Gutenberg Open Science (Univ. Mainz)
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Implementierung des da Vinci Single-Port Robotersystems in der Klinik für Allgemein-, Viszeral- und Transplantationschirurgie der Universitätsmedizin Mainz
Full text link62 Seiten ; Diagramm
Islamophobia in Western Europe is unrelated to religiosity but highly correlated with far right attitudes
Full text linkThe far right’s relationship with religion has become a major focus of current research. Even in Western Europe, one of the most rapidly secularising areas of the world, far right actors claim to defend Christian values against the alleged threat of Islam and Muslim immigrants, a rhetorical strategy known as ‘Christianism’. Yet, little is known about how religiosity, Islamophobia, and populist far-right ideology are connected at the level of mass belief systems in Western Europe. Most of the literature is focused either on religiosity’s effect on voting or on the connection between religiosity and ethnic prejudice, without considering religiosity’s relationships with the wider spectrum of far-right ideology. The present article fills this gap by analysing survey data from Britain, France, Germany, and the Netherlands. It uses SEM to uncover the relationships between Christian religiosity on the one hand and Islamophobia and far-right attitudes on the other. The results are broadly similar across different contexts: religiosity is mostly unrelated to Islamophobia, nativism, right-wing authoritarianism, and populism. Conversely, Islamophobia overlaps considerably with both nativism and authoritarianism: people who perceive immigration as a threat and favour strict laws and harsh enforcement also tend to reject Islam, but not for religious reasons. This pattern is compatible with the strategy of Christianism, which is largely devoid of religiosity, yet facilitates the “othering” of Muslims as a cultural out-group. It also helps to explain why there is no genuine, electorally relevant religious far right in Western Europe
Einfluss unterschiedlicher Wirkmechanismen der oralen Antikoagulation auf das Rekanalisationsergebnis der mechanischen Thrombektomie bei zerebralem Großgefäßverschluss – Eine retrospektive Analyse des German Stroke Registry
No full textZusammenfassung
Hintergrund:
Die mechanische Thrombektomie (MT) ist eine wirksame Behandlungsmethode bei ischämischen Schlaganfällen mit Großgefäßverschluss. Gleichzeitig stellt die prästa-tionäre orale Antikoagulation (OAK) mit direkten oralen Antikoagulantien (DOAK), wie Thrombininhibitoren (Dabigatran) und Faktor-Xa-Inhibitoren, eine zentrale Strategie in der Sekundärprävention von Schlaganfällen bei Patienten mit Vorhofflimmern dar. Es bleibt jedoch unklar, wie sich eine bestehende OAK auf die Sicherheit und Effekti-vität der MT auswirkt.
Zielsetzung:
Ziel der Arbeit war es, den Einfluss einer antikoagulatorischen Vortherapie auf die Erfolgsrate der MT, das funktionelle Outcome, sowie die periprozeduralen Komplika-tionen zu untersuchen. Dabei wurde ein Vergleich zwischen Dabigatran und
Faktor-Xa-Inhibitoren durchgeführt.
Methodik:
Es wurden retrospektiv 1.906 Patient*innen aus dem „German Stroke Registry-Endovascular Treatment“ (GSR-ET) analysiert, die aufgrund eines ischämischen Schlaganfalls mit MT behandelt wurden. Die Kohorte umfasste 146 Patient*innen mit Dabigatran und 1.760 Patient*innen mit Faktor-Xa- Inhibitoren. Analysiert wurden die prozeduralen Erfolgsraten, funktionelle Outcomes (modifizierte Rankin-Skala, mRS), Sicherheitsparameter (z. B. symptomatische intrakranielle Blutungen, sICH) und Komplikationen.
Ergebnisse:
Die Erfolgsrate der MT, gemessen am mTICI-Score (≥2b), zeigte keine signifikanten Unterschiede zwischen Dabigatran und Faktor- Xa-Inhibitoren. Auch in Bezug auf periprozedurale Komplikationen, wie sICH und maligne Mediainfarkte, zeigten sich keine signifikanten Unterschiede. Das funktionelle Outcome (mRS ≤2 nach 90 Tagen) war zwischen den beiden Gruppen vergleichbar, wobei patientenspezifische Fakto-ren wie Alter und Komorbiditäten eine wesentliche Rolle spielten. Schlussfolgerung: Eine antikoagulatorische Vortherapie mit Dabigatran oder Faktor-Xa-Inhibitoren scheint die Sicherheit und Effektivität der MT nicht wesentlich zu beeinträchtigen. Aufgrund des fehlenden Vergleichs mit einer DOAK-freien Kontrollgruppe lassen sich jedoch keine
abschließenden Aussagen über den generellen Einfluss einer OAK auf die MT tref-fen. Die höhere Rate an begleitender Thrombolyse in der Dabigatran-Gruppe sollte bei der Interpretation der Ergebnisse berücksichtigt werden. Weitere Studien sind notwendig, um die optimale antikoagulatorische Strategie im Kontext der MT zu defi-niereVI, 80 Seiten ; Illustrationen, Diagramm
Type 1 diabetes and other autoimmune diseases : epidemiology, pathophysiology and screening
No full textIntroduction:
The interplay between type 1 diabetes (T1D) and concomitant autoimmune diseases (AID) is both clinically and scientifically relevant. In this review, we delineate the epidemiological, pathophysiological and practical aspects underlying polyautoimmunity with a focus on T1D.
Method:
A comprehensive review of literature on T1D and associated AID was conducted, with the aim of drawing informed conclusions relevant to clinical practice. It draws on a targeted PubMed search conducted March–May 2025, emphasising recent peer-reviewed articles in English.
Results:
Epidemiological data consistently indicate that individuals with T1D exhibit a significantly increased prevalence of additional AID. Familial aggregation of discordant AID and the concept of polyglandular autoimmune syndromes (PAS) or autoimmune polyendocrinopathy highlight that multiple AID can cluster and occur in a sequential and overlapping fashion, with T1D frequently acting as either an early or a subsequent manifestation. Thereby, genetic susceptibility, environmental triggers and epigenetic factors are pivotal in the initiation and progression of autoimmunity. Clinically, the coexistence of T1D with other AID poses significant challenges in disease management, often necessitating adjustments in therapeutic regimens and careful monitoring to mitigate complications. Early detection via stratified autoantibody testing is important for timely intervention and improved long-term outcomes.
Conclusions:
Accordingly, screening for T1D-associated autoantibodies in individuals with a personal or family history of AIDs, and vice versa, should be implemented in clinical practice
Inflammatory stromal and T cells mediate human bone marrow niche remodeling in clonal hematopoiesis and myelodysplasia
No full textSomatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP) and progression to myelodysplastic syndromes (MDS). Using single-cell and anatomical profiling of a large cohort of human bone marrow (BM), we show that the HSPC BM niche in CHIP and MDS is undergoing inflammatory remodeling. This includes loss of CXCL12⁺ adipogenic stromal cells and the emergence of a distinct population of inflammatory mesenchymal stromal cells (iMSCs), which arise in CHIP and become more prevalent in MDS. Functional studies in primary BM HSPC-MSC co-cultures reveals that healthy aged and CHIP HSPCs activate stromal support, while MDS HSPCs fail to do so. In contrast, MDS blasts further suppress HSPC support and trigger inflammation, indicating disease-stage-specific stromal disruption. In parallel, we show that iMSCs retain partial support and angiogenic potential in MDS, coinciding with expanded BM vasculature. Additionally, we identify IFN-responsive T cells that preferentially interact with iMSCs, potentially reinforcing local inflammation. These findings position iMSCs as central mediators of early BM niche dysfunction and potential therapeutic targets for intercepting pre-malignant hematopoiesis
Protocol for the differentiation of induced pluripotent stem cells into retinal pigment epithelial cells
No full textInduced pluripotent stem cells (iPSCs) are emerging as a valuable system for modeling tissues and organs. Here, we describe a highly scalable protocol for the differentiation of iPSCs into retinal pigment epithelium (RPE), including a new step that makes it easier for researchers to obtain a high-purity culture. We also describe a cryopreservation technique for RPE progenitor cells to enable their storage. The use of cryopreserved cells allows a subsequent reduction in differentiation time compared to the full protocol
Digital and AI-assisted multimodal supportive care, combining physical activity, nutrition, and pain management during chemotherapy for advanced pancreatic cancer patients : study protocol of the European multicenter randomized controlled trial of the RELEVIUM project
No full textBackground
Multimodal care, including nutritional support, physical exercise, and pain management, is essential to address complex therapeutic challenges in advanced pancreatic cancer. There is an increasing prevalence worldwide in pancreatic cancer and the disease is often diagnosed late leading to limited treatment options and poor prognosis. Advanced pancreatic cancer patients experience a wide range of adverse symptoms that affect their quality of life and require comprehensive and interdisciplinary patient care early in treatment. Integrating digital health, particularly through remote monitoring, plays a vital role in addressing the therapeutic challenges and improving data-driven clinical decision-making. Therefore, the European project RELEVIUM examines the effect of a personalized, digitally assisted multimodal supportive care intervention on health-related quality of life in patients with pancreatic cancer aiming to improve early access to multidisciplinary, cost-effective palliative care.
Methods
In cancer centers in Estonia, Israel, and Germany, 132 patients will be randomly assigned in the prospective randomized controlled trial RELEVIUM-RCT into two groups. Both groups receive standard chemotherapy. The control group follows usual care, while the intervention group receives personalized, digitally assisted multimodal support integrated into usual care. The intervention includes guidance and monitoring on pain, nutrition, fatigue, sarcopenia, and physical activity. Patients track their physical activities, nutritional behavior and rate pain and fatigue daily via a smartwatch and mobile app. The physician analyses these longitudinal data on a dashboard and counsels the patients every two weeks during clinical visits, assisted by an interdisciplinary team and digital support system. The primary endpoint of the study is health-related quality of life including factors such as time until a definitive deterioration in selected dimensions (physical functioning and/or appetite loss) assessed at 8 weeks. Secondary endpoints include longitudinal analyses of efficacy related to pain, physical function, nutrition, sarcopenia, and socioeconomic factors.
Discussion
The RELEVIUM-RCT investigates the efficacy of digital health support for individuals with advanced pancreatic cancer in conjunction with conventional treatments in three European countries. Longitudinal data on the interplay of chemotherapy toxicity, fatigue, pain, physical activity, and nutrition will provide valuable extended insights on multimodal pancreatic cancer care. Moreover, this data can help demonstrate the benefits of digital health in clinical decision-making, ultimately contributing to improved quality of care in Europe
Einfluss der Phosphoinositid-Biosynthese auf Lokalisation und Toxizität von Alpha-Synuclein in Saccharomyces cerevisiae
No full text169 Seiten ; Illustrationen, Diagramm
Early recurrence of atrial arrhythmia following catheter ablation of atrial tachycardia consecutive to ablation of atrial fibrillation using the updated blanking period
No full textBackground:
In patients undergoing catheter ablation of atrial fibrillation (AF), arrhythmia recurrence during the blanking period is usually not considered a failure of treatment. The prognostic significance of early recurrence (ER) of atrial arrhythmia after ablation of atrial tachycardia (AT) subsequent to AF ablation is less certain.
Objective:
This study aimed to explore the association between early and late recurrence of atrial arrhythmia after ablation of AT subsequent to AF ablation.
Methods:
Patients undergoing a first ablation of AT subsequent to AF ablation between 2015 and 2021 were included in this retrospective, single-center, observational cohort study. Recurrent atrial arrhythmia was defined as AT or AF lasting more than 30 seconds. Regression models were built to assess the association between early (within 56 days) and late (beyond 56 days) recurrence of AT.
Results:
A total of 194 patients were included (mean age 67 ± 10 years, 63% male), of whom 71 (37%) had pulmonary vein isolation only, and 123 (63%) had received complex AF ablation during their index procedure. Fifty-two patients (27%) had ER of atrial arrhythmia. During a mean follow-up of 23.6 ± 15.5 months, 118 patients (61%) had late recurrence of atrial arrhythmia (111 with AT, 7 with AF). ER was associated with late recurrence (hazard ratio 1.53; 95% confidence interval 1.05–2.34; P = .02).
Conclusion:
One in 4 patients undergoing catheter ablation of AT subsequent to AF ablation had recurrent atrial arrhythmia within 56 days after ablation. ER was associated with late recurrence of atrial arrhythmia
Neue Syntheserouten und -methoden zur Herstellung von N-Heterozyklen für Pharmaka und mRNA-Therapeutika
No full textDie vorliegende Arbeit befasst sich mit drei unterschiedlichen Themenbereichen: Im ersten Teil wird
sich mit der Ausarbeitung neuer Synthesewege für bestehende N-heterozyklische Pharmazeutika und
pharmazeutischen Bausteinen befasst. Im zweiten Teil liegt der Fokus auf der Anwendung von
ω-Azidotriflaten in der Synthese von γ- und δ-Lactamen und im dritten Teil auf der Entwicklung
kationisch ionisierbarer Lipide für den mRNA-Transport in Lipid Nanopartikeln (LNP).
Bei der Entwicklung neuer Synthesewege für Pharmazeutika lag der Fokus zunächst darauf, eine neue
und innovative Synthese für das Benzodiazepin Midazolam auszuarbeiten. Dabei sollte eine möglichst
kurze Route mit einer guten Atomökonomie entwickelt werden. Zuerst werden unterschiedliche
Syntheseansätze und dann die erfolgreich erarbeite Syntheseroute für Midazolam durch eine MICHAEL-Addition gefolgt von einer Zyklisierung zum Siebenring durch eine Reduktion gezeigt.
Im folgenden Kapitel werden die Versuche zur Substitution von Bromacetonitril in der Synthese eines
Fragmentes des Coronamedikaments Nirmatrelvir beschrieben. Dabei wurden viele synthetisierte und
kommerziell erhältliche Reagenzien zur Substitution von Bromacetonitril getestet. Schließlich wurde
eine Synthesestrategie entwickelt, die Bromacetonitril durch 2-Azidoethyltrifluormethansulfonat
ersetzt und eine innovative Flow-Reduktion zur Synthese des Nirmatrelvirbausteins Methyl (S)-2-((tert-butoxycarbonyl)amino)-3-((S)-2-oxopyrrolidin-3-yl)propanoate beinhaltet.
Im zweiten Teil wird die erarbeitete Methode zur Synthese des Nirmatrelvirbausteins aufgegriffen und
daraus eine neue Methode zur Synthese von 3-substituierten Pyrrolidonen und Piperidonen
entwickelt. Dabei wurden Methylester über eine α-Alkylierung mit 2-Azidoethyltrifluormethansulfonat
oder 3-Azidopropyltrifluormethansulfonat zu Azidoestern umgesetzt und durch eine Reduktion zum
Amin zum jeweilige δ-Lactam oder γ-Lactam zyklisiert. Es wird die Optimierung der Methode und das
getestete Substratspektrum gezeigt.
Der dritte Teil dieser Arbeit beschäftigt sich mit der Entwicklung neuer kationisch ionisierbarer Lipide
mit Pyridinen und Benzolen als „Tail-junction“. Des Weiteren lag der Fokus darauf Schwefel in die
„Tails“ der Lipide einzubauen. Die Lipide wurden im Rahmen des KIWI-Projektes vom Projektpartner
bei BioNTech in bereits bestehenden LNP-Formulierungen verwendet und hinsichtlich ihrer Fähigkeit
mRNA zu transportieren getestet. Anhand der Ergebnisse der Biotests wurden die Strukturen der
Lipide als Teil des ZiEL-Unterprojektes weiterentwickelt.XIII, 423 Seiten ; Illustrationen, Diagramm