Amsterdam Neuroscience

Cell competition is an evolutionarily conserved quality control mechanism that eliminates less-fit cells to ensure optimal tissue integrity during development, homeostasis, and regeneration. Beyond these physiological roles, recent evidence implicates a role for cell competition in disease, particularly in cancer, where it can function by either suppressing or promoting malignant progression. In this review, we provide an overview of the different molecular mechanisms that drive cell competition and their impact on cancer development and progression. We will evaluate the current state-of-the-art in vitro experimental systems that can be employed to study these processes. Ranging from classical 2D co-culture systems to advanced organoid and organ-on-chip platforms, these model systems collectively enhance our understanding of the complex cellular interactions that underlie the competitive differences between cells. By integrating insights from diverse model systems, we highlight how cell competition shapes tumor dynamics and discuss how this knowledge could inspire novel therapeutic strategies to prevent or control tumor growth.

Impaired awareness is common among people with Alzheimer's disease (AD) and the related disorders Huntington's disease (HD), and Korsakoff's syndrome (KS). Individuals with impaired awareness have an altered perception of their situation or functioning, which may pose challenges for care staff in nursing home settings. Yet, little is known about their experiences with impaired awareness. We conducted five focus groups with professional caregivers (N = 28) of nursing home residents with AD, HD and KS about their experiences with impaired awareness (two AD, one HD, one KS and one mixed focus group). Participants were certified nursing assistants, vocationally trained nurses and social workers. Conversations were audio-taped and transcribed verbatim. Data were analyzed using thematic analysis. We identified three main themes: (1) Manifestations of impaired awareness, including observed expressions of impaired awareness and impact on resident interactions. These manifestations were consistent across all three disease groups. (2) Reflections and emotions on these manifestations (characterized by compassion, astonishment and uncertainty). Impaired awareness increased the overall emotional burden for professional caregivers. Additionally, they sometimes felt uncertain about whether impaired awareness was intentional or disease-related. (3) Dealing with impaired awareness, by balancing between moving along and setting boundaries. Caregivers had difficulties determining the most effective approach to deal with impaired awareness. Impaired awareness impacts the work of caregivers of residents with AD, HD and KS. Gaining a better understanding of how impaired awareness affects residents' emotions and behavior can contribute to the development of effective care approaches for caregivers.

Background Children with posterior fossa tumors (PFTs) are at risk of long-term neurocognitive deficits, yet the impact of tumor grade and treatment intensity on cortical development remains poorly understood. The aim of this study was to determine whether cortical thickness trajectories differ between children with low- versus high-grade PFTs and whether radiation dose influences cortical development in medulloblastoma patients. We conducted a retrospective longitudinal study of 55 children (37 low-grade, 18 high-grade medulloblastoma) diagnosed between 2018 and 2020. A total of 406 T1-weighted MRI scans acquired up to five years post-diagnosis were processed using CAT12 in SPM12 to estimate cortical thickness. Vertex-wise linear mixed-effects models assessed cortical thickness changes over time, adjusting for age at diagnosis, sex, and hydrocephalus. Within the high-grade group, we evaluated the effect of craniospinal irradiation (CSI) dose (23.4 vs. ≥36 Gy) on cortical development. Children with low-grade tumors showed significant bilateral cortical thinning over time, consistent with typical neurodevelopment. In contrast, medulloblastoma patients treated with surgery, chemotherapy, and radiation therapy showed relative cortical stability across follow-up. Significant group-by-time interactions were observed, with low-grade patients demonstrating greater cortical thinning in parietal, temporal, and occipital regions. No significant differences in cortical trajectories were found between high- and standard-dose CSI subgroups. Cortical development trajectories in pediatric PFT survivors differ by tumor grade and treatment intensity. While low-grade patients exhibit expected maturational thinning, cortical stability in high-grade patients may reflect disrupted neurodevelopment. These findings underscore the need for longitudinal neuroimaging in pediatric neuro-oncology survivorship care.

Metacarpal fractures are common injuries that are frequently managed with repeated radiological follow-up, although the clinical value of routine imaging is uncertain. The aim of this study was to evaluate the frequency and clinical impact of follow-up imaging in patients with metacarpal fractures treated operatively or non-operatively, and to quantify the associated financial and environmental impact. This retrospective study evaluated adult patients with metacarpal fractures treated non-operatively or operatively at a Dutch level 2 trauma center between 2017 and 2022. Radiology reports and medical records were reviewed to assess whether follow-up imaging led to treatment modification. Additionally, the corresponding financial and environmental impact was calculated. A total of 2342 patients were included (median age 32years; 28% female). Among initially non-operatively treated patients (n = 1978), 1.1% (n = 22) required conversion to surgery. The overall cost associated with this 1% conversion amounted to €230,000, with an estimated environmental impact of 2711kg CO₂-eq. Among operatively treated patients (n = 386), postoperative imaging rarely prompted re-operation (0.3%, n = 1). The total costs associated with 0.3% re-operation were €171,000 and an associated environmental impact of 1801kg CO₂-eq. Together, the impact equals almost one trip around the world by car. Routine radiological follow-up after the initial decision for operative or non-operative treatment in metacarpal fractures provided minimal clinical benefit. A symptom-driven approach may optimize care while reducing unnecessary financial and environmental burden. Level IV.

WHAT IS KNOWN : •Helmholtz invented the ophthalmoscope in 1850 and published his observations in a monograph in 1851. However, he did not include an illustration of what he observed; •The first published retinal paintings were created in 1853 by the artistically gifted physician Adrien Christophe van Trigt. •Shortly after Helmholtz's publication of the ophthalmoscope, the Amsterdam instrument maker Epkens designed and constructed a table-model ophthalmoscope that left the dominant hand free; •The ophthalmologist Donders in Utrecht recognized in Epkens' table model ophthalmoscope the opportunity to produce retinal paintings for publication purposes. He recruited the artistically skilled physician Adrien van Trigt as PhD student to carry out this work; •The collaboration of Donders, Van Trigt and Epkens resulted within 19 months following Helmholtz' monograph, in the publication of retinal paintings - a remarkably fast achievement, given that retinal photography was not yet available.

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Alzheimer’s disease (AD) is the most common cause of dementia and a growing healthcare challenge. Amyloid-targeting therapies (ATT) may slow progression, but implementation is limited by logistical and economic barriers. As primary care is the first contact for most patients with cognitive concerns, quantifying treatment eligibility in this setting is essential. The purpose of this study was to estimate the proportion of primary care patients presenting with cognitive symptoms who are eligible for ATT. This cohort study included patients presenting with cognitive symptoms in primary care across the region Skåne, in southern Sweden, recruited between January 2020 and April 2025. Stepwise exclusion criteria based on clinical diagnosis, comorbidities, and treatment contraindications were applied, in alignment with appropriate use recommendations for lecanemab and donanemab, respectively. Eligibility was further refined using CSF biomarkers (Aβ42/40 ratio), cognitive performance, and MRI findings. In a full diagnostic work-up of 607 patients with sequential exclusions, 86 patients (14.2%) and 78 patients (12.8%) ultimately met the eligibility criteria for lecanemab and donanemab, respectively. Due to comorbidities, medication use, and age/BMI, around 1/3 of the original population was excluded. Most ineligible patients met more than one exclusion criterion. The eligible population was 63% female, mean age 77 years. Around 65% of the individuals had mild cognitive impairment (MCI), and 35% mild dementia. About 13-14% of primary care patients evaluated for cognitive complaints were eligible for ATT. Compared with clinical trials, the eligible population was older and consisted of more women. BioFINDERPrimary Care study (NCT06120361, Registration date 2 November 2023 https//biofinder.se).