CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Human pancreatic cancer single cell atlas reveals association of CXCL10+ fibroblasts and basal subtype tumor cells.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard of care treatments and have significantly worse overall survival (OS) compared to patients with classical subtype enriched tumors. It is important to develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner.

Experimental Design: We compiled a single cell RNA sequencing (scRNAseq) atlas of the human pancreas with 229 patient samples, aggregated from publicly available raw data.

Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1 LDS mice by single-cell transcriptomics to identify molecular determinants of this vulnerability.

Characteristics and Predictors of Fluctuating Attention-Deficit/Hyperactivity Disorder in the Multimodal Treatment of ADHD (MTA) Study.

Recent studies report a fluctuating course of attention-deficit/ hyperactivity disorder (ADHD) across development characterized by intermittent periods of remission and recurrence. In the Multimodal Treatment of ADHD (MTA) study, we investigated fluctuating ADHD including clinical expression over time, childhood predictors, and between- and within-person associations with factors hypothesized as relevant to remission and recurrence. Children with ADHD, combined type (N 483), participating in the MTA adult follow-up were assessed 9 times from baseline (mean age = 8.

Mindful Awareness Practices (MAPs) in Adolescents With ADHD and Cognitive Disengagement Syndrome (CDS): A Pilot Open Trial.

Very few studies have investigated intervention approaches that may be efficacious for youth with ADHD and co-occurring cognitive disengagement syndrome (CDS) symptoms. This study examined the feasibility, acceptability, and preliminary efficacy of a mindfulness-based intervention for adolescents with ADHD and co-occurring CDS symptoms. Fourteen adolescents ages 13 to 17 years (35.

SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins.

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology.

PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment.

Comprehension of Miranda warnings in adults with chronic, moderate-severe traumatic brain injury.

Introduction: To compare comprehension of Miranda rights in adults with traumatic brain injury (TBI) versus adults without TBI as measured by response accuracy on the Miranda Right Comprehension Instruments.

Methods: Data were collected virtually via teleconferencing from July 2022 to February 2023. Participants included 25 adults with moderate-severe TBI (12 females, 13 males) and 25 adults without TBI (12 females, 13 males), ages 20-55 years.

Diversity of Research Participant Gender, Race, and Ethnicity in Communication Sciences and Disorders: A Systematic Review and Quantitative Synthesis of American Speech-Language-Hearing Association Publications in 2020.

Purpose: One manifestation of systemic inequities in communication sciences and disorders (CSD) is the chronic underreporting and underrepresentation of sex, gender, race, and ethnicity in research. The present study characterized recent demographic reporting practices and representation of participants across CSD research.

Methods: We systematically reviewed and extracted key reporting and participant data from empirical studies conducted in the United States (US) with human participants published in the year 2020 in journals by the American Speech-Language-Hearing Association (ASHA; = 407 articles comprising a total = 80,058 research participants, search completed November 2021).

Intrinsic expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of LDS mice by single cell and spatial transcriptomics.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells.

CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy.

Personalized cancer vaccines aim to activate and expand cytotoxic antitumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy.

Memory and Traumatic Brain Injury: Assessment and Management Practices of Speech-Language Pathologists.

Purpose: Memory impairments are among the most commonly reported deficits and among the most frequent rehabilitation targets for individuals with traumatic brain injury (TBI). Memory and learning are also critical for rehabilitation success and broader long-term outcomes. Speech-language pathologists (SLPs) play a central role in memory management for individuals with TBI across the continuum of care.

Inferring cellular and molecular processes in single-cell data with non-negative matrix factorization using Python, R and GenePattern Notebook implementations of CoGAPS.

Non-negative matrix factorization (NMF) is an unsupervised learning method well suited to high-throughput biology. However, inferring biological processes from an NMF result still requires additional post hoc statistics and annotation for interpretation of learned features. Here, we introduce a suite of computational tools that implement NMF and provide methods for accurate and clear biological interpretation and analysis.

Measurement of Direct-Photon Cross Section and Double-Helicity Asymmetry at sqrt[s]=510 GeV in p[over →]+p[over →] Collisions.

We present measurements of the cross section and double-helicity asymmetry A_{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510  GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider.

Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant.

Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables).

Design, Setting, And Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study.

Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics.

Insulin is amongst the human genome's most well-studied genes/proteins due to its connection to metabolic health. Within this article, we review literature and data to build a knowledge base of Insulin () genetics that influence transcription, transcript processing, translation, hormone maturation, secretion, receptor binding, and metabolism while highlighting the future needs of insulin research. The gene region has 2076 unique variants from population genetics.

Comparison of In Vitro and In Silico Assessments of Human Galactose-1-Phosphate Uridylyltransferase Coding Variants.

Introduction Human pathogenic coding variations of the galactose-1-phosphate uridylyltransferase (GALT) gene cause classic galactosemia, a recessive disease of galactose metabolism. Unfortunately, there are many variants of uncertain significance (VUS) that need to be characterized in order to be able to predict the likelihood of classic galactosemia for all possible genotypes. There are many bioinformatic resources available that attempt to predict the pathogenicity of a human variant, but it is unclear if these methods realistically predict the consequence of these variants.

Lessons Learned in Centering Youth Voices in HIV Prevention: The Adolescent Health Working Group.

Background: There remains critical need for community-based approaches to HIV prevention which center youth voices and needs.

Objectives: We established an adolescent health working group (AHWG) to convene youth, parents, providers, and advocates in agenda-setting for interventions to increase pre-exposure prophylaxis uptake in Durham.

Methods: Our three study phases included six AHWG meetings from 2019 to 2020, youth-only meetings guided by a participatory engagement framework (Youth Generate and Organize), and interviews (n=13) and surveys with youth in the community (N=87).

The Winchcombe meteorite, a unique and pristine witness from the outer solar system.

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid.

Multi-omic analyses of changes in the tumor microenvironment of pancreatic adenocarcinoma following neoadjuvant treatment with anti-PD-1 therapy.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy necessitates optimization and maintenance of activated effector T cells (Teff). We prospectively collected and applied multi-omic analyses to paired pre- and post-treatment PDAC specimens collected in a platform neoadjuvant study of granulocyte-macrophage colony-stimulating factor-secreting allogeneic PDAC vaccine (GVAX) vaccine ± nivolumab (anti-programmed cell death protein 1 [PD-1]) to uncover sensitivity and resistance mechanisms. We show that GVAX-induced tertiary lymphoid aggregates become immune-regulatory sites in response to GVAX + nivolumab.

Parental perspectives on attention-deficit/hyperactivity disorder treatments for children.

This study investigated parental perspectives and experiences on the evaluation and treatment process associated with attention-deficit/hyperactivity disorder (ADHD). Five hundred sixty-eight parents of youth 2-28 years-old (M = 9.37; SD = 4.