Gene silencing dynamics are modulated by transiently active regulatory elements.

Transcriptional enhancers have been extensively characterized, but cis-regulatory elements involved in acute gene repression have received less attention. Transcription factor GATA1 promotes erythroid differentiation by activating and repressing distinct gene sets. Here, we study the mechanism by which GATA1 silences the proliferative gene Kit during murine erythroid cell maturation and define stages from initial loss of activation to heterochromatinization.

Measures of Admission Immunocoagulopathy as an Indicator for In-Hospital Mortality in Patients with Necrotizing Fasciitis: A Retrospective Study.

Unlabelled: Necrotizing fasciitis is a rapidly progressive infection with a high mortality rate. Pathogens evade the host containment and bactericidal mechanisms by hijacking the coagulation and inflammation signaling pathways, leading to their rapid dissemination, thrombosis, organ dysfunction, and death. This study examines the hypothesis that measures of immunocoagulopathy upon admission could aid in the identification of patients with necrotizing fasciitis at high risk for in-hospital mortality.

Distinct properties and functions of CTCF revealed by a rapidly inducible degron system.

CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor implicated in a wide range of functions, including genome organization, transcription activation, and elongation. To explore the basis for CTCF functional diversity, we coupled an auxin-induced degron system with precision nuclear run-on. Unexpectedly, oriented CTCF motifs in gene bodies are associated with transcriptional stalling in a manner independent of bound CTCF.

Effect of Machine Settings on Ultrasound Assessment of B-lines.

Objectives: B-lines are a lung ultrasound (LUS) artifact that often indicate pathology. Little is known about the optimal ultrasound machine settings to assess B-lines. We compared settings typically used to evaluate B-lines at our institution with adjusted settings based on recent studies.

Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.

Background And Aims: Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance.

Approach And Results: We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks.

Shared Mental Models Among Clinical Competency Committees in the Context of Time-Variable, Competency-Based Advancement to Residency.

Purpose: To evaluate response process validity evidence for clinical competency committee (CCC) assessments of first-year residents on a subset of General Pediatrics Entrustable Professional Activities (EPAs) and milestones in the context of a national pilot of competency-based, time-variable (CBTV) advancement from undergraduate to graduate medical education.

Method: Assessments of 2 EPAs and 8 milestones made by the trainees' actual CCCs and 2 different blinded "virtual" CCCs for 48 first-year pediatrics residents at 4 residency programs between 2016 and 2018 were compared. Residents had 3 different training paths from medical school to residency: time-variable graduation at the same institution as their residency, time-fixed graduation at the same institution, or time-fixed graduation from a different institution.

Focal Length Fluidity: Research Questions in Medical Education Research and Scholarship.

Research and scholarship in health professions education has been shaped by intended audience (i.e., producers vs users) and the purpose of research questions (i.

Evidence of Chronic Allograft Injury in Liver Biopsies From Long-term Pediatric Recipients of Liver Transplants.

Background & Aims: A substantial proportion of pediatric liver transplant recipients develop subclinical chronic allograft injury. We studied whether there are distinct patterns of injury based on histopathologic features and identified associated immunologic profiles.

Methods: We conducted a cross-sectional study of 157 stable, long-term pediatric recipients of transplanted livers (70 boys; > 6 years old at time of transplantation; mean, 8.

Friend to Friend: A Randomized Trial for Urban African American Relationally Aggressive Girls.

Objective: To determine the effectiveness of the Friend to Friend (F2F) aggression intervention through a clinical trial with urban African American girls.

Method: A randomized parallel-group study design was conducted comparing the effectiveness of F2F to an attention control condition (called Homework Study Skills and Organization, HSO) among relationally aggressive girls from six urban low-income elementary schools. Analyses of covariance were utilized for comparing post-test measurement between the two conditions while adjusting for pre-test measurement.

Conclusions and future directions for the REiNS International Collaboration.

The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development.

Achieving consensus for clinical trials: the REiNS International Collaboration.

The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials.

Guidelines for Adapting Manualized Interventions for New Target Populations: A Step-Wise Approach Using Anger Management as a Model.

The use of manual-based interventions tends to improve client outcomes and promote replicability. With an increasingly strong link between funding and the use of empirically supported prevention and intervention programs, manual development and adaptation have become research priorities. As a result, researchers and scholars have generated guidelines for developing manuals from scratch, but there are no extant guidelines for adapting empirically supported, manualized prevention and intervention programs for use with new populations.

Inflammation-induced preterm birth in a murine model is associated with increases in fetal macrophages and circulating erythroid precursors.

The presence of intrauterine inflammation has been associated with adverse neurologic outcomes in preterm infants, but the precise mechanisms of fetal brain injury remain unclear. We sought to evaluate inflammatory cell trafficking, fetal organ damage, and molecular regulation in the fetoplacental unit using an established mouse model of preterm birth associated with intrauterine inflammation. Gestational sacs were harvested 6 hours after intrauterine infusion of saline or lipopolysaccharide (LPS).

Growth failure in the child with inflammatory bowel disease.

Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. In IBD, growth failure may be the only clinical presentation; it is imperative to perform a detailed history and physical examination to search for other systemic and gastrointestinal manifestations of the disease. IBD can have a significant impact on linear growth, weight gain, and bone mineralization, and can cause delays in the onset of puberty.