencing technologies have generated massive genetic and genomic data in human disease, translation of these findings into new patient treatment has not materialized by lack of effective approaches, such as Artificial Intelligence (AL) and Machine Learning (ML) tools.

Method: To address this problem, we have used AI/ML approaches, Mendelian randomization (MR), and large patient's genetic and functional genomic data to evaluate druggable targets using Alzheimer's disease (AD) as a prototypical example. We utilized the genomic instruments from 9 expression quantitative trait loci (eQTL) and 3 protein quantitative trait loci (pQTL) datasets across five human brain regions from three biobanks.

Basic Science and Pathogenesis.

Background: In this introductory talk, we embark on a journey of through the genomic frontiers of Alzheimer's research via the revolutionary Alzheimer's Disease Sequencing Project (ADSP).

Method: ADSP integrates together various components that collectively unravel the intricate genetic landscape of Alzheimer's disease with the ultimate goal of advancing precision medicine for the millions affected globally by this devastating disease. With a goal of sequencing and analyzing up to 150,000 complete genomes and associated clinical and functional data in the next five years, ADSP has amassed an unprecedented wealth of genomic data from diverse populations, providing a comprehensive and holistic understanding of the genetic underpinnings of Alzheimer's disease.

Basic Science and Pathogenesis.

Background: Many independent studies have found rare variants associated with AD. Current gene-based tests for rare-variants generally consider the impact of low-frequency coding variants as an independent effect from the common regulatory variants that surround them. In this work, we propose to increase the statistical power of kernel-based rare-variant association tests by accounting for the surrounding cis-regulatory variants' effects on gene expression.

Basic Science and Pathogenesis.

Background: Annotation of target genes of non-coding GWAS loci remains a challenge since 1) regulatory elements identified by GWAS can be metabases away from its actual target, 2) one regulatory element can target multiple genes, and 3) multiple regulatory elements can target one gene. AD GWAS in populations with different ancestries have identified different loci, suggesting ancestry-specific genetic risks. To understand the connection between associated loci (potential regulatory elements) and their target genes, we conducted Hi-C analysis in frontal cortex of African American (AA) and Non-Hispanic Whites (NHW) AD patients to map chromatin loops, which often represent enhancer-promoter (EP) interactions.

Basic Science and Pathogenesis.

Background: Emerging evidence links Alzheimer's disease (AD) to dysfunction of the primary cilium, a historically overlooked organelle that serves as the neuron's antenna. All neurons harbor a single primary cilium that projects from the membrane to sense changes in the extracellular environment. Primary cilia dysfunction leads to a group of diseases called 'ciliopathies', which are associated with reduced hippocampal and cortical mass, as well as neurocognitive impairment.

Basic Science and Pathogenesis.

Background: Age is the largest risk factor for late-onset Alzheimer's Disease (LOAD). Although >80 genetic loci have been associated with LOAD, little is known about the age dependencies of these associations except the APOE region.

Method: We performed cross-ancestry and ancestry-specific genome-wide gene-age interaction and age-stratified association study using TOPMed-imputed genome-wide association study (GWAS) data from Alzheimer's Disease Genetics Consortium (ADGC) including 34,833 non-Hispanic Whites (NHW), 7,264 African Americans (AA), 3,232 East Asians (EA), and 2,024 Caribbean Hispanics (CH) aged 60 years and older.

Basic Science and Pathogenesis.

Background: "SuperAgers" are older adults (ages 80+) whose cognitive performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary aging are underexplored in large, racially diverse cohorts. Using eight cohorts, we investigated the frequency of APOE genotypes in SuperAgers compared to middle-aged and older adults.

Basic Science and Pathogenesis.

Background: Prior studies have shown differences in the genetic etiology and clinical presentation of Alzheimer's Disease across populations. For example, for multiple genetic loci associated with AD, effect sizes can vary drastically between individuals of different ancestral backgrounds. Few investigations into differences in epigenetic features like DNA methylation have been conducted in AD, particularly in diverse individuals.