Leiden University Scholary Publications
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One-year practice effects predict long-term cognitive outcomes in Parkinson's disease
Full text linkHealth and Well-bein
MtDNA barcoding illuminates native diversity and introduction pathways of slow worms in The Netherlands
Full text linkoai:scholarlypublications.universiteitleiden.nl:item_4282025Animal sciencesNaturali
Substrates and inhibitors to study and modulate ER-I α-glucosidase activity
Full text linkThis thesis describes research aimed at discovering inhibitors selective for either of the two endoplasmic reticulum α-glucosidases, ER-I and ER-II, with the overarching goal of discovering new antiviral agents to treat viruses that rely on host N-glycosylation for proliferation. It also describes assays that measure the activity of these enzymes and the effects of inhibitors on them.Medical Biochemistr
Deep learning in the detection of early inflammatory signs in rheumatoid arthritis
Full text linkIn this study, we have developed a series of models and methods for quantifying inflammation, predicting future RA development, interpreting DL models, aggregating information to reach population-level conclusions, and combining all these methods to discover potential new imaging biomarkers that contribute to RA prediction.LKEB: Medis medical imagingLUMC / Geneeskund
Systemic immune dynamics in cancer
Full text linkBreast cancer is the most common cancer in women and a major cause of mortality. The immune system plays a crucial role in recognizing and combating tumors, but in breast cancer this role is complex and varies greatly by disease subtype and stage. In my research, I investigated how the immune system changes in breast cancer and how this knowledge may contribute to improved understanding and treatment of the disease.Through extensive analyses of blood samples from patients with different forms of breast cancer, I found that the immune system becomes dysregulated in advanced disease. This was particularly evident in the aggressive triple-negative subtype (TNBC), where pronounced abnormalities were observed, especially in certain white blood cells such as neutrophils. In patients with metastatic TNBC, these cells were not only more abundant but also more active and functionally distinct compared with those in healthy individuals.In addition, we studied how immunotherapy—a treatment that enhances the body’s own immune response—works in breast cancer. In patients with early-stage TNBC, a short course of immunotherapy before surgery could already induce strong immune activation and, in some cases, complete tumor disappearance. In metastatic TNBC, we identified another immune cell type, the eosinophil, as important for a favorable response to immunotherapy.These findings provide new insight into the interaction between breast cancer and the immune system and may contribute to more targeted, effective, and less burdensome treatments for patients.LUMC / Geneeskund
Recurrent glioblastoma in the era of molecular diagnostics: practice variation and practical implications
Full text linkThe journey of a patient with recurrent glioblastoma is subject to practice variation in diagnostics and treatments, in which the clinical implementation of WGS results in the context of precision oncology has currently little support from treating physicians, accompanied by some ethical objections that need to be considered. Another important conclusion is that routine WGS-based diagnostics might help the (future) patient, since WGS - which was proven fast and feasible in our population - has a great potential to not only create a lot of new knowledge about the biology of glioblastomas, but also to unravel novel targets for treatment.LUMC / Geneeskund
Pandemic visits a doctor
Full text link The COVID-19 pandemic revealed global vulnerability to infectious diseases and highlighted the need for pandemic preparedness built on three pillars: slowing transmission, optimizing healthcare capacity, and ensuring safe, effective vaccination. This thesis addresses these pillars in two parts. Part 1 focuses on early-pandemic surveillance using population-derived data. The COVID RADAR app enabled large-scale symptom and behavior reporting, correlating strongly with national case trends and predicting primary care demand when diagnostic resources were limited. App data also showed that 5–10% of community cases experienced post-acute COVID symptoms 100 days after infection, with distinct symptom clusters suggesting multiple underlying mechanisms.Part 2 examines coagulation and thrombotic events related to SARS-CoV-2 infection and vaccination. Pre-existing coagulation potential did not increase infection risk but may worsen outcomes in older adults with comorbidities. Both intradermal and intramuscular vaccination temporarily increased inflammatory and coagulation markers, more strongly after intramuscular dosing. Vaccines were associated with venous thromboembolism (VTE), though overall vaccination reduced VTE events by lowering COVID-19 incidence. The thesis highlights strengths and limitations of syndromic surveillance and vaccine-safety methods, recommending case-control designs during pandemics. Finally, it stresses the need for improved public communication to strengthen vaccine acceptance and promote collective responsibility. LUMC / Geneeskund
Macrophage cell models for the investigation of Gaucher disease
Full text linkGaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes. This buildup is particularly present in macrophages residing in the liver and spleen. Currently, it is difficult to make an accurate genotype-phenotype correlation for this disease. In order to rectify this situation, an accurate, reliable and readily available model of this disease must be established. In this thesis, different macrophage cell lines and primary macrophages were investigated in their potential use as a model for Gaucher disease. GBA1 deficiency was induced by chemical inactivation of GBA1 using specific small molecule inhibitors. While all macrophages showed accumulation of glucosylceramide, the primary macrophages isolated from blood resembled best the macrophages as found in Gaucher disease patients. These primary macrophages were subsequently investigated on the appearance of their lysosomes both in a Gaucher disease state as well as in an endogenous state. Further research with Gaucher disease models originating from primary macrophages should shed light on the underlying molecular disease mechanisms in Gaucher disease.Medical Biochemistr
The economic foundations of Greco-Roman urbanism
No full textThe Unification of the Mediterranean World 400 BC - 400 A
Time to tip the scales: tackling overweight and obesity in primary care
Full text linkObesity management in primary care needs to adapt to the increasing prevalence of obesity: Time to tip the scales on obesity and find balance.This dissertation aims to provide a contribution to the improvement of obesity management in primary care by focusing on the current practices of obesity management in primary care and the identification of patients with obesity at increased risk of further long-term weight gain or cardiovascular disease.We concluded that body mass index and waist circumference are currently rarely recorded in primary healthcare records. Overcoming the barriers for general practitioners to discussing weight, diagnosing and referring patients with obesity requires not only improving knowledge and skills, but also establishing long-term relationships, creating a supportive environment and addressing their beliefs about consequences. Proactive attention is needed for patients with depressive symptoms and patients who have experienced negative life events, as they are more likely to gain weight over time. In addition, we recommend measuring waist circumference in primary care, as it is a cost-effective and simple measurement that identifies patients at increased risk of developing cardiovascular disease. Ultimately, obesity management should focus more on prevention rather than treating its effects.LUMC / Geneeskund