Altered Neural Responses to Punishment Learning in Conduct Disorder.

Objective: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs).

Methods: 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Transcranial direct current stimulation (tDCS) in psychiatric disorders in early childhood (aged under 10 years): a systematic review.

Transcranial direct current stimulation (tDCS) remains experimental for many psychiatric disorders in adults. Particularly in childhood, there is limited research on the evidence for the efficacy and mechanisms of action of tDCS on the developing brain. The objective of this review is to identify published experimental studies to examine the efficacy and mechanisms of tDCS in children with psychiatric or developmental disorders in early (prepubertal) childhood (aged under 10 years).

SARS-CoV-2 Activated Peripheral Blood Mononuclear Cells (PBMCs) Do Not Provoke Adverse Effects in Trophoblast Spheroids.

Problem: Although it is still uncertain whether Severe Acute Respiratory Coronavirus (SARS-CoV-2) placental infection and vertical transmission occur, inflammation during early pregnancy can have devastating consequences for gestation itself and the growing fetus. If and how SARS-CoV-2-specific immune cells negatively affect placenta functionality is still unknown.

Method Of Study: We stimulated peripheral blood mononuclear cells (PBMCs) from women of reproductive age with SARS-CoV-2 peptides and cocultured them with trophoblast spheroids (HTR-8/SVneo and JEG-3) to dissect if SARS-CoV-2-activated immune cells can interfere with trophoblast functionality.

PCA-based spatial domain identification with state-of-the-art performance.

Motivation: The identification of biologically meaningful domains is a central step in the analysis of spatial transcriptomic data.

Results: Following Occam's razor, we show that a simple PCA-based algorithm for unsupervised spatial domain identification rivals the performance of ten competing state-of-the-art methods across six single-cell spatial transcriptomic datasets. Our reductionist approach, NichePCA, provides researchers with intuitive domain interpretation and excels in execution speed, robustness, and scalability.

Infant Crying, Sleeping, and Feeding Problems in Times of Societal Crises: The Mediating Role of Parenting Stress on Parenting Behavior in Fathers and Mothers.

Background/objectives: Infant regulatory problems (RPs), i.e., crying, sleeping, and feeding problems, are associated with unfavorable outcomes in later childhood.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

Accelerometry-assessed sleep clusters and obesity in adolescents and young adults: a longitudinal analysis in GINIplus/LISA birth cohorts.

Background: Some studies have revealed various sleep patterns in adolescents and adults using multidimensional objective sleep parameters. However, it remains unknown whether these patterns are consistent from adolescence to young adulthood and how they relate to long-term obesity.

Methods: Seven-day accelerometry was conducted in German Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development (GINIplus) and Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany (LISA) birth cohorts during the 15-year and 20-year follow-ups, respectively.

Phenotype Spectrum of TRPM3-Associated Disorders.

Objective: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.

Methods: We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22).

Risk factors and surgical outcomes in pediatric patients with congenital heart disease and ischemic colitis.

Introduction: This study investigates risk factors and surgical outcomes in pediatric patients with congenital heart defects (CHD) who develop ischemic colitis (IC). Previous research indicates a higher IC risk in very low birth weight neonates with CHD.

Methods: A retrospective analysis compared an IC-CHD group to a CHD-only group.

Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry.

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Dominant negative mutations cause ADA2 deficiency in heterozygous carriers.

Human ADA2 deficiency (DADA2) is an inborn error of immunity with a broad clinical phenotype which encompasses vasculopathy including livedo racemosa and lacunar strokes, as well as hemato-immunological features. Diagnosis is based on the combination of decreased serum ADA2 activity and the identification of biallelic deleterious alleles in the gene. DADA2 carriers harbor a single pathogenic variant in and are mostly considered healthy and asymptomatic.

RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I.

The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I.

Psychometric properties of the parent-rated assessment scale of positive and negative parenting behavior (FPNE) in a German sample of school-aged children.

Background: The aim of this study was to develop and psychometrically evaluate a parent-rated parenting assessment scale including positive and negative dimensions of parenting. Factorial validity, reliability, measurement invariance, latent mean differences and construct validity of the Assessment Scale of Positive and Negative Parenting Behavior (FPNE) were tested in a pooled sample of five studies of 1,879 school-aged children (6.00 to 12.

[Surgery of premature infants-Perspectives and limitations].

The continuous improvement in the quality of modern perinatology, sociodemographic changes and the increasing spread of reproductive medicine have resulted in an increasing number of premature infants to be treated. The treatment of preterm infants (< 37th week of pregnancy) and especially extremely premature infants (< 28th week of pregnancy) is challenging due to immature organ development, which differs considerably from that of other age groups. While the fate of premature infants and especially extremely premature infants was unfavorable 100 years ago, the survival of premature infants > 1000 g has now shifted to survival in over 80% of cases [30].

Tonabersat enhances temozolomide-mediated cytotoxicity in glioblastoma by disrupting intercellular connectivity through connexin 43 inhibition.

Glioblastoma cells rely on connexin 43 (Cx43)-based gap junctions (GJs) for intercellular communication, enabling them to integrate into a widely branched malignant network. Although there are promising prospects for new targeted therapies, the lack of clinically feasible GJ inhibitors has impeded their adoption in clinical practice. In the present study, we investigated tonabersat (TO), a blood-brain-barrier-penetrating drug with GJ-inhibitory properties, in regard to its potential to disassemble intercellular connectivity in glioblastoma networks.

Age-stratification reveals age-specific intestinal microbiota signatures in juvenile idiopathic arthritis.

Objective: Juvenile Idiopathic Arthritis (JIA) comprises diverse chronic inflammatory conditions driven by malfunction of the immune system. The intestinal microbiota is considered a crucial environmental factor correlating with chronic inflammatory diseases, and for JIA certain alterations in the microbiota have already been described.

Methods: Here, we have characterized intestinal microbiota samples from 54 JIA patients and 38 pediatric healthy controls by conventional 16S rRNA sequencing and by single-cell analysis for phenotypic features by multi-parameter microbiota flow cytometry (mMFC), which complements the population-based taxonomic profiling with the characterization of individual bacterial cells.

Clinical relevance of feto-maternal microchimerism in (hematopoietic stem cell) transplantation.

Toleration of a semi-allogeneic fetus in the mother's uterus as well as tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) appear to share some immunologic concepts. The existence of microchimeric cells, and the original idea of a bidirectional cell trafficking between mother and child during pregnancy have been known for decades. Today, origins and mechanisms of persistence of microchimeric cells are intensively being elucidated.