Use of Adaptive Conjoint Analysis-Based Values Clarification in a Patient Decision Aid Is Not Associated with Better Perceived Values Clarity or Reduced Decisional Conflict but Enhances Values Congruence.

Background: Evidence is lacking on the most effective values clarification methods (VCMs) in patient decision aids (PtDAs). We tested the effects of an adaptive conjoint analysis (ACA)-based VCM compared with a ranking-based VCM and no VCM on several decision-related outcomes, with the decisional conflict and its subscale "perceived values clarity" as primary outcomes.

Design: Online experimental study with 3 conditions: no VCM versus ranking-based VCM versus -based VCM ( = 282; = 63.

Keeping pace in the age of innovation: The perspective of Dutch pharmaceutical science students on the position of machine learning training in an undergraduate curriculum.

Background: Over the years, approaches of the pharmaceutical industry to discover and develop drugs have changed rapidly due to new scientific trends. Among others, they have started to explore Machine Learning (ML), a subset of Artificial Intelligence (AI), as a promising tool to generate new hypotheses regarding drug candidate selections for clinical trials and to predict adverse side effects. Despite these recent developments, the possibilities of ML in pharmaceutical sciences have so far hardly penetrated the training of pharmaceutical science students.

NOTCH and PTP4A3 alterations emerge as novel predictive biomarkers and potential therapeutic targets in pleural mesothelioma.

Background: Previous studies showed opposite effects of NOTCH1 and NOTCH2 on mesothelioma cell survival under hypoxia. Mechanisms underlying these effects are not still clear and this pathway plays a key role in angiogenesis and cancer stem cells (CSCs) self-renewal processes.

Purpose: In this study we evaluated whether NOTCH1, NOTCH2 copy number alterations (CNAs) might predict prognosis of patients with pleural mesothelioma (PM) and if the modulation of this pathway might target CSCs, potentiating pemetrexed activity, also in hypoxic conditions.

Assessing motivational interviewing integrity in the Toddler Oral Health Intervention study.

Objectives: The Toddler Oral Health Intervention (TOHI) was launched in 2017 to promote oral health prevention at well-baby clinics, with a focus on parents with children aged 6-48 months. This study aims to evaluate the integrity of motivational interviewing (MI) as one of the core intervention pillars in the TOHI study.

Methods: The TOHI study was conducted at nine well-baby clinics in the central and southern regions of the Netherlands, with 11 trained oral health coaches (OHCs) delivering a tailored individual counselling programme.

Prodromal symptoms of a first manic episode: a qualitative study to the perspectives of patients with bipolar disorder and their caregivers'.

Background: Diagnosing bipolar disorder (BD) is challenging, and adequate treatment is of major importance to minimalize the consequences of the illness. Early recognition is one way to address this. Although in clinical research the prodromal phase of BD is gaining interest, the perspective of patients with BD and their caregivers on prodromal symptoms is still lacking.

From advisors to mentors: fostering supportive mentorship in academia.

A supportive mentorship has long-lasting effects on shaping students' personal and professional development. Here, we outline important aspects of mentoring and indicators of good mentors, focusing on effective mutualistic interaction. We believe that traditional academic advice should be expanded to include supportive group mentoring to foster future top scientific talent.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Background: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer.

Cost-effectiveness of Implementing a Genotype-Guided De-Escalation Strategy in Patients with Acute Coronary Syndrome.

Aims: A genotype-guided P2Y12-inhibitor de-escalation strategy, switching acute coronary syndrome (ACS) patients without a CYP2C19 loss-of-function allele from ticagrelor or prasugrel to clopidogrel, has shown to reduce bleeding risk without affecting effectivity of therapy by increasing ischemic risk. We estimated the cost-effectiveness of this personalized approach compared to standard dual antiplatelet therapy (DAPT; aspirin plus ticagrelor/prasugrel) in the Netherlands.

Methods And Results: We developed a one-year decision tree based on results of the FORCE-ACS registry, comparing a cohort of ACS patients who underwent genotyping with a cohort of ACS patients treated with standard DAPT.

Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy.

Porcine epidemic diarrhea virus (PEDV) is a harmful coronavirus infecting pigs, which is resulting in substantial financial losses in the global pig industry. The lack of effective vaccines or treatments underscores the pressing need for new antiviral strategies. Antimicrobial peptides (AMPs), specifically cathelicidins such as LL-37, have demonstrated promising activity against a range of viruses.

CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals.

This preclinical AD CSF proteome study identified a panel of 12-CSF markers detecting amyloid positivity and clinical progression to AD with high accuracy; some of these CSF proteins related to immune function, neurotrophic processes, energy metabolism and endolysosomal functioning (e.g., ITGB2, CLEC5A, IGFBP-1, CST3) changed before amyloid positivity is established.

Inhibition of lysophosphatidic acid receptor 2 attenuates neonatal chronic lung disease in mice by preserving vascular and alveolar development.

Aim: Bronchopulmonary dysplasia (BPD) is a common morbidity in extremely premature infants. Previous studies demonstrated the important role of lysophosphatidic acid (LPA) in inflammation in BPD. However, the role of LPA and its receptors in hyperoxia-induced vascular malformations in BPD remains to be elucidated.

Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren's histological classification.

Background: The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren's histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.

Protein requirement in obesity.

Purpose Of Review: The combined obesity and ageing pandemic require action to avoid a total health system infarct. Obesity is largely challenged with caloric restriction and endurance exercise, likely to be assisted by drugs. The older adults with the highest obesity levels may face extreme loss of muscle mass and increased risk of sarcopenic obesity.

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes.

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters.

Short-term Frailty Index Fluctuations in Older Adults: Noise or Signal?

Background: Reversible short-term fluctuations in the frailty index (FI) are often thought of as representing only noise or error. Here, we assess (i) the size and source of short-term FI fluctuations, (ii) variation across sociodemographic characteristics, (iii) association with chronic diseases, (iv) correlation with age, frailty level, frailty change, and mortality, and (v) whether fluctuations reflect discrete health transitions.

Methods: Nationwide, biweekly longitudinal data from 426 community-dwelling older adults (70+) were collected in the FRequent health Assessment In Later life (FRAIL70+) study using a measurement burst design (5 122 repeated observations, median of 13 repeated observations per person).

Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.

Redo phalloplasty and/or urethraplasty after previous flap failure in phalloplasty in transgender men: surgical considerations and outcomes.

Background: Primary phalloplasty in transgender men can be performed using a single or double free or pedicled flap to reconstruct the shaft and, if desired, the urethra. Vascular complications may result in total or partial loss of the used flap(s). Surgical management after flap loss in primary phalloplasty presents a challenge to the reconstructive surgeon.

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires.