Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

Characterization of the Phenotypic Consequences of the Duffy-Null Genotype.

A wealth of research focused on African American populations has connected rs2814778-CC ("Duffy-null") to decreased neutrophil (neutropenia) and leukocyte counts (leukopenia). While it has been proposed that this variant is benign, prior studies have shown that the misinterpretation of Duffy-null associated neutropenia and leukopenia can lead to unnecessary bone marrow biopsies, inequities in cytotoxic and chemotherapeutic treatment courses, under-enrollment in clinical trials, and other disparities. To investigate the phenotypic correlates of Duffy-null status, we conducted a phenome-wide association study (PheWAS) across more than 1,400 clinical conditions in All of Us, the Vanderbilt University Medical Center's Biobank, and the Million Veteran Program.

Internalization of help-seeking stigma and the moderating role of familism among Latine adults with chronic pain.

Latine adults with chronic pain face heightened stigmatization of seeking professional psychological help. However, research is needed to test whether stigma is internalized and to identify protective factors. We focus on familism, a value commonly found in collectivist cultures that emphasizes family bonds.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Influence of edentulous areas on the accuracy of the maximum intercuspal position recorded by using different intraoral scanners or an artificial intelligence-based program.

Statement Of Problem: Intraoral scans can be articulated in maximum intercuspal position (MIP) by using an artificial intelligence (AI) based program; however, the impact of edentulous areas on the accuracy of the MIP located using this AI-based program is unknown.

Purpose: The purpose of this in vitro study was to assess the impact of edentulous areas (0, 1, 2, 3, and 4 posterior mandibular teeth) on the accuracy of the MIP located using 3 intraoral scanners (IOSs) and an AI-based program.

Material And Methods: Stone casts articulated in MIP in an articulator were digitized (T710).

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study.

Background: Authorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season.

An Examination of predictors of prospective changes in self-reported drinker identity and changes in drinker identity as a predictor of changes in alcohol use and associated consequences.

Purpose: Self-reported drinker identity, the extent to which one views oneself as a drinker, is associated with alcohol consumption and related harms in young adults. The current study examined changes in self-reported drinker identity, theoretically relevant factors associated with drinker identity development, and drinker identity's association with changes in drinking and alcohol-related consequences. We hypothesized that drinker identity would increase over time; theoretically relevant factors would be significantly and positively associated with that increase, and increases in drinking identity would be associated with elevated drinking and related consequences.

The effect of the foreign body response on drug elution from subdermal delivery systems.

Contrasting findings are presented in the literature regarding the influence of foreign body response (FBR) on drug release from implantable drug delivery systems. To this end, here we sought direct evidence of the effect of the fibrotic tissue on subcutaneous drug release from long-acting drug delivery implants. Specifically, we investigated the pharmacokinetic impact of fibrotic encapsulation on a small molecule drug, islatravir (293 Da), and a large protein, IgG (150 kDa), administered via biocompatible implants.

Research on the PFAS release and migration behavior of multi-layer outdoor jacket fabrics.

Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) release from textiles is a source of human exposure, but the mechanisms behind this release remain insufficiently studied. This research investigates the release and transport mechanisms of PFAS in outdoor jacket fabrics treated with a short side-chain fluorinated polymers (CF-SFPs) for durable water repellency (DWR). PA-based and PET-based fabrics were exposed to outdoor conditions and subjected to accelerated aging, followed by abrasion, washing, and drying experiments to simulate wear and degradation.

Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

Kinematic analysis of upper limb fractures: Insights for rehabilitation strategies.

Background: Upper limb fractures significantly alter movement, impacting function and recovery. Three-dimensional motion analysis allows precise assessment of these changes.

Methods: Sixty patients were divided into four groups: shoulder, elbow, wrist fractures, and controls.

Neurodevelopmental and Mental Health Outcomes in a National Clinical Sample of Youth With Sex Chromosome Trisomies Compared With Matched Controls.

Objective: To compare the prevalence of neurodevelopmental and mental health diagnoses in a national sample of youth with sex chromosome trisomies (SCTs) with matched controls.

Methods: Patients in PEDSnet and a diagnosis code mapping to 47,XXY/Klinefelter syndrome (n = 1171), 47,XYY/Double Y syndrome (n = 243), or 47,XXX/Trisomy X syndrome (n = 262) were matched with controls using propensity scores. Generalized estimating equations computed odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of diagnoses within the neurodevelopmental and mental health composites, psychotropic medication prescriptions, and encounters with behavioral health and therapy providers.

Separation and recycling of hydrofluorocarbon refrigerant mixtures with fluoropolymer-coated hollow fiber membranes.

Many hydrofluorocarbon refrigerants used in air-conditioning and refrigeration equipment are being phased out based on international restrictions to reduce global warming. Over 1 billion kilograms of hydrofluorocarbons are in use, and recycling is imperative to preventing the release of these greenhouse gases into the atmosphere. We report on composite hollow fiber membranes that can efficiently separate a mixture of difluoromethane and pentafluoroethane that is used worldwide in air conditioners.

Stimulating the regenerative capacity of the human retina with proneural transcription factors in 3D cultures.

Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of or combinations of proneural factors in Müller glia (MG) induce regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited.

Evaluating the effects, implementation experience and political economy of primary healthcare facility autonomy reforms within counties in Kenya: a mixed methods study protocol.

Introduction: There is a growing emphasis on improving primary health care services and granting frontline service providers more decision-making autonomy. In October 2023, Kenya enacted legislation mandating nationwide facility autonomy. There is limited understanding of the effects of health facility autonomy on primary health care (PHC) facilities performance.

The power of personas: Exploring an innovative model for understanding stakeholder perspectives in an oncology learning health network.

Introduction: Learning health networks (LHNs) improve clinical outcomes by applying core tenets of continuous quality improvements (QI) to reach community-defined outcomes, data-sharing, and empowered interdisciplinary teams including patients and caregivers. LHNs provide an ideal environment for the rapid adoption of evidence-based guidelines and translation of research and best practices at scale. When an LHN is established, it is critical to understand the needs of all stakeholders.

Total Percutaneous Transfemoral Endovascular Treatment of Non-A Non-B Aortic Dissection.

Although open repair remains the mainstream treatment for aortic arch dissection, its surgical complexity and perioperative complications are significant. We developed a novel stentgraft system for less-invasive endovascular aortic arch repair. We successfully performed a total percutaneous transfemoral endovascular repair of aortic arch dissection using a novel off-the-shelf endograft system.