Driving gigs in Oman: women and techno-fixes in the platform economy

Middle Eastern Studie

Absence of functional autoantibodies targeting angiotensin II receptor type 1 and endothelin-1 type A receptor in circulation and purified IgG from patients with systemic sclerosis

Objective. Systemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. Although previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II receptor type 1 (AT1) and endothelin-1 type A receptor (ETAR), leading to autoantibodymediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays. Our aim was to replicate previous findings and to investigate the functional effects of IgG derived from patients with SSc (SSc IgG) on AT1 and ETAR signaling, the downstream EC response, and the presence of AT1-binding autoantibodies in circulation. Methods. Quantitative polymerase chain reaction and cytokine enzyme-linked immunosorbent assay, alongside a real-time cell analyzer, were used to assess receptor-specific functional characteristics of purified SSc IgG (n = 18). Additionally, a novel protein capture assay using solubilized epitope-tagged AT1 was developed to detect AT1-binding autoantibodies in plasma samples from patients with SSc (n = 28) and healthy donors (n = 14). Results. No evidence for EC activation in an AT1- or ETAR-dependent manner was revealed. Furthermore, stimulation with SSc IgG did not induce receptor activation or alter G protein-coupled receptor signaling on agonist stimulation in a model with receptor overexpression. Lastly, no AT1-binding autoantibodies were detected in plasma samples from patients with SSc when using epitope-tagged solubilized AT1. Conclusion. Overall, our study did not provide evidence to support the presence of AT1- or ETAR-activating autoantibodies in purified SSc IgG or AT1-binding autoantibodies in the circulation of patients with SSc.</p

Surfactin facilitates establishment of Bacillus subtilis in synthetic communities

Microbial Biotechnolog

Submission on the European Commission Art. 28 draft guidelines

Effective Protection of Fundamental Rights in a pluralist worl

Draft genome sequences of a novel Escherichia coli K-12 MG1655 L-form strain and its evolved variant

Microbial Biotechnolog

Towards appropriate care in old-age medicine: exploring the professional identity of medical students and doctors in relation to older persons

The community of practice of medical care is guided by the social contract with society in which doctors serve the needs of their patients. Given that health problems in older age differ from those of younger patients the growing population of older persons leads to a change in society’s healthcare expectations and needs regarding the doctor. Therefore medical school and curriculum committees have the responsibility to create medical education that prepares medical students for older persons’ health care.Becoming a doctor is an interplay of building competencies and the development of a professional identity. To prepare medical students for older persons’ health care geriatric competencies have been defined. As the development of a professional identity is considered a fundamental attribute for becoming a doctor, an appropriate professional identity will help medical students to become a doctor capable of providing the health care that older people need.The objective of this thesis is to gain insight in the professional identity formation of medical students in relation to older persons’ health care and describes the essential elements of the professional identity and its formation that enables future doctors to give older persons the health care they need. LUMC / Geneeskund

Representativeness of surgical controls in aortic valve replacement trials: comparison with routine surgical cohorts

Background Randomised controlled trials (RCTs) comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have significantly influenced treatment guidelines for aortic stenosis, expanding the use of TAVI into lower risk populations. However, the patients enrolled in the SAVR arms of these trials may differ from those typically undergoing SAVR in routine clinical practice. This study aims to critically assess the representativeness of SAVR patients in these RCTs by comparing their characteristics and outcomes to those of patients undergoing SAVR in routine clinical practice.Methods A systematic literature review was conducted across PubMed, Embase, Web of Science, Emcare and the Cochrane Library, focusing on RCTs and large prospective studies (n≥500 SAVR patients), enrolling low-risk or intermediate-risk patients since 2010. Patient characteristics, early outcomes and 5-year survival were compared between RCT SAVR cohorts and those treated in routine clinical practice settings. Meta-analyses of pooled data and reconstructed Kaplan-Meier survival analyses were performed, with stratification by risk category.Results Nineteen studies (9 RCTs and 10 studies describing routine clinical practice), encompassing 74 797 SAVR patients, were included. SAVR patients in routine clinical practice demonstrated comparable early mortality to SAVR patients in RCTs but experienced fewer periprocedural complications, including lower rates of stroke, pacemaker implantation and myocardial infarction. At 5 years, overall survival was notably higher in patients treated in routine clinical practice compared to those in the SAVR arms of RCTs, both for low-risk (HR 0.64, 95% CI 0.55 to 0.75) and intermediate-risk patients (HR 0.55, 95% CI 0.470.64).Conclusions Compared with typical SAVR patients treated in routine practice, RCT SAVR patients experienced higher complication rates and worse long-term survival, despite similar or lower surgical risk scores. These findings question the external validity of SAVR versus TAVI trials.Thoracic Surger

Immune cell networks in Inflammatory Bowel Disease: towards novel therapeutic approaches

Inflammatory bowel disease (IBD), comprising of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract characterized by a relapse-remitting disease course. Although treatment options—such as biologics and small molecule therapies—have expanded, many patients still experience poor or diminishing responses and side effects. This variability in how patients respond to treatment might be due to differences in the underlying biology of their disease. Currently, IBD treatment follows a "one-size-fits-all" approach. Comprehensive profiling of the cellular immune system in IBD enhances patient classification and might aid in the development of personalized strategies. In this thesis, we applied multidimensional technologies, such as single-cell mass cytometry, imaging-mass cytometry and spectral flow cytometry on intestinal tissue, fistula scraping and blood samples from patients with IBD and controls to gain a more comprehensive understanding of the immunological components involved in this disease. We also explored the microbial composition of perianal fistulas to distinguish between CD-associated and cryptoglandular fistulas. In patients with ulcerative proctitis, we investigated the local injection of allogeneic mesenchymal stromal cells (MSCs) as a novel therapy. MSC treatment was found to be safe, feasible, and associated with changes in the tissue immune environment.ChipsoftLUMC / Geneeskund

The ascending arousal system and its impact on cognition

Arousal plays a crucial role in how our brain functions, influencing thoughts, emotions, and behaviour. It fluctuates throughout the day and is driven by four major neurotransmitter systems: the noradrenergic, cholinergic, serotonergic and dopaminergic systems. These systems together form the ascending arousal system. This thesis explored arousal from three angles: tracking natural fluctuations, modulating arousal with brain stimulation, and examining its impact on memory. The first part of this thesis examined natural fluctuations in arousal at rest. By simultaneously measuring pupil size and brain activity, we found that pupil changes reflect activity across the broader arousal system—not just the noradrenergic locus coeruleus, but also dopamine-, serotonin-, and acetylcholine-related regions. The second part tested whether transcutaneous vagus nerve stimulation (tVNS), a non-invasive technique delivering mild electrical stimulation to the ear, can modulate arousal. While tVNS increased pupil size, suggesting elevated arousal, it did not reliably alter brain activity or motivation, indicating that more research is needed to understand its effects. The final section explored how arousal impacts memory. We tested whether anticipating a reward during learning boosts memory performance. Reward anticipation increased arousal, as shown by pupil size and brain activity, and was associated with improved memory for reward-related items.Action Contro

Beyond the paradigm of unity: embedded minilateralism in European foreign policy

History and International Studies 1900-presentInstitutions, Decisions and Collective Behaviou