5,10-methenyltetrahydrofolate synthetase deficiency: An extreme rare defect of folate metabolism in two Dutch siblings.

Two siblings, presenting with a neurometabolic phenotype, were identified with 5, 10-methenyltetrahydrofolate synthetase (MTHFS) deficiency. Whole genome sequencing in both patients demonstrated an homozygous variant NM_006441.3():c.

Suppressed IgG4 class switching in dupilumab- and TNF inhibitor-treated patients after mRNA vaccination.

Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL-4-signaling along the T helper 2-axis may be instrumental in IgG4 class switching. Recently, repeated SARS-CoV-2 mRNA vaccination has been linked to IgG4 skewing.

The relationship between frailty and social vulnerability: a systematic review.

Both frailty (reduced physiological reserve) and social vulnerability (scarcity of adequate social connections, support, or interaction) become more common as people age and are associated with adverse consequences. Analyses of the relationships between these constructs can be limited by the wide range of measures used to assess them. In this systematic review, we synthesised 130 observational studies assessing the association between frailty and social vulnerability, the bidirectional longitudinal relationships between constructs, and their joint associations with adverse health outcomes.

Treatment resistance in pancreatic and biliary tract cancer: molecular and clinical pharmacology perspectives.

Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment.

Differences in gut microbiota between Dutch and South-Asian Surinamese: potential implications for type 2 diabetes mellitus.

Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities.

Alkaline phosphatase treatment of acute kidney injury-an update.

Through improved insights into the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy still does not exist. Finding one is complicated by a multifactorial pathophysiology and by heterogeneity in the patient population.

Correlation between Histopathological Prognostic Tumor Characteristics and [F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer.

Background: In metastatic breast cancer (MBC), [F]fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [F]FDG uptake in corresponding metastases.

Patients And Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [F]FDG-PET.

Prevalence of disabling musculoskeletal pain in children and adolescents in Brazil: A cross-sectional study.

Background: Estimates of prevalence of musculoskeletal pain in children and adolescents vary considerably and the impact of pain on children's life is often not considered.

Objective: To determine the one-month prevalence of disabling musculoskeletal pain in children and adolescents. The secondary aims are to: 1) determine the body region with the highest prevalence; 2) understand the characteristics of the children with disabling musculoskeletal pain; and 3) describe the parents' perception of the prevalence.

The associations between sleep quality, mood, pain and appetite in community dwelling older adults: a daily experience study.

Objectives: To investigate the daily life experiences of sleep, mood, and pain in relation to appetite in community-dwelling older adults aged 75 years and older, stratified by sex.

Design: Existing data from a daily experience study embedded in the Longitudinal Aging Study Amsterdam (LASA) among the oldest-old (≥75 years).

Setting: LASA is an ongoing cohort study of a nationally representative sample of older adults aged ≥55 years from three culturally distinct regions in the Netherlands.

Athletes who have already experienced an injury are more prone to adhere to an injury risk reduction approach than those who do not: an online survey of 7870 French athletics (track and field) athletes.

Objective: To compare the perception towards injury risk reduction approach between athletes who have already experienced an injury and those who have not.

Methods: We conducted a cross-sectional study using a one-time online survey asking athletics athletes licensed at the French Federation of Athletics (http://www.athle.

Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021.

Background: The prognosis of advanced melanoma patients has significantly improved over the years. We aimed to evaluate the survival per year of diagnosis.

Methods: All systemically treated patients diagnosed with advanced melanoma from 2013 to 2021 were included from the Dutch Melanoma Treatment Registry.

Validation of resting full-cycle ratio and diastolic pressure ratio with [O]HO positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy.

Associations between meat consumption and all-cause and cause-specific mortality in middle-aged and older adults with frailty.

Objectives: This study aimed to explore the associations between different types of meat consumption and mortality risk among people with frailty.

Design: Longitudinal study.

Setting And Participants: We included 19,913 physically frail participants from the UK Biobank.

Pharmacological Characterization and Radiolabeling of VUF15485, a High-Affinity Small-Molecule Agonist for the Atypical Chemokine Receptor ACKR3.

Atypical chemokine receptor 3 (ACKR3), formerly referred to as CXCR7, is considered to be an interesting drug target. In this study, we report on the synthesis, pharmacological characterization and radiolabeling of VUF15485, a new ACKR3 small-molecule agonist, that will serve as an important new tool to study this -arrestin-biased chemokine receptor. VUF15485 binds with nanomolar affinity (pIC = 8.

Age-related subtypes of late life depression and mortality: A prospective clinical cohort study.

Objectives: Late Life Depression (LLD) is associated with increased mortality rates, but it remains unclear which depressed patients are at increased risk. This study examined the mortality risk of previously identified subgroups of depressed older patients based on age-related clinical features (the presence of physical and cognitive frailty).

Methods: A six-year follow-up of a clinical cohort study including 375 depressed older patients and 132 non-depressed persons (NESDO).

Design and evaluation of a smart passive dynamic arm support for robotic-assisted laparoscopic surgery.

Surgeons performing robotic-assisted laparoscopic surgery experience physical stress and overuse of shoulder muscles due to sub-optimal arm support during surgery. The objective is to present a novel design and prototype of a dynamic arm support for robotic laparoscopic surgery to evaluate its ergonomics and performance on the AdLap-VR simulation training device. The prototype was designed using the mechanical engineering design process: Technical requirements, concept creation, concept selection, 3D-design and built of the prototype.

A prediction model for response to immune checkpoint inhibition in advanced melanoma.

Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy.

Associations between healthy lifestyle and mortality across different social environments: a study among adults with frailty from the UK Biobank.

Background: Among people living with frailty, adherence to a healthy lifestyle may be a low-cost and effective strategy to decrease frailty-induced health risks across different social environments.

Methods: We included 15 594 frail participants at baseline from the UK Biobank study. We used four lifestyle factors to create a composite healthy lifestyle score and 17 social factors to construct a polysocial score.

Exploring the therapeutic potential of focal adhesion kinase inhibition in overcoming chemoresistance in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion.

Exploring Vitreous Haze as a Potential Biomarker for Accelerated Glymphatic Outflow and Neurodegeneration in Multiple Sclerosis: A Cross-Sectional Study.

Background: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space.

Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial.

Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis.