Tagless LysoIP for immunoaffinity enrichment of native lysosomes from clinical samples.

Lysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.

Development of the Dutch translational knowledge agenda for inherited metabolic diseases.

Background: Inherited metabolic diseases (IMDs) may have considerable implications for patients and their families. Despite their individual rarity, covering a spectrum of over 1800 distinct diseases, the diseases collectively exert a significant impact, with often lifelong disabilities. The United for Metabolic Diseases consortium was established to catalyze research with translation into the best possible care.

Decay Rates of Maternal Tetanus, Diphtheria, and Pertussis Antibody Levels in Early and Moderate-to-Late Preterm and Term Infants at Birth and at Two Months.

A post hoc analysis of maternally derived antibodies at birth and age 2 months following second trimester maternal Tdap vaccination between 20 and 24 weeks' gestational age (GA) showed a faster decay rate of Tdap-related immunoglobulin G in early preterms born before 32 weeks' GA compared with moderate-to-late preterms and full-terms. This is different from previous studies and merits further research.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Physiological versus time based cord clamping in very preterm infants (ABC3): a parallel-group, multicentre, randomised, controlled superiority trial.

Background: Physiological-based cord clamping (PBCC) in preterm infants is beneficial for cardiovascular transition at birth and may optimize placental transfusion. Whether PBCC can improve clinical outcomes is unknown. The aim of the Aeration, Breathing, Clamping (ABC3) trial was to test whether PBCC results in improved intact survival in very preterm infants.

Machine-learning based prediction of appendicitis for patients presenting with acute abdominal pain at the emergency department.

Background: Acute abdominal pain (AAP) constitutes 5-10% of all emergency department (ED) visits, with appendicitis being a prevalent AAP etiology often necessitating surgical intervention. The variability in AAP symptoms and causes, combined with the challenge of identifying appendicitis, complicate timely intervention. To estimate the risk of appendicitis, scoring systems such as the Alvarado score have been developed.

Nosocomial transmission of NDM-1-containing Klebsiella pneumoniae ST147 in a Dutch pediatric oncology center associated with patients from Ukraine.

We studied nosocomial transmission of multidrug-resistant bla-containing Klebsiella pneumoniae ST147 in a Dutch pediatric oncology center. Whole-genome multilocus sequence typing revealed two genetic clusters consisting of 2 and 5 K. pneumoniae isolates, both from Ukrainian medical evacuees and Dutch patients.

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.

Interhospital variations in diagnostic work-up following recall at biennial screening mammography-a population-based study.

Objectives: Quality control in breast cancer screening programmes has been subject of several studies. However, less is known about the clinical diagnostic work-up in recalled women with a suspicious finding at screening mammography. The current study focuses on interhospital differences in diagnostic work-up strategies.

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

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas.

Aligned with the mission of the Dutch Pharmacogenetics Working Group (DPWG) to promote the implementation of pharmacogenetics (PGx), this guideline is specifically designed to optimize pharmacotherapy of cholesterol lowering medication (statins) and glucose lowering medication (sulfonylureas). The SLCO1B1 c.521 T > C variant reduces the activity of the SLCO1B1 transporter involved in statin transport out of the blood into the liver.

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.

Nails and skin co-infection by Fusarium verticillioides and Proteus vulgaris secondary to arterial occlusion of lower extremity.

Background: Post-traumatic Fusarium infection is rare. Arterial occlusive disease, a common vascular disorder in the elderly, often leads to ischemic necrosis of the lower extremities, which in turn increases the likelihood of secondary infections. Those secondary infections can be caused by bacteria, virus, or fungi.

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.