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Krol, L.; Remmerswaal, L.; Groen, M.; Beek, J.G. van der; Sikkema, R.S.; Dellar M.E.; ... ; Schrama M.J.J. 2026

Landscape level associations between birds, mosquitoes and microclimates: possible consequences for disease transmission?

Article / Letter to editor

open access

Kalkreuth, R.T.; Vasicek, Z.; Husa, J.; Vermetten, D.L.; Ye, F.; Bäck, T.H.W. 2025

General Boolean function benchmark suite

Article in monograph or in proceedings

open access

Robinson-Garcia, N., Corona-Sobrino, C., Chinchilla-Rodríguez, Z., Torres-Salinas, D.; Costas Comesana, R. 2025

Informetric methods for studying the diversity of the scientific workforce: towards a state-of-the-art

Event

metadata only

Tulp, T.; Tietema, A.; Loon, E.E. van; Ebben, B.; Hall, R.L. van; Son, Mm. van; Barmentlo, S.H. 2025

Biomonitoring of dairy farm emitted ammonia in surface waters using phytoplankton and periphyton

Article / Letter to editor

open access

Welander, N.Z.; Rukh, G.; Rask-Andersen, M.; Harder, A.V.E.; Maagdenberg, A.M.J.M. van den; Schioth, H.B.; ... ; Int Headache Genetics Consortium 2025

Migraine, inflammatory bowel disease and celiac disease: a Mendelian randomization study

Article / Letter to editor

open access

ObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac... Show moreObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.MethodsLinkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.ResultsMigraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.ConclusionsWe found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes. Show less

Shalgunov, V.; Broek, S.L. van den; Andersen, I.V.; Raval, N.R.; Schäfer, G.; Barz, M.; ... ; Battisti, U.M. 2024

Evaluation of F-537-Tetrazine in a model for brain pretargeting imaging: comparison to N-(3-[18F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine

Article / Letter to editor

open access

Brain pretargeted nuclear imaging for the diagnosis of various neurodegenerative diseases is a quickly developing field. The tetrazine ligation is currently the most explored approach to achieve... Show moreBrain pretargeted nuclear imaging for the diagnosis of various neurodegenerative diseases is a quickly developing field. The tetrazine ligation is currently the most explored approach to achieve this goal due to its remarkable properties. In this work, we evaluated the performance of F-537-Tetrazine, previously developed by Biogen, and N-(3-[18F]fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine, previously developed in our group, thereby allowing for the direct comparison of these two imaging probes. The evaluation included synthesis, radiolabeling and a comparison of the physicochemical properties of the compounds. Furthermore, their performance was evaluated by in vitro and in vivo pretargeting models. This study indicated that N-(3-[18F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine might be more suited for brain pretargeted imaging. Show less

Dang, H.; Verhoeve, D.A.; Basiliya, K.; Boonstra, J.J. 2024

Endoscopic intermuscular dissection of early anal cancer

Article / Letter to editor

open access

Zobl, W.; Bitsch, A.; Blum, J.; Boei, J.J.W.A.; Capinha, L.; Carta, G.; ... ; Escher, S.E. 2024

Protectiveness of NAM-based hazard assessment: which testing scope is required?

Article / Letter to editor

open access

Hazard assessment (HA) requires toxicity tests to allow deriving protective points of departure (PoDs) for risk assessment irrespective of a compound's mode of action (MoA). The scope of in vitro... Show moreHazard assessment (HA) requires toxicity tests to allow deriving protective points of departure (PoDs) for risk assessment irrespective of a compound's mode of action (MoA). The scope of in vitro test batteries (ivTB) thereby necessitated for systemic toxicity is still unclear. We explored the protectiveness regarding systemic toxicity of an ivTB with a scope, which was guided by previous findings from rodent studies, where examining six main targets, including liver and kidney, was sufficient to predict the guideline scope-based PoD with high probability. The ivTB comprises human in vitro models representing liver, kidney, lung and the neuronal system covering transcriptome, mitochondrial dysfunction and neuronal outgrowth. Additionally, 32 CALUX®- and 10 HepG2 BAC-GFP reporters cover a broad range of disturbance mechanisms. Eight compounds were chosen for causing adverse effects such as immunotoxicity or anemia in vivo, i.e., effects not directly covered by assays in the ivTB. PoDs derived from the ivTB and from oral repeated dose studies in rodents were extrapolated to maximum unbound plasma concentrations for comparison. The ivTB-based PoDs were one to five orders of magnitude lower than in vivo PoDs for six of eight compounds, implying that they were protective. The extent of in vitro response varied across test compounds. Especially for hematotoxic substances, the ivTB showed either no response or only cytotoxicity. Assays better capturing this type of hazard would be needed to complement the ivTB. This study highlights the potentially broad applicability of ivTBs for deriving protective PoDs of compounds with unknown MoA. Show less

Kunnen, S.J.; Arnesdotter, E.; Willenbockel, C.T.; Vinken, M.; Water, B. van de 2024

Qualitative and quantitative concentration-response modelling of gene co-expression networks to unlock hepatotoxic mechanisms for next generation chemical safety assessment

Article / Letter to editor

open access

Next generation risk assessment of chemicals revolves around the use of mechanistic information without animal experimentation. In this regard, toxicogenomics has proven to be a useful tool to... Show moreNext generation risk assessment of chemicals revolves around the use of mechanistic information without animal experimentation. In this regard, toxicogenomics has proven to be a useful tool to elucidate the underlying mechanisms of adverse effects of xenobiotics. In the present study, two widely used human in vitro hepatocyte culture systems, namely primary human hepatocytes (PHH) and human hepatoma HepaRG cells, were exposed to liver toxicants known to induce liver cholestasis, steatosis or necrosis. Benchmark concentration-response modelling was applied to transcriptomics gene co-expression networks (modules) to derive benchmark concentrations (BMCs) and to gain mechanistic insight into the hepatotoxic effects. BMCs derived by concentration-response modelling of gene co-expression modules recapitulated concentration-response modelling of individual genes. Although PHH and HepaRG cells showed overlap in deregulated genes and modules by the liver toxicants, PHH demonstrated a higher responsiveness, based on the lower BMCs of co-regulated gene modules. Such BMCs can be used as transcriptomics point of departure (tPOD) for assessing module-associated cellular (stress) pathways/processes. This approach identified clear tPODs of around maximum systemic concentration (Cmax) levels for the tested drugs, while for cosmetics ingredients the BMCs were 10-100-fold higher than the estimated plasma concentrations. This approach could serve next generation risk assessment practice to identify early responsive modules at low BMCs, that could be linked to key events in liver adverse outcome pathways. In turn, this can assist in delineating potential hazards of new test chemicals using in vitro systems and used in a risk assessment when BMCs are paired with chemical exposure assessment. Show less

Diederiks, N.M.; Ruhaak, L.R.; Romijn, F.P.H.T.M.; Pieterse, M.M.; Smit, N.P.M.; Cobbaert, C.M. 2024

An LC-MS-based designated comparison method with similar performance to the Lp(a) reference measurement procedure to guide molar Lp(a) standardization

Article / Letter to editor

open access

BackgroundThe 2022 consensus statement of the European Atherosclerosis Society (EAS) on lipoprotein(a) (Lp(a)) recognizes the role of Lp(a) as a relevant genetically determined risk factor and... Show moreBackgroundThe 2022 consensus statement of the European Atherosclerosis Society (EAS) on lipoprotein(a) (Lp(a)) recognizes the role of Lp(a) as a relevant genetically determined risk factor and recommends its measurement at least once in an individual's lifetime. It also strongly urges that Lp(a) test results are expressed as apolipoprotein (a) (apo(a)) amount of substance in molar units and no longer in confounded Lp(a) mass units (mg/dL or mg/L). Therefore, IVD manufacturers should transition to molar units. A prerequisite for this transition is the availability of an Lp(a) Reference Measurement Procedure (RMP) that allows unequivocal molecular detection and quantification of apo(a) in Lp(a). To that end an ISO 17511:2020 compliant LC-MS based and IFCC-endorsed RMP has been established that targets proteotypic peptides of apolipoprotein(a) (apo(a)) in Lp(a). The RMP is laborious and requires highly skilled operators. To guide IVD-manufacturers of immunoassay-based Lp(a) test kits in the transition from mass to molar units, a Designated Comparison Method (DCM) has been developed and evaluated.MethodsTo assess whether the DCM provides equivalent results compared to the RMP, the procedural designs were compared and the analytical performance of DCM and RMP were first evaluated in a head-to-head comparison. Subsequently, apo(a) was quantified in 153 human clinical serum samples. Both DCM and RMP were calibrated using external native calibrators that produce results traceable to SRM2B. Measurement uncertainty (MU) was checked against predefined allowable MU.ResultsThe major difference in the design of the DCM for apo(a) is the use of only one enzymatic digestion step. The analytical performance of the DCM and RMP for apo(a) is highly similar. In a direct method comparison, equivalent results were obtained with a median regression slope 0.997 of and a median bias of - 0.2 nmol/L (- 0.2%); the intermediate imprecision of the test results was within total allowable error (TEa) (CVa of 10.2% at 90 nmol/L).ConclusionsThe semi-automated, higher throughput, LC-MS-based method for Lp(a) meets the predefined analytical performance specifications and allowable MU and is hence applicable as a higher order Designated Comparison Method, which is ideally suited to guide IVD manufacturers in the transition from Lp(a) mass to molar units. Show less

Senjor, E.; Pirro, M.; Svajger, U.; Prunk, M.; Sabotic, J.; Jewett, A.; ... ; Kos, J. 2024

Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells

Article / Letter to editor

open access

Cystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell... Show moreCystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell stage, called split-anergy. We show that N-glycosylation determines the localization and cellular function of cystatin F. Cystatin F mostly exhibited high-mannose glycosylation in U-937 cells, both high-mannose and complex glycosylation in NK-92 and primary NKs, and predominantly complex glycosylation in super-charged NKs. Manipulating N-glycosylation with kifunensine increased high-mannose glycosylation of cystatin F and lysosome localisation, which decreased cathepsin C activity and reduced NK cytotoxicity. Mannose-6-phosphate could significantly reduce the internalization of extracellular cystatin F. By comparing NK cells with different cytotoxic potentials, we found that high-mannose cystatin F was strongly associated with lysosomes and cathepsin C in NK-92 cell line. In contrast, in highly cytotoxic super-charged NKs, cystatin F with complex glycosylation was associated with the secretory pathway and less prone to inhibit cathepsin C. Modulating glycosylation to alter cystatin F localisation could increase the cytotoxicity of NK cells, thereby enhancing their therapeutic potential for treating cancer patients. Show less

Ruitenberg, M.F.L. 2024

Cognition and movement in neurodegenerative disorders: a dynamic duo

Article / Letter to editor

open access

Nagtzaam, M.A.M.; Louwerse, T.P. 2024

Geographical representation under a single nationwide district: the case of the Netherlands

Article / Letter to editor

open access

Previous studies have demonstrated the common occurrence of constituency focus in parliamentary questions, which is most often attributed to electoral incentives. If an electoral system makes use... Show morePrevious studies have demonstrated the common occurrence of constituency focus in parliamentary questions, which is most often attributed to electoral incentives. If an electoral system makes use of a single nationwide district, however, these district-oriented electoral incentives do not apply. MPs may still substantively represent a geographical region, because they are motivated to stand up for a specific region for other reasons. This article explores the extent to which Dutch MPs pay attention in parliamentary questions and debates to specific regions. We find that those with stronger ties to a region, and especially MPs who reside in a region, are more likely to mention it in parliamentary questions and speeches. In addition, we find that this effect is stronger for provinces where regional attachment among residents is relatively stronger. Show less

Baca, M.; Popović, D.; Agadzhanyan, A.K.; Baca, K.; Conard, N.J.; Fewlass, H.; ... ; Nadachowski, A. 2024

Ancient DNA of narrow-headed vole reveal common features of the Late Pleistocene population dynamics in cold-adapted small mammals

Article / Letter to editor

open access

The narrow-headed vole, collared lemming and common vole were the most abundant small mammal species across the Eurasian Late Pleistocene steppe-tundra environment. Previous ancient DNA studies of... Show moreThe narrow-headed vole, collared lemming and common vole were the most abundant small mammal species across the Eurasian Late Pleistocene steppe-tundra environment. Previous ancient DNA studies of the collared lemming and common vole have revealed dynamic population histories shaped by climatic fluctuations. To investigate the extent to which species with similar adaptations share common evolutionary histories, we generated a dataset comprised the mitochondrial genomes of 139 ancient and 6 modern narrow-headed voles from several sites across Europe and northwestern Asia covering approximately the last 100 thousand years (kyr). We inferred Bayesian time-aware phylogenies using 11 radiocarbon-dated samples to calibrate the molecular clock. Divergence of the main mtDNA lineages across the three species occurred during marine isotope stages (MIS) 7 and MIS 5, suggesting a common response of species adapted to open habitat during interglacials. We identified several time-structured mtDNA lineages in European narrow-headed vole, suggesting lineage turnover. The timing of some of these turnovers was synchronous across the three species, allowing us to identify the main drivers of the Late Pleistocene dynamics of steppe- and cold-adapted species. Show less

Todtenhaupt, P.; Kuipers, T.B.; Dijkstra, K.L.; Voortman, L.M.; Franken, L.A.; Spekman, J.A.; ... ; Meeren, L.E. van der 2024

Twisting the theory on the origin of human umbilical cord coiling featuring monozygotic twins

Article / Letter to editor

open access

The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the... Show moreThe human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell–cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development. Show less

Morwani-Mangnani, J.; Rodriguez-Girondo, M.; Singh-Povel, C.; Verlaan, S.; Beekman, M.; Slagboom, P.E. 2024

Physical activity and fiber intake beneficial for muscle mass and strength preservation during aging: a comprehensive cross-sectional study in the UK biobank cohort

Article / Letter to editor

open access

Background: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing... Show moreBackground: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, physical activity, and sleep impact on FFM and handgrip strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health. Methods: The cross-sectional analysis of the UK Biobank involved 45,984 individuals (54 % women) aged 40–70 years with a complete dataset. Multiple linear regression explored determinants of FFM and handgrip strength, considering traditional, socio-demographics, medication use and smoking as covariates, with sex and age (younger and older than 55 years) stratifications. Results: In older men and women, higher physical activity beneficially affect both FFM (respectively В = 3.36 × 10− 3 , p-value = 1.66 × 10− 3 ; В = 2.52 × 10− 3 , p-value = 3.57 × 10− 4 ) and handgrip strength (В = 6.05 × 10− 3 , p-value = 7.99 × 10− 5 , В = 8.98 × 10− 3 , p-value = 2.95 × 10− 15). Similar results were found in fiber intake for FFM in older men and women (respectively B = 3.00 × 10− 2 , p-value = 2.76 × 10− 5 ; B = 2.68 × 10− 2 , p-value = 1.78 × 10− 9 ) and handgrip strength (В = 3.27 × 10− 2 , p-value = 1.40 × 10− 3 ; В = 3.12 × 10− 2 , p-value = 1.34 × 10− 5 ). Other lifestyle factors influence FFM and handgrip strength differently. Key determinants influencing handgrip strength included higher protein intake, lower water intake, higher alcohol intake, and extended sleep duration whereas mainly higher water intake is associated with higher FFM. Conclusions: In both men and women, the main factors associated with FFM and handgrip strength are physical activity and fiber intake, which may underlie a connection between gut and muscle health. Given the observed complexity of muscle health in the age and sex strata, further longitudinal research is needed to provide personalized lifestyle recommendations. Show less

Vriens, D.; Koster, E.J. de; Geus-Oei, L.F. de; Oyen, W.J.G.; EfFECTS trial consortium 2024

Preoperative stratification of cytologically indeterminate thyroid nodules by [18F]FDG-PET: can Orpheus bring back Eurydice?

Article / Letter to editor

open access

Marciello, M.; Cusati, V.; Nicolosi, F.; Saavedra-Rubio, K.; Pierrat, E.; Thonemann, N.; Laurent, A. 2024

Evaluating the economic landscape of hybrid-electric regional aircraft: a cost analysis across three time horizons

Article / Letter to editor

under embargo until 2025-01-16

This article presents the results of a prospective cost analysis of future regional aviation solutions, specifically focusing on hybrid-electric regional aircraft for 50 passengers. The study spans three time horizons (short term, medium term, long term) and employs a validated workflow to estimate costs for various solutions, including conventional, hybrid-electric, and hydrogen-based architectures. A specialized cost model is introduced to assess the electric components of the powertrain, emphasizing maintenance expenses and energy costs. Despite the environmental promise of hybrid and electric solutions, the results reveal significantly higher direct operating costs (up to 69.8%) compared to conventional options. The study highlights the importance of targeted policies to incentivize sustainable alternatives, suggesting potential solutions such as discouraging kerosene-based aircraft and promoting sustainable aviation fuel. These insights provide valuable guidance for industry stakeholders navigating the path toward a more sustainable and economically viable aviation future.

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Groen, R.A.; Barbero, F.L.; Fischer, S.E.; Dijkman, P.R.M. van; Bax, J.J.; Tushuizen, M.E.; ... ; Graaf, M.A. de 2024

Coronary artery calcium assessment on non-gated chest CT to optimize pre-operative cardiac screening in liver transplantation

Article / Letter to editor

open access

BackgroundGuidelines recommend standard pre-operative cardiac screening in all liver transplantation (LT) recipients, despite the relatively low prevalence of obstructive coronary artery disease.... Show moreBackgroundGuidelines recommend standard pre-operative cardiac screening in all liver transplantation (LT) recipients, despite the relatively low prevalence of obstructive coronary artery disease. Most LT recipients often have non-gated computed tomography (CT) performed of the chest and abdomen. This study evaluated the ability of coronary artery calcification (CAC) assessment on consecutively available scans, to identify a selection of low-risk patients, in whom further cardiac imaging can be safely withheld.MethodsLT recipients with prior non-gated CT chest-abdomen were included. CAC was visually scored on a semi-quantitative ordinal scale. Stress myocardial perfusion, coronary CT angiography (CCTA) and invasive coronary angiography (ICA) were used as golden standard. The sensitivity and specificity of CAC to exclude and predict obstructive CAD were assessed. In addition, peri- and postoperative mortality and cardiac events were analyzed.Results149 LT recipients (ranged 31–71 years) were included. In 75% of patients, no CAC and mild CAC could rule out obstructive CAD on CCTA and ICA with 100% certainty. The threshold of mild CAC had a sensitivity of 100% for both CCTA and ICA and a specificity of 91% and 68%, respectively. None of the patients with no or mild calcifications experienced peri- and post-operative cardiac events or died of cardiac causes.ConclusionVisual evaluation of CAC on prior non-gated CT can accurately and safely exclude obstructive CAD in LT recipients. Incorporation of these already available data can optimize cardiac screening, by safely withholding or correctly allocating dedicated cardiac imaging in LT recipients. Thereby, reducing patients' test burden and save health care expenses. Show less

Rietjens, S.J.H. 2024

Innovatie in de schaduw: de strijd van geheime diensten

Inaugural lecture

open access

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