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.

Caregiver alignment with triage acuity levels and drivers for discrepancy between caregiver assessment and triage acuity levels: a cross-sectional questionnaire based study.

Background: Caregiver concern is the main driver to paediatric emergency departments visits. Understanding caregiver worries is crucial to guide patients to the most appropriate healthcare setting. Previous research shows mixed findings on the accordance between caregiver assessment and professional triage.

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.

Evolution of the umbilical cord blood proteome across gestational development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth.

Biostimulants with glycine betaine or kelp extract alleviate heat stress in red raspberry (Rubus idaeus).

Biostimulants are an emerging and innovative class of products that may mitigate the adverse effects of extreme heat, but research on their efficacy in fruit crops is limited. This study addressed this knowledge gap by evaluating the performance of three biostimulants, FRUIT ARMOR™, Optysil®, and KelpXpress™ [active ingredients glycine betaine, silicon, and kelp (Ascophyllum nodosum) extract, respectively] applied to three raspberry genotypes exposed to high temperatures (T ≥ 35 °C/day) inside a glasshouse. 'Meeker' consistently maintained high chlorophyll fluorescence (F/F) and photosynthesis under control and biostimulant treatments.

Inflammatory biomarkers profiles and cognition among older adults.

Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune pathways and characterize the overall inflammatory profile of individuals.

An image dataset for surveillance of personal protective equipment adherence in healthcare.

Proper personal protective equipment (PPE) use is critical to prevent disease transmission to healthcare providers, especially those treating patients with a high infection risk. To address the challenge of monitoring PPE usage in healthcare, computer vision has been evaluated for tracking adherence. Existing datasets for this purpose, however, lack a diversity of PPE and nonadherence classes, represent single not multiple providers, and do not depict dynamic provider movement during patient care.

Global urban activity changes from COVID-19 physical distancing restrictions.

During the COVID-19 pandemic changes in human activity became widespread through official policies and organically in response to the virus's transmission, which in turn, impacted the environment and the economy. The pandemic has been described as a natural experiment that tested how social and economic disruptions impacted different components of the global Earth System. To move this beyond hypotheses, locally-resolved, globally-available measures of how, where, and when human activity changed are critically needed.

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).

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.

Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

TGR5 attenuates DOCA-salt hypertension through regulating histone H3K4 methylation of ENaC in the kidney.

Epithelial sodium channel (ENaC), located in the collecting duct principal cells of the kidney, is responsible for the reabsorption of sodium and plays a critical role in the regulation of extracellular fluid volume and consequently blood pressure. The G protein-coupled bile acid receptor (TGR5) is a membrane receptor mediating effects of bile acid and is implicated in kidney diseases. The current study aims to investigate whether TGR5 activation in the kidney regulated ENaC expression and potential mechanism.

Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability.

Objective: Callous-unemotional traits (CU), characterized as a lack of guilt and empathy; and irritability, a tendency to show anger and frustration; are 2 risk factors for externalizing behavioral problems. Externalizing problems, CU and irritability are all heritable. However, there is a dearth of studies examining the genetic and environmental associations between the 3 domains.

A randomized controlled trial to assess whether a telehealth-based contingency management intervention reduces alcohol use for individuals with alcohol use disorder.

Background: Contingency management (CM) is an intervention for alcohol use disorder (AUD) that reinforces abstinence, as confirmed by alcohol biomarkers. CM is usually brief (12-16 weeks) despite evidence that longer interventions have better long-term outcomes. Most CM models are in-person which can also be a barrier for treatment.

Infection-induced host extinction: Deterministic and stochastic models for environmentally transmitted pathogens.

Worldwide amphibian decline and extinction have been observed, highlighting the importance of identifying the underlying factors. This issue has long been recognized as highly significant and continues to receive substantial attention in conservation ecology. Pathogen infection, in particular the chytrid fungus Batrachochytrium dendrobatidis, is postulated as a key factor contributing to the decline of certain species within specific regions.

Frontal Fibrosing Alopecia (FFA) Part I - Diagnosis and Clinical Presentation.

Frontal Fibrosing Alopecia (FFA) is a primary lymphocytic cicatricial alopecia predominantly affecting postmenopausal Caucasian women. It is characterized by a progressive frontotemporal hairline recession that presents as a scarring hairless band and is often accompanied by eyebrow and body hair loss. Although initially described in postmenopausal women, FFA has been observed in a broader demographic, including premenopausal women and occasionally men.