Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Mature chromatin packing domains persist after RAD21 depletion in 3D.

Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.

SPT5 regulates RNA polymerase II stability via Cullin 3-ARMC5 recognition.

The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate.

Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies.

Background: The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.

Objective: This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

Multi-ancestry genome-wide association analyses: a comparison of meta- and mega-analyses in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Background: There is increasing need for effective incorporation of high-dimensional genetics data from individuals with varied ancestry in genome-wide association (GWAS) analyses. Classically, multi-ancestry GWAS analyses are performed using statistical meta-analysis to combine results conducted within homogeneous ancestry groups. The emergence of cosmopolitan reference panels makes collective preprocessing of GWAS data possible, but impact on downstream GWAS results in a mega-analysis framework merits investigation.

Utility of Hybrid Angio-CT in Interventional Radiology: Case-Based Examples.

Although cone-beam computed tomography (CBCT) is the predominant cross-sectional imaging modality used by interventional radiologists, advancements in hybrid angiography-computed tomography (Angio-CT) technology have demonstrated a strong potential for increased utilization in the angiography suite. The benefits of increased workflow efficiency, decreased relative cost, multipurpose utility, and most importantly improved patient care, may encourage institutions to accept the higher upfront cost of Angio-CT rooms for potential long-term benefits. Hybrid Angio-CT setups are less prone to motion and streak artifacts and may provide superior image quality compared to CBCT.

Comparison of Acute and Protracted Gamma Irradiation Effects During Perinatal Development in Beagle Dogs.

Ionizing radiation exposure during perinatal development can produce various biological effects on the developing offspring. These effects are dependent on a number of factors, including total dose, dose rate and the developmental processes occurring at the time of irradiation. The present study conducted an analysis of historical radiobiological archived data involving 60Co-gamma irradiation of beagle dogs at specific periods of prenatal or postnatal development.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Distribution of opioid analgesics by community racial/ethnic and socioeconomic profiles, 2011-2021.

Rapid declines in opioid analgesics dispensed in American communities since 2011 raise concerns about inadequate access to effective pain management among patients for whom opioid therapies are appropriate, especially for those living in racial/ethnic minority and socioeconomically deprived communities. Using 2011 to 2021 national data from the Automated Reports and Consolidated Ordering System and generalized linear models, this study examined quarterly per capita distribution of oxycodone, hydrocodone, and morphine (in oral morphine milligram equivalents [MMEs]) by communities' racial/ethnic and socioeconomic profiles. Communities (defined by 3-digit-zip codes areas) were classified as "majority White" (≥50% self-reported non-Hispanic White population) vs "majority non-White.

Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.

Background: Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells.

Microsurgical Repair of Large Nasal Septal Defects: Microsurgical Repair of Large Nasal Septal Defects.

Background: Nasal septal defects cause considerable morbidity and represent a challenging reconstructive problem. Traditional repair techniques have employed local intranasal tissues and allograft adjuncts. For large septal defects (>4-5 cm2), less than half are successfully resolved.

Social determinants of health and health outcomes in older cancer survivors.

Purpose Of The Review: Today, two-thirds of all cancer survivors are at least 65 years old. Older cancer survivors have complex care needs, and addressing their social determinants of health (SDoH) is critical for improving and managing survivorship outcomes for this uniquely vulnerable population, yet research specifically examining these associations remains limited and emergent. To this end, we describe the emergent body of evidence on the associations between SDoH domains and older cancer survivors' outcomes.

7. Cervical facet pain: Degenerative alterations and whiplash-associated disorder.

Introduction: Pain from the cervical facet joints, either due to degenerative conditions or due to whiplash-related trauma, is very common in the general population. Here, we provide an overview of the literature on the diagnosis and treatment of cervical facet-related pain with special emphasis on interventional treatment techniques.

Methods: A literature search on the diagnosis and treatment of cervical facet joint pain and whiplash-associated disorders (WAD) was performed using PubMed, Cochrane, and Embase databases.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Principal investigator gender and clinical trial success: analysis of over 3000 obstetrics and gynecology trials.

Background: In obstetrics and gynecology (OBGYN) research, gender disparities permeate through leadership, funding, promotion, mentorship, publishing, compensation, and publicity. Few studies have investigated OBGYN clinical trial leadership as it relates to investigator gender. Thus, we undertook an investigation of principal investigator (PI) gender and clinical trial success.

A meta-analysis of the American college of surgeons risk calculator's predictive accuracy among different surgical sub-specialties.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) provides risk estimates of postoperative complications. While several studies have examined the accuracy of the ACS-Surgical Risk Calculator (SRC) within a single specialty, the respective conclusions are limited by sample size. We sought to conduct a meta-analysis to determine the accuracy of the ACS-SRC among various surgical specialties.