University of Augsburg

Aortic dissection continues to be responsible for significant morbidity and mortality, although recent advances in medical data assimilation and in experimental and in silico models have improved our understanding of the initiation and progression of the accumulation of blood within the aortic wall. Hence, there remains a pressing necessity for innovative and enhanced models to more accurately characterize the associated pathological changes. Early on, experimental models were employed to uncover mechanisms in aortic dissection, such as hemodynamic factors and alterations in wall microstructure, and to assess the efficacy of medical implants. While experimental models were once the only option available, more recently they are also being used to validate in silico models. Based on an improved understanding of the deteriorated microstructure of the aortic wall, numerous multi-scale computational models have been proposed in recent decades to study the state of stress in dissected aortas, including the changes associated with damage and failure. Furthermore, when integrated with accessible patient-derived medical data, in silico models prove to be an invaluable tool for identifying correlations between hemodynamics, wall stresses, or thrombus formation in the deteriorated aortic wall. They are also advantageous for model-guided design of medical implants with the aim of evaluating the deployment and migration of implants in patients. Nonetheless, the utility of these in silico models depends largely on patient-derived medical data, such as chosen boundary conditions or tissue properties. In this review article, our objective is to provide a thorough summary of medical data elucidating the pathological alterations associated with this disease. Concurrently, we aim to assess experimental models, as well as multi-scale material and patient data-informed in silico models, that investigate various aspects of aortic dissection. In conclusion, we present a discourse on future perspectives, encompassing aspects of disease modeling, numerical challenges, and clinical applications, with a particular focus on aortic dissection. The aspiration is to inspire future studies, deepen our comprehension of the disease, and ultimately shape clinical care and treatment decisions.

A growing number of studies aim to evaluate gastrointestinal (GI) endoscopy services from the perspective of their environmental impact. However, there are currently no guidelines or frameworks which provide specifically for the reporting of endoscopy sustainability studies, and a variety of metrics and assessment tools have been employed in the literature. To improve the clarity, transparency, and quality of reporting, the European Society of Gastrointestinal Endoscopy (ESGE) has developed a reporting framework for the community of researchers interested in conducting studies on sustainable GI endoscopy. ‡ Joint first authors * Joint senior authors

Resilience is a concept addressing states’ reactions to external shocks. For Ukraine, stabilizing its legal system is one of the critical components of successful accession to the EU. The research focuses on the impacts of legislative and regulatory approximation for ensuring the resilience and stability of Ukraine’s legal system. The question of how the Ukrainian legal system will manage these two external pressures is vital from practical and theoretical perspectives. From a practical perspective, it is crucial to understand which features of the Ukrainian legal system will trigger progress in gaining access to the EU. From a theoretical perspective, the research question is what elements make the Ukrainian legal system resilient during wartime and what needs to be prioritized during the post-war recovery. Resilience is quite a new concept that has colonized policy-making and political agenda discourses worldwide, focusing predominantly on political and economic aspects. In contrast, the legal pattern remains largely not covered, or as Ruhl et al. (Multisystemic Resilience: Adaptation and Transformation in Changing Contexts, Oxford University Press, 2021) notice, legal theory has just started to conceptualize resilience to legal systems. This research will focus on the current state of Ukraine’s cooperation with the EU as part of the broader debate on ensuring stability and strengthening resilience in the region. The central hypothesis is that legislative and regulatory approximation is vital for ensuring the resilient resistance against Russia and stable progress on Ukraine’s road towards EU membership. The main tasks of the research are (1) to conceptualize Ukraine’s experiences in terms of the resilience debate and (2) to analyze Ukrainian practices for approximation in terms of ensuring the reform process and stability. The research results can also be used for policy development regarding EU-Ukraine relations for the EU and Ukrainian institutions. The methodology is based on desktop research, including the analysis of Ukrainian approximation practices at the level of relevant legislation, decisions of administrative bodies, and rulings of domestic constitutional and highest courts, as well as national doctrinal approaches to the peculiarities of the interaction between the domestic legal orders and the EU legal order.

Continuing the digital revolution, AI is capable to transform our world. Thanks to its novelty, we can define how we, as a society, envision this fascinating technology to integrate with existing processes. The EU AI Act follows a risk-based approach, and we argue that addressing the human influence, which poses risks along the AI lifecycle is crucial to ensure the desired quality of the model’s transition from research to reality. Therefore, we propose a holistic approach that aims to continuously guide the involved stakeholders’ mindset, namely developers and domain experts, among others towards Responsible AI (RAI) lifecycle management. Focusing on the development view with regard to regulation, our proposed four pillars comprise the well-known concepts of Generalizability, Adaptability and Translationality. In addition, we introduce Transversality (Welsch in Vernunft: Die Zeitgenössische Vernunftkritik Und Das Konzept der Transversalen Vernunft, Suhrkamp, Frankfurt am Main, 1995), aiming to capture the multifaceted concept of bias, and base the four pillars on Education, and Research. Overall, we aim to provide an application-oriented summary of RAI. Our goal is to distill RAI-related principles into a concise set of concepts that emphasize implementation quality. Concluding, we introduce the ethical foundation’s transition to an applicable ethos for RAI projects as part of on-going research.

Sex work and transactional sex (SWTS), as well as Chemsex, the intentional use of specific substances aiming to enhance sexual experiences among men who have sex with men (MSM), are associated with high-risk sexual behaviors including unprotected sex and injection drug use and are consequently associated to worse health outcomes, such as higher rates of several sexually transmitted infections (STIs). The main objective of this project was to investigate the prevalence of SWTS among chemsex users and analyze the factors influencing their health outcomes. We conducted an online survey in three European German-speaking countries, and the recruitment took place between March and December 2023 and was performed by convenience sampling, such as placing advertisements and flyering in public places. Eligible participants were MSM aged 18 years old or older who had been sexually active in the past 12 months. There were 399 sexually active MSM included and categorized into three sub-groups: 129 MSM engaging in chemsex (MSM-CX), 128 MSM engaging in sexualized substance use with non-chemsex substances (MSM-SSU), and 142 MSM not engaging in sexualized substance use (MSM-NSU). MSM-CX reported significantly higher rates of SWTS compared to both MSM-SSU (p = .032) and MSM-NSU (p < .001). Chemsex and SWTS were both individually associated with a higher prevalence of HIV (p < .001 and p = .042, respectively) and multiple STIs (p < .001 and p = .023, respectively), MSM-CX engaging in SWTS were younger (p = .006), had more sexual partners (p = .029), and reported significantly higher rates of use and sexualized use of several substances. However, among MSM-CX, SWTS were not significantly linked to higher rates on HIV (p = .702) or multiple STIs (p = .380). Our findings have shown that participants involved in chemsex and participants involved in SWTS face overall poorer health outcomes when compared with controls. The results underscore the need for targeted prevention and intervention measures that address these specific needs and risks of MSM-CX and SWTS. There is an urgent need for more representative studies as well as longitudinal studies on chemsex.

We investigated the clinical and functional role of the miR-106a-363 cluster in adult acute myeloid leukemia (AML). LAML miRNA-Seq TCGA analyses revealed that high expression of miR-106a-363 cluster members was associated with inferior survival, and miR-106a-5p and miR-20b-5p levels were significantly elevated in patients with adverse risk AML. Overexpression of the miR-106a-363 cluster and its individual members in a murine AML model significantly accelerated leukemogenesis. Proteomics analysis of leukemic bone marrow cells from these models emphasized the deregulation of proteins involved in intracellular transport, protein complex organization and mitochondrial function, driven predominantly by miR-106a-5p. These molecular alterations suggested mitochondrial activation as a potential mechanism for the observed increase in leukemogenicity. High-resolution respirometry and STED microscopy confirmed that miR-106a-5p enhances mitochondrial respiratory activity and increases mitochondrial volume. These findings demonstrate that the miR-106a-363 cluster, and particularly miR-106a-5p, contribute to AML progression through modulation of mitochondrial function and deregulation of mitochondria-coordinated pathways.

The spiral spin liquid (SSL) is a highly degenerate state characterized by a continuous contour or surface in reciprocal space spanned by a spiral propagation vector. Although the SSL state has been predicted in a number of various theoretical models, very few materials are so far experimentally identified to host such a state. Via combined single-crystal wide-angle and small-angle neutron scattering, we report observation of the SSL in the quasi-two-dimensional delafossite-like AgCrSe2. We show that it is a very close realization of the ideal Heisenberg J1–J2–J3 frustrated model on the triangular lattice. By supplementing our experimental results with microscopic spin-dynamics simulations, we demonstrate how such exotic magnetic states are driven by thermal fluctuations and exchange frustration.

Background Despite revolutionary efficacy of CD19-CAR-T cell therapy (CAR-T) in aggressive B cell lymphoma, many patients still relapse mostly early. In early failure, distinct drugs support CAR-T which makes reliable and early prediction of imminent relapse/refractoriness critical. A complete metabolic remission (CR) on Fluor-18-Deoxyglucose (FDG) Positron-Emission-Computed Tomography (PET) 30 days after CAR-T (PET30) strongly predicts progression-free survival (PFS), but still fails in a relevant proportion of patients. We aimed to identify additional routine parameters in PET evaluation to enhance CAR-T response prediction. Results Thirty patients with aggressive B cell lymphoma treated with CAR-T were retrospectively analyzed. Pre-CAR-T, LDH was the strongest PFS-predictor also by multivariate analysis. Post-CAR-T, 10 out of 14 patients (71.4%) with PET30-CR remained in disease remission, while 12 out of 16 patients (75%) with incomplete metabolic remission (PET30-nCR) relapsed after CAR-T. 28.6% of patients with PET30-CR ultimately progressed. Change of liver FDG-uptake from baseline to day30 (Delta-Liver-SUVmean) was identified as an independent biomarker for response. PET30-nCR and a decrease of Delta-Liver-SUVmean were associated with a high risk of tumor progression (HR 4.79 and 3.99, respectively). The combination of PET30 and Delta-Liver-SUVmean identified patients at very low, at intermediate and at very high risk of relapse (PFS not reached, 7.5 months, 1.5 months, respectively). Conclusion Additionally to PET30 metabolic remission, longitudinal metabolic changes in Delta-Liver-SUVmean predicted CAR-T efficiency. Our results may guide early intervention studies aiming to enhance CAR-T particularly in the very high-risk patients.

The article explores the legal and organizational aspects of autopsies in Germany. Despite their importance in clinical medicine, the number of clinical autopsies has been declining for decades due to work-related, organizational, and legal challenges. The COVID-19 pandemic led to a temporary resurgence of interest in autopsies, although this interest has since waned. Initiatives like the National Autopsy Network (NATON) and the National Autopsy Register (NAREG) have been established to promote research and quality assurance. Legally, autopsies in Germany are regulated at both federal and state levels. Variations in regulations between states, especially concerning consent and the definition of a corpse, complicate the process. Social insurance-related autopsies are crucial in clarifying occupational diseases and accidents. Organizationally, autopsies require consent from relatives, which is often a challenging step. However, the introduction of remuneration for clinical autopsies has improved the framework. Initiatives such as the S1 guideline and international research projects have reinforced the role of autopsies. The article underscores the importance of autopsies in quality assurance and research, especially given the rise in occupational diseases and the need for improved clinical diagnoses.