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.

Neonatal Seizures and Associated Neurobehavioral Profiles in Preschool Age Children.

Background: Neonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone.

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.

Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study.

Background: Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time-course immune reprogramming after sepsis was evaluated to explore whether the host is immunocompromised.

Evaluating post-cardiac arrest blood pressure thresholds associated with neurologic outcome in children: Insights from the pediRES-Q database.

Background: Current Pediatric Advanced Life Support Guidelines recommend maintaining blood pressure (BP) above the 5th percentile for age following return of spontaneous circulation (ROSC) after cardiac arrest (CA). Emerging evidence suggests that targeting higher thresholds, such as the 10th or 25th percentiles, may improve neurologic outcomes. We aimed to evaluate the association between post-ROSC BP thresholds and neurologic outcome, hypothesizing that maintaining mean arterial pressure (MAP) and systolic blood pressure (SBP) above these thresholds would be associated with improved outcomes at hospital discharge.

Regional Anesthesia and Surgical Volume in Children Undergoing Nuss Repair: A Multicenter Review.

Introduction: Regional anesthetic approach and surgical volume have been shown to outcomes in patients undergoing Nuss procedure for pectus excavatum. However, their independent relationship is not described. We investigated how regional anesthesia and surgical volume are associated with length of stay (LOS), postoperative opioid use, operating room utilization, and complications.

Diaci v3.0: chromosome-level assembly, de novo transcriptome, and manual annotation of Diaphorina citri, insect vector of Huanglongbing.

Background: Diaphorina citri is an insect vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems, and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission.

Smoking carcinogen induced inflammation promotes lung carcinogenesis via IRAK4 activation.

Purpose: Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(α)pyrene (BaP) have not been tested in models that mimic inhaled exposure for prolonged periods of time.

Experimental Design: ICR mice were treated with intratracheal delivery of NNK and BaP (NB) for 18 months.

Rhabdoid Tumor of the Kidney and Soft Tissues: Results from National Wilms Tumor Study-5 and Children's Oncology Group Study AREN0321.

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients And Methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1).

Specialization of the brain for language in children with Fragile X Syndrome: a functional Near Infrared Spectroscopy study.

Specialization of the brain for language is early emerging and essential for language learning in young children. Fragile X Syndrome (FXS) is a neurogenetic disorder marked by high rates of delays in both expressive and receptive language, but neural activation patterns during speech and language processing are unknown. We report results of a functional Near Infrared Spectroscopy (fNIRS) study of responses to speech and nonspeech sounds in the auditory cortex in a sample of 2- to 10-year-old children with FXS and typically developing controls (FXS n = 23, TDC n = 15, mean age = 6.

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 health care 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.

Deriving Human Intestinal Organoids with Functional Tissue-Resident Macrophages All From Pluripotent Stem Cells.

Background & Aims: Organs of the gastrointestinal tract contain tissue-resident immune cells that function during tissue development, homeostasis, and disease. However, most published human organoid model systems lack resident immune cells, thus limiting their potential as disease avatars. For example, human intestinal organoids (HIOs) derived from pluripotent stem cells contain epithelial and various mesenchymal cell types but lack immune cells.

Delays in Care for Children With Low Anorectal Malformations in Southwestern Uganda.

Introduction: Disparities in anorectal malformation (ARM) outcomes between high- and low-income countries may be due to delayed diagnosis in the latter setting. The Three Delays model, comprising delays in seeking, accessing, and receiving care, provides a framework for exploring these challenges. We sought to examine the frequency and nature of the preoperative delays in children presenting for surgical correction of low ARMs.

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 Osteochondritis Dissecans Lesions Will Heal Nonoperatively? An Application of Machine Learning to the ROCK Prospective Cohort.

Background: There are limited evidence-based guidelines to predict which osteochondritis dissecans (OCD) lesions will heal with nonoperative treatment.

Purpose: To train a set of classification algorithms to predict nonoperative OCD healing while identifying new clinically meaningful predictors.

Study Design: Case-control study; Level of evidence, 3.

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.

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.

Engaging adolescents and young adults in decisions about return of genomic research results: study protocol for a mixed-methods longitudinal clinical trial protocol.

Background: To protect minors' future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child's secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process.

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.