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A Linear Time Algorithm for Local Minimum and Maximum Filters
No full textWe present a linear-time algorithm for computing sliding window maximum and minimum filters over one-dimensional signals. The algorithm is based on a single forward pass using a double-ended queue (deque) and requires only a small amount of memory. It supports in-place and streaming implementations. We provide a self-contained description of the algorithm, including illustrative examples, pseudocode, a practical implementation in C, and an analysis of its runtime behavior. We compare the performance of the algorithm against the well-known Van Herk–Gil–Werman (HGW) algorithm, which performs three scans over the data and offers data-independent performance.</p
Vitamin C and Benzoic Acid Intake in Patients with Kidney Disease:Is There Risk of Benzene Exposure?
No full textVitamin C is a small water-soluble molecule primarily cleared by the kidneys. Therefore, its plasma concentration would be expected to increase as kidney function declines. However, studies in patients with chronic kidney disease (CKD) and kidney transplant recipients have shown the opposite: a positive correlation between kidney function and plasma vitamin C levels. In this review, we discuss potential explanations for this counterintuitive finding and suggest alternative mechanisms influencing vitamin C bioavailability in this population. We also explore the hypothesis that this phenomenon may be linked to benzoic acid (benzoate) exposure. Benzoic acid is a widely used food preservative that, like vitamin C, is water-soluble and renally excreted. In individuals with impaired kidney function, reduced clearance may lead to elevated circulating benzoic acid levels, which could increase the likelihood of an in vivo chemical reaction between benzoic acid and vitamin C, resulting in the formation of benzene, which is a known toxic and carcinogenic compound. We summarize experimental evidence demonstrating the vitamin C–benzoic acid reaction in vitro, along with preliminary animal studies suggesting it may also occur in vivo. We also discuss the potential clinical consequences of benzene exposure in the context of patients with kidney function impairment. Given the widespread use of benzoic acid as a food preservative and the ongoing discussion around vitamin C supplementation in patients with kidney disease, this review invites further investigation to evaluate whether this reaction represents a health hazard for this population.</p
Gestational Diabetes Mellitus:intracellular pH and hydrogen sulfide as determinants of endothelial function and nitric oxide synthase regulation
No full textGestational diabetes mellitus (GDM) is a pregnancy-related condition that impacts both maternal and fetal health. It is marked by elevated maternal blood sugar and increased insulin levels in the fetus. This thesis explores how GDM alters the function of the umbilical vein, particularly the endothelium—a layer of cells essential for nutrient and oxygen transport between mother and baby. In GDM, this layer becomes dysfunctional, impairing vascular tone and nutrient transport.A central issue identified is the disruption of intracellular pH (pHi), driven by overactive sodium/proton exchangers (NHEs), which make the internal environment of endothelial cells too alkaline. The naturally produced gas molecule hydrogen sulfide (H₂S) was found to help correct this imbalance by inhibiting NHE activity, thereby lowering pHi and helping restore normal cell behavior. The thesis also considers how environmental exposures—such as vitamin and mineral deficiencies or pollutants like heavy metals—may worsen placental dysfunction in GDM.Using human umbilical vein endothelial cells (HUVECs) from both normal and GDM pregnancies, the research demonstrates that maternal pre-pregnancy body mass index significantly affects pHi regulation and adenosine transport—both vital for vascular health. The study also reveals that H₂S modulates nitric oxide (NO) production through its effects on pHi, either promoting or suppressing NO synthesis depending on the cellular context.Overall, the findings suggest that targeting pHi regulation and H₂S signaling could offer novel strategies for preventing or reducing vascular complications associated with GDM, while also underscoring the influence of maternal health and environmental exposures during pregnancy
Development and Validation of a Prognostic Model for Persistent Hypoparathyroidism After Total or Completion Thyroidectomy
No full textBackground: The aim of this study was to develop and validate a clinical prediction model to predict the occurrence of persistent hypoparathyroidism after total or completion thyroidectomy. Methods: This multicentre retrospective cohort study included patients who underwent total or completion thyroidectomy between January 2010 and June 2021 in 12 Dutch hospitals. Results: Of the 366 patients included, 44 (12.0%) patients developed persistent hypoparathyroidism in the first year follow-up after surgery. Multivariable logistic regression analysis showed that ΔPTH the day after surgery, corrected calcium the day after surgery, and not identifying at least one parathyroid during surgery were strong predictors for persistent hypoparathyroidism. The discriminative ability of the model was excellent (optimism-corrected C-index: 0.88, 95% CI: 0.84–0.92) with moderately calibrated predictions. Conclusions: The model proposed in this study could be used to perform an individual assessment of patients at risk for persistent hypoparathyroidism after total thyroidectomy.</p
Deciphering Phospholamban Cardiomyopathy:Towards Precision Medicine for Genetic Heart Disease
No full textHeart failure is a major cause of illness and death worldwide, and occurs when the heart is no longer able to pump enough blood to meet the demand of the body. In some patients, heart failure is caused by inherited changes in the DNA that affect how the heart muscle functions. One example is a change in the phospholamban (PLN) gene, known as the PLN p.Arg14del (R14del) variant. This variant can lead to a severe and unpredictable heart disease and commonly occurs in the Netherlands, affecting approximately 1 in 5.000 to 10.000 individuals.This thesis investigates how the PLN R14del variant causes heart disease and how this knowledge can improve diagnosis and treatment. First, an overview is provided of current knowledge of PLN-related heart disease and available treatment options. Next, the DECIPHER-PLN cohort is established, in which PLN R14del carriers across the disease spectrum are followed over time to improve understanding of the disease.Using advanced techniques, this thesis identifies proteins and metabolites in the blood that may help predict which PLN R14del carriers are at increased risk of disease progression. In addition, changes in proteins and their regulation are found to lead to disruptions in calcium handling and contraction of the heart muscle. Subsequently, a novel treatment strategy is investigated: RNA therapy. In a human heart cell model, this therapy reduced harmful aggregation of the PLN protein and improved heart cell function. Lastly, the potential of RNA therapy for heart failure beyond PLN R14del is explored.Together, these findings contribute to a better understanding of inherited heart diseases such as PLN R14del and to the development of personalized treatments for patients with inherited heart disease
Phylogeny of waterfowl (Anseriformes) constructed using genome sequences provides insights into topological incongruences
No full textThe evolutionary history of waterfowl (Anseriformes) has long been a focal point of avian research. However, previous phylogenetic investigations have focused primarily on morphology or mitochondrial DNA or have lacked sufficient taxon sampling. Accompanied by observed phylogenetic incongruence and incomplete resolution, waterfowl phylogenetic branching patterns remain uncertain at various taxonomic ranks. To further validate phylogenetic relationships among higher waterfowl taxa and assess presence of conflicting signal, we assembled and analyzed 24 waterfowl genomes representing all waterfowl families and several subfamilies. Utilizing both newly acquired and previously obtained genomes, we constructed and analyzed seven DNA data classes, which yielded highly resolved phylogenetic trees including a time-calibrated tree. Most of these trees consistently and completely resolved the phylogenetic relationships of the included waterfowl species. Despite these efforts, our analysis across chromosomes uncovered four instances of phylogenetic incongruous signal. After minimizing tree estimation error through focus on whole-genome alignment dataset and by sequence simulation, analyses revealed that incomplete lineage sorting and gene introgression essentially contributed to all gene-tree discordance. The variable impact of both factors across distinct waterfowl nodes reflects an underlying complexity that warrants further interpretation. This study not only presents a strongly-supported and well-resolved phylogenetic backbone for the major waterfowl lineages, but also provides foundational data for subsequent comparative genomics studies of a more expanded set of waterfowl taxa.</p
Tone Representation and Learning
No full textThis thesis explores how people from different linguistic backgrounds perceive, understand, and learn tones from tonal languages, where pitch variations can change word meanings. It examines the cognitive and brain activities involved in tone perception and learning, and how native experience with a tonal language, like Mandarin, influences this ability.The research is based on four studies. The first looks at how native experience with tones helps people learn patterns involving tones. It shows that Mandarin speakers generally perform better at learning these patterns than non-tone speakers, though some non-tone speakers can also pick up on them. This variation suggests that experience with tonal languages can have a complex effect on tone perception and learning.The next two studies explore in what way tonal language experience lead to these differences. They reveal that Mandarin speakers process tones in an organized way linked to word meanings, while Dutch speakers, with no tonal experience, use pitch patterns to separate speech sounds into isolate units, which could later become meaningful words.The final study shows that non-tone speakers can learn tonal differences when exposed to tonal speech patterns, even without prior tonal experience. This suggests that the adult brain can adapt to tonal learning.Overall, the thesis highlights how both experience with tonal languages and the brain’s innate ability to recognize patterns are crucial for learning tones, offering new insights into speech processing and language learning
High riverine metal oxide input provides substrates for metal-dependent methane oxidation in Baltic Sea sediments
No full textThis a dataset for thesis manuscript "High riverine metal oxide input provides substrates for metal-dependent methane oxidation in Baltic Sea sediments".
Entrepreneurial, precarious or leaving altogether? Work trajectories in the creative industries in the Netherlands
No full textThis article seeks to identify variety in work trajectories in the cultural and creative industries (CCI) and the extent to which structural inequalities can be observed in who ends up in which trajectory. The omnipresent inequalities in the sector suggest that some might be in a better position to escape precarious trajectories than others. Multichannel sequence analysis is used to map the work trajectories of employees, employers and self-employed workers in the CCI in the Netherlands over 10 years. The results show that more than half of them leave the sector during the observation window. Contrary to what is often assumed, characteristics of traditional careers can be observed alongside flexible ones. Work trajectories characterised by flexible labour market positions are also the most precarious in terms of income, but make it more likely that workers stay. However, staying in the sector is less achievable for marginalised groups.</p