Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

A gated hydrophobic funnel within BAX binds long-chain alkenals to potentiate pro-apoptotic function.

Mitochondria maintain a biochemical environment that cooperates with BH3-only proteins (e.g., BIM) to potentiate BAX activation, the key event to initiate physiological and pharmacological forms of apoptosis.

Updated Geriatrics Competencies for Graduating Medical Students: Training Physicians to Provide Age-Friendly Care.

Purpose: Medical student education in geriatrics is a critical need for every doctor-in-training as the population ages, with fewer than 7,000 geriatricians, and older patients, who now approach 20% of the U.S. population, having unique health care needs.

Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database.

Macular patterns of neuronal and visual field loss in recovered optic neuritis identified by machine learning.

We used machine learning to investigate the residual visual field (VF) deficits and macula retinal ganglion cell (RGC) thickness loss patterns in recovered optic neuritis (ON). We applied archetypal analysis (AA) to 377 same-day pairings of 10-2 VF and optical coherence tomography (OCT) macula images from 93 ON eyes and 70 normal fellow eyes ≥ 90 days after acute ON. We correlated archetype (AT) weights (total weight = 100%) of VFs and total retinal thickness (TRT), inner retinal thickness (IRT), and macular ganglion cell-inner plexiform layer (GCIPL) thickness.

Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure.

Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.

Vitamin D binding protein genetic isoforms, serum vitamin D, and cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Associations between vitamin D biochemical status and cancer may be modified by vitamin D binding protein isoforms which are encoded by GC (group-specific component). We examined interactions between serum 25-hydroxyvitamin D [25(OH)D], the Gc isoforms Gc1-1, Gc1-2, and Gc2-2, and cancer risk within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort based on 3,795 cases and 3,856 controls. Multivariable-adjusted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk according to 25(OH)D quantiles, stratified by Gc isoform.

Posttraumatic stress disorder and its cross-generational familial relationship with drug use disorder and alcohol use disorder: an extended Swedish adoption study.

Information on how parental risk for posttraumatic stress disorder (PTSD) relates to their children's risk for drug use disorder (DUD) and alcohol use disorder (AUD) is limited. This study is the first to utilize an extended adoption design which can address questions about the degree of, and sources of, cross-generational and cross-disorder transmission of PTSD and substance use disorders. We examined diagnoses using Swedish National registries for parents and their adult offspring ( = 2,194,171, born 1960-1992) from six types of families (intact (1), not lived with biological father (2) or mother (3), step father (4), step mother (5), and adoptive (6)).

Archetypal Analysis Reveals Consistent Visual Field Patterns for Stimulus Sizes III and V in Glaucoma and NAION.

Purpose: Disorders of the anterior optic nerve cause quantifiable patterns, or archetypes (AT), in visual fields (VFs) obtained using standardized automated perimetry using stimulus size III (size III). VFs with stimulus size V (size V) can reduce retest variability in eyes with moderate to severe loss. We postulated that VF testing using both stimuli would show similar ATs in eyes with glaucoma and nonarteritic anterior ischemic optic neuropathy (NAION).

A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in mouse models of tumor-associated and provoked seizures.

Tumor associated epilepsy is a common and debilitating co-morbidity of brain tumors, for which inadequate treatments are available. Additionally, animal models suggest a potential link between seizures and tumor progression. Our group has previously described a mouse model of diffusely infiltrating glioma and associated chronic epilepsy.

Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures, and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing (snRNA-seq) and analyzed 50,708 high quality nuclei targeting the diencephalon, including the subthalamic nucleus and adjacent structures, from human post-mortem PSP brains with varying degrees of pathology compared to controls.

A multi-regional human brain atlas of chromatin accessibility and gene expression facilitates promoter-isoform resolution genetic fine-mapping.

Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions.

Nasopharynx Cancer in the United States: Racial and Ethnic Disparities in Stage at Presentation.

Introduction: Although nasopharynx cancer (NPC) is rare in the United States, global epidemiology varies greatly. Therefore, understanding NPC disparities in the diverse US setting is critical.

Methods And Materials: Data from the National Cancer Database (NCDB, 2004-2021) identified patients with NPC; NCDB allows disaggregation by Asian American (AA) subgroups.