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.

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.

Enrichment of cell cycle pathways in progesterone-treated endometrial organoids of infertile women compared to fertile women.

Purpose: To investigate whether the transcriptome profile differs between progesterone-treated infertile and fertile endometrial organoids.

Methods: Endometrial biopsies were obtained from 14 infertile and seven fertile women, after which organoids were generated from isolated epithelial cells. To mimic the secretory phase, organoids were sequentially treated with 17β-estradiol (E2) and progesterone (P4) and subjected to RNA sequencing.

Chemotherapy-induced intestinal epithelial damage directly promotes galectin-9-driven modulation of T cell behavior.

The intestine is vulnerable to chemotherapy-induced damage due to the high rate of intestinal epithelial cell (IEC) proliferation. We have developed a human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced IEC damage on T cell behavior. Exposure of intestinal organoids to busulfan, fludarabine, and clofarabine induced damage-related responses affecting both the capacity to regenerate and transcriptional reprogramming.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

Background & Aims: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality.

Methods: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands.

Position Paper: fragmented youth healthcare services in the Netherlands endanger treatment of teenage boys with psychiatric disorders.

For children who show strongly deviant behaviour in the Netherlands, a distinction is made between behavioural problems and psychiatric problems. As a result, two different domains have emerged over time, each with its own legal frameworks and inclusion and exclusion criteria. Consequently, there is no well-organized, coherent system for youth mental health care in the Netherlands.

An unbiased approach of molecular characterization of the endometrium: toward defining endometrial-based infertility.

Infertility is a complex condition affecting millions of couples worldwide. The current definition of infertility, based on clinical criteria, fails to account for the molecular and cellular changes that may occur during the development of infertility. Recent advancements in sequencing technology and single-cell analysis offer new opportunities to gain a deeper understanding of these changes.

The Effect of Genetic HLA Matching on Liver Transplantation Outcome: A Systematic Review and Meta-Analysis.

Objective: We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.

Background: Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations.

Performance of a Nonlinear Magnetic Handheld Probe for Intraoperative Sentinel Lymph Node Detection: A Phantom Study.

Objective: This study investigates the performance of the DiffMag handheld probe (nonlinear magnetometry), to be used for sentinel lymph node detection. Furthermore, the performance of DiffMag is compared with a gamma probe and a first-order magnetometer (Sentimag, linear magnetometry).

Methods: The performance of all three probes was evaluated based on longitudinal distance, transverse distance, and resolving power for two tracer volumes.

Prognostic factors for multi-organ dysfunction in pediatric oncology patients admitted to the pediatric intensive care unit.

Background: Pediatric oncology patients who require admission to the pediatric intensive care unit (PICU) have worse outcomes compared to their non-cancer peers. Although multi-organ dysfunction (MOD) plays a pivotal role in PICU mortality and morbidity, risk factors for MOD have not yet been identified. We aimed to identify risk factors at PICU admission for new or progressive MOD (NPMOD) during the first week of PICU stay.

Chemotherapy-induced intestinal injury promotes Galectin-9-driven modulation of T cell function.

The intestine is vulnerable to chemotherapy-induced toxicity due to its high epithelial proliferative rate, making gut toxicity an off-target effect in several cancer treatments, including conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). In allo-HCT, intestinal damage is an important factor in the development of Graft-versus-Host Disease (GVHD), an immune complication in which donor immune cells attack the recipient's tissues. Here, we developed a novel human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced intestinal epithelial damage on T cell behavior.

Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2-4.

Hereditary proximal spinal muscular atrophy causes weakness and increased fatigability of repetitive motor functions. The neuromuscular junction is anatomically and functionally abnormal in patients with spinal muscular atrophy. Pharmacological improvement of neuromuscular transmission may therefore represent a promising additional treatment strategy.

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes.

Clinical Relevance of Random Biopsies From the Esophagogastric Junction After Complete Eradication of Barrett's Esophagus is Low.

Background & Aims: Although random histological sampling from the esophagogastric junction (EGJ) after complete eradication of Barrett's esophagus (BE) is recommended, its clinical relevance is questionable. This study aimed to assess the incidence and long-term outcomes of findings from random EGJ biopsies in a nationwide cohort with long-term follow-up.

Methods: We included all patients with successful endoscopic eradication therapy (EET), defined as complete endoscopic eradication of all visible BE (CE-BE), for early BE neoplasia from the Dutch registry.

Validation of a modified bedside Pediatric Early Warning System score for detection of clinical deterioration in hospitalized pediatric oncology patients: A prospective cohort study.

Background: Hospitalized pediatric oncology patients are at risk of severe clinical deterioration. Yet Pediatric Early Warning System (PEWS) scores have not been prospectively validated in these patients. We aimed to determine the predictive performance of the modified BedsidePEWS score for unplanned pediatric intensive care unit (PICU) admission and cardiopulmonary resuscitation (CPR) in this patient population.

A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.

The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However, direct comparison of hepatocyte models is currently challenging. We systematically searched the literature and compared different HLCs, but reported functions were limited to a small subset of hepatic functions.

Today's Mistakes and Tomorrow's Wisdom… in the Management of T1b Barrett's Adenocarcinoma.

Background: Given the limitation that endoscopic resection only enables local intraluminal treatment without lymphadenectomy, the standard treatment of esophageal adenocarcinoma (EAC) with invasion of the submucosa (T1b) has long been surgical esophageal resection. However, in recent literature, the risk of lymph node metastases (LNM) associated with T1b EAC appears to be lower than previously assumed, and endoscopic management is increasingly being considered a valid and less invasive alternative to surgery.

Summary: Surgical esophageal resection performed after radical endoscopic resection of T1b EAC often does not show any residual tumor or LNM in the resected specimen.

Challenges and opportunities targeting mechanisms of epithelial injury and recovery in acute intestinal graft-versus-host disease.

Despite advances in immunosuppressive prophylaxis and overall supportive care, gastrointestinal (GI) graft-versus-host disease (GVHD) remains a major, lethal side effect after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has become increasingly clear that the intestinal epithelium, in addition to being a target of transplant-related toxicity and GVHD, plays an important role in the onset of GVHD. Over the last two decades, increased understanding of the epithelial constituents and their microenvironment has led to the development of novel prophylactic and therapeutic interventions, with the potential to protect the intestinal epithelium from GVHD-associated damage and promote its recovery following insult.

GATA-1 Defects in Diamond-Blackfan Anemia: Phenotypic Characterization Points to a Specific Subset of Disease.

Diamond−Blackfan anemia (DBA) is one of the inherited bone marrow failure syndromes marked by erythroid hypoplasia. Underlying variants in ribosomal protein (RP) genes account for 80% of cases, thereby classifying DBA as a ribosomopathy. In addition to RP genes, extremely rare variants in non-RP genes, including GATA1, the master transcription factor in erythropoiesis, have been reported in recent years in patients with a DBA-like phenotype.

Dysplastic Recurrence After Successful Treatment for Early Barrett's Neoplasia: Development and Validation of a Prediction Model.

Background & Aims: The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment.

Development and External Validation of a Model to Predict Complex Treatment After Radiofrequency Ablation for Barrett's Esophagus With Early Neoplasia.

Background & Aims: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes.

Analysis of metastases rates during follow-up after endoscopic resection of early "high-risk" esophageal adenocarcinoma.

Background And Aims: After endoscopic resection (ER) of early esophageal adenocarcinoma (EAC), the optimal management of patients with high-risk histologic features for lymph node metastases (ie, submucosal invasion, poor differentiation grade, or lymphovascular invasion) remains unclear. We aimed to evaluate outcomes of endoscopic follow-up after ER for high-risk EAC.

Methods: For this retrospective cohort study, data were collected from all Dutch patients managed with endoscopic follow-up (endoscopy, EUS) after ER for high-risk EAC between 2008 and 2019.