Publications by authors named "Leeuwen A"

Chemotherapy is included in the standard of care for cancer treatment during pregnancy. However, whether prenatal exposure to maternal chemotherapy treatment has a mutagenic impact on the fetal genome, remains unexplored. Therefore, we investigated mutation accumulation in hematopoietic stem and progenitor cells (HSPCs) from neonates born to pregnant cancer patients treated with chemotherapy, as well as healthy pregnant women and untreated pregnant cancer patients.

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The study of somatic mutations in single cells provides insights into aging and carcinogenesis, which is complicated by the dependency on whole-genome amplification (WGA). Here, we describe a detailed workflow starting from single-cell isolation to WGA by primary template-directed amplification (PTA), sequencing, quality control, and downstream analyses. A machine learning approach, the PTA Analysis Toolkit (PTATO), is used to filter the hundreds to thousands of artificial variants induced by WGA from true mutations at high sensitivity and accuracy.

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Childhood is an obvious period for motor learning, since children's musculoskeletal and nervous systems are still in development. Adults adapt movements based on reward feedback about success and failure, but it is less established whether school-age children also exhibit such reward-based motor learning. We designed a new 'circle-drawing' task suitable for assessing reward-based motor learning in both children (7-17 years old) and adults (18-65 years old).

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Article Synopsis
  • Endothelial disorders leading to edema and poor tissue oxygenation are common in cardiac surgery with CPB, prompting researchers to investigate the protective effects of albumin as a component in the CPB circuit.
  • In a study with male rats, CPB primed with LR/albumin/mannitol resulted in lower pulmonary edema compared to 6% hydroxyethyl starch (HES) despite similar renal edema levels, indicating potential benefits of using albumin in surgical settings.
  • Although microcirculatory perfusion was impaired during CPB for both groups and did not improve post-CPB, the LR/albumin/mannitol group needed significantly less fluid and medication to maintain adequate blood flow, alongside showing reduced inflammatory markers
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Background: Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa.

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  • Shallow coastal and estuarine habitats are crucial for fish species, providing areas for spawning, nursery, and feeding, but these habitats are threatened by human activities that degrade their quality and availability.
  • Different fish species utilize these habitats at various life stages, leading to their classification into functional guilds, which experience the impacts of habitat changes differently.
  • Using size-structured population models, the study examines how reduced food productivity in estuaries affects two guilds: estuarine residents and marine estuarine-dependent species, finding that while overall fish biomass declines, juvenile populations of the latter can increase under certain conditions due to shifts in resource competition and availability.
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Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest.

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Climate change may exacerbate the impact of invasive parasites from warmer climates through pre-existing temperature adaptations. We investigated temperature impacts on two closely related marine parasitic copepod species that share the blue mussel () as host: has invaded the system from a warmer climate <20 years ago, whereas its established congener has had >90 years to adapt. In laboratory experiments with temperatures 10-26°C, covering current and future temperatures as well as heat waves, the development of both life cycle stages of both species accelerated with increasing temperature.

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Mediolateral gait stability can be maintained by coordinating our foot placement with respect to the center-of-mass (CoM) kinematic state. Neurological impairments can reduce the degree of foot placement control. For individuals with such impairments, interventions that could improve foot placement control could thus contribute to improved gait stability.

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Introduction: Critical illness is associated with organ failure, in which endothelial hyperpermeability and tissue edema play a major role. The endothelial angiopoietin/Tie2 system, a regulator of endothelial permeability, is dysbalanced during critical illness. Elevated circulating angiopoietin-2 and decreased Tie2 receptor levels are reported, but it remains unclear whether they cause edema independent of other critical illness-associated alterations.

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Article Synopsis
  • Landscapes of fear influence ecosystem dynamics by causing prey to change their behaviors and characteristics to avoid predation, which indirectly impacts other species and can lead to significant ecological effects like trophic cascades.
  • Researchers are working to understand how these dynamics also affect interactions between parasites and their hosts, particularly in terms of how predation risk alters behaviors like parasite avoidance and host tolerance to infections.
  • The study outlines a conceptual framework for these interactions, identifies gaps in current knowledge regarding the links between individual behaviors and broader population dynamics, and suggests future research directions to fill these gaps.
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Climate warming is affecting the suitability and utilization of coastal habitats by marine fishes around the world. Phenological changes are an important indicator of population responses to climate-induced changes but remain difficult to detect in marine fish populations. The design of large-scale monitoring surveys does not allow fine-grained temporal inference of population responses, while the responses of ecologically and economically important species groups such as small pelagic fish are particularly sensitive to temporal resolution.

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Allergic rhinitis, caused by airborne pollen, is a common disease with a great impact on the quality of life for patients and high costs for society. Prevention of high pollen concentrations in the air is relevant for creating a safe environment for allergic patients. Due to climate change, the heat in cities during the summer is a recurring problem.

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Ocean warming and acidification, decreases in dissolved oxygen concentrations, and changes in primary production are causing an unprecedented global redistribution of marine life. The identification of underlying ecological processes underpinning marine species turnover, particularly the prevalence of increases of warm-water species or declines of cold-water species, has been recently debated in the context of ocean warming. Here, we track changes in the mean thermal affinity of marine communities across European seas by calculating the Community Temperature Index for 65 biodiversity time series collected over four decades and containing 1,817 species from different communities (zooplankton, coastal benthos, pelagic and demersal invertebrates and fish).

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Variation in life history traits in animals and plants can often be structured along major axes of life history strategies. The position of a species along these axes can inform on their sensitivity to environmental change. For example, species with slow life histories are found to be less sensitive in their long-term population responses to environmental change than species with fast life histories.

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Background: The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin/Tie2 system and edema formation.

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Falls are a problem, especially for older adults. Placing our feet accurately relative to the center-of-mass helps us to prevent falling during gait. The degree of foot placement control with respect to the center-of mass kinematic state is decreased in older as compared to young adults.

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Background: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.

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In the field of AI in education, there is a movement toward human-centered design in which the primary stakeholders are collaborators in establishing the design and functionality of the AI system (participatory design). Several authors have noted that there is a potential tension in participatory design between involving stakeholders and, thus, increasing uptake of the system on the one hand, and the use of educational theory on the other hand. The goal of the present perspective article is to unpack this tension in more detail, focusing on the example of teacher dashboards.

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Mediolateral ankle moment control contributes to gait stability. Ankle moments can be constrained by walking with a shoe with a ridge underneath the sole, narrowing the mediolateral support surface. In our previous study, such ankle moment constraints resulted in an increased step width and a decrease in the degree of foot placement control, as defined by the percentage of variance in foot placement that can be explained by CoM state.

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External lateral stabilization can help identify stability control mechanisms during steady-state walking. The degree of step-by-step foot placement control and step width are known to decrease when walking with external lateral stabilization. Here, we investigated the effect of external lateral stabilization on ankle moment control in healthy participants.

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Background: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline.

Methods: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study.

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Unlabelled: Childhood cancer survivors are confronted with various chronic health conditions like therapy-related malignancies. However, it is unclear how exposure to chemotherapy contributes to the mutation burden and clonal composition of healthy tissues early in life. Here, we studied mutation accumulation in hematopoietic stem and progenitor cells (HSPC) before and after cancer treatment of 24 children.

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Mutational signatures have been identified in cancer genomes, providing information about the causes of cancer and treatment vulnerabilities. This protocol describes an assay to determine the genotoxic mechanisms underlying these signatures using cord-blood derived hematopoietic stem and progenitor cells (CB-HSPCs). CB-HSPCs have a low mutation background, enabling sensitive detection of mutations.

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Purpose: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses.

Methods And Materials: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later.

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