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 also 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.

Factors underlying the association between , subspecies infection and colorectal cancer: a mini review.

, subspecies (Sgg) is a gram-positive bacterium associated with infective endocarditis and colorectal cancer (CRC). Sgg has features that allow the bacterium to thrive in the colorectal tumor microenvironment and further progress the development of CRC to facilitate its survival. Sgg contains 3 pili that facilitate colonic cell adhesion and translocation through phase variation.

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.

Planning a Phased Guideline Implementation Strategy Across the Multicenter Ventilation Liberation for Kids (VentLib4Kids) Collaborative.

Objectives: To evaluate contextual factors relevant to implementing pediatric ventilator liberation guidelines and to develop an implementation strategy for a multicenter collaborative.

Design: Cross-sectional qualitative analysis of a 2023/2024 survey.

Setting: International, multicenter Ventilation Liberation for Kids (VentLib4Kids) collaborative.

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.

Interleukin 8-CXCR2 mediated neutrophil extracellular trap (NET) formation in biliary atresia associated with NET-Induced stellate cell activation.

Background Aims: Biliary atresia (BA) entails an inflammatory sclerosing lesion of the biliary tree, with prominent fibrosis in infancy. Previous studies revealed neutrophil-activating IL-8 and neutrophil extracellular traps (NETs) positively correlated with bilirubin and risk of liver transplant. The aims of this study were to determine the mechanism of NET formation (NETosis) in BA and if NETs induce stellate cell activation.

A single 1-min brain MRI scan for generating multiple synthetic image contrasts in awake children from quantitative relaxometry maps.

Background: Diagnostically adequate contrast and spatial resolution in brain MRI require prolonged scan times, leading to motion artifacts and image degradation in awake children. Rapid multi-parametric techniques can produce diagnostic images in awake children, which could help to avoid the need for sedation.

Objective: To evaluate the utility of a rapid echo-planar imaging (EPI)-based multi-inversion spin and gradient echo (MI-SAGE) technique for generating multi-parametric quantitative brain maps and synthetic contrast images in awake pediatric participants.

The Green Heart Project: Objectives, Design, and Methods.

The Green Heart Project is a controlled, community-based clinical trial to evaluate the effects of increasing greenery on community health. The study was initiated in 2018 in a low-to-middle-income residential area of nearly 30,000 racially diverse residents in Louisville, KY. Community engagement was maintained throughout the project, with feedback integrated into its design and implementation.

Factors associated with accelerated parenteral weaning in children with intestinal failure: A descriptive cohort study.

Background: The goal of intestinal rehabilitation in children is to wean from parenteral nutrition (PN). The aim of this study was to identify factors associated with accelerated weaning and to evaluate long-term outcomes of children receiving long-term PN.

Methods: This was a retrospective study of children managed by the Intestinal Rehabilitation Center at Cincinnati Children's Hospital.

Implementation of a Child Maltreatment Screening Tool in the Prehospital Setting.

Objectives: Emergency Medical Services (EMS) clinicians are in a unique position to screen for child maltreatment as they are often the first point of contact with the health care system and they may encounter children in their home environment. However, EMS training regarding the signs of child maltreatment is lacking. Although several child maltreatment screening tools have been developed for the primary care and Emergency Department (ED) settings, there appears to be no published literature describing or evaluating a prehospital screening aid.

Machine Learning-Based Prediction Model for ICU Mortality After Continuous Renal Replacement Therapy Initiation in Children.

Background: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

Objective: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

Albuminuria Prevalence in Fontan Patients: A Systematic Review and Meta-Analysis.

Patients with a Fontan circulation are at risk for chronic kidney disease (CKD), which is defined as persistently reduced glomerular filtration rate (GFR) <60ml/min/1.73 or elevated marker of kidney injury such as urinary albumin-to-creatinine ratio (UACR) >30mg/g. We determined the prevalence of albuminuria in patients with a Fontan circulation.

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study.

Background: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

Methods: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network.