ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.

Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

Elucidating assembly and function of VirB8 cell wall subunits refines the DNA translocation model in Gram-positive T4SSs.

Bacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria.

Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment.

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics.

Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review.

Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes.

Intravitreal Enzyme Replacement Therapy Slows Retinopathy in Late Infantile Ceroid Lipofuscinosis Type 2.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

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.

RICTOR variants are associated with neurodevelopmental disorders.

RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene.

Establishment of Stable Knockdown of MACC1 Oncogene in Patient-Derived Ovarian Cancer Organoids.

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance.

Exposure Profiles for the Long-Term Use of Disinfectants and Cleaning Products and Asthma.

Background: Using disinfectants and cleaning products (DCPs) at home and work is known to influence both the onset and course of asthma, but most epidemiological studies did not consider the multiplicity and correlations of exposures to DCPs. We aimed to identify exposure profiles for the long-term weekly use of DCPs by latent class analysis (LCA) and assess their associations with asthma.

Methods: LCA was conducted on data from 1143 young adults initially recruited in the German centers of Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and followed up three times.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Corticospinal and Clinical Effects of Muscle Tendon Vibration in Neurologically Impaired Individuals. A Scoping Review.

This review verified the extent, variety, quality and main findings of studies that have tested the neurophysiological and clinical effects of muscle tendon vibration (VIB) in individuals with sensorimotor impairments. The search was conducted on PubMed, CINAHL, and SportDiscuss up to April 2024. Studies were selected if they included humans with neurological impairments, applied VIB and used at least one measure of corticospinal excitability using transcranial magnetic stimulation (TMS).

A core genome MLST scheme for Borrelia burgdorferi sensu lato improves insights into the evolutionary history of the species complex.

Multi-locus sequence typing (MLST) based on eight genes has become the method of choice for Borrelia typing and is extensively used for population studies. Whole-genome sequencing enables studies to scale up to genomic levels but necessitates extended schemes. We have developed a 639-loci core genome MLST (cgMLST) scheme for Borrelia burgdorferi sensu lato (s.

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

Characterization of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a broad spectrum of neurological disorders.

Objective: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) have been identified in ophthalmological and neurological diseases. Since PHOMS were found more frequently in these cohorts compared to healthy controls, it is assumed that the presence of PHOMS reflects a secondary disease marker of unknown significance. The extent to which disease-specific differences are reflected in PHOMS has not yet been sufficiently investigated.

TTC7A missense variants in intestinal disease can be classified by molecular and cellular phenotypes.

Biallelic mutations in tetratricopeptide repeat domain 7A (TTC7A) give rise to intestinal and immune disorders. However, our understanding of the genotype-phenotype relationship is limited, because TTC7A variants are mostly compound heterozygous and the disease phenotypes are highly diverse. This study aims to clarify how different TTC7A variants impact the severity of intestinal epithelial disorders.

-related disorder in 87 adults: Natural history and self-sustainability.

Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

Enforced CARD11/MALT1 signaling in dendritic cells triggers hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome fueled by uncontrolled mononuclear phagocyte activity, yet the innate immune mechanisms driving HLH pathogenesis remain elusive. Germline gain-of-function (GOF) mutations in CARD11, a pivotal regulator of lymphocyte antigen receptor signaling, cause the lymphoproliferative disease B-cell expansion with NF-κB and T-cell anergy, which is frequently associated with HLH development. Given that CARD11 is physiologically expressed not only in lymphocytes but also in dendritic cells (DCs), we explored whether enforced CARD11 signaling in DCs contributes to immunopathology.

Childhood interstitial lung disease survivors in adulthood: a European collaborative study.

Background: Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood.

Aim: To characterize chILD-survivors and identify their impact on adult-ILD centers.

Severe Disease Activation after Fingolimod Discontinuation in a Pediatric Multiple Sclerosis Patient: A Case Report and Literature Review.

Adult reports of unexpected severe disease worsening, often termed "rebound," shortly after discontinuing fingolimod in a subset of patients with multiple sclerosis (MS), have grown over the last decade. This phenomenon, however, remains poorly described in pediatric MS patients. We present findings of a 15-year-old who experienced a debilitating relapse 4 weeks after stopping fingolimod to switch to ocrelizumab.

ImpENSA eHealthy Conversation Skills training for healthcare professionals aimed at improving micronutrient status during the first 1000 days in South Africa.

Individuals' lifestyle behaviours determine health. Improving Early Nutrition and Health in South Africa ("ImpENSA"), an EU Erasmus+ co-funded project, aims to tackle the triple burden of malnutrition in South Africa through equipping healthcare professionals (HCPs) with knowledge and skills to effectively support healthy nutritional choices among pregnant women and mothers/infant caregivers. Healthy Conversation Skills (HCS) is a behaviour change intervention utilising open discovery questions, active listening, reflection on practice and goal-setting support through SMARTER (Specific, Measured, Action-oriented, Realistic, Timed, Evaluated and Reviewed) planning as core competences.