Amyloid-β-driven synaptic deficits are mediated by synaptic removal of GluA3-containing AMPA-receptors.

The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer's disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology and AMPA-receptor (AMPAR) imaging on mice and rat neurons to demonstrate that GluA3 expression in neurons lacking GluA3 is sufficient to re-sensitize their synapses to the damaging effects of Aβ, indicating that GluA3-containing AMPARs at synapses are necessary and sufficient for Aβ to induce synaptic deficits.

Effectiveness of bi-monthly long-acting injectable cabotegravir and rilpivirine as maintenance treatment for HIV-1 in the Netherlands: results from the Dutch ATHENA national observational cohort.

Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands.

Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands.

A Missed Opportunity? Exploring Changes in Influenza Vaccination Coverage During the COVID-19 Pandemic: Data From 12 Countries Worldwide.

Background: Vaccination is a key measure in influenza control, yet global coverage rates remain low, although previous research reported an increase in influenza vaccination coverage rates (VCR) after the onset of the COVID-19 pandemic. This study aims to assess whether these changes were sustained over time by analyzing VCR trends from 2012 to 2023 in the countries included in the FluCov project.

Methods: Data on influenza VCR from 2012 to 2023 for different age and risk groups were extracted from national health organizations and international sources for countries included in the FluCov project.

VCSAP: Online reinforcement learning exploration method based on visitation count of state-action pairs.

In the domain of online reinforcement learning, strategies that leverage inherent rewards for exploration tend to achieve commendable outcomes within contexts characterized by deceptive or sparse rewards. Counting through the visitation of states is an efficient count-based exploration method to get the proper intrinsic reward. However, only the novelty of the states encountered by the agent is considered in this exploration method, resulting in the over-exploration of a certain state-action pair and falling into a locally optimal solution.

The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Deintensification of Radiotherapy Use in Treatment of Ductal Carcinoma In Situ in the Netherlands-A Nationwide Overview From 2008 Until 2022.

Aims: Ductal Carcinoma In Situ (DCIS) treated by breast-conserving surgery followed by radiotherapy aims to decrease the probability of locally recurrent disease. The role of whole breast irradiation, specifically in DCIS having low recurrence risk and low risk of becoming invasive, is increasingly debated. Also, the added value of applying boost irradiation in DCIS has been questioned.

Navigating choices: understanding the decision-making journey of patients with localised kidney cancer.

Objective: To explore patients' experience of decision making regarding treatment of localised kidney cancer.

Methods: A total of 21 patients with localised kidney cancer, across three countries, participated in either four focus groups or seven semi-structured interviews that lasted on average 2 h. Focus groups and interviews were all conducted in the participants' native language, recorded, transcribed and (if applicable) translated into English.

Contemporary Use of Post-Dilatation for Stent Optimization During Percutaneous Coronary Intervention; Results From the Netherlands Heart Registration.

Backgrounds: Post-dilatation after stenting with a non-compliant (NC) balloon can be used to improve overall percutaneous coronary intervention (PCI) result. Due to lack of evidence on the effect of post-dilatation on adverse clinical endpoints there is no consensus whether post-dilatation should be used routinely. The aim of the current study was to determine the contemporary practice of post-dilatation.

Multiple Perspectives on the Need for Real-World Evidence to Inform Regulatory and Health Technology Assessment Decision-Making: Scoping Review and Stakeholder Interviews.

Purpose: Real-world evidence (RWE) is increasingly considered in regulatory and health technology assessment (HTA) decision-making, though perspectives on its relevance may vary. Expanding on a recent review regarding regulatory decisions, this study aimed to identify factors influencing the need for RWE in HTA decision-making, confirm and enrich factors with stakeholder views, and evaluate similarities and differences between regulatory and HTA needs.

Methods: Previous scoping review methodology was used to identify factors influencing the need for RWE in HTA decision-making.

The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!

Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment.

Neuroimaging of postoperative pediatric cerebellar mutism syndrome: a systematic review.

Background: Postoperative pediatric cerebellar mutism syndrome (ppCMS) poses serious morbidity after posterior fossa tumor surgery. Neuroimaging studies aim to understand its pathophysiology, yet these vary in methodology and outcome measures. Therefore, we systematically reviewed the current literature to evaluate the evidence for differences in neuroimaging features between children with and without ppCMS.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.

Health recommender systems to facilitate collaborative decision-making in chronic disease management: A scoping review.

Objective: Health recommender systems (HRSs) are increasingly used to complement existing clinical decision-making processes, but their use for chronic diseases remains underexplored. Recognizing the importance of collaborative decision making (CDM) and patient engagement in chronic disease treatment, this review explored how HRSs support patients in managing their illness.

Methods: A scoping review was conducted using the framework proposed by Arksey and O'Malley, advanced by Levac et al.

Symptom management in isocitrate dehydrogenase mutant glioma.

According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality.

Reliability and validity of four cognitive interpretation bias measures in the context of social anxiety.

People with social anxiety disorder tend to interpret ambiguous social information in a negative rather than positive manner. Such interpretation biases may cause and maintain anxiety symptoms. However, there is considerable variability in the observed effects across studies, with some not finding a relationship between interpretation biases and social anxiety.

The challenge of preventing gastric cancer in patients under surveillance for familial adenomatous polyposis.

Several extra-colonic manifestations, including duodenal polyposis and desmoid tumors, are well-described manifestations in familial adenomatous polyposis (FAP). More recently, an increase in gastric cancer diagnoses has been observed in FAP. This case series presents nine patients with FAP who were diagnosed with gastric cancer at our FAP expertise center, of whom eight were diagnosed between 2017 and 2023, while before 2017 the only diagnosis of gastric cancer was in 2001.

New gantry angle-dependent beam control optimization with Elekta linear accelerator for VMAT delivery.

Introduction: This paper describes a method to improve gantry-dependent beam steering for Elekta traveling wave linear accelerators by applying the measured and filtered beam servo corrections to the existing lookup table (LUT). Beam steering has a direct influence on the treatment accuracy by affecting the beam symmetry and position. The presented method provides an improved LUT with respect to the default Elekta method to reduce treatment delivery interruptions.

AI as an intervention: improving clinical outcomes relies on a causal approach to AI development and validation.

The primary practice of healthcare artificial intelligence (AI) starts with model development, often using state-of-the-art AI, retrospectively evaluated using metrics lifted from the AI literature like AUROC and DICE score. However, good performance on these metrics may not translate to improved clinical outcomes. Instead, we argue for a better development pipeline constructed by working backward from the end goal of positively impacting clinically relevant outcomes using AI, leading to considerations of causality in model development and validation, and subsequently a better development pipeline.

Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma.

Objective: Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.

Design And Methods: Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study.

Long-term mortality of Dutch COVID-19 patients admitted to the intensive care medicine: a retrospective analysis from a national quality registry.

Objective: To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use.

Methods: We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup.

Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation.

Rationale: Psychedelic-assisted therapy is increasingly applied within mental health treatment.

Objectives: This study focused on factors moderating changes in the acute and long-term effects of an individual psilocybin-assisted program on depression, anxiety, PTSD and personality structures by including demographic factors, subjective experience and degree of mystical type experiences during the dosing, as well as emotional breakthrough and personal growth after the program.

Methods: At baseline, 1 week and 3 months after the psilocybin program participants completed the Generalized Anxiety Disorder Assessment (GAD-7), Patient Health Questionnaire (PHQ-9), PTSD Checklist for DSM-5 (PCL-5) and NEO Five-Factor Inventory-3 (NEO-FFI-3).