Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.

Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved as a cancer treatment. In this study, we use patient-derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers.

Randomized controlled trials - The what, when, how and why.

Randomized controlled trials (RCTs) are at the top of the pyramid of evidence as they offer the best answer on the efficacy of a new treatment. RCTs are true experiments in which participants are randomly allocated to receive a certain intervention (experimental group) or a different intervention (comparison group), or no treatment at all (control or placebo group). Randomization, along with other methodological features such as blinding and allocation concealment, safeguard against biases.

Uneven Distribution of Purkinje Cell Injury in the Cerebellar Vermis of Term Neonates with Hypoxic-Ischemic Encephalopathy.

In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated.

Clinical Characterization of a National Cohort of Patients With Germline Variants Including Late-Onset Phenotypes.

Introduction: disorder is a recently introduced term for phenotypes associated with germline Wilms Tumor 1 () variants, including glomerulopathy, urogenital anomalies, and Wilms tumor. Previous studies showed a bias toward missense variants in the DNA-binding/Zinc-finger domain of (exon 8 and 9) and patients with early-onset glomerulopathy. Thorough genotype-phenotype correlations including follow-up data on late-onset glomerulopathy risk are lacking.

Exploring the "shared" in shared decision-making in the care for children with chronic diseases or disabilities: what are the roles of parents and professionals?

There is a growing body of literature that recognizes the importance of shared decision-making (SDM) in the care for children with chronic conditions and/or disabilities. Although participation in SDM can be more or less active, the tuning between parents and professionals about the way they want to participate in SDM is often an implicit process, limiting parents' optimal involvement. Role definitions may support both partners in the process of SDM.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction: results of a large, multicenter cohort study (the OPTICORE study).

Background: Early-onset fetal growth restriction as consequence of placental insufficiency frequently requires iatrogenic, preterm birth. Administration of antenatal corticosteroids reduces risks of neonatal morbidity and mortality following preterm birth and is most beneficial if the neonate is delivered within two weeks following treatment. International guidelines on fetal growth restriction pregnancies do not provide directives regarding the timing of antenatal corticosteroids, resulting in practice variation.

EV-Elute: A universal platform for the enrichment of functional surface marker-defined extracellular vesicle subpopulations.

Intercellular communication via extracellular vesicles (EVs) has been identified as a vital component of a steadily expanding number of physiological and pathological processes. To accommodate these roles, EVs have highly heterogeneous molecular compositions. Given that surface molecules on EVs determine their interactions with their environment, EV functionality likely differs between subpopulations with varying surface compositions.

Definitions matter: Multicenter investigation of incidence and outcome of poor graft function after hematopoietic cell transplantation.

Despite advances in allogeneic hematopoietic cell transplantation (HCT), poor graft function (PGF) remains an important complication with substantial morbidity and mortality. The investigation of preventive and therapeutic PGF treatments is hindered by inconsistencies in reported incidence and outcomes across studies, which may be explained by heterogeneity in PGF definition. To assess the impact of definition heterogeneity, we conducted a multicenter study, analyzing over 35.

How accurate is high-resolution computed tomography of the chest in differentiating between pulmonary invasive fungal infections and other pulmonary infections in children with cancer?

Background: Pulmonary invasive fungal infections pose a serious risk for immunocompromised patients. Although diagnostic imaging plays an important role in the early detection of pulmonary invasive fungal infections, radiological differentiation between invasive fungal infection and other pulmonary infections is challenging.

Objective: The aim of this study was to assess the accuracy of chest high-resolution computed tomography (HRCT) in the differentiation between pulmonary invasive fungal infections and other pulmonary infections in paediatric cancer patients.

Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort.

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed View Article and Find Full Text PDF

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.

Does primary posterior tracheopexy prevent collapse of the trachea in newborns with oesophageal atresia and tracheomalacia? A study protocol for an international, multicentre randomised controlled trial (PORTRAIT trial).

Introduction: Tracheomalacia (TM) often occurs in children with oesophageal atresia (OA), leading to recurrent respiratory symptoms and in severe cases to blue spells or ultimately respiratory arrest. In some patients, a secondary posterior tracheopexy may then be indicated. This secondary surgery, as well as respiratory morbidity, may be prevented by performing a primary posterior tracheopexy (PPT) concurrent with primary OA correction.

Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports.

Purpose: Molybdenum cofactor deficiency (MoCD) classically presents shortly after birth, with neurological symptoms ascribed to postnatal toxicity of accumulating sulphite. Case reports suggest that cerebral damage associated with MoCD may have a prenatal onset.

Methods: A meta-analysis of case reports was performed on individuals with genetically proven MoCD retrieved through a systematic review and in-house search.

Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation.

Aminoacyl-tRNA synthetases (ARSs) couple tRNAs with their corresponding amino acids. While ARSs can bind structurally similar amino acids, extreme specificity is ensured by subsequent editing activity. Yet, we found that upon isoleucine (I) restriction, healthy fibroblasts consistently incorporated valine (V) into proteins at isoleucine codons, resulting from misacylation of tRNAIle with valine by wildtype IARS1.

Grandmothers matter: how grandmothers promote maternal perinatal mental health and child development.

Low social support has been identified as a risk factor for maternal perinatal mental health problems. However, previous studies have predominantly focused on general social support or support from the partner, often overlooking the roles of grandparents. This mini review discusses recent developments in perinatal health research showing that supportive grandparents may constitute a protective factor against the development of maternal perinatal mental health problems.

The respiratory microbiome is linked to the severity of RSV infections and the persistence of symptoms in children.

Respiratory syncytial virus (RSV) is the leading cause of infant respiratory infections and hospitalizations. To investigate the relationship between the respiratory microbiome and RSV infection, we sequence nasopharyngeal samples from a birth cohort and a pediatric case-control study (Respiratory Syncytial virus Consortium in Europe [RESCEU]). 1,537 samples are collected shortly after birth ("baseline"), during RSV infection and convalescence, and from healthy controls.

Time trends in antithrombotic therapy during pregnancy and maternal and perinatal outcomes in the Netherlands (2013-19): a nationwide cohort study.

Background: Considering the paucity of data, we aimed to describe nationwide time trends in antithrombotic therapy during pregnancy and risks of maternal and perinatal outcomes in the Netherlands.

Methods: In this nationwide cohort study, all female individuals aged 16-45 years with delivery records in the Dutch perinatal registry between Jan 1, 2013, and Dec 31, 2019, and their infants, were included. Individually linked data from Statistics Netherlands on outpatient medication prescriptions, in-hospital diagnoses, and mortality were used to evaluate time trends in antithrombotic therapy during pregnancy, and risks of maternal and perinatal outcomes (including thromboembolism, bleeding, preeclampsia and eclampsia, and low birthweight).

The neonatal gut microbiota: A role in the encephalopathy of prematurity.

Preterm birth correlates with brain dysmaturation and neurocognitive impairment. The gut microbiome associates with behavioral outcomes in typical development, but its relationship with neurodevelopment in preterm infants is unknown. We characterize fecal microbiome in a cohort of 147 neonates enriched for very preterm birth using 16S-based and shotgun metagenomic sequencing.

Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations.

Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen-reactive CD8+ T-cell clone without inducing cytotoxicity.

Respiratory syncytial virus (RSV) prevention: Perception and willingness of expectant parents in the Netherlands.

Background: Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Recent approval of preventive measures like a long-acting monoclonal antibody and a maternal vaccine signals a potential shift in early-life RSV infection control. However, success hinges on acceptance.

Transient impact of chronic social stress on effort-based reward motivation in non-food restricted mice: Involvement of corticosterone.

Chronic stress has been connected to a reduced effort and motivational deficits. To study effort-based motivation in rodents, operant conditioning is often employed. However, caloric restriction is typically imposed simultaneously.

Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations.

Mevalonate kinase deficiency (MKD), a rare auto-inflammatory disorder, arises from mutations in the gene, disrupting isoprenoid biosynthesis, and affecting cellular processes. This comprehensive review provides an updated perspective on MKD, including its aetiology, pathogenesis, diagnostic modalities, and therapeutic strategies. Based on recent research and clinical advances, our objective is to bridge the knowledge gaps in the 2015 SHARE guidelines.

Impact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents.

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity.