Leiden University Scholary Publications
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Tracking the vascular signature of brain tumors by exploring the field of perfusion MRI
Full text linkThis thesis provides some important insights on the use of perfusion MRI in clinical practice and the steps that were taken towards optimization of DSC-MRI acquisition and image processing strategies. The studies contained in this thesis form the basis for an optimized scan protocol for glioma at 3 T and 7 T, which could be used for noninvasive characterization of the tumor type by determining the vascular signature as well as early prediction of tumor progression.Netherlands Organisation for Scientific Research (NWO), project number 17079.LUMC / Geneeskund
Small, non-coding RNAs: their modifications, and their detection in cardiovascular diseases
Full text linkCardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, with common mechanisms including endothelial dysfunction, vascular inflammation, and altered cellular signaling. Small non-coding RNAs (sncRNAs), such as microRNAs and tRNA-derived fragments (tRFs), have emerged as key regulators of cardiovascular homeostasis and pathology, influencing processes like cardiac remodeling, ischemia-induced vascular remodeling, and plaque formation. This thesis investigates the epitranscriptomic regulation of sncRNAs and their functional consequences in cardiovascular disease. It demonstrates that 5’ isomiRs, exemplified by ISO-miR-411, are differentially processed and exhibit distinct targetomes, affecting angiogenesis under ischemic conditions. The role of m6A-modified miRNAs, such as miR-494-3p, in intracranial atherosclerosis is also highlighted, revealing modulation of endothelial tight junction proteins and vascular integrity. Furthermore, tRFs were assessed as potential circulating biomarkers for acute stroke, showing promising but currently limited diagnostic performance due to technical challenges. Finally, a DNA-functionalized hydrogel platform was developed for rapid, sequence-specific detection of sncRNAs, demonstrating robust and homogeneous signal response. Collectively, this work integrates molecular insights with translational applications, providing new understanding of sncRNA regulation in CVD and advancing strategies for biomarker development and rapid diagnostics.LUMC / Geneeskund
Combined oral contraceptives and venous thrombosis: still unravelling ... half a century later...
Full text linkThe risk of Venous Thrombosis in women using combined oral contraceptives is increased and this is well documented. However, there are still some unanswered questions, such as the risk of thrombosis in women who switch combined oral contraceptives, which contraceptives can be considered in women who have inherited thrombophilia and building a risk prediction model for thrombosis in women starting oral contraceptives.LUMC / Geneeskund
Intradermally administered retinoic acid or vitamin D3-loaded liposomes induce tolerogenic skin dendritic cells
Full text linkIn vivo targeting of dendritic cells (DCs) with nanocarriers containing tolerogenic adjuvants is an attractive strategy to dampen inflammation. Here, we used ex vivo skin vaccination to examine the effect of intradermal injection of liposomes loaded with the tolerogenic adjuvants all-trans retinoic acid (RA) and vitamin D3 (VD3). We investigated the effect of intradermal liposome injection on skin DCs and the skin DC-induced T cell response. Our study shows that intradermal injection of RA or VD3-loaded anionic phospholipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) liposomes selectively induces CD14+ dermal DC (DDC) migration while reducing migration of CD1a dim DDCs. Migrated CD14+ DDCs displayed a partially immature phenotype. RA or VD3 liposome-treated CD1a dim DDCs exhibited reduced expression of maturation markers and induced expression of coinhibitory immunoglobulin-like transcript 3 (ILT3). VD3 liposome-treated CD14+ DDCs, as well as, CD1a dim DDCs, exhibited reduced expression of maturation markers, induction of coinhibitory molecules ILT3, and programmed death-ligand 1 (PD-L1). Migrated DCs from RA or VD3 liposome-injected skin differentiated naïve CD4+ T cells into FoxP3+ CD127 low and ICOS+ Tregs, expressing functional regulatory markers. Thus, our findings provide further substantiation for in vivo DC-modulating vaccines with tolerogenic liposomes as a putative clinical therapy for autoimmune diseases and allergies.Biopharmaceutic
Nanoplastics in duckweed: single-cell responses and recovery
No full textMicro- and nanoplastics have emerged as critical contaminants in aquatic ecosystems due to their small size, persistent nature, and potential for bioaccumulation. Nanoplastics are particularly concerning because they can be widespread in aquatic environments and ingested by aquatic organisms, posing potential risks to ecological health and environmental sustainability. However, the response and recovery of aquatic plants to nanoplastics, as well as the cell-specific molecular mechanisms underlying these processes, remain unclear. By integrating single-cell transcriptomics, enzymatic assays, and europium-doped nanoplastic tracing, we comprehensively investigated the response of duckweed to polystyrene nanoplastics at environmentally relevant and high doses over exposure and recovery phases. Nanoplastics exposure reduced plant reproduction and root length by inducing oxidative damage, with partial recovery after removal. Single-nucleus RNA sequencing revealed cell-type-specific responses of duckweed to nanoplastics, particularly in mesophyll, mestome sheath, epidermis, and parenchyma cells. Interestingly, recovery triggered a greater number of differentially expressed genes mechanistically linked to carbon metabolism, membrane transport, and stress-responsive pathways. Nanotracer quantification demonstrated root/frond absorption and 36.8–51.4% postrecovery excretion. These multiscale lines of evidence decipher the molecular strategies of duckweed to nanoplastics at single-cell resolution, providing mechanistic insights into the interactions between aquatic plants and nanoplastics contamination.Environmental Biolog
Written artefacts, transmitted literature and missing evidence: an introduction
Full text linkMiddle Eastern Studie
PET/CT to optimize treatment management of high-risk stage III and IV melanoma
Full text linkMelanoma is an aggressive form of skin cancer that can spread rapidly throughout the body. PET/CT imaging plays an important role in detecting and monitoring this disease. This thesis investigated how PET/CT can be used to optimize treatment strategies for patients with stage III and IV melanoma. Most studies used the commonly applied tracer [18F]FDG, which visualizes glucose metabolism, while a smaller exploratory study focused on [18F]FLT, a tracer that reflects cell proliferation. This research shows that [18F]FDG PET/CT is highly effective in detecting recurrent melanoma early, both after surgery and during treatment. This allows physicians to adjust therapy sooner and to treat new metastases before symptoms occur. In addition, early metabolic changes on PET/CT scans during targeted therapy with BRAF/MEK inhibitors were associated with disease outcome, suggesting that PET/CT can help identify which treatments are most effective for each patient. Although PET/CT cannot yet predict all treatment responses, it contributes significantly to more personalized and efficient care for patients with advanced melanoma. This knowledge helps to avoid unnecessary therapies and improve treatment selection. LUMC / Geneeskund
Phylogenetic analysis of NEAT1 and MALAT1 long non-coding RNAs highlights structure-function relationships in paraspeckle biology
Full text linkParaspeckles are nuclear bodies essential for gene regulation and stress response, and they are built upon the long non-coding RNA NEAT1. Together with the syntenic MALAT1, these are the only lncRNAs that use the tRNA-processing machinery for maturation, yet they differ in function and evolutionary conservation. To investigate these differences, we identified NEAT1 and MALAT1 orthologs across 545 mammals. For NEAT1, we found that G-quadruplexes, short motifs interacting with DBHS proteins and TDP-43, long gene length, and self-complementary regions are highly conserved features that likely stabilize paraspeckle integrity. Transposable elements also contributed structural modules potentially recognized by DBHS proteins, underscoring their role in NEAT1 evolution. The NEAT1Short isoform was present in all orthologs, and the TDP-43-mediated isoform switch appears to be conserved. In contrast, MALAT1 function likely relies on its conserved primary sequence and regions under purifying selection. This is the first large-scale phylogenetic study of NEAT1 - a lncRNA that lacks sequence similarity between orthologs while maintaining functional and syntenic conservation.Toxicolog
Between breaking and restoring boundaries: conceptualizing responsiveness in street-level decision-making
No full textStreet-level responsiveness is often framed as an individual binary decision: frontline workers either prioritize client needs or strictly adhere to institutional boundaries. This ethnographic study of three home care organizations in Amsterdam challenges this assumption by examining how frontline actors balance responsiveness with rules, resource limitations, and role expectations. Drawing on 140 hours of shadowing and 15 interviews with home care workers and managers, we analyze responsiveness as an organizational achievement. Frontline workers and managers often collaborate in boundary work when being responsive—not just crossing institutional boundaries around rules, resources, and roles, but subsequently also reinstating them. We identify three shared practices—response repertoires—through which responsiveness takes shape: temporary boundary work (addressing acute needs), structural boundary work (managing ongoing vulnerabilities), and performative boundary work (building trust while clarifying service limits). This study contributes to the street-level literature by: (1) identifying diverse forms of and motivations for responsiveness linked to different client needs; (2) unpacking the sequenced nature of responsive decision-making, offering the boundary work lens to study street-level decision-making processually; and (3) offering a dialectic understanding of responsiveness, where frontline actors are as much breakers as conservers of institutions. Together, these insights deepen understanding of how responsiveness is enacted, constrained, and institutionalized in everyday public service work.The politics and administration of institutional chang
Reflecties op ‘the making of’ een handboek over de Nederlandse politiek
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