Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial.

Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.

Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

Wolffia globosa, a novel crop species for protein production in space agriculture.

Space agriculture, pivotal for sustainable extraterrestrial missions, requires plants that can adapt to altered gravitational conditions. This study delves into the adaptive responses to altered gravity of Wolffia globosa, an aquatic plant known for its rapid growth and high nutritional value. The research aimed to analyse the effect of simulated microgravity and hypergravity on relative growth rate (RGR), morphological characteristics, protein content, and the correlation between plant size and growth rate of Wolffia globosa.

Association Between PD-L1 Score and the Outcomes of Consolidation Durvalumab in a Large Nationwide Series of Patients With Stage III NSCLC Treated With Chemoradiotherapy.

Background: The Pacific trial reported improved outcomes when durvalumab was administered following concurrent chemoradiotherapy (CRT) for stage III NSCLC. Post-hoc subgroup analysis did not show favorable results for PD-L1 negative cases. We compared nationwide survival data with the trial outcomes, and evaluated the influence of PD-L1.

Shaping the skeleton: impact of GnRH analogue and sex hormone therapy on skeletal dimensions in transgender individuals.

Context: Skeletal dimensions vary between sexes. Men typically have broader shoulders and women a wider pelvis. If gender affirming hormone therapy (GAHT) with or without prior puberty suppression (PS) alters these dimensions in transgender individuals remains unclear.

Comprehensive phenotypic characterization of an allelic series of zebrafish models of NEB-related nemaline myopathy.

Nemaline myopathy (NM) is a rare congenital neuromuscular disorder characterized by muscle weakness and hypotonia, slow gross motor development, and decreased respiratory function. Mutations in at least twelve genes, all of each encode proteins that are either components of the muscle thin filament or regulate its length and stability, have been associated with NM. Mutations in Nebulin (NEB), a giant filamentous protein localized in the sarcomere, account for more than 50% of NM cases.

Population-based survival rates after curative surgical and non-surgical treatment of stage III NSCLC since 2017.

Objectives: In stage III non-small cell lung cancer (NSCLC), curative treatment approaches used to include neoadjuvant therapy followed by surgery, and definitive chemoradiotherapy followed by consolidation durvalumab (CRT-ICI). Surgical strategies included either neoadjuvant chemotherapy (CTx-surg) or chemoradiotherapy (CRT-surg). We studied the outcomes of these three radical intent strategies in the Netherlands Cancer Registry (NCR) for patients diagnosed from 2017 to 2021.

Effects of altered gravity on growth and morphology in Wolffia globosa implications for bioregenerative life support systems and space-based agriculture.

Understanding the response of plants to varied gravitational conditions is vital for developing effective food production in space bioregenerative life support systems. This study examines the impact of altered gravity conditions on the growth and morphological responses of Wolffia globosa (commonly known as "water lentils" or "duckweed"), assessing its potential as a space crop. Although an experiment testing the effect of simulated microgravity on Wolffia globosa has been previously conducted, for the first time, we investigated the effect of multiple gravity levels on the growth and morphological traits of Wolffia globosa plants.

Neurodevelopmental outcome at 5.5 years in Dutch preterm infants born at 24-26 weeks' gestational age: the EPI-DAF study.

Objective: After lowering the Dutch threshold for active treatment from 25 to 24 completed weeks' gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that this guideline has been implemented, an accurate description of neurodevelopmental outcome at school age is needed.

Design: Population-based cohort study.

Changes in multidisciplinary team decisions in a high volume head and neck oncological center following those made in its preferred partner.

Objective: Head and neck cancer care is highly complex, and multidisciplinary team meetings (MDTs) are vital for improved outcomes. In the Netherlands, head and neck cancer care is practiced in eight high-volume head and neck oncologic centers (HNOC) and six affiliated hospitals preferred partner (PP) centers. Patients treated in the PP are presented and discussed in the HNOC.

Methotrexate Polyglutamates Exposure - Response Modeling in a Large Cohort of Rheumatoid Arthritis Patients Starting Methotrexate.

Methotrexate polyglutamates (MTX-PG) concentrations in red blood cells (RBCs) have been suggested as a biomarker of response in patients with rheumatoid arthritis (RA) receiving low-dose MTX therapy. We investigated the association and interpatient variability between RBC-MTX-PG -exposure and response in patients with RA starting MTX. Data of three prospective cohorts were available.

Methotrexate Provokes Disparate Folate Metabolism Gene Expression and Alternative Splicing in Ex Vivo Monocytes and GM-CSF- and M-CSF-Polarized Macrophages.

Macrophages constitute important immune cell targets of the antifolate methotrexate (MTX) in autoimmune diseases, including rheumatoid arthritis. Regulation of folate/MTX metabolism remains poorly understood upon pro-inflammatory (M1-type/GM-CSF-polarized) and anti-inflammatory (M2-type/M-CSF-polarized) macrophages. MTX activity strictly relies on the folylpolyglutamate synthetase (FPGS) dependent intracellular conversion and hence retention to MTX-polyglutamate (MTX-PG) forms.

Factors influencing motivation of patients diagnosed with depression to have electroconvulsive therapy.

WHAT IS KNOWN ON THE SUBJECT?: The clinical effect of electroconvulsive therapy (ECT) has been confirmed for a majority of patients with several psychiatric disorders. ECT is mostly used in patients with severe depression. Choosing, persevering with and completing ECT depends on the patients' motivation for undergoing this therapy.

Effectiveness of Self-guided Tailored Implementation Strategies in Integrating and Embedding Internet-Based Cognitive Behavioral Therapy in Routine Mental Health Care: Results of a Multicenter Stepped-Wedge Cluster Randomized Trial.

Background: Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine practice. One-size-fits-all strategies are likely to be ineffective.

Comparing the SARS-CoV-2-specific antibody response in human milk after homologous and heterologous booster vaccinations.

Human milk contains SARS-CoV-2-specific antibodies after COVID-19 vaccination. These milk antibodies decrease several months post-vaccination. Whether booster immunization restores human milk antibody levels, potentially offering prolonged passive immunity for the infant, remains unknown.

Personalized Dietary Advice to Increase Protein Intake in Older Adults Does Not Affect the Gut Microbiota, Appetite or Central Processing of Food Stimuli in Community-Dwelling Older Adults: A Six-Month Randomized Controlled Trial.

Expert groups argue to raise the recommended daily allowance for protein in older adults from 0.8 to 1.2 g/kg/day to prevent undernutrition.

First Adolescent Romantic and Sexual Experiences in Individuals With Differences of Sex Development/Intersex Conditions.

Purpose: Adolescence is an important period for sexual development, including sexual debut. The purpose of this study was to assess first romantic and sexual experiences and debut age in individuals with differences of sex development (DSD/intersex) and compare these with age-matched and gender-matched population control values.

Methods: Questionnaire data on sociodemographic characteristics, romantic and sexual milestones (e.

Real-time quantification of osteoclastic resorptive activity by electric cell-substrate impedance sensing.

In several diseases, bone resorption by osteoclasts is dysregulated. Thus far, no simple technique for real-time measurement of resorption is available. Here, we introduce an impedimetric bioassay for real-time monitoring of resorption by making use of the electrical insulating properties of the resorbable substrate calcium phosphate.

Which precocial rodent species is more suitable as the experimental model of microgravity influence on prenatal musculosketal development on international space station?

The International Space Station (ISS) has the possibility to perform experiments regarding rodent reproduction in microgravity. The musculoskeletal system at birth in precocial rodent species more resembles the human than that of altricial rodent species. For precocial rodent species with body weight ≤ 500 g (limit of ISS) determined were: adult body mass, newborn body mass, head-body length, tail length, existing variants (wild, domesticated, laboratory), single/group housing, dry food consumption/24 h, water intake/24 h, basal metabolic rate mlO2/g/h, environmental temperature, sand baths, urine output ml/24 h, fecal output g/24 h, size of fecal droplet, hair length, life span, length of oestrus cycle, duration of pregnancy, building nest, litter size, stage of musculoskeletal maturity at birth, and the duration of weaning.

Incidence and risk factors of deep vein thrombosis after extracorporeal life support.

Background: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS.

Routine reporting of grey-white matter differentiation in early brain computed tomography in comatose patients after cardiac arrest: A substudy of the COACT trial.

Aim: A multimodal approach is advised for neurological prognostication in comatose patients after out-of-hospital cardiac arrest (OHCA). Grey-white matter differentiation (grey-white ratio, GWR) obtained from a brain CT scan performed < 24 hours after return of circulation can be part of this approach. The aims of this study were to investigate the frequency and method of reporting the GWR in brain CT scan reports and their association with outcome.

The association between patient attendance to a perioperative group-based lifestyle program and weight loss after bariatric surgery.

Background: To enable maximal and sustainable weight loss after bariatric surgery, bariatric lifestyle programs through multidisciplinary support are advised.

Objectives: To assess the association between patient attendance to a perioperative group-based bariatric lifestyle program (GBLP) and weight loss up to 48 months postoperatively.

Setting: A multicenter retrospective cohort study in the Netherlands.

Dispatch and delivery at the ER-Golgi interface: how endothelial cells tune their hemostatic response.

Von Willebrand factor (VWF) is a glycoprotein that is secreted into the circulation and controls bleeding by promoting adhesion and aggregation of blood platelets at sites of vascular injury. Substantial inter-individual variation in VWF plasma levels exists among the healthy population. Prior to secretion, VWF polymers are assembled and condensed into helical tubules, which are packaged into Weibel-Palade bodies (WPBs), a highly specialized post-Golgi storage compartment in vascular endothelial cells.