open_UMR

Aaron Beller

Welcome to open_UMR!

Open_UMR is a cross faculty publication hub. We collect scientific publications, resources, research data and software from members of Philipps-University Marburg and make it openly accessible. To ensure high standards of quality and re-usability, submissions to open_UMR are subject to curation.

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Recent Submissions

Open Access
Einsatz von KI-basierten Anwendungen zur Symptombeurteilung als entscheidungsunterstützende Systeme in der Notaufnahme
(2026-01-14) Cotte, Fabienne; Timmermann, Lars; Jerrentrup, Andreas
Gesundheitssysteme stehen weltweit vor Herausforderungen wie einer alternden Bevölkerung, zunehmender Prävalenz chronischer Krank- heiten und Multimorbidität sowie einem Mangel an Gesundheits- personal. Infolgedessen sind viele Notaufnahmen überfüllt, was zu längeren Wartezeiten, verzögerten Behandlungen und suboptimalen Behandlungsergebnissen führt. Um diese Probleme anzugehen, werden KI-basierte Anwendungen zur Symptombeurteilung (Symptom Assessment Applications, SAAs) in Gesundheitsnetzwerke integriert. SAAs sollen Patienten den Weg zu einer angemessenen Versorgung weisen, indem sie personalisierte medizinische Informationen bereitstellen und Empfehlungen darüber geben, ob, wann und wo sie medizinischen Rat aufsuchen sollten. Einige SAAs ermöglichen es Patienten darüber hinaus, ihren Symptombericht ihrem behandelnden Arzt bereitzustellen. Ziel dieser Arbeit war die Evaluierung des Einsatzes einer SAA in der Notfallversorgung durch zwei prospektive klinische Studien: In Studie 1 wurden 378 Patienten in der Notaufnahme des Universitätsklinikums Marburg eingeschlossen und die Dringlichkeitsempfehlungen der SAA mit der des Manchester Triage Systems (MTS) für Patienten in den drei niedrigsten MTS-Kategorien verglichen. Die Ergebnisse zeigten, dass in 91% der Fälle gleich oder konservativer triagiert wurde, während 5% der Fälle als potenziell vermeidbare Gefahrensituationen (avoidable hazardous situations, AHS) eingestuft wurden. Darüber hinaus wurde bei 43% der sich in der Notaufnahme befindlichen Patienten keine Notfallversorgung für notwendig erachtet. In Studie 2 wurden 81 Patienten der Notaufnahme des Katharinenkrankenhauses in Stuttgart eingeschlossen, um prospektiv die Akzeptanz der SAA und die Nützlichkeit des von einer SAA erstellten Symptomberichts zu untersuchen. In 74% der Fälle empfanden Ärzte die Konsultation als erleichtert, jedoch nur in 35% als potenziell zeitsparend. Patienten nahmen den Einsatz der SAA in 90% 2 der Fälle positiv wahr, wobei 86% die Inhalte verständlich fanden und 75% sich durch die Übermittlung des Berichts von ihrem behandelnden Arzt besser verstanden fühlten. Die Ergebnisse dieser Arbeit deuten darauf hin, dass SAAs für Patienten mit geringerer Akuität in Notaufnahmen meist sicher und einfach zu verwenden sind und der Symptombericht das klinische Gespräch zwischen Patienten und Ärzten erleichtern kann. Des Weiteren könnte es zu einer Reduzierung der Anzahl an Patienten in Notaufnahmen kommen, wenn diese die SAA vor Ihrem Besuch genutzt hätten. Weitere Forschung sollte die Auswirkungen der Verwendung von SAAs durch die Patienten zu Hause ermitteln, insbesondere um festzustellen, ob sie den Empfehlungen der SAA folgen würden, und um zu ermitteln, ob dies zu einer Umverteilung der Patienten auf das gesamte Gesundheitssystem führen würde. Healthcare systems worldwide are facing significant challenges such as an aging population, increased prevalence of chronic diseases and multimorbidity, and a shortage of skilled healthcare workers. Consequently, emergency departments are becoming overcrowded, leading to longer waiting times, delayed treatment, and suboptimal outcomes. To tackle these issues, AI-based Symptom Assessment Applications (SAAs) are being integrated into healthcare networks. These SAAs aim to guide patients towards appropriate care by providing personalised medical information and recommendations on if, when and where to seek care to support their decision-making process. Some SAAs are furthermore allowing them to share their symptom report with their healthcare professionals (HCPs). The objective of this work was to prospectively evaluate the use of an SAA in emergency care through two clinical trials. In Study 1, 378 patients at Marburg University Hospital's emergency department were enrolled, comparing the urgency advice provided by the SAA with the Manchester Triage Scale (MTS) for patients in the three lowest MTS 3 categories. The results showed that 91% of cases were triaged the same or more conservatively, while 5% of cases were considered potentially avoidable hazardous situations (AHS). Furthermore, 43% of patients seeking emergency care were not deemed to require emergency care. In Study 2, 81 patients at Katharinenkrankenhaus in Stuttgart's emergency department were enrolled to prospectively assess patients' and physicians' acceptance and perception of the usefulness of the information transfer report generated by an SAA. The findings indicated that in 74% of cases, doctors perceived the consultation as facilitated, but only 35% considered the integration as potentially time-saving. On the other hand, patients perceived the use of the SAA positively in 90% of cases, with 86% found the content understandable and 75% felt better understood by their treating physician through the report delivery. The results of this work suggest that SAAs are mostly safe and easy to use for lower acuity patients in emergency departments and that the symptom report can facilitate the clinical conversation between patients and doctors. Further research is required to assess the impact of patients using the SAA at home, specifically to evaluate if they would follow the suggested advice and to determine if this would lead to a more balanced distribution of patients across the healthcare ecosystem.
Open Access
Molecular insights into the mechanism of ParABS-mediated chromosome segregation
(2025-12-16) Schnabel, Lucas; Graumann, Peter; Schuller, Jan Michael; Thanbichler, Martin
DNA segregation is an essential process in living organisms that ensures the physical distribution of genetic material to the nascent daughter cells prior to cell division. In most bacteria this process is mediated by the highly conserved ParABS system, which has been found to mediate the partition of bacterial chromosomes and low-copy plasmids. The system relies on interactions between two partitioning proteins, the CTPase ParB and the Walker ATPase ParA, as well as the origin-proximal centromeric sequence parS. After the start of chromosome replication, ParB dimers form CTP-dependent clamps on the parS sites and condense the replicated origin region into a large nucleoprotein partition complex that is subsequently transferred across the cell by the interaction of ParB with ParA-ATP dimers bound to the nucleoid. Although the function of the ParABS system has been studied intensively for the past 30 years the exact mechanism by which these interactions facilitate DNA segregation remains incompletely understood. In this work, we provide a comprehensive mechanistic analysis of the interactions within the ParABS system, by investigating the nucleotide-dependent interplay between ParB, ParA and parS at a molecular level in the model organism Myxococcus xanthus. To this end, we characterize interaction- and hydrolysis-deficient ParB and ParA variants using a broad range of methods, including biolayer interferometry, NMR spectroscopy, hydrogen-deuterium exchange mass spectrometry, enzymatic assays and in vivo localization studies. The results obtained uncover the determinants for the interaction of the two partition proteins and give insight into structural and catalytical mechanisms that ensure robust and directed segregation of their DNA cargo. Collectively, our work demonstrates the importance of CTP-dependent N-terminal dimerization of ParB for the interaction with ParA and identifies a previously unmapped ParB-binding region on the ParA dimer interface. Moreover, we show that the interaction with ParB increases the DNA-binding affinity of ParA, thereby promoting the formation of stable ParB-ParA-DNA complexes, which are then dissociated by the ParB-dependent stimulation of ParA ATPase activity. Lastly, we investigate the prevalence of ParB and ParA interaction determinants within orthologous systems, highlight a conserved mode of action between chromosomal and plasmid-derived (Type I) Par systems and define regions of ParB and ParA that can possibly be evolutionary modulated to either avoid cross-talk with analogous systems or adapt ParABS function towards the requirements of the specific organism. Collectively, our findings shed new light on a key aspect of ParABS function and thus significantly advance our understanding of the molecular mechanisms mediating prokaryotic DNA segregation.
Open Access
Metabolic analysis of HPV positive and negative HNSCC cell lines after irradiation with carbon-12 (12C) particles
(2025-11-18) Al Rabadi, Hytham; Mandic, Robert; Theiß, Ulrike
Cancer cells are highly heterogeneous regarding their metabolic activity and phenotype. Proliferation of these cells is a rapid and dynamic process that needs significant energy. Generally, compared to normal cells, cancer cells to a large extent use the so-called Warburg effect, or aerobe glycolysis, for energy production. Metabolic parameters of six (three HPV-ve and three HPV+ve) head and neck squamous cell carcinoma (HNSCC) cancer cell lines with diverse anatomic origins and with different genetic backgrounds (UM-SCC-3, UM-SCC-29, UT-SCC-26A, UM-SCC-47, UM-SCC-104, UPCI-SCC-154) were analyzed under standard culture conditions and after radiation with 12C particles. Metabolic studies were performed with the Agilent Seahorse XF96 analyzer using the XF Real-Time ATP rate assay. With this assay, the oxygen consumption rate (OCR) in pmol/min and extracellular acidification rate (ECAR) in mpH/min, were measured and converted to mitochondrial ATP production rate (oxidative phosphorylation) and glycolytic ATP production rate (glycolysis) respectively. Cells to be irradiated were seeded together with control cells in the same Seahorse tissue culture microplate, so that metabolic analysis could be performed for irradiated as well as non-irradiated control cells at the same time. Different doses (1, 2, 4, 8 and 12 Gy) of 12C particle irradiation were used and the energy metabolism of the cancer cell lines was evaluated at different time points (2, 6, 10 and 24 hours) after irradiation. A decrease of glycolytic activity and mitochondrial respiration in the tested HNSCC cell lines was observed after exposure to irradiation, which was reflected by a reduction of the glycolytic as well as mitochondrial ATP production rate in irradiated cells compared with the control cells in most of our assays. This effect was more pronounced after application of higher irradiation doses. The reduction in glycolysis was more obvious and statistically significant in HPV ve HNSCC cell lines compared with HPV+ve HNSCC cell lines. Moreover, there was some significant increase of glycolytic ATP production rate in irradiated HPV+ve HNSCC cell lines cells compared to control cells with low irradiation dose. At the same time, a significant reduction of mitochondrial ATP production rate in irradiated cells compared with the control cells was observed in most of the assays for HPV+ve HNSCC cell lines. On the other hand, mitochondrial ATP production rate for HPV-ve HNSCC cell lines tend to increase in irradiated cells compared to control cells with low irradiation dose at the early time points. With higher irradiation doses it tends to decrease significantly at the late time points. Based on previous results when comparing HPV-ve and HPV+ve HNSCC cell lines, ATP production in HPV+ve HNSCC cell lines was significantly more derived from oxidative phosphorylation and significantly less from glycolysis compared with HPV-ve HNSCC cell lines. which means that 12C particle irradiation could be more selective in affecting the dominant energy production mechanism in cancer cells. however, there is limited understanding of the exact mechanism. There are only few reports regarding the effect of radiation therapy, especially particle therapy, on cancer cell metabolism, wherefore there is an increasing demand for such studies. The present study could contribute to a better understanding of metabolic changes in HPV-ve and HPV+ve HNSCC after 12C particle irradiation thereby helping to exploit potential metabolic weak points of HNSCC cells after 12C irradiation, which could be used for therapeutic targeting. Future studies will test inhibitors of the glycolytic pathway for their potential use as radiosensitizers that could be implemented in the therapy scheme of head & neck cancer patients.
Open Access
Betrachtung der Pharmakotherapie im Rahmen des Systolischen-Extinktions-Trainings bei Fibromyalgie-Patienten
(2025-12-18) Kubon, Philipp; Thieme, Kati; Wulf, Hinnerk
Ziel dieser Ausarbeitung ist die Betrachtung der Pharmakotherapie bei Patienten mit einer gesicherten Fibromyalgie, welche im Rahmen der SET (Systemisches Extinktions Training)-Studie (Thieme et al. 2019) therapiert wurden. Das Therapieprinzip des Systolischen Extinktions Trainings (SET) stützt sich auf die Pathophysiologie der veränderten zentralen Schmerzwahrnehmung bei Fibromyalgiepatienten. Mittels kardial getriggerter elektrischer Stimulation wird eine Desensibilisierung der Schmerzwahrnehmung erreicht. Infolgedessen erfolgt eine Erhöhung der Schmerzschwelle. Dadurch gelingt eine Schmerz- und Symptomreduktion bei dem Patientenkollektiv. Wir konnten eine signifikante langfristige Reduktion der Analgetikaeinnahme durch die SET-Therapie im Vergleich zu den Kontrollgruppen bei Patienten mit Fibromyalgie nachweisen. Dementsprechend scheint die SET-Therapie bei den untersuchten Patientenkollektiv eine sinnvolle Behandlungsalternative zu sein.
Open Access
Slides zum Workshop "Bequem oder souverän? Der Cloud-basierte Arbeitsplatz der Zukunft"
(Philipps-Universität Marburg, 2025-12-18) Weiß, Tobias; Gabriel, Andreas; Arendt, Thorsten
Dieser Themenraum widmete sich der Frage, wie moderne Arbeitsplätze in Verwaltung, Forschung und Lehre sowohl benutzerfreundlich als auch souverän gestaltet werden können – am konkreten Beispiel von openDesk, einer innovativen Open Source Arbeitsplatzplattform. Die Teilnehmenden konnten im Rahmen einer Hands-on-Session mit der Plattform arbeiten, um eigene Use-Cases zu entwickeln.