A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.

Development of circadian rhythms in mammalian systems.

In mammals, molecular mechanisms of circadian rhythms involve a time-delayed negative feedback loop generating autonomous oscillations of ∼24 h. Most cell types in mammals possess circadian rhythms regulating temporal organization of cellular and physiological processes. Intriguingly, pluripotent stem cells do not possess circadian rhythms and oscillations arise after a defined period of differentiation.

STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex.

Development of the iManage SCD mobile health application for transition.

Objective: This paper outlines the design and implementation of iManage SCD, a self-management mobile health application for adolescents and young adults (AYA) with sickle cell disease (SCD) during transition from pediatric to adult health care.

Methods: The Integrate, Design, Assess, Share (IDEAS) framework, emphasizing user insights, iterative design, rigorous assessment, and knowledge sharing, guided the development process. The design team consisted of researchers, psychologists, physicians, social workers, AYA with SCD, and parents of AYA with SCD (n = 16) across three states.

Update on Eisenmenger syndrome - Review of pathophysiology and recent progress in risk assessment and management.

Longstanding left-to-right shunting associated with congenital heart disease (CHD) can ultimately lead to pulmonary vascular remodeling, pulmonary arterial hypertension, and shunt reversal, the hallmark feature of Eisenmenger Syndrome (ES). ES is a multisystem disease, with hematologic, cardiovascular, renal, neurologic, immune, and other manifestations, each of which inform its management. Many of the most distinct and clinically important consequences relate to chronic hypoxemia.

Stathmin 1 Expression in Neuroendocrine and Proliferating Prostate Cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. While PCa initially responds to androgen deprivation therapy, a significant portion progresses to castration-resistant PCa. Approximately 20-25% of these cases acquire aggressive neuroendocrine (NE) features, ultimately leading to neuroendocrine prostate cancer (NEPC).

Effects of elevated body mass index on the success of total knee and total hip arthroplasty: a comprehensive overview.

Introduction: The average body mass index (BMI) in the United States has tripled over the last five decades despite concerted population-based efforts for weight management. Elevated BMI and, in particular, obesity are risk factors for osteoarthritis. This trend has led to increased demands for total knee (TKA) and total hip arthroplasty (THA), necessitating an in-depth understanding of how elevated BMI impacts TKA and THA.

Dilated cardiomyopathy variant R14del increases phospholamban pentamer stability, blunting dynamic regulation of calcium.

The sarco(endo)plasmic reticulum Ca ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise.

Structural Dynamics of Rho GTPases.

Rho family GTPases are a part of the Ras superfamily and are signaling hubs for many cellular processes. While the detailed understanding of Ras structure and function has led to tremendous progress in oncogenic Ras-targeted drug discovery, studies of the related Rho GTPases are still catching up as the recurrent cancer-related Rho GTPase mutations have only been discovered in the last decade. Like that of Ras, an in-depth understanding of the structural basis of how Rho GTPases and their mutants behave as key oncogenic drivers benefits the development of clinically effective therapies.

Achieving Medication-Free Remission in Patients With Juvenile Dermatomyositis.

Objective: Prognostic factors associated with medication discontinuation in children with juvenile dermatomyositis (JDM) remain largely elusive. We aim to identify the predictors of medication-free remission (MFR) in children with JDM.

Methods: In this retrospective study, patients diagnosed with JDM according to Peter & Bohan criteria and followed for ≥18 months at a tertiary care center from 2006 through 2022 were included.

Twist1 Acts Upstream of the Dlx5-Hand2 Pathway to Pattern the Mammalian Jaw.

Both the upper and lower jaws develop from cranial neural crest cells (CNCCs) populating the first pharyngeal arch in all gnathostomes. Previous studies showed that the Edn1/Ednra-Dlx5/Dlx6-Hand2 signaling pathway is necessary for lower jaw formation and that ectopic expression of or throughout the CNCCs partly transformed the upper jaw to lower jaw structures, but the molecular mechanisms regulating upper jaw development remain unclear. Here we show that the basic helix-loop-helix transcription factor Twist1 is required for upper jaw development.

Development and Validation of a Modality-Invariant 3D Swin U-Net Transformer for Liver and Spleen Segmentation on Multi-Site Clinical Bi-parametric MR Images.

To develop and validate a modality-invariant Swin U-Net Transformer (UNETR) deep learning model for liver and spleen segmentation on abdominal T1-weighted (T1w) or T2-weighted (T2w) MR images from multiple institutions for pediatric and adult patients with known or suspected chronic liver diseases. In this IRB-approved retrospective study, clinical abdominal axial T1w and T2w MR images from pediatric and adult patients were retrieved from four study sites, including Cincinnati Children's Hospital Medical Center (CCHMC), New York University (NYU), University of Wisconsin (UW) and University of Michigan / Michigan Medicine (UM). The whole liver and spleen were manually delineated as the ground truth masks.

Pediatric to Adult Care Transition in the Hospital Context (PATCH) Tool: A Novel Tool to Assess Pediatric Institutional Guidelines for Inpatient Care of Adults.

Objective: The growing number of adults with childhood onset chronic conditions (COCC) is reflected in the increase of adult-aged admissions to pediatric institutions. Despite national bodies advising pediatric institutions to have a pediatric to adult healthcare transition (HCT) policy, little guidance is available on if or how to include inpatient care. We sought to create a framework-based Pediatric to Adult Transitional Care in the Hospital Context (PATCH) tool to assess how inpatient care of adults is addressed in pediatric institutional guidelines or policies (hereafter guidelines) as a first step towards informing future PATCH guideline development.

Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn's disease.

Inflammatory bowel disease (IBD)-associated fibrosis causes significant morbidity. Mechanisms are poorly understood but implicate the microbiota, especially adherent-invasive Escherichia coli (AIEC). We previously demonstrated that AIEC producing the metallophore yersiniabactin (Ybt) promotes intestinal fibrosis in an IBD mouse model.

Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses.

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains.

Symptoms, Quality of Life, and Executive Function in Children Who Snore.

Introduction: Mild sleep-disordered breathing (mSDB) in children is associated with both neurobehavioral morbidity and reduced quality of life (QOL). However, the association between symptom burden and QOL with executive function is not well understood, and it is not known whether QOL and symptom burden may help identify children with neurocognitive dysfunction.

Objective: To assess associations among executive function, QOL, and symptom burden in children with mSDB.

Which casein micelle removal method is suitable for studies of human milk extracellular vesicles? A systematic comparison of four different treatments for casein depletion before extracellular vesicle isolation from human milk.

This study aimed to systematically compare four casein micelle removal methods on the particle and protein characteristics of the isolated human milk EVs. The defatted milk was treated with 1% sodium citrate, 20 mM ethylenediaminetetraacetic acid (EDTA), 1% acetic acid, or 1% chymosin/calcium chloride for 30 min at 4 °C to remove casein micelles. EV isolation was performed using qEV size exclusion chromatography.

A narrative clinical trials review in the realm of focal therapy for localized prostate cancer.

Background And Objective: The role of focal therapy in the treatment of localized prostate cancer is evolving. However, despite accumulating evidence, current guidelines and regulatory bodies refrain from endorsing focal therapy outside of clinical trials. Our goal was the to review the focal therapy realm for ongoing clinical trials and high impact recently published trials.

A Double-Blind, Placebo-Controlled Study of Adjunctive Topiramate in Adolescents With Co-Occurring Bipolar and Cannabis Use Disorders.

Objective: To evaluate the efficacy of adjunctive topiramate (TPM) for the treatment of cannabis use disorder in adolescents with bipolar I disorder.

Method: We conducted a 16-week, double-blind, randomized, placebo-controlled investigation of quetiapine plus TPM (median dose = 208 mg) vs quetiapine plus placebo in adolescents with bipolar I and cannabis use disorder. All subjects participated in a Motivational Interview and Compliance Enhancement Therapy.

Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children.

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

Methods: Data were drawn from a surveillance study of households with children ( = 1913) recruited from 12 U.

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

A novel minimally invasive neurosurgical cranial fixation device for improved accuracy of intraventricular catheter placement: an experimental animal study.

Background: External ventricular drain (EVD) insertion is one of the most commonly performed neurosurgical procedures. Herein, we introduce a new concept of a cranial fixation device for insertion of EVDs, that reduces reliance on freehand placement and drilling techniques and provides a simple, minimally invasive approach that provides strong fixation to minimal thickness skulls.

Methods: An experimental device for catheter insertion and fixation was designed and tested in both ex-vivo and in-vivo conditions to assess accurate cannulation of the ventricle and to test the strength of fixation to the skull.

Recommendations for the optimization of student led free vision screening programs.

Purpose: To report the summary characteristics of operational models associated with Student Led Free Vision Screening Programs (SLFVSP) and to identify opportunities for program optimization.

Methods: An 81-question mixed methods survey was distributed to SLFVSP leaders nationwide and Medical Student Educators within the American University Ophthalmology Professors (AUPO) Association. Survey responses were analyzed using Mann Whitney U and Fisher's Exact tests.