Exploring peripheral fluid biomarkers for early detection of Alzheimer's disease in Down syndrome: A literature review.

People with Down Syndrome (DS) are at high risk of developing Alzheimer's disease dementia (AD) and cerebral amyloid angiopathy, which is a critical factor contributing to dementia in sporadic AD. Predicting and monitoring the decline and onset of dementia is a diagnostic challenge and of essence in daily care and support for people with DS. In this literature scoping review, we first summarize the different blood-based biomarkers for AD in DS.

Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial.

Purpose: Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3).

Nephrectomy in Autosomal Dominant Polycystic Kidney Disease: A consensus statement of the ERA Genes & Kidney Working Group.

A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD.

Root-cause analysis of mortality after pancreatic resection in a nationwide cohort.

Background: This study evaluates leading causes of in-hospital mortality after pancreatic resection nationwide to determine areas for improvement.

Methods: This observational cohort study included all in-hospital mortality after pancreatic resection in the Netherlands (2014-2019). Each fatality was considered to be caused by local complications (i.

Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

Intrapatient 16α-[F]Fluoro-17β-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

Intrapatient heterogeneity of estrogen receptor (ER) expression on 16α-[F]fluoro-17β-estradiol ([F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [F]FES PET heterogeneity score (i.e.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations.

Diagnostic accuracy of point-of-care ultrasound of the posterior fatpad in elbow fractures.

Background: Point-of-care ultrasound (POCUS) can potentially be used in the triage of patients with elbow injuries. However, the diagnostic accuracy of POCUS performed by non-radiologists for the exclusion of elbow fractures is yet unknown. This study aimed to investigate the diagnostic potential of POCUS of the posterior fatpad performed by non-radiologists in the workup of adult patients presenting with elbow injuries.

Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial.

Background: For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases.

Methods: Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0-2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Computational Study on the Dynamics of a Bis(benzoxazole)-Based Overcrowded Alkene.

Understanding and controlling molecular motions is of pivotal importance for designing molecular machinery and functional molecular systems, capable of performing complex tasks. Herein, we report a comprehensive theoretical study to elucidate the dynamic behavior of a bis(benzoxazole)-based overcrowded alkene displaying several coupled and uncoupled molecular motions. The benzoxazole moieties give rise to 4 different stable conformers that interconvert through single-bond rotations.

Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis.

Rationale: Psilocybin shows promise for treating neuropsychiatric disorders. However, insight into its acute effects on cognition is lacking. Given the significant role of executive functions in daily life and treatment efficacy, it is crucial to evaluate how psilocybin influences these cognitive domains.

Identification of a Biosynthetic Gene Cluster for the Production of the Blue-Green Pigment Xylindein by the Fungus .

Xylindein is a blue-green pigment produced by the fungi and Its stunning color and optoelectronic properties make xylindein valuable for textiles and as a natural semiconductor material. However, producing xylindein from culture broths remains challenging because of the slow growth of the species and the poor solubility of xylindein in organic solvents. An alternative production route for obtaining pure xylindein is heterologous expression of the xylindein biosynthetic genes.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Maternity Care Providers' Experiences with Providing Information on Newborn Bloodspot Screening During Pregnancy: A Dutch Survey Study.

Newborn bloodspot screening (NBS) aims to detect treatable disorders in newborns to offer early interventions. According to the official Dutch national NBS guidance, parents in the Netherlands should be informed about NBS during pregnancy by maternity care providers (MCPs), providing two leaflets and oral information. This study investigated what, how, and when information about NBS is given during pregnancy according to Dutch MCPs.

Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria.

Investigating the Relationship Between Midazolam Serum Concentrations and Paediatric Delirium in Critically Ill Children.

Objectives: Intravenous midazolam is widely used for sedation in critically ill children. Sometimes, these children develop a paediatric delirium (PD). Our aim was to determine the relationship between midazolam serum concentration and the development of new PD in critically ill children.

Cholinergic Denervation Patterns in Parkinson's Disease Associated With Cognitive Impairment Across Domains.

Cognitive impairment is considered to be one of the key features of Parkinson's disease (PD), ultimately resulting in PD-related dementia in approximately 80% of patients over the course of the disease. Several distinct cognitive syndromes of PD have been suggested, driven by different neurotransmitter deficiencies and thus requiring different treatment regimes. In this study, we aimed to identify characteristic brain covariance patterns that reveal how cholinergic denervation is related to PD and to cognitive impairment, focusing on four domains, including attention, executive functioning, memory, and visuospatial cognition.

Understanding identity development in context: comparing reflective and situated approaches to identity.

Many recent approaches to identity share a foundational similarity with ecological psychology, namely, to place identity in its context. That is, they explicitly place identity in its physical and social environments. Yet, we can distinguish at least two different approaches that diverge fundamentally with regards to the role that this "context" has in identity.

Exploring Untested Feasibilities: Critical Pedagogy's Approach to Addressing Abuse and Oppression in Medical Education.

Abuse and oppression in medical education persists. Particularly when transitioning to practice, students and residents face dissonance between what they perceive as the ideals of patient care and reality. They witness, and eventually take part in, joking about fellow students and patients, discriminating against minorities, and imposing unbearable workload to subordinates, to mention some practices that have been normalized as the reality of medical training, beyond any possibility of change.

Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials.

Aims: The sodium-glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized.

Methods And Results: In this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.

A review on the role of extrapolation as basis for paediatric marketing authorization applications of medicines in the EU.

Aims: For new medicines, drug companies obtain regulatory approval on the strategy to generate evidence in the paediatric population, which can be supported by extrapolation of evidence obtained in a reference population. This study investigated whether paediatric marketing authorization applications (PMAAs) supported by extrapolation based on exposure-matching were more successful-i.e.

Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids.

Background: Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers.

Systemic disease activity measured with ESSDAI varies largely over 5 years in a prospective, longitudinal cohort of patients with Sjögren's disease.

Objectives: The objectives are to evaluate variation in systemic disease activity (European Alliance of Associations For Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI)) over time at group and individual patient level and to assess associations of ESSDAI low disease activity (LDA) with other outcome measures in a standard-of-care cohort of patients with Sjögren's disease (SjD).

Methods: Patients with SjD participating in a prospective longitudinal study (REgistry of Sjögren Syndrome LongiTudinal cohort) fulfilling the 2016 American College of Rheumatology/EULAR classification criteria with ≥2 years of follow-up were included. ESSDAI was assessed at least yearly, up to 5 years.