A collaborative network analysis for the interpretation of transcriptomics data in Huntington's disease.

Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research.

The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force.

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use.

The Long-Term Uptake of Home Spirometry in Regular Cystic Fibrosis Care: Retrospective Multicenter Observational Study.

Background: Home spirometers have been widely implemented in the treatment of people with cystic fibrosis (CF). Frequent spirometry measurements at home could lead to earlier detection of exacerbations. However, previous research indicates that the long-term use of home spirometry is not well maintained by people with CF.

Barriers and facilitators for adequate calcium intake during pregnancy: A mixed methods study.

Objective: This study evaluates the effectiveness of calcium supplementation as a preventive measure for pregnant women with insufficient calcium intake, examining adherence to the recommended 1000 mg daily intake and identifying influencing factors.

Methods: A survey (Expect cohort II, n = 823) evaluated calcium adherence among pregnant women, followed by interviews with sixteen purposefully selected participants. Verbatim transcripts were independently analyzed to identify key themes.

Loss-of-function GHSR variants are associated with short stature and low IGF-I.

Context: The growth hormone (GH) secretagogue receptor, encoded by GHSR, is expressed on somatotrophs of the pituitary gland. Stimulation with its ligand ghrelin, as well as its constitutive activity, enhances GH secretion. Studies in knock-out mice suggest that heterozygous loss-of-function of GHSR is associated with decreased GH response to fasting, but patient observations in small case reports have been equivocal.

Introduction of Ivacaftor/Lumacaftor in Children With Cystic Fibrosis Homozygous for F508del in the Netherlands: A Nationwide Real-Life Study.

Introduction: Lumacaftor/ivacaftor (lum/iva) was introduced in the Netherlands in 2017. We investigated 1-year efficacy of lum/iva on lung function and small airway and structural lung disease evaluated by multiple breath nitrogen washout and CT scan. Additionally, we investigated effects of lum/iva on exacerbations, anthropometry, sweat chloride and safety in children with CF in the Netherlands.

Achieving excellence in paediatric cardiac care in resource limited and resource plentiful settings and building successful care networks across different countries.

Background: The delivery of paediatric cardiac care across the world occurs in settings with significant variability in available resources. Irrespective of the resources locally available, we must always strive to improve the quality of care we provide to our patients and simultaneously deliver such care in the most efficient and cost-effective manner. The development of cardiac networks is used widely to achieve these aims.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Automatically optimized vectorcardiographic features are associated with recurrence of atrial fibrillation after electrical cardioversion.

Electrical cardioversion presents one of the treatment options for atrial fibrillation (AF). However, the early recurrence rate is high, reaching ~40% three months after the procedure. Features based on vectorcardiographic signals were explored to find association with early recurrence of AF.

Evaluating the Implementation of Home-Based Sexual Health Care Among Men Who Have Sex with Men: Limburg4zero.

Home-based sexual health care (including self-sampling testing) could reduce barriers to clinic-based testing. This study systematically evaluated the implementation of home-based sexual health care ('Limburg4Zero') among men who have sex with men (MSM) in a mixed urban-rural region of the Netherlands. We systematically assessed implementation outcomes (contextual domains, population reached, effectiveness, adoption by health care providers (HCP), implementation fidelity, and maintenance) using the practical, robust implementation and sustainability model.

Training and validating a treatment recommender with partial verification evidence.

Background: Current clinical decision support systems (DSS) are trained and validated on observational data from the clinic in which the DSS is going to be applied. This is problematic for treatments that have already been validated in a randomized clinical trial (RCT), but have not yet been introduced in any clinic. In this work, we report on a method for training and validating the DSS core before introduction to a clinic, using the RCT data themselves.

The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Seeding and feeding milestones: the role of human milk microbes and oligosaccharides in the temporal development of infant gut microbiota.

Breastfeeding represents a strong selective factor for shaping the infant gut microbiota. Besides providing nutritional requirements for the infant, human milk is a key source of oligosaccharides, human milk oligosaccharides (HMOs), and diverse microbes in early life. This study aimed to evaluate the influence of human milk microbiota and oligosaccharides on the composition of infant faecal microbiota at one, three, and nine months postpartum.

Long-term mortality of Dutch COVID-19 patients admitted to the intensive care medicine: a retrospective analysis from a national quality registry.

Objective: To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use.

Methods: We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup.

Predicting clinical outcomes in a blended care intervention for early psychosis: Acceptance and Commitment Therapy in Daily-Life (ACT-DL).

ACT in Daily Life (ACT-DL) is a blended-care Ecological Momentary Intervention that extends ACT into the daily life of individuals, improving psychotic distress, negative symptoms, and global functioning. However, it remains unclear whether ACT-DL works equally for everyone. We investigated whether moderators (i.

High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy.

The aim of this work was to describe the DNA methylation signature and to identify genes associated with neuropathic pain in type 2 diabetes mellitus. We analyzed two independent diabetic neuropathy cohorts: PROPGER consisting of 72 painful and 67 painless patients recruited at the German Diabetes Center in Düsseldorf (DE), and PROPENG comprising 27 painful and 65 painless diabetic neuropathy patients recruited at the University of Manchester (UK). Genome-wide methylation data was generated using Illumina Infinium Methylation EPIC v1.

The effects of recent stressful life events on outcomes in individuals at clinical high risk for psychosis: results from the longitudinal EU-GEI high-risk study.

Background: Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

Methods: The study used longitudinal data from the EU-GEI High Risk study.

Zuyderland Hip Inference for Survival and Lifetime Expectancy (ZHISLE) following hip fracture surgery: validation of the model that demonstrated good predictive power.

Purpose: Proximal femoral fractures are common within the elderly population and are associated with a high risk of mortality and reduced quality of life. Hemiarthroplasty or osteosynthesis (extramedullary or intramedullary) is the primary treatment option for these fractures. However, within this fragile patient population many comorbidities, among others dementia, are seen.

The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases.

The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights.

The Role of ctDNA in the Management of Non-Small-Cell Lung Cancer in the AI and NGS Era.

Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic insights. LB can be applied in both early-stage disease settings, for the diagnosis and monitoring of minimal residual disease (MRD), and advanced disease settings, for monitoring treatment response and understanding the mechanisms behind disease progression and tumour heterogeneity.

Establishing an Extracorporeal Cardiopulmonary Resuscitation Program.

Extracorporeal cardiopulmonary resuscitation (ECPR) is a complex, life-saving procedure that uses mechanical support for patients with refractory cardiac arrest, representing the pinnacle of extracorporeal membrane oxygenation (ECMO) applications. Effective ECPR requires precise patient selection, rapid mobilization of a multidisciplinary team, and skilled cannulation techniques. Establishing a program necessitates a cohesive ECMO system that promotes interdisciplinary collaboration, which is essential for managing acute cardiogenic shock and severe pulmonary failure.

Meta-Analysis of MINIject vs. Two iStents as Standalone Treatment for Glaucoma with 24 Months of Follow-Up.

This study compares the long-term intraocular pressure (IOP)-lowering efficacy of standalone MINIject (iSTAR Medical, Belgium) suprachoroidal implantation and two iStent (Glaukos, CA, USA) trabecular bypass implantation using a systematic review and meta-analysis. Systematic review of standalone implantation of MINIject or iStent inject with at least 24 months of follow up. The mean and standard deviation of IOP and the number of IOP-lowering medications at baseline and at 24 months were extracted.

Physical Activity and Frailty Are Impaired in Older Adults with Benign Paroxysmal Positional Vertigo.

: Benign Paroxysmal Positioning Vertigo (BPPV), diagnosed in 46% of older adults with complaints of dizziness, causes movement-related vertigo. This case-control study compared physical activity, frailty and subjective well-being between older adults with BPPV (oaBPPV) and controls. : Thirty-seven oaBPPV (mean age 73.