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Johannes van Deventer, Sint Agatha en de Nederrijn. Een inleiding
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Measurement of the top quark mass with the ATLAS detector using tt¯ events with a high transverse momentum top quark
No full textItem does not contain fulltextThe mass of the top quark is measured using top-antitop-quark pair events with high transverse momentum top quarks. The dataset, collected with the ATLAS detector in proton--proton collisions at TeV delivered by the Large Hadron Collider, corresponds to an integrated luminosity of 140 fb . The analysis targets events in the lepton-plus-jets decay channel, with an electron or muon from a semi-leptonically decaying top quark and a hadronically decaying top quark that is sufficiently energetic to be reconstructed as a single large-radius jet. The mean of the invariant mass of the reconstructed large-radius jet provides the sensitivity to the top quark mass and is simultaneously fitted with two additional observables to reduce the impact of the systematic uncertainties. The top quark mass is measured to be GeV, which is the most precise ATLAS measurement from a single channel
Targeting interferon responses in juvenile dermatomyositis: Siglec-1 as an in vitro biomarker for JAK inhibitor efficacy.
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322835.pdf (Publisher’s version ) (Open Access)OBJECTIVES: For IFN-driven diseases, such as juvenile dermatomyositis (JDM), there is a critical need for targeted therapies. We aimed to develop an in vitro model, using Siglec-1 as read-out, to evaluate inhibition of IFN-mediated responses with different JAK inhibitors (JAKi). METHODS: Healthy donor (HD) PBMCs were cultured with type I and II IFNs, TLR agonists and plasma or serum from patients (JDM, DM, JSLE, COVID-19) and HDs. Siglec-1 expression on CD14+ monocytes was analyzed using flow cytometry. Inhibitory assays involved pre-incubation with JAKi (filgotinib, tofacitinib, baricitinib, ruxolitinib, deucravacitinib) and interferon-α/β receptor (IFNAR)-blocking antibody. Correlations between plasma-induced Siglec-1 levels and clinical disease activity were analyzed in JDM patients, as well as correlations with IFN-α and -β plasma levels. RESULTS: Siglec-1 was induced after 18 h of stimulation with type I IFNs and TLR-3/7/9 agonists, with minimal induction by IFN-γ. IFNAR blockade prevented type I IFN- and TLR-mediated induction. JAKi inhibited Siglec-1 induction by IFN-α and -β in a dose-dependent manner. Co-culture with plasma or serum from patients with IFN-driven diseases induced Siglec-1 expression on healthy monocytes, which could be inhibited by JAKi and IFNAR blockade. Siglec-1 levels induced by JDM plasma correlated strongly with clinical disease activity and IFN-β plasma levels. CONCLUSION: Siglec-1 is an easy and reliable in vitro marker for type I IFN responses. Its induction can be inhibited by JAKi. The type I IFN signature in JDM is likely predominantly driven by IFN-β. This assay holds promise for precision treatment strategies in JDM and other IFN-driven diseases
Intercostal or Paravertebral Block vs Thoracic Epidural in Lung Surgery: A Randomized Noninferiority Trial
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322938.pdf (Publisher’s version ) (Closed access)25 juni 202510 p
No effect of additional education on long-term brain structure, a preregistered natural experiment in thousands of individuals
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321842.pdf (Publisher’s version ) (Open Access)19 p
Long-term effects of BCG vaccination on telomere length and telomerase activity.
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322301.pdf (Publisher’s version ) (Open Access)This study explores the effects of Bacillus Calmette-Guérin (BCG) vaccination on telomere maintenance, an aging-related process, in immune cells. While BCG reduces systemic inflammation and enhances innate immune responsiveness by inducing trained immunity, its effects on other immune aging hallmarks, such as telomere shortening, are not fully understood. We assessed telomere length in two independent human cohorts before and three months after BCG vaccination. Telomere shortening was consistently observed after BCG, but not after placebo vaccination. Trained immunity non-responders were likelier to lose telomere length, but only among males. Higher pre-vaccination testosterone levels were associated with greater telomere loss in males. In vitro, BCG training activated telomerase, particularly in females, and this was partially prevented by exogenous testosterone. These findings suggest BCG vaccination influences telomere dynamics in a sex-specific manner, contributing to understanding BCG's broader effects on aging-related processes
A family affair: Repeated interviews with people with dementia and a euthanasia wish and their families.
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323905.pdf (Publisher’s version ) (Open Access)This study examines the reasons of people with dementia request euthanasia and how these reasons change over time with a special focus on reasons related to family. In addition, it examines how family relates to their loved one's euthanasia wish. Seven people with dementia and a euthanasia wish in the Netherlands were interviewed, and three years later, two of them and five family members were interviewed again. Four themes were identified using thematic analyses: (1) Protecting the relationship from the impact of dementia; (2) Private domain as the primary setting to discuss euthanasia; (3) Implicit expectation to respect and agree with the euthanasia wish; (4) Experienced responsibilities of family regarding the euthanasia wish. Professionals should be aware of the position of family and the interrelatedness of the person's concern for family happiness and families' moral commitment to agree and support the wish
Semi-automated three-dimensional analysis of maxillary anomalies in patients with Muenke syndrome, Saethre-Chotzen syndrome or<i> TCF12</i>-related craniosynostosis: A retrospective study
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321827.pdf (Publisher’s version ) (Open Access)8 p
Assessing the MUC5B promoter variant in a large cohort of systemic sclerosis-associated interstitial lung disease
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324623.pdf (Publisher’s version ) (Open Access)OBJECTIVE: The common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date. METHODS: Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their association in a meta-analysis to increase the consistency of the results, including 10 European ancestry cohorts comprising 2363 patients with SSc-ILD, 3526 SSc patients without ILD and 15 076 controls. RESULTS: Meta-analysis showed no significant association between rs35705950 and SSc-ILD, either comparing patients with SSc with and without ILD (p value: 0.588, OR: 1.05, 95% CI: 0.87 to 1.27) nor patients with SSc-ILD with controls (p value: 0.061, OR: 1.16, 95% CI: 0.99 to 1.36). Moreover, none of the additional 903 variants tested in the genomic region reached statistical significance. CONCLUSION: Despite analysing the largest and most statistically powered SSc-ILD cohort to date, we found no evidence of association between the MUC5B promoter variant rs35705950 and its surrounding SNPs with SSc-ILD. These results suggest that the pathogenic mechanisms underlying SSc-ILD may only partially overlap with those of other similar ILDs, such as IPF or RA-ILD. This highlights the need for further studies regarding their genetic architecture
Rewriting Global Orthodoxy: Contemporary Oriental Orthodox Textual Traditions in Europe
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324700.pdf (Publisher’s version ) (Open Access