NMR-Based Analysis of Cellular Central Energy Metabolism and Exchange Rates.

Cell cultures are widely used in studies to gain mechanistic insights of metabolic processes. The foundation of these studies lies on the quantification of intracellular and extracellular metabolites, and nuclear magnetic resonance (NMR) is one of the key analytical platforms used to this aim. Among the factors influencing the quality of the produced data are the sampling procedures as well as the acquisition and processing of spectroscopic data.

Lipoprotein (Sub)Fraction Analysis on the Bruker B.I. LISA Platform.

The Bruker B.I. LISA platform provides a method for human plasma/serum lipoprotein analysis and yields data on the particle numbers and lipids of the main lipoprotein classes (VLDL, IDL, LDL, HDL), and the subfractions within those classes.

Rapid Analysis of Sterols in Blood-Derived Samples.

Dysregulations of cholesterol biosynthesis are known to be associated with several pathologies. Due to the rapid growth of clinical investigations in this research area, a specific, fast, and valid method for analyzing cholesterol, its precursors, and metabolites is required. Here, we describe a rapid method for sample preparation, separation, and quantification of sterols in blood-derived samples using polymeric solid phase extraction followed by gas chromatography-mass spectrometry.

LC-MS/MS Quantification of Endocannabinoids in Tissues.

Endocannabinoids (ECBs) are lipid-derived endogenous molecules with important physiological roles such as regulation of energy balance, immunity, or neural development. Quantitation of ECBs helps better understand their physiological role and modulation of biological processes. This chapter presents the simultaneous quantification of 14 ECBs and related molecules in the brain, liver, and muscle, as well as white and brown adipose tissue using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

(Pre)Clinical Metabolomics Analysis.

Metabolomics is the scientific field with the eager goal to comprehensively analyze the entirety of all small molecules of a biological system, i.e., the metabolome.

Pharmacogenetic Panel Testing: A Review of Current Practice and Potential for Clinical Implementation.

Pharmacogenetics (PGx) aims to optimize drug treatment outcomes by using a patient's genetic profile for individualized drug and dose selection. Currently, reactive and pretherapeutic single-gene PGx tests are increasingly applied in clinical practice in several countries and institutions. With over 95% of the population carrying at least one actionable PGx variant, and with drugs impacted by these genetic variants being in common use, pretherapeutic or preemptive PGx panel testing appears to be an attractive option for better-informed drug prescribing.

Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis.

Background: Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins.

Out-of-phase treatment with the synthetic glucocorticoid betamethasone disturbs glucose metabolism in mice.

Objective: Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e.

Instrumental activities of daily living in neuro-oncology: International validation of the EORTC IADL-BN32 questionnaire.

Background: Neurocognitive impairments are common in patients with a brain tumour, and may negatively impact on functioning in daily life, particularly on instrumental activities of daily living (IADL). The EORTC IADL-BN32 questionnaire was developed to measure IADL in this patient population.

Methods: In this international validation study, we evaluated the EORTC IADL-BN32 questionnaire on several psychometric properties in a large sample of patients with a primary or metastatic brain tumour.

Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.

Purpose: Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment.

Exploring Sex Differences in Pain Manifestation of Coronary Artery Disease through Mendelian Randomization.

Pain manifestation following coronary artery disease (CAD) disease differs between men and women. Here, we aimed to provide evidence favoring possible differences in pain manifestation between men and women following CAD using Mendelian randomization (MR). We used summary-level data from sex-stratified genome-wide association studies on CAD and self-reported and clinically diagnosed chest, neck and shoulder, back, and facial pain using data from the UK Biobank cohort ( > 450,000) followed by two-sample MR (sensitivity) analyses.

Targeting epigenetic regulation and post-translational modification with 5-Aza-2' deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy.

Background: Cellular immunotherapy using modified T cells offers new avenues for cancer treatment. T-cell receptor (TCR) engineering of CD8 T cells enables these cells to recognize tumor-associated antigens and tumor-specific neoantigens. Improving TCR T-cell therapy through increased potency and in vivo persistence will be critical for clinical success.

A realistic benchmark for differential abundance testing and confounder adjustment in human microbiome studies.

Background: In microbiome disease association studies, it is a fundamental task to test which microbes differ in their abundance between groups. Yet, consensus on suitable or optimal statistical methods for differential abundance testing is lacking, and it remains unexplored how these cope with confounding. Previous differential abundance benchmarks relying on simulated datasets did not quantitatively evaluate the similarity to real data, which undermines their recommendations.

Large-scale genome-wide interaction analyses on multiple cardiometabolic risk factors to identify age-specific genetic risk factors.

The genetic landscape of cardiometabolic risk factors has been explored extensively. However, insight in the effects of genetic variation on these risk factors over the life course is sparse. Here, we performed genome-wide interaction studies (GWIS) on different cardiometabolic risk factors to identify age-specific genetic risks.

Professional identity formation of medical students in relation to older persons' healthcare: exploring the views of older persons living in the Netherlands - a qualitative study.

Objectives: Given the growing population of older persons, medical students need to develop an appropriate professional identity to comply with older persons' healthcare needs. In this study, we explored the needs and expectations of older persons regarding their doctor to gain more insight into the characteristics of this professional identity.

Design: A qualitative study based on a constructivist research paradigm was conducted, based on individual semistructured, in-depth interviews using a letter as a prompt, and focus groups.

The effectiveness of Function Focused Care among patients acutely admitted to hospital: A stepped wedge cluster trial.

Background: During acute hospital admission, patients often experience loss of functional status. A low level of physical activity is associated with higher levels of loss of functional status. Stimulating physical activity to maintain functional status is considered essential nursing care.

The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology.

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma.