Basic Science and Pathogenesis.

Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relationship between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.

Clinical Manifestations.

Background: The Amsterdam Instrumental ADL Questionnaire (A-IADL-Q) has shown promising performance in detecting subtle impairment in IADL independency. Importantly, it has not been validated in older people in a primary care setting, i.e.

NGF-mediated crosstalk: unraveling the influence of metabolic deregulation on the interplay between neural and pancreatic cancer cells and its impact on patient outcomes.

Neural invasion is one of the most common routes of invasion in pancreatic cancer and it is responsible for the high rate of tumor recurrence after surgery and the pain generation associated with pancreatic cancer. Several molecules implicated in neural invasion are also responsible for pain onset including NGF belonging to the family of neutrophins. NGF released by cancer cells can sensitize sensory nerves which in turn results in severe pain.

Interstitial lipoid pneumonia-A complication of intravenous administration of lipid emulsions in critically ill patients.

Lipoid pneumonia is a rare entity most often associated with inhalation of foreign material (i.e. "fire-eater's lung"), silicone injection, and severe trauma.

Investigating the Immunomodulatory Impact of Fecal Bacterial Membrane Vesicles and Their IgA Coating Patterns in Crohn's Disease Patients.

The human intestinal tract contains trillions of bacteria that coexist in a symbiotic relationship with human cells. Imbalances in this interaction can lead to disorders such as Crohn's disease (CD). Bacteria membrane vesicles (MVs), which are released by almost all bacteria, have been demonstrated to play a crucial role in bacteria-host interactions.

A convenient viral transduction based method for advanced multi-engineering of primary human (CAR) T-cells.

The past decades have illustrated the power of T-cell engineering in the development of new and successful cell therapies, such as chimeric antigen receptor (CAR) T-cells. Despite clinical success in hematological malignancies, it also becomes increasingly clear that additional T-cell engineering will be required to improve efficacy and safety and expand the application to solid tumors. Engineering is most often achieved by viral delivery of transgenes, however, viral vector capacity limitations make efficient and reproducible generation of multi transgene expressing T-cell therapeutics technically challenging.

Detecting Colorectal Neoplasia Using Specific Fecal Fluorogenic Protease-Sensitive Substrates: A Pilot Study.

Background: identification and removal of advanced adenomas (AA) reduce colorectal cancer (CRC) incidence and potentially mortality. CRC screening often uses fecal immunochemical testing to select high-risk individuals for colonoscopy, despite its low sensitivity for AA and relatively high false-positivity rate. Previous studies have linked proteases to CRC development through their ability to facilitate angiogenesis and immunoregulation.

Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials.

Aims/hypothesis: Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

Predictors of dropping out from a home tele-exercise programme: A cohort study derived from a randomised controlled trial.

Background: Online home exercises represent opportunities to increase physical activity levels. However, high dropout rates are commonly reported in such programmes. This study aimed to investigate the predictors of dropping out from an online home exercise programme.

Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.

Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

Implications of the microbiome after pancreatic cancer resection with regard to morbidity and mortality.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an extremely poor prognosis. The most common complications after a pancreaticoduodenectomy (PD) include surgical site infection (SSI), postoperative pancreatic fistula (POPF), and delayed gastric emptying (DGE). The potential role and mechanisms of microbial colonization of key surgical sites resulting in perioperative complications after PD remain to be fully elucidated.

International study to develop a patient-reported outcome measure to evaluate outcomes of gender-affirming care - the GENDER-Q.

Background: To meaningfully understand outcomes of gender-affirming care, patient-reported outcome measures (PROMs) that are grounded in what matters to individuals seeking care are urgently needed. The objective of this study was to develop a comprehensive PROM to assess outcomes of gender-affirming care in clinical practice, research, and quality initiatives (the GENDER-Q).

Methods: Internationally established guidelines for PROM development were used to create a field test version of the GENDER-Q.

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.

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.

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).

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.

Sexual education and development after early childhood sexual abuse: A qualitative study of experiences of parents and children.

Background: In the Amsterdam Sexual Abuse Case (ASAC), infants and toddlers experienced childhood sexual abuse (CSA). The perpetrator was convicted, and psychosocial care was offered to children and families. A research project was established to investigate the impact of CSA at an early age, with this study specifically focusing on sexual education and development.