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Graph neural networks for assessing the reliability of the medium-voltage grid☆
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317068.pdf (Publisher’s version ) (Open Access
Targeting oxidative stress-induced lipid peroxidation enhances podocyte function in cystinosis.
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317490.pdf (Publisher’s version ) (Open Access)BACKGROUND: Cystinosis is a rare, incurable lysosomal storage disease caused by mutations in the CTNS gene encoding the cystine transporter cystinosin, which leads to lysosomal cystine accumulation in all cells of the body. Patients with cystinosis display signs of podocyte damage characterized by extensive loss of podocytes into the urine at early disease stages, glomerular proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) lesions. Although standard treatment with cysteamine decreases cellular cystine levels, it neither reverses glomerular injury nor prevents the loss of podocytes. Thus, pathogenic mechanisms other than cystine accumulation are involved in podocyte dysfunction in cystinosis. METHODS: We used immortalized patient-derived cystinosis, healthy, and CTNS knockdown podocytes to investigate podocyte dysfunction in cystinosis. The results were validated in our newly in-house developed fluorescent ctns(-/-)[Tg(fabp10a:gc-EGFP)] zebrafish larvae model. To understand impaired podocyte functionality, static and dynamic permeability assays, tracer-metabolomic analysis, flow cytometry, western blot, and chemical and dynamic redox-sensing fluorescent probes were used. RESULTS: In the current study, we discovered that cystinosis podocytes demonstrate increased ferroptotic cell death caused by mitochondrial reactive oxygen species (ROS)-driven membrane lipid peroxidation. Moreover, cystinosis cells present a fragmented mitochondrial network with impaired tricarboxylic acid cycle (TCA) cycle and energy metabolism. Targeting mitochondrial ROS and lipid peroxidation improved podocyte function in vitro and rescued proteinuria in vivo in cystinosis zebrafish larvae. CONCLUSIONS: Mitochondrial ROS contribute to podocyte injury in cystinosis by driving lipid peroxidation and ferroptosis, which in turn lead to podocyte detachment. This finding adds cystinosis to the list of podocytopathies associated with mitochondrial dysfunction. The identified mechanisms reveal new therapeutic targets and highlight lipid peroxidation as an exploitable vulnerability of cystinosis podocytes
Predicting reading comprehension in Creole Papiamento and Dutch in a post-colonial context
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317116.pdf (Publisher’s version ) (Open Access)In postcolonial contexts, children usually learn to read in a language other than their main socialization language, usually a creole. To understand how this affects reading acquisition we examined the early Creole Papiamento (L1) and Dutch (L2) reading skills of 128 Caribbean children. We investigated the impact of instructional order, first Papiamento then Dutch (Papiamento-first group), and vice versa (Dutch-first group), and cognitive and linguistic predictors on grade 2 reading comprehension. The study also explored linguistic interdependence. Results showed a significant positive effect of instructional order on Dutch reading comprehension for the Dutch-first group, but no differences between groups on Papiamento reading comprehension. Both linguistic and cognitive precursors predicted reading comprehension in Papiamento and Dutch. We found that reading comprehension in Papiamento and Dutch is interdependent, influenced by instruction language, especially in the Dutch-first group. This underlines the crucial role of L1 in shaping reading comprehension in both L1 and L2.24 februari 202534 p
A voice-enabled intelligent virtual agent for people with memory impairments: Thematic analysis of focus group results
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315748.pdf (Author’s version preprint ) (Open Access)8th International Workshop, CONVERSATIONS 2024 (Thessaloniki, Greece, December 4-5, 2024
Quality of life of women with a screen-detected versus clinically detected breast cancer in the Netherlands: a prospective cohort study.
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317478.pdf (Publisher’s version ) (Open Access)PURPOSE: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands. METHODS: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results. RESULTS: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC. CONCLUSIONS: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited.01 januari 202
A super-Chandrasekhar mass type Ia supernova progenitor at 49 pc set to detonate in 23 Gyr
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318149.pdf (Publisher’s version ) (Open Access
Schade en schande
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315506.pdf (Publisher’s version ) (Open Access)Na ruim dertig jaar ervaring als advocaat en vijfentwintig jaar als curator overdenkt Bert Jansen op deze Blauwe pagina’s zijn werkend leven15 januari 20252 p
RRAGD variants cause cardiac dysfunction in a zebrafish model
No full textItem does not contain fulltextThis collection contains the raw data for "RRAGD variants cause cardiac dysfunction in a zebrafish model" which was published in AJP Heart and Circulatory Physiology in 2024, and a chapter in a PhD thesis. The raw data are in excel formats or as image files (PNG/JPEG). The Ras-related GTP-binding protein D (RRAGD) gene plays a crucial role in cellular processes. Recently, RRAGD variants found in patients have been implicated in a novel disorder with kidney tubulopathy and dilated cardiomyopathy. Currently, the consequences of RRAGD variants at the organismal level are unknown. Therefore, this study investigated the impact of RRAGD variants on cardiac function using a zebrafish embryo model. Furthermore, the potential usage of rapamycin, an mTOR inhibitor, as a therapy was assessed in this model. Zebrafish embryos were injected with RRAGD p.S76L and p.P119R cRNA and the resulting heart phenotypes were studied. Our findings reveal that overexpression of RRAGD mutants resulted in decreased ventricular fractional shortening, ejection fraction, and pericardial swelling. In RRAGD S76L-injected embryos, lower survival and heartbeat were observed, whereas survival was unaffected in RRAGD P119R embryos. These observations were reversible following therapy with the mTOR inhibitor rapamycin. Moreover, no effects on electrolyte homeostasis were observed. Together, these findings indicate a crucial role of RRAGD in cardiac function. In the future, the molecular mechanisms by which RRAGD variants result in cardiac dysfunction and if the effects of rapamycin are specific for RRAGD-dependent cardiomyopathy should be studied in clinical studies
Survival of periodontal ligament myofibroblasts after short-term mechanical strain in rats and in vitro: Could myofibroblasts contribute to orthodontic relapse?
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317658.pdf (Publisher’s version ) (Open Access)OBJECTIVES: To investigate in vivo whether myofibroblasts formed in the PDL after exposure to short-term high experimental orthodontic forces in rats survive. To study in vitro whether human PDL fibroblasts can differentiate into myofibroblasts and survive when chemical or mechanical stimuli are removed. DESIGN: Nine 6-week-old male Wistar rats were used in this experiment. Rat molars were exposed to high but rapidly decreasing experimental orthodontic forces by applying a rubber band and analyzed for the presence of myofibroblasts using ASMA staining. In vitro, human periodontal ligament (PDL) fibroblasts were exposed to transforming growth factor β1 (TGFβ1) and/or mechanical stress and monitored for myofibroblast formation and survival after these stimuli were abrogated. RESULTS: In vivo exposure to orthodontic forces strongly induced myofibroblast formation in the stretched regions of the PDL. Furthermore, many PDL myofibroblasts remained present 6 days after exposure to these short-term high orthodontic forces. Human PDL fibroblasts were shown to differentiate into myofibroblasts after 2 days of TGFβ1 exposure and survive for at least 2 more days after removing chemical stimuli (TGFβ1) or mechanical strain. Under in vitro conditions, both TGFβ1 and mechanical strain for 3 days promoted (myo)fibroblast formation, and these cells persisted for 3 more days after the removal of both stimuli. CONCLUSIONS: PDL myofibroblasts survive after the removal of mechanical strain in vivo and in vitro. This supports the hypothesis that myofibroblasts, which form in response to mechanical strain and chemical cues in the periodontal ligament (PDL), play a role in relapse following orthodontic tooth movement.01 april 202
Chatting your way to quitting: A longitudinal exploration of smokers' interaction with a cessation chatbot
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317079.pdf (Publisher’s version ) (Open Access)Background: Cigarette smoking poses a major public health risk, requiring scalable and accessible interventions. Chatbots offer a promising solution, given their potential in providing personalized, long-term interactions. Despite their promise, limited research has examined their efficacy and the intertwined relationship between user experience and effectiveness over an extended period of time. Methods: In this prospective, single-arm study, we developed and evaluated Roby, a 5-session chatbot intervention incorporating motivational interviewing and cognitive behavioral therapy to help smokers quit. Roby engaged Dutch adult smokers (N = 102) in conversations covering topics such as setting a quit date, managing withdrawal and cravings, and relapse prevention. The primary outcome was the continuous abstinence rate at the end of the intervention, and secondary outcomes included 7-day point prevalence abstinence, self-efficacy, and cravings. User engagement, therapeutic alliance, and interaction satisfaction were measured weekly, and the trajectory was analyzed using Linear Mixed Models. Results: Following an intention-to-treat principle, 18.6 % of participants achieved continuous abstinence, and 37.3 % achieved 7-day point prevalence abstinence. Self-efficacy significantly improved over the intervention, and cravings decreased over time. A slight decreasing trend was observed in engagement and satisfaction, likely due to a novelty effect. However, the decrease did not affect the intervention's outcomes. Conclusion: This study demonstrates the feasibility and initial usefulness of Roby, highlighting the potential for chatbots in long-term cessation support. Future research should further validate these findings with randomized controlled trials. Additional efforts should focus on monitoring and maintaining user experience in the long term to enhance effectiveness.9 p