Cell-type-specific auditory responses in the striatum are shaped by feedforward inhibition.

The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and is important for behaviors that require sensorimotor integration. The output neurons of the striatum, D1 and D2 striatal projection neurons (SPNs), which make up the direct and indirect pathways, are thought to play distinct functional roles, although it remains unclear if these neurons show cell-type-specific differences in their response to sensory stimuli. Here, we examine the strength of synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Anticipated Responses to Genetic Testing for Alzheimer's Disease Susceptibility among Latinos in Northern Manhattan.

Alzheimer's disease (AD) is a debilitating neurodegenerative illness that has become a growing concern for older adults. As such, apolipoprotein E (APOE) genetic testing has become more commonly used to identify individuals' susceptibility to AD. An underrepresented population in AD research, Latinos will be disproportionately affected by AD in the coming decades.

Accuracy of machine learning models for pre-diagnosis and diagnosis of pancreatic ductal adenocarcinoma in contrast-CT images: a systematic review and meta-analysis.

Purpose: To evaluate the diagnostic ability and methodological quality of ML models in detecting Pancreatic Ductal Adenocarcinoma (PDAC) in Contrast CT images.

Method: Included studies assessed adults diagnosed with PDAC, confirmed by histopathology. Metrics of tests were interpreted by ML algorithms.

Long-term Changes in Pain, Depression, Function and Informal Caregiving after Major Elective Surgeries Among Seriously Ill Older Adults.

Objective: To compare differences in pain, depression, function, and informal caregiving pre-and-post major elective surgery among older adults with and without serious illness; and determine if serious illness was independently associated with increasing pain, depression, assistance in activities of daily living (ADLs) and informal caregiving post-surgery.

Background: The American College of Surgeons has endorsed the integration of palliative care (PC) into surgical care in adults with serious illness but targets for PC during surgical episodes such as pain, depression, function, and informal caregiving are understudied.

Methods: We used Health and Retirement Study-linked Medicare data (2008-2018) to identify older (≥66 y) adults with and without serious illness who had major elective surgery.

Establishing the Research Priorities of ADHD Professionals: An International Delphi Study.

Objectives: To determine ADHD research priorities from the perspective of ADHD professionals internationally.

Method: A two-stage modified Delphi design was used. In Stage 1 (qualitative), participants listed research questions relating to ADHD that they perceived to be most important ( = 132).

Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults.

I'm Getting a Migraine: A Comparative Evaluation of Patient and Clinician Interpretations of Migraine Symptoms.

Patients and providers vary in how they describe common otolaryngology-related complaints. These differences can lead to miscommunication and frustration that may affect patient outcomes and satisfaction. The aim of this cross-sectional survey-based study was to explore the differences in migraine symptom selection by otolaryngology patients and clinicians.

Maternal Literacy Skills and Children's Kindergarten Outcomes in Rural Communities with Low Incomes: The Moderating Role of Hours in Child Care.

Based on theoretical premises of ecological systems theory and the compensatory hypothesis, a subset of data from the Family Life Project ( = 773), a population-based study of rural families with low incomes, were used to test for associations between maternal literacy in infancy and children's academic outcomes and teacher-reported problem behaviors in kindergarten. A second aim tested whether increased time in child care averaged from 6-36 months moderated such relations. Results indicated that maternal literacy was significantly positively related to academic outcomes ( = .

Statement in Support of Diversity, Equity, and Inclusion for AGU GeoHealth Section.

This commentary presents the American Geophysical Union's GeoHealth section statement in support of diversity, equity, and inclusion (DEI). The GeoHealth section is an open community that represents diverse backgrounds in the geophysical, biological, and public health sciences that share a passion for research at the nexus of Earth and health sciences. The GeoHealth section will aim to advance our understanding of the interactions between the environment, human health, and well-being while supporting DEI topics.

Immune regulatory adjuvant approach to mitigate subcutaneous immunogenicity of monoclonal antibodies.

Introduction: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner.

Methods: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an immunoregulatory adjuvant.

Results: Formulations of adalimumab, trastuzumab or rituximab with OPLS showed reduction in relative immunogenicity in mice compared to vehicle formulations, indicated by reduced anti-drug antibody development and significant reductions in CD138+ plasma cell differentiation in bone marrow.

DNA aptamers that modulate biological activity of model neurons.

There is an urgent need for agents that promote health and regeneration of cells and tissues, specifically to treat diseases of the aging nervous system. Age-associated nervous system degeneration and various diseases are driven by many different biochemical stresses, often making it difficult to target any one disease cause. Our laboratory has previously identified DNA aptamers with apparent regenerative properties in murine models of multiple sclerosis by selecting aptamers that bind oligodendrocyte membrane preparations.

Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer's disease.

Brain waste clearance from the interstitial fluid environment is challenging to measure, which has contributed to controversy regarding the significance of glymphatic transport impairment for neurodegenerative processes. Dynamic contrast enhanced MRI (DCE-MRI) with cerebrospinal fluid administration of Gd-tagged tracers is often used to assess glymphatic system function. We previously quantified glymphatic transport from DCE-MRI data utilizing regularized optimal mass transport (rOMT) analysis, however, information specific to glymphatic clearance was not directly derived.

A highly efficient, scalable pipeline for fixed feature extraction from large-scale high-content imaging screens.

Applying artificial intelligence (AI) to image-based morphological profiling cells offers significant potential for identifying disease states and drug responses in high-content imaging (HCI) screens. When differences between populations (e.g.

International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.

Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact).

Prioritizing cases from a multi-institutional cohort for a dataset of pathologist annotations.

Objective: With the increasing energy surrounding the development of artificial intelligence and machine learning (AI/ML) models, the use of the same external validation dataset by various developers allows for a direct comparison of model performance. Through our High Throughput Truthing project, we are creating a validation dataset for AI/ML models trained in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC).

Materials And Methods: We obtained clinical metadata for hematoxylin and eosin-stained glass slides and corresponding scanned whole slide images (WSIs) of TNBC core biopsies from two US academic medical centers.

Development and Characterization of Novel Dental Composites Using Locally Sourced Materials in Pakistan.

Background And Objective: Dental composites' dependence on pricey imported components often raises price concerns and restricts accessibility in restorative dentistry. In Pakistan, using locally produced materials presents a viable alternative for more affordable and environmentally friendly dental treatments. This study aimed to develop and evaluate dental composites sourced from locally available materials in Pakistan for cost-effectiveness, performance, and durability.

Validation of empirical equations for determining the suitability of the territory for the setting of cemeteries - Implications for worldwide application.

The final disposal of corpses is one of the activities that generates the greatest pollution. Chemicals, embalming fluids, greenhouse gas emissions, and other factors trigger contamination of soils and water sources in towns near cemeteries. This study aimed to validate empirical environmental equations to determine the suitability of territories for cemetery location in several cantons of Central Ecuador, address study variables measured in the field, and update the bibliography as a rapid decision-making tool for decentralized governments.

Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease.

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis.

Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement.

Background: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This Scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research.

Methods: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions.

Regenerative characteristics of the immortal jellyfish, Turritopsis dohrnii, and their potential implications for human aging.

The jellyfish Turritopsis dohrnii (T. Nutricala) is a cnidarian of the Oceaniidae family that lives in the Mediterranean Sea. It is known as the immortal jellyfish since, through a process of cell development called transdifferentiation, it manages to return to a polyp state.

Age-friendly CMS measure implementation: Leveraging geriatric quality programs in an age-friendly health system.

The age-friendly approach ensures older adults receive care that optimizes their well-being, particularly through episodes of illness and at end-of-life. Geriatric clinical quality organizations, including NICHE, establish age-friendly standards and provide education and implementation resources to healthcare organizations. The Centers for Medicare and Medicaid Services will require organizations participating in the inpatient prospective payment system and the long-term care hospital payment system to submit data about compliance with the Age-Friendly Measure starting in 2025.

3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.

Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.

A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.

The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes.