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Multicentre, 26-week, open-label phase 2 trial of the JAK inhibitor filgotinib in Behçet's disease, idiopathic inflammatory myopathies and IgG4-related disease: DRIMID study protocol.
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316993.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) faces significant challenges, including small patient populations, complex clinical trial design and difficulties in patient recruitment. Patients with Behçet's disease (BD), idiopathic inflammatory myopathies (IIM) and IgG4-related disease (IgG4-RD) typically undergo treatment involving prolonged administration of high-dose glucocorticoids and immunosuppressants. Both are associated with an increased risk of infection. Additionally, glucocorticoids carry long-term toxicity risks. Thus, there is an urgent need to develop more targeted and effective anti-inflammatory treatments. Given the activation of the type 1 interferon pathway in BD, IIM and IgG4-RD, inhibition of the Janus kinase (JAK) STAT pathway emerges as a promising therapeutic strategy. The Drug Rediscovery in IMIDs (DRIMID) consortium aims to conduct a prospective pilot basket trial to investigate the effects of filgotinib, a JAK1 preferential inhibitor approved for ulcerative colitis and rheumatoid arthritis, on disease activity, quality of life and safety in patients with refractory BD, IIM and IgG4-RD. METHODS AND ANALYSIS: In this investigator-initiated, multicentre, open-label phase 2 study, up to 60 patients with rare IMIDs will be enrolled for a 26-week treatment period with filgotinib 200 mg once daily. The trial consists of two stages, each involving a consecutively treated cohort of up to 20 patients per disease. An interim analysis is conducted between these stages, where the trial will proceed only in diseases showing potential effectiveness. Baseline, 3-month and 6-month assessments will include data on quality of life, disease activity, corticosteroid toxicity and biomarkers. The coprimary endpoints are disease activity and quality of life across and within each disease. ETHICS AND DISSEMINATION: The study received approval from the Medical Research Ethics Committee in Utrecht, Netherlands. A Data Safety Monitoring Board has been established to monitor the trial's safety and progress. TRIAL REGISTRATION NUMBER: NCT06285539
Internationale Bildungskooperationsforschung im Fach Deutsch als Fremdsprache: Annäherung an ein Forschungsfeld
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313418.pdf (Publisher’s version ) (Open Access
The King and the Individual or the Individual King in Parthian Art. Hung-e Azhar, Hatra, and beyond
No full textItem does not contain fulltextCarving the individual; self-representations in Parthian rock art, 06 maart 2025Invited lectur
A commentary on Bazzoli (2024): Toward a nuanced and rigorous model evaluation
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311292.pdf (Publisher’s version ) (Open Access)11 p
With A Little Help From Your Friends: Semi-Cooperative Games Via Joker Moves
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317942.pdf (Publisher’s version ) (Open Access
Flattening Combinations of Arrays and Records
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317292.pdf (Publisher’s version ) (Open Access)TFP 202
Daytime sleepiness and health-related quality of life in patients with childhood-onset craniopharyngioma.
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317765.pdf (Publisher’s version ) (Open Access)Overall survival rates after craniopharyngioma (CP) are high (92%), but frequently quality of life (QoL) is impaired in patients with CP involving hypothalamic structures. Tumour- and/or treatment-related hypothalamic lesions may result in disturbances of circadian rhythms including increased daytime sleepiness. We investigated the relationship between health-related QoL and daytime sleepiness in patients with childhood-onset CP. After a median follow-up of 10 years (range: 1-39), 119 CP patients (63 female), who were recruited 2000-2022 in the KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 trials, were assessed for daytime sleepiness using the Epworth Sleepiness Scale (ESS) and for QoL by EORTC QLQ-C30 questionnaire. CP patients with increased daytime sleepiness (ESS score > 10, n = 34) had worse self-assessment of QoL (p = 0.003), when compared to CP patients with normal ESS scores (n = 85). Increased daytime sleepiness was negatively correlated with QoL (r=-0.395; p < 0.001). Surgical hypothalamic lesions, detectable after surgical intervention in 92.9% of the reference-assessed patients, were associated with significantly higher ESS scores, whereas such impact could not be observed for presurgical hypothalamic involvement of the CP (72.4% of the reference-assessed patients). Compared to patients with an ESS score in the normal range, patients with increased daytime sleepiness suffered from impaired QoL in all functional scales and the global QoL scale of the EORTC QLQ-C30. As increased daytime sleepiness plays an important role for QoL in survivors of CP, hypothalamus-sparing surgical treatment strategies should be considered as state of the art in patients with CP for prevention of increased daytime sleepiness.Clinical trial registration NCT01272622; NCT04158284, NCT00258453
Ultrasound Strain Imaging for Characterizing Atherosclerotic Plaque in the Carotid Arteries of Asymptomatic Subjects.
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314655.pdf (Publisher’s version ) (Open Access)OBJECTIVE: The rupture of vulnerable plaques in the carotid artery is a leading cause of strokes. While magnetic resonance imaging (MRI) is the standard for quantifying plaque composition, its high costs and lengthy procedure times limit large-scale use. Compound ultrasound strain imaging (CUSI) ultrasound offers a non-invasively alternative by assessing tissue deformation/strain within the arterial wall. Previous studies have demonstrated the relationship between strain values and plaque composition, primarily focusing on longitudinal acquisitions, which only image the proximal and distal parts of the wall. This study examines CUSI in transverse imaging planes, which enables visualization of the entire cross-section of the vessel wall. CUSI has already been validated on a symptomatic population. Therefore, the aim is to determine whether CUSI can differentiate plaque composition in asymptomatic individuals with an increased cardiovascular risk profile, validated by MRI. METHODS: This cross-sectional study included 42 plaques in 28 participants. Ultrasound data were acquired with a Samsung Medison Accuvix V10 with an L5-13IS transducer and RF-interface. An experienced neuroradiologist classified plaques with MRI using the Siemens 3.0T MAGNETOM Skyra MRI (Erlangen, Germany) with a dedicated coil. Strain differences were compared across four plaque categories (calcified, lipid, hemorrhagic, fibrous/aspecific) and for vulnerable versus stable plaques. RESULTS: A difference in strain values was found between lipid and calcified plaques (Kruskal-Wallis test, p < 0.05). Additionally, vulnerable plaques exhibited higher strain values than stable plaques (independent samples test, p < 0.05). CONCLUSION: CUSI values differ between lipid and calcified and between stable and vulnerable plaques. Minor differences were found between the other plaque types.01 februari 202
Solar flare observations with the Radio Neutrino Observatory Greenland (RNO-G)
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309800.pdf (Publisher’s version ) (Open Access
The impact on astrometry by solar-wind effect in pulsar timing
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314507.pdf (Publisher’s version ) (Open Access