Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

Posterior Reversible Encephalopathy Syndrome in Children and Adolescents.

Purpose Of Review: Posterior reversible encephalopathy syndrome, or PRES, is a constellation of severe, acute hypertension and specific brain imaging findings. This may be caused by failure of the cerebral autoregulatory system to manage acute or severe changes in blood pressure. The incidence in children is unknown but estimated to be more common in children with predisposing factors including renal disease, autoimmune disease, malignancy, solid organ transplantation, stem cell transplantation, hypertension, sepsis, and exposure to certain medications.

Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines.

Introduction: Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge.

Methods: Four patient-derived pediatric glioma models were investigated to model rebound growth in vitro based on viable cell counts in response to MAPKi treatment and withdrawal.

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase.

Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase.

The dimerization of RAF kinases represents a key event in their activation cycle and in RAS/ERK pathway activation. Genetic, biochemical and structural approaches provided key insights into this process defining RAF signaling output and the clinical efficacy of RAF inhibitors (RAFi). However, methods reporting the dynamics of RAF dimerization in living cells and in real time are still in their infancy.

Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.

The persistence of leukemic stem cells (LSCs) represents a problem in the therapy of chronic myeloid leukemia (CML). Hence, it is of utmost importance to explore the underlying mechanisms to develop new therapeutic approaches to cure CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1 mouse model for chronic phase CML, we previously demonstrated that the loss of the docking protein GAB2 counteracts the infiltration of mast cells (MCs) in the bone marrow (BM) of BCR::ABL1 positive mice.

Long term renal outcome and risk of elevated blood pressure in children undergoing complete primary repair of bladder exstrophy (CPRE).

Introduction: Since the initiation of staged reconstruction for bladder exstrophy (BE), hypertension has been a known complication of the procedure. Hypertension is a well-established risk factor for chronic kidney disease (CKD) progression and associated with cardiovascular/cerebrovascular morbidity and mortality. Few studies exist evaluating the risk of developing hypertension among patients with bladder exstrophy who underwent CPRE.

Effect of Age on Hypertension Recognition in Children With Chronic Kidney Disease: A Report From the Chronic Kidney Disease in Children Study.

Background: Young age has been associated with poorer control of hypertension in children with chronic kidney disease (CKD). Using data from the CKiD Study (Chronic Kidney Disease in Children), we examined the relationship between age, hypertensive blood pressure (BP) recognition, and pharmacologic BP control in children with nondialysis-dependent CKD.

Methods: Participants included 902 CKiD Study participants with CKD stages 2 to 4.

Burnout in Pediatric Nephrology Fellows and Faculty: Lessons From the Sustainable Pediatric Nephrology Workforce Project (SUPERPOWER).

Physician well-being is an important contributor to both job satisfaction and patient outcomes. Rates of burnout among physicians vary by specialty, ranging from 35 to 70%. Among pediatric residents, longitudinal data demonstrates consistent rates of burnout around 50-60%, although little is known about burnout among pediatric subspecialty fellows.

[DNVF Memorandum Health Literacy (Part 2) - Operationalisation and Measuring of Health Literacy from a Health Services Research Perspective].

The "DNVF Memorandum Health Literacy (Part 2): Operationalization and Measurement of Health Literacy from the Perspective of Health Services Research" of the German Network for Health Services Research represents the continuation of the memorandum "DNVF Memorandum Health Literacy (Part 1): Background, Subject and Issues in Health Services Research". In addition to the general requirements for the measurement of health literacy, this memorandum also deals with the specific requirements, such as the differentiation of health literacy from related constructs, the differences between performance-based and self-assessment methods, the differences between generic and specific instruments, the use of screening instruments, and the measurement of health literacy in special populations. Furthermore, special considerations about the measurement of digital health literacy, potentials of qualitative and participatory research approaches as well as research ethics in the measurement of health literacy will be elaborated on.

Defense Mechanisms and Repressive Coping Among Male Breast Cancer Patients.

The concept of defense mechanisms has undergone extensive revision and expansion since Freud first described these processes. Initially formulated as an unconscious repression of unpleasant memories, with further development focusing on the role of defense mechanisms in the regulation of internal conflicts, the concept shifted and evolved to incorporate the adaptation to external demands, including intrapsychic and interpersonal handling of burden of illness. In addition to defense mechanisms, coping provides another perspective on human adjustment to difficult life events.

Gab2 deficiency prevents Flt3-ITD driven acute myeloid leukemia in vivo.

Internal tandem duplications (ITD) of the FMS-like tyrosine kinase 3 (FLT3) predict poor prognosis in acute myeloid leukemia (AML) and often co-exist with inactivating DNMT3A mutations. In vitro studies implicated Grb2-associated binder 2 (GAB2) as FLT3-ITD effector. Utilizing a Flt3-ITD knock-in, Dnmt3a haploinsufficient mouse model, we demonstrate that Gab2 is essential for the development of Flt3-ITD driven AML in vivo, as Gab2 deficient mice displayed prolonged survival, presented with attenuated liver and spleen pathology and reduced blast counts.

Comprehensive support for families with parental cancer (Family-SCOUT), evaluation of a complex intervention: study protocol for a non-randomized controlled trial.

Background: Families with minor children affected by parental cancer are at risk of considerable emotional and organizational stress that can severely burden all family members. So far, there has been a lack of comprehensive support services for affected families. The aim of this project is to implement and evaluate a complex psychosocial intervention for these families by providing advice, information, and care on an emotional, psycho-social, and communicative level during and after the cancer experience and across healthcare sectors.

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.

Purpose: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature.

Impact of the COVID-19 Pandemic on Nephrology Fellow Training and Well-Being in the United States: A National Survey.

Background: The coronavirus disease 2019 (COVID-19) pandemic's effects on nephrology fellows' educational experiences, preparedness for practice, and emotional wellbeing are unknown.

Methods: We recruited current adult and pediatric fellows and 2020 graduates of nephrology training programs in the United States to participate in a survey measuring COVID-19's effects on their training experiences and wellbeing.

Results: Of 1005 nephrology fellows-in-training and recent graduates, 425 participated (response rate 42%).

Occupational rehabilitation of male breast cancer patients: Return patterns, motives, experiences, and implications-A qualitative study.

Objective: Knowledge regarding the occupational rehabilitation of male breast cancer patients (MBCPs) is currently scarce; however, there may exist unmet needs of men affected by this rare disease. Therefore, this exploratory study investigated the experiences of MBCPs in their return to work (RTW).

Methods: Interview data from 14 men with a breast cancer diagnosis were used for qualitative content analysis.

[Interactive Health Literacy, Sociodemographic Characteristics and the Uptake of Psychotherapeutic or Pharmacological Interventions - are there Social Inequalities in the Treatment of Social Anxiety Disorder?].

Aim: The aim is to investigate the association between sociodemographic characteristics and the interactive health literacy and the time to treatment of social anxiety disorder.

Methods: An online survey of N = 311 patients was carried out (response rate 54.1 %).

Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans.

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis. We found that T cells of patients relapsing with AML after allo-HCT exhibited reduced glycolysis and interferon-γ production. Functional studies in multiple mouse models of leukemia showed that leukemia-derived lactic acid (LA) interfered with T cell glycolysis and proliferation.