TY - THES A1 - von Andrian-Werburg, Maximilian T. P. T1 - Sex/Gender: A Revised Integrative Model for Sex/Gender Differences and Its Application on Media Research T1 - Geschlecht?! Eine Revision des Integrativen Modells für Geschlechtsunterschiede und dessen medienpsychologische Anwendung N2 - Far more women than men like to watch sad films, and far more men than women use video-based pornography. Do sex-affiliated biological-evolutionary influences cause these apparent differences, are they caused by social-cultural ones associated with gender, or do these dimensions interact? In the first step of this thesis, the Integrative Model for Sex/Gender Differences was thoroughly discussed and substantially revised. The model subsumed the current state of knowledge in psychology, which is based on wrong assumptions or outdated knowledge. In the second chapter, the Revised Integrative Model for Sex/Gender Differences yielded a theoretical guide to drive an extensive literature review for studies that used biological- evolutionary variables to predict sex/gender differences in media selection, use, and effects. In the study process, a large number of 6231 study titles and, if these appeared promising, abstracts were assessed for eligibility. In sum, only 39 studies were discovered that were attached to the topics of the revised integrative model and briefly outlined. Topics researched were as broad as exploring the potential of online dating advertisements to evaluate Sexual Strategies Theory and assess neuronal sex differences that affect video game and website use. The following chapter dealt with biopsychosocial predictor variables of pornography use, which appeared to be strongly affected by biological-evolutionary variables like the sex drive. The last empirical chapter assessed predictor variables for sad film use, which were social-culturally driven variables, such as the masculine gender role affecting the use of sad films. Men are taught that the sadness a sad film induces in them is not a socially desirable emotion to experience for them. Therefore, they like to watch sad films less in the first place. The final discussion highlighted that in line with recent acknowledgments in psychology science, human behavior can only be sufficiently explained if nature and nurture approaches for research are combined. N2 - Weit mehr Frauen als Männer sehen sich gerne traurige Filme an, und weit mehr Männer als Frauen nutzen videobasierte Pornografie. Diese beiden offensichtlichen Geschlechtsunterschiede dienen in empirischen Beispielen in der vorliegenden Dissertation der Erforschung der Frage ob Geschlechtsunterschiede eher auf biologisch-evolutionäre Einflüsse (sex), auf soziokulturelle Einflüsse (gender), oder aber aus Interaktionen aus beiden Themengebieten zurückzuführen sind. Im ersten Schritt dieser Arbeit wurde hierzu das Integrative Modell für Geschlechtsunterschiede diskutiert und grundlegend überarbeitet. Das Modell subsumiert den vorhergehenden Wissens- stand zur Entstehungsgeschichte von Geschlechtsunterschieden in der Psychologie, welcher jedoch zu Teilen auf falschen Annahmen oder veraltetem Wissen beruht. Im zweiten Kapitel lieferte das überarbeitete Integrative Modell für Geschlechtsunterschiede einen theoretischen Leitfaden für eine umfangreiche Literaturrecherche nach Studien, die biologisch-evolutionäre Variablen zur Vorhersage von Geschlechtsunterschieden bei der Medienauswahl, -nutzung und -wirkung verwendeten. Dabei wurde eine große Anzahl von 6231 Studientiteln und, falls die Titel vielversprechend erschienen, auch Abstracts auf ihre Eignung geprüft. Insgesamt wurden 39 Studien gefunden, die den Themen des überarbeiteten integrativen Modells zugeordnet werden konnten. Diese untersuchten breitgefächerte Themen wie die Erforschung des Inhalts von Online-Dating-Anzeigen zur Evaluation der Sexual Strategies Theory hin zur Untersuchung von neuronalen Geschlechtsunterschieden, die in Verdacht stehen die Nutzung von Videospielen und Websiten zu beeinflussen. Das darauffolgende Kapitel befasste sich mit biopsychosozialen Prädiktorvariablen von Pornografiekonsum, welcher offenbar stark von biologisch-evolutionären Variablen wie dem Sexualtrieb beeinflusst wird. Im letzten empirischen Kapitel wurden Prädiktorvariablen für die Nutzung trauriger Filme untersucht. Das Gefallen trauriger Filme wird stark von sozial-kulturellen Variablen, wie z. B. durch die männliche Geschlechterrolle, beeinflusst. Männern wird durch Erziehung beigebracht, dass die Trauer, die solch Film in ihnen auslöst, keine sozial akzeptable Emotion für sie ist. Daher sehen sie sich traurige Filme von vornherein weniger gern an. In der abschließenden Diskussion wird hervorgehoben, dass nach neueren Erkenntnissen der Psychologie menschliches Verhalten nur dann hinreichend erklärt werden kann, wenn biologisch-evolutionäre und sozial-kulturelle Forschungsansätze kombiniert werden. N2 - Few topics have been the subject of more controversy than those encapsulated by the terms "sex" and "gender". Social-cultural and biological-evolutionary argumentation patterns frequently clash and especially the public debate appears to be stuck in a stalemate between the two competing parties. From a psychological perspective both topics appear deeply intertwined and are not easy to be separated. This study pursues an integrative approach to better understand the roots of differences best subsumed under the term sex/gender. It will become apparent that both nature and nurture variables interact and form the complex system of human behavior and experience. KW - Geschlecht KW - Neue Medien KW - Pornografie KW - Drama KW - Evolutionspsychologie KW - Sex/Gender KW - Biopsychosocial KW - Media Research Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-345669 SN - 978-3-95826-236-2 SN - 978-3-95826-237-9 N1 - Parallel erschienen als Druckausgabe bei Würzburg University Press, ISBN 978-3-95826-236-2, 33,80 Euro. PB - Würzburg University Press CY - Würzburg ER - TY - JOUR A1 - Kern, Christian S. A1 - Haags, Anja A1 - Egger, Larissa A1 - Yang, Xiaosheng A1 - Kirschner, Hans A1 - Wolff, Susanne A1 - Seyller, Thomas A1 - Gottwald, Alexander A1 - Richter, Mathias A1 - de Giovannini, Umberto A1 - Rubio, Angel A1 - Ramsey, Michael G. A1 - Bocquet, François C. A1 - Soubatch, Serguei A1 - Tautz, F. Stefan A1 - Puschnig, Peter A1 - Moser, Simon T1 - Simple extension of the plane-wave final state in photoemission: bringing understanding to the photon-energy dependence of two-dimensional materials JF - Physical Review Research N2 - Angle-resolved photoemission spectroscopy (ARPES) is a method that measures orbital and band structure contrast through the momentum distribution of photoelectrons. Its simplest interpretation is obtained in the plane-wave approximation, according to which photoelectrons propagate freely to the detector. The photoelectron momentum distribution is then essentially given by the Fourier transform of the real-space orbital. While the plane-wave approximation is remarkably successful in describing the momentum distributions of aromatic compounds, it generally fails to capture kinetic-energy-dependent final-state interference and dichroism effects. Focusing our present study on quasi-freestanding monolayer graphene as the archetypical two-dimensional (2D) material, we observe an exemplary E\(_{kin}\)-dependent modulation of, and a redistribution of spectral weight within, its characteristic horseshoe signature around the \(\bar {K}\) and \(\bar {K´}\) points: both effects indeed cannot be rationalized by the plane-wave final state. Our data are, however, in remarkable agreement with ab initio time-dependent density functional simulations of a freestanding graphene layer and can be explained by a simple extension of the plane-wave final state, permitting the two dipole-allowed partial waves emitted from the C 2p\(_z\) orbitals to scatter in the potential of their immediate surroundings. Exploiting the absolute photon flux calibration of the Metrology Light Source, this scattered-wave approximation allows us to extract E\(_{kin}\)-dependent amplitudes and phases of both partial waves directly from photoemission data. The scattered-wave approximation thus represents a powerful yet intuitive refinement of the plane-wave final state in photoemission of 2D materials and beyond. Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350330 VL - 5 IS - 3 ER - TY - JOUR T1 - Search for Multimessenger Sources of Gravitational Waves and High-energy Neutrinos with Advanced LIGO during Its First Observing Run, ANTARES, and IceCube JF - The Astrophysical Journal N2 - Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes. KW - gravitational waves KW - neutrinos KW - Electromagnetic signals KW - Events GW150914 KW - ray KW - emission Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-360189 VL - 870 IS - 2 PB - The American Astronomical Society ER - TY - JOUR A1 - Schade, A. A1 - Bader, A. A1 - Huber, T. A1 - Kuhn, S. A1 - Czyszanowski, T. A1 - Pfenning, A. A1 - Rygała, M. A1 - Smołka, T. A1 - Motyka, M. A1 - Sęk, G. A1 - Hartmann, F. A1 - Höfling, S. T1 - Monolithic high contrast grating on GaSb/AlAsSb based epitaxial structures for mid-infrared wavelength applications JF - Optics Express N2 - We demonstrate monolithic high contrast gratings (MHCG) based on GaSb/AlAs0.08Sb0.92 epitaxial structures with sub-wavelength gratings enabling high reflection of unpolarized mid-infrared radiation at the wavelength range from 2.5 to 5 µm. We study the reflectivity wavelength dependence of MHCGs with ridge widths ranging from 220 to 984 nm and fixed 2.6 µm grating period and demonstrate that peak reflectivity of above 0.7 can be shifted from 3.0 to 4.3 µm for ridge widths from 220 to 984 nm, respectively. Maximum reflectivity of up to 0.9 at 4 µm can be achieved. The experiments are in good agreement with numerical simulations, confirming high process flexibility in terms of peak reflectivity and wavelength selection. MHCGs have hitherto been regarded as mirrors enabling high reflection of selected light polarization. With this work, we show that thoughtfully designed MHCG yields high reflectivity for both orthogonal polarizations simultaneously. Our experiment demonstrates that MHCGs are promising candidates to replace conventional mirrors like distributed Bragg reflectors to realize resonator based optical and optoelectronic devices such as resonant cavity enhanced light emitting diodes and resonant cavity enhanced photodetectors in the mid-infrared spectral region, for which epitaxial growth of distributed Bragg reflectors is challenging. KW - monolithic grating KW - high contrast KW - mid-infrared wavelength applications KW - epitaxial structures KW - GaSb/AlAsSb Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350346 VL - 31 IS - 10 ER - TY - JOUR A1 - Schürger, Peter A1 - Engel, Volker T1 - On the relation between nodal structures in quantum wave functions and particle correlation JF - AIP Advances N2 - We study the influence of nodal structures in two-dimensional quantum mechanical densities on wave packet entanglement. This is motivated by our recent study [Entropy, 25, 970 (2023)], which showed that the mutual information derived from the momentum-space probability density of a coupled two-particle system exhibits an unusual time dependence, which is not encountered if the position-space density is employed in the calculation. In studying a model density, here, we identify cases where the mutual information increases with the number of nodes in the wave function and approaches a finite value, whereas in this limit, the linear correlation vanishes. The results of the analytical model are then applied to interpret the correlation measures for coupled electron-nuclear dynamics, which are treated by numerically solving the time-dependent Schrödinger equation. KW - nodal structures KW - information theory entropy KW - particle correlations KW - time-dependent Schrodinger equation KW - covariance and correlation KW - quantum wave functions KW - Schroedinger equation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350361 VL - 13 IS - 12 ER - TY - JOUR A1 - Willems, Suzanne A1 - Detta, Elena A1 - Baldini, Lorenzo A1 - Tietz, Deniz A1 - Trabocchi, Andrea A1 - Brunschweiger, Andreas T1 - Diversifying DNA-tagged amines by isocyanide multicomponent reactions for DNA-encoded library synthesis JF - ACS Omega N2 - In DNA-encoded library synthesis, amine-substituted building blocks are prevalent. We explored isocyanide multicomponent reactions to diversify DNA-tagged amines and reported the Ugi-azide reaction with high yields and a good substrate scope. In addition, the Ugi-aza-Wittig reaction and the Ugi-4-center-3-component reaction, which used bifunctional carboxylic acids to provide lactams, were explored. Five-, six-, and seven-membered lactams were synthesized from solid support-coupled DNA-tagged amines and bifunctional building blocks, providing access to structurally diverse scaffolds. KW - DNA-tagged amines KW - DNA-encoded library synthesis KW - isocyanide multicomponent reactions KW - Ugi-azide reaction KW - lactams Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349809 SN - 2470-1343 VL - 9 IS - 7 ER - TY - JOUR A1 - Schmidt, Sebastian A1 - Holzgrabe, Ulrike T1 - Do the enantiomers of ketamine bind enantioselectively to human serum albumin? JF - European Journal of Pharmaceutical Sciences N2 - The binding of drugs to plasma proteins is an important process in the human body and has a significant influence on pharmacokinetic parameter. Human serum albumin (HSA) has the most important function as a transporter protein. The binding of ketamine to HSA has already been described in literature, but only of the racemate. The enantiomerically pure S-ketamine is used as injection solution for induction of anesthesia and has been approved by the Food and Drug Administration for the therapy of severe depression as a nasal spray in 2019. The question arises if there is enantioselective binding to HSA. Hence, the aim of this study was to investigate whether there is enantioselective binding of S-and R-ketamine to HSA or not. Ultrafiltration (UF) followed by chiral capillary electrophoretic analysis was used to determine the extent of protein binding. Bound fraction to HSA was 71.2 % and 64.9 % for enantiomerically pure R- and S-ketamine, respectively, and 66.5 % for the racemate. Detailed binding properties were studied by Saturation Transfer Difference (STD)-, waterLOGSY- and Carr-Purcell-Meiboom-Gill (CPMG)-NMR spectroscopy. With all three methods, the aromatic ring and the N-methyl group could be identified as the structural moieties most strongly involved in binding of ketamine to HSA. pK\(_{aff}\) values determined using UF and NMR indicate that ketamine is a weak affinity ligand to HSA and no significant differences in binding behavior were found between the individual enantiomers and the racemate. KW - protein binding KW - albumin KW - electrophoresis KW - nuclear magnetic resonance spectroscopy KW - ultrafiltration KW - enantioselectivity Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349791 VL - 192 ER - TY - THES A1 - Adhikari, Bikash T1 - Targeted degradation of Myc-interacting oncoproteins T1 - Gezielte Degradation von mit Myc interagierenden Onkoproteinen N2 - The hallmark oncoprotein Myc is a major driver of tumorigenesis in various human cancer entities. However, Myc’s structural features make it challenging to develop small molecules against it. A promising strategy to indirectly inhibit the function of Myc is by targeting its interactors. Many Myc-interacting proteins have reported scaffolding functions which are difficult to target using conventional occupancy- driven inhibitors. Thus, in this thesis, the proteolysis targeting chimera (PROTAC) approach was used to target two oncoproteins interacting with Myc which promote the oncogenicity of Myc, Aurora-A and WDR5. PROTACs are bifunctional small molecules that bind to the target protein with one ligand and recruit a cellular E3- ligase with the other ligand to induce target degradation via the ubiquitin- proteasome system. So far, the most widely used E3-ligases for PROTAC development are Cereblon (CRBN) and von Hippel–Lindau tumor suppressor (VHL). Furthermore, there are cases of incompatibility between some E3-ligases and proteins to bring about degradation. Hence there is a need to explore new E3- ligases and a demand for a tool to predict degradative E3-ligases for the target protein in the PROTAC field. In the first part, a highly specific mitotic kinase Aurora-A degrader, JB170, was developed. This compound utilized Aurora-A inhibitor alisertib as the target ligand and thalidomide as the E3-ligase CRBN harness. The specificity of JB170 and the ternary complex formation was supported by the interactions between Aurora-A and CRBN. The PROTAC-mediated degradation of Aurora-A induced a distinct S- phase defect rather than mitotic arrest, shown by its catalytic inhibition. The finding demonstrates that Aurora-A has a non-catalytic role in the S-phase. Furthermore, the degradation of Aurora-A led to apoptosis in various cancer cell lines. In the second part, two different series of WDR5 PROTACs based on two protein- protein inhibitors of WDR5 were evaluated. The most efficient degraders from both series recruited VHL as a E3-ligase and showed partial degradation of WDR5. In addition, the degradation efficiency of the PROTACs was significantly affected by the linker nature and length, highlighting the importance of linker length and composition in PROTAC design. The degraders showed modest proliferation defects at best in cancer cell lines. However, overexpression of VHL increased the degradation efficiency and the antiproliferative effect of the PROTACs. In the last part, a rapamycin-based assay was developed to predict the degradative E3-ligase for a target. The assay was validated using the WDR5/VHL and Aurora- A/CRBN pairs. The result that WDR5 is degraded by VHL but not CRBN and Aurora-A is degraded by CRBN, matches observations made with PROTACs. This technique will be used in the future to find effective tissue-specific and essential E3-ligases for targeted degradation of oncoproteins using PROTACs. Collectively, the work presented here provides a strategy to improve PROTAC development and a starting point for developing Aurora-A and WDR5 PROTACs for cancer therapy. N2 - Das Onkoprotein Myc ist ein wichtiger Faktor bei der Tumorentstehung in verschiedenen menschlichen Krebsarten. Die strukturellen Merkmale von Myc machen es jedoch schwierig, kleine Moleküle gegen dieses Protein zu entwickeln. Eine vielversprechende Strategie zur indirekten Hemmung der Funktion von Myc besteht darin, auf seine Interaktoren abzuzielen. Viele Proteine, die mit Myc interagieren, haben Gerüstfunktionen, die mit herkömmlichen Inhibitoren nur schwer zu hemmen sind. Daher wurde in dieser Arbeit der PROTAC-Ansatz (Proteolysis Targeting Chimera) verwendet, um zwei Onkoproteine, die mit Myc interagieren und die Onkogenität von Myc fördern, ins Visier zu nehmen: Aurora-A und WDR5. PROTACs sind bifunktionale kleine Moleküle, die mit einem Liganden an das Zielprotein binden und mit dem anderen Liganden eine zelluläre E3-Ligase rekrutieren, um den Abbau des Zielproteins über das Ubiquitin-Proteasom-System einzuleiten. Die bisher am häufigsten verwendeten E3-Ligasen für die Entwicklung von PROTACs sind Cereblon (CRBN) und der von Hippel-Lindau-Tumorsuppressor (VHL). Außerdem gibt es Fälle von Inkompatibilität zwischen einigen E3-Ligasen und Proteinen, die abgebaut werden sollen. Daher besteht die Notwendigkeit, neue E3-Ligasen zu erforschen und Werkzeuge zur Vorhersage abbauender E3-Ligasen für das Zielprotein zu entwickeln. Im ersten Teil wurde ein hochspezifischer Degrader der mitotischen Kinase Aurora-A, JB170, entwickelt. Bei dieser Verbindung wurde der Aurora-A-Inhibitor Alisertib als Zielligand und Thalidomid als Binder für die E3-Ligase CRBN verwendet. Die Spezifität von JB170 und die ternäre Komplexbildung wurden durch die Wechselwirkungen zwischen Aurora-A und CRBN unterstützt. Der durch PROTAC vermittelte Abbau von Aurora-A führte zu einem deutlichen Defekt in der S-Phase und nicht zu einem mitotischen Stillstand, wie es für dessen katalytische Hemmung beobachtet wurde. Dies zeigt, dass Aurora-A eine nicht-katalytische Funktion in der S-Phase hat. Außerdem führte der Abbau von Aurora-A in verschiedenen Krebszelllinien zur Apoptose. Im zweiten Teil wurden zwei verschiedene Serien von WDR5 PROTACs auf der Grundlage von zwei Protein-Protein-Inhibitoren von WDR5 untersucht. Die effizientesten Degrader aus beiden Serien rekrutierten VHL als E3-Ligase und zeigten einen teilweisen Abbau von WDR5. Darüber hinaus wurde die Abbaueffizienz der PROTACs erheblich von der Art und Länge des Linkers beeinflusst, was die Bedeutung der Linkerlänge und -zusammensetzung bei der Entwicklung von PROTACs unterstreicht. Die Abbauprodukte zeigten bestenfalls bescheidene Proliferationsdefekte in Krebszelllinien. Eine Überexpression von VHL erhöhte jedoch die Abbaueffizienz und den antiproliferativen Effekt der PROTACs. Im letzten Teil wurde ein auf Rapamycin basierender Assay entwickelt, um die abbauende E3-Ligase für ein Target vorherzusagen. Der Assay wurde anhand der Paare WDR5/VHL und Aurora-A/CRBN validiert. Das Ergebnis, dass WDR5 von VHL, aber nicht von CRBN abgebaut wird und Aurora-A von CRBN abgebaut wird, stimmt mit den Beobachtungen überein, die mit PROTACs gemacht wurden. Diese Technik wird in Zukunft eingesetzt werden, um wirksame gewebespezifische und essentielle E3-Ligasen für den gezielten Abbau von Onkoproteinen mit Hilfe von PROTACs zu finden. Insgesamt bieten die hier vorgestellten Arbeiten eine Strategie zur Verbesserung der PROTAC-Entwicklung und einen Ausgangspunkt für die Entwicklung von Aurora-A- und WDR5-PROTACs für die Krebstherapie. KW - Degradation KW - PROTACs KW - Oncoprotein KW - Cancer KW - Onkoprotein Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-317326 ER - TY - THES A1 - Dekant, Raphael H. T1 - Species-differences in the \(in\) \(vitro\) biotransformation of trifluoroethene (HFO-1123) T1 - Speziesunterschiede in der \(in\) \(vitro\) Biotransformation von Trifluorethen (HFO-1123) N2 - 1,1,2-trifluoroethene (HFO-1123) is intended for use as a refrigerant. Inhalation studies on HFO-1123 in rats suggested a low potential for toxicity, with no-observed-adverse-effect levels greater then 20,000 ppm. However, single inhalation exposure of Goettingen Minipigs and New Zealand White Rabbits resulted in mortality. It was assumed that conjugation of HFO-1123 with glutathione, via glutathione S-transferase, gives rise to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH), which is then transformed to the corresponding cysteine S-conjugate (S-(1,1,2-trifluoroethyl)-L-cysteine, 1123-CYS). Subsequent beta-lyase mediated cleavage of 1123-CYS may result in monofluoroacetic acid, a potent inhibitor of aconitase. Species-differences in 1123-GSH formation and 1123-CYS cleavage to MFA may explain species-differences in HFO-1123 toxicity. This study was designed to test the hypothesis, that GSH-dependent biotransformation and subsequent beta-lyase mediated formation of monofluoroacetic acid, a potent inhibitor of aconitase in the citric acid cycle, may play a key role in HFO-1123 toxicity and to evaluate if species-differences in the extent of MFA formation may account for the species-differences in HFO-1123 toxicity. The overall objective was to determine species-differences in HFO-1123 biotransformation in susceptible vs. less susceptible species and humans as a basis for human risk assessment. To this end, in vitro biotransformation of HFO-1123 and 1123-CYS was investigated in renal and hepatic subcellular fractions of mice, rats, humans, Goettingen Minipigs and NZW Rabbits. Furthermore, cytotoxicity and metabolism of 1123-CYS was assessed in cultured renal epithelial cells. Enzyme kinetic parameters for beta-lyase mediated cleavage of 1123-CYS in renal and hepatic cytosolic fractions were determined, and 19F-NMR was used to identify fluorine containing metabolites arising from 1123-CYS cleavage. Quantification of 1123-GSH formation in hepatic S9 fractions after incubation with HFO-1123 was performed by LC-MS/MS and hepatic metabolism of HFO-1123 was monitored by 19F-NMR. Rates of 1123-GSH formation were increased in rat, mouse and NZW Rabbit compared to human and Goettingen hepatic S9, indicating increased GSH dependent biotransformation in rats, mouse and NZW Rabbits. NZW Rabbit hepatic S9 exhibited increased 1123-GSH formation in the presence compared to the absence of acivicin, a specific gamma-GT inhibitor. This indicates increased gamma-GT mediated cleavage of 1123-GSH in NZW Rabbit hepatic S9 compared to the other species. 19F-NMR confirmed formation of 1123-GSH as the main metabolite of GSH mediated biotransformation of HFO-1123 in hepatic S9 fractions next to F-. Increased F- formation was detected in NZW Rabbit and Goettingen Minipig hepatic S9 in the presence of an NADPH regenerating system, indicating a higher rate of CYP-450 mediated metabolism in these species. Based on these findings, it is possible that CYP-450 mediated metabolism may contribute to HFO-1123 toxicity. In contrast to the increased formation of 1123-GSH in rat, mouse and NZW Rabbit hepatic S9 (compared to human and Goettingen Minipig), enzyme kinetic studies revealed a significantly higher beta-lyase activity towards 1123-CYS in renal cytosol of Goettingen Minipigs compared to cytosol from rats, mice, humans and NZW Rabbits. However, beta-lyase cleavage in renal NZW Rabbit cytosol was slightly increased compared to rat, mouse and human renal cytosols. 19F-NMR analysis confirmed increased time-dependent formation of MFA in renal Goettingen Minipig cytosol and NZW Rabbit (compared to human and rat cytosolic fractions). Three structurally not defined MFA-derivatives were detected exclusively in NZW Rabbit and Goettingen Minipig cytosols. Also, porcine kidney cells were more sensitive to cytotoxicity of 1123-CYS compared to rat and human kidney cells. Overall, increased beta-lyase mediate cleavage of 1123-CYS to MFA in Goettingen Minipig and NZW Rabbit kidney (compared to human and rat) may support the hypothesis that enzymatic cleavage by beta-lyases may account for the species-differences in HFO-1123 toxicity. However, the extent of GST mediated biotransformation in the liver as the initial step in HFO-1123 metabolism does not fully agree with this hypothesis, since 1123-GSH formation occurs at higher rates in rat, mouse and NZW Rabbit S9 as compared to the Goettingen Minipig. Based on the inconsistencies between the extent of GST and beta-lyase mediated biotransformation of HFO-1123 obtained by this study, a decisive statement about an increased biotransformation of HFO-1123 in susceptible species with a direct linkage to the species-specific toxicity cannot be drawn. Resulting from this, a clear and reliable conclusion regarding the risk for human health originating from HFO-1123 cannot be made. However, considering the death of Goettingen Minipigs and NZW Rabbits after inhalation exposure of HFO-1123 at concentrations great than 500 ppm and greater than 1250 ppm, respectively, this indicates a health concern for humans under peak exposure conditions. For a successful registration of HFO-1123 and its use as a refrigerant, further in vitro and in vivo investigations addressing uncertainties in the species-specific toxicity of HFO-1123 are urgently needed. N2 - 1,1,2-Trifluorethen (HFO-1123) besitzt hervorragende klimatische und thermische Eigenschaften für den Einsatz als Kühlmittel. In Inhalationsstudien an Ratten, Kaninchen und Schweinen, die im Rahmen der regulatorischen Toxizitätsprüfung durchgeführt wurden, konnten ausgeprägte Speziesunterschiede in der Toxizität von HFO-1123 nachgewiesen werden. In Ratten zeigte HFO-1123 ein geringes Potential für akute und chronische Toxizität, mit NOAELs („No-Observed-Adverse-Effect Level“) größer als 20.000 ppm. Im Gegensatz dazu führte die einmalige HFO-1123 Exposition von Goettingen Minischweinen und Weißen Neuseeländer Kaninchen zum Tod von Versuchstieren. Bereits die niedrigste verwendete Raumkonzentrationen von 65 ppm führten bei Goettingen Minischweinen zu ausgeprägter Toxizität (Kardiotoxizität, Neurotoxizität). Auf Grundlage der inhalativen Toxizität, sowie detaillierter Kenntnis der Biotransformation strukturverwandten Substanzen wurde vermutet, dass Speziesunterschiede in der Toxizität auf einer speziesspezifischen Biotransformation von HFO-1123 beruhen. Der erste Schritt in der vermuteten Bioaktivierung von HFO-1123 könnte demnach eine Glutathion S-transferase abhänge Konjugation mit Glutathion beinhalten und zur Bildung von S-(1,1,2-trifluoroethyl)-L-Glutathion (1123-GSH) führen. Das gebildete Glutathion-Konjugat könnte gamma-Glutamyltransferase, sowie Dipeptidase und Aminotransferase abhängig zu seinem korrespondierenden Cystein S-Konjugat, S-(1,1,2-trifluoroethyl)-L-Cysteine (1123-CYS) abgebaut werden. Wie andere Cystein S-Konjugate mit elektronegativen Substituenten am Schwefelatom, könnte dieses mittels Cysteinkonjugat-beta-Lyasen (beta-Lyasen) zu einem Thionoacylfluorid- Intermediat umgewandelt werden. Nach Hydrolyse entsteht voraussichtlich Monofluoressigsäure (MFA) als stabiler Metabolit. MFA greift in den Zitronensäurezyklus ein, indem das Enzym Aconitase irreversible gehemmt wird. Die Hemmung der Aconitase führt zu einem Abbruch des Zitronensäurezyklus und somit zu einem erheblichen Eingriff in die Energiegewinnung des Organismus. Speziesunterschiede in der Bildung von 1123-GSH sowie der Spaltung von 1123-CYS zu MFA könnten die speziespezifische Toxizität von HFO-1123 erklären. Ziel dieser Arbeit war es die im vorherigen Absatz aufgestellte Arbeitshypothese, einer Glutathion-abhängigen Biotransformation von HFO-1123, gefolgt von einer beta-Lyase vermittelten Bildung von MFA zu überprüfen um deren Beitrag in der speziesspezifischen Toxizität von HFO-1123 einzuschätzen. Unterschiede im Ausmaß der Bildung von MFA könnten ursächlich für die Speziesunterschiede in der Toxizität von HFO-1123 sein. Ergebnisse dieser Untersuchungen sollen als Grundlage für die Risikobewertung von HFO-1123 im Menschen dienen. Im Rahmen dieser Arbeit, wurde die in vitro Biotransformation von HFO-1123 und 1123-CYS in subzellulären Fraktionen von Leber und Niere der Spezies Ratte, Maus, Goettingen Minischwein, Kaninchen und Mensch untersucht. Zusätzlich wurde die Zytotoxizität und der Metabolismus von 1123-CYS in Nierenepithelzellen überprüft. Die Bildung von 1123-GSH wurde mittel LC-MS/MS in hepatischen S9 Fraktionen quantitativ bestimmt und die Entstehung weiterer Metabolite mittels 19F-NMR analysiert. Weiterhin wurde die Enzymkinetik der beta-Lyase vermittelten Spaltung von 1123-CYS in cytosolischen Leberfraktionen bestimmt und fluorhaltige Metabolite dieser Spaltung mittels 19F-NMR aufgezeichnet. In Leber S9 Fraktionen von Ratten, Mäusen und WN Kaninchen wurde eine gesteigerte Bildung von 1123-GSH im Vergleich zu S9 Fraktionen von Goettingen Minischweinen und Menschen beobachtet. Dies deutet auf eine gesteigerte Glutathion-abhängige Biotransformation in Ratten, Mäusen und WN Kaninchen hin. Zusätzlich zeigten Leber S9 Fraktionen von WN Kaninchen eine erhöhte Bildung von 1123-GSH in Anwesenheit von Acivicin, einem spezifischen gamma-GT Inhibitor. Dies deutet auf eine gesteigerte gamma-GT abhängige Spaltung von 1123-GSH in hepatischen S9 Fraktionen von WN Kaninchen hin. Zusätzlich bestätigten 19F-NMR Untersuchungen - neben anorganischem Fluorid (F-) - 1123-GSH als Hauptmetaboliten der Glutathion-abhängigen Biotransformation von HFO-1123. Die erhöhte Bildung von F- in Leber S9 Fraktionen von Goettingen Minischweinen und WN Kaninchen in Anwesenheit eines NADPH regenerierenden Systems, deutet weiterhin auf eine gesteigerte CYP-450 vermittelte Biotransformation in diesen Spezies hin. Jedoch ist der Beitrag der CYP-450 vermittelten Biotransformation von HFO-1123 zur speziesspezifischen Toxizität nicht geklärt. Im Gegensatz zur gesteigerten Bildung von 1123-GSH in Leber S9 Fraktionen von Ratten, Mäusen und Kaninchen (verglichen mit Leber S9 Fraktionen von Goettingen Minischweinen und Menschen), wurde in enzymkinetischen Untersuchungen eine erhöhte beta-Lyase Aktivität gegenüber 1123-CYS in Nierenzytosol von Goettingen Minischweinen im Vergleich zu zytosolischen Fraktionen von Ratten, Mäusen, Menschen und WN Kaninchen beobachtet. Trotz der niedrigeren beta-Lyase Aktivität in WN Kaninchen (verglichen mit Goettingen Minischwein), zeigte diese zytosolische Fraktion eine leicht erhöhte Aktivität im Vergleich zu Nierenzytosol von Ratten, Mäusen und Menschen. Im Einklang damit wurde eine erhöhte Bildung von MFA in Nierenzytosol von Goettingen Minischweinen und WN Kaninchen (im Vergleich zu zytosolischen Fraktionen von Menschen und Ratten) mittels 19F-NMR beobachtet. Interessanterweise wurde ausschließlich im Zytosol von Goettingen Minischweinen und WN Kaninchen die Bildung von drei strukturell nicht charakterisierten MFA-Derivaten nachgewiesen. Unterstützt wird die erhöhte beta-Lyase Aktivität in Nierenzytosol von Goettingen Minischweinen durch eine erhöhte Zytotoxizität von 1123-CYS in Nierenepithelzellen von Schweinen (Verglichen mit humanen und Ratten Nierenzellen). Grundsätzlich bestätigt die erhöhte beta-Lyase abhängige Spaltung von 1123-CYS zu MFA in Goettingen Minischweinen und WN Kaninchen die Annahme, dass eine beta-Lyase vermittelte Spaltung von 1123-CYS einen wichtigen Beitrag zur Toxizität von HFO-1123 leistet. Jedoch steht dem eine verminderte GST vermittelte Bildung von 1123-GSH in Goettingen Minischwein Leber S9 Fraktionen im Vergleich zu Ratten, Maus und WN Kaninchen entgegen. Auf Basis der bisher erhobenen Daten ist der Beitrag der Glutathion-abhängigen und beta-Lyase vermittelten Biotransformation zur Toxizität von HFO-1123 nicht abschließend geklärt und lässt eine eindeutige Aussage über eine vermehrte Biotransformation von HFO-1123 zu toxischen Metaboliten in empfindlichen Spezies im Zusammenhang mit der speziesspezifischen Toxizität nicht zu. Diese Unsicherheiten lassen keine Rückschlüsse über das Ausmaß der Biotransformation und Toxizität im Menschen zu. Für die Registrierung von HFO-1123 und seiner zukünftigen Verwendung als Kühlmittel sind weiter in vitro und in vivo Untersuchungen nötig, um die Sicherheit bei der Verwendung von HFO-1123 für die menschliche Gesundheit zu gewährleisten. KW - Biotransformation KW - Risikoanalyse KW - 19F-NMR KW - LC-MS/MS KW - Mercapturic acid pathway KW - Trifluoroethene KW - HFO-1123 Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314035 ER - TY - THES A1 - Hajduk, Maurice Martin T1 - Darf es etwas mehr sein? Neuroenhancement im Studium – eine Befragung an Würzburger Hochschulen T1 - Can it be a little more? Neuroenhancement during studies - a survey at Würzburg universities N2 - Neuroenhancement (NE) bezeichnet die Einnahme psychotroper Substanzen mit dem Ziel der geistigen Leistungssteigerung oder Beruhigung. NE wird durch gesunde Perso- nen genutzt. Es besteht somit keine Indikation zur Einnahme psychotroper Wirkstoffe. Zum NE genutzte Substanzen sind z.B. Koffeintabletten, verschreibungspflichtige Medi- kamente oder illegale Substanzen. Die bisherige Forschung findet Hinweise auf einen Zusammenhang zwischen NE und ADHS-Symptomen, einigen Aspekten psychischer Gesundheit, sowie Substanzkonsum. Bisher gibt es keine Forschung zu NE am Hoch- schulstandort Würzburg. Es wurde eine anonyme online Querschnittsbefragung im ersten Quartal 2021 durchge- führt. Eingeladen waren 5600 Studierende der Julius-Maximilians-Universität Würzburg und der Hochschule für angewandte Wissenschaften Würzburg Schweinfurt. Der Frage- bogen bestand aus 53 Items und enthielt u. a. die folgenden validierten Messinstrumente: ASRS, PSS-10, PHQ-4 und AUDIT-C. Die Response Rate lag bei 18% (n = 1011). Das Wissen über NE war weit unter den Stu- dierenden verbreitet. Die Prävalenz für Neuroenhancement im Studium lag bei 12.7%. Die drei meistgenannten Substanzen waren Koffeintabletten (6.6%), Cannabis (4.5%) und Methylphenidat (4.3%). Häufigster Anlass für NE war die Prüfungsvorbereitung. Es zeigten sich deutliche Unterschiede zwischen den Fachbereichen, u.a. hinsichtlich der Prävalenz von NE. ADHS-Symptomen, Stress, Ängstlichkeit, und Depressivität waren positiv mit NE assoziiert. Ein stärkerer Effekt ergab sich für den Zusammenhang zwi- schen NE und riskanten Alkoholkonsum bzw. Tabakkonsum. Diese Ergebnisse wurden durch eine binomial logistische Regression bestätigt. Die konsumierten Substanzen, das Wissen über NE, die Prävalenz von NE und die Gründe für dessen Nutzung fügen sich nahtlos in die bisherige Forschung ein. Auch die Assoziation zwischen ADHS-Symptomen, Stress, Ängstlichkeit, Depressivität, riskan- tem Alkoholkonsum und Tabakkonsum bestätigt bisherige Forschungsergebnisse. Es konnte gezeigt werden, dass rund ein Zehntel der Studierenden NE bereits genutzt haben. In Anbetracht der gesundheitlichen Gefahren, die mit NE einhergehen ist die Etab- lierung bzw. der Ausbau von Aufklärung-, Beratungs- und Hilfsangeboten für Studie- rende anzustreben sowie weitere Forschung zum Thema indiziert. N2 - Neuroenhancement (NE) refers to the use of psychotropic substances with the aim of increasing mental performance or calming down. NE is used by healthy people. There is therefore no indication to take psychotropic substances. Substances used for NE include caffeine tablets, prescription drugs or illegal substances. Research has found evidence of a link between NE and ADHD symptoms, some aspects of mental health, and substance use. Up to now there has been no research on NE at the Würzburg university site. An anonymous online cross-sectional survey was conducted in the first quarter of 2021. 5,600 students from Julius-Maximilians-Universität Würzburg and the University of Applied Sciences Würzburg Schweinfurt were invited to participate. The questionnaire consisted of 53 items and included the following validated screening instruments: ASRS, PSS-10, PHQ-4 and AUDIT-C. The response rate was 18% (n = 1011). Knowledge about NE was widespread among the students. The prevalence of neuroenhancement during studies was 12.7%. The three most frequently mentioned substances were caffeine tablets (6.6%), cannabis (4.5%) and methylphenidate (4.3%). The most common reason for NE was exam preparation. There were clear differences between the subject areas, especially with regard to the prevalence of NE. ADHD symptoms, stress, anxiety and depression were positively associated with NE. A stronger effect was found for the relationship between NE and risky alcohol consumption or tobacco use. These results were confirmed by binomial logistic regression. The substances consumed, the knowledge about NE, the prevalence of NE and the reasons for its use fit in seamlessly with previous research. The association between ADHD symptoms, stress, anxiety, depression, risky alcohol consumption and tobacco consumption also confirms previous research findings. It was shown that around a tenth of students have already used NE. In view of the health risks associated with NE, the establishment or expansion of educational programs, counseling and support services for students is desirable and further research on the topic is indicated. KW - Psychische Gesundheit KW - Neuroenhancement KW - Cognitive Enhancement KW - Brain doping Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359812 ER - TY - JOUR A1 - Tessmer, Ingrid A1 - Margison, Geoffrey P. T1 - The DNA alkyltransferase family of DNA repair proteins: common mechanisms, diverse functions JF - International Journal of Molecular Sciences N2 - DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O\(^6\)-alkylguanine and O\(^4\)-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O\(^6\)-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms. Nevertheless, between species, subtle as well as more extensive differences that affect target lesion preferences and/or introduce additional protein functions have evolved. Examining these differences and their functional consequences is intricately entwined with understanding the details of their DNA repair mechanism(s) and their biological roles. In this review, we will present and discuss various aspects of the current status of knowledge on this intriguing protein family. KW - DNA repair KW - O6-alkylguanine-DNA alkyltransferase KW - alkylation damage Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355790 SN - 1422-0067 VL - 25 IS - 1 ER - TY - JOUR A1 - Scheuplein, Nicolas Julian A1 - Lohr, Theresa A1 - Vivoli Vega, Mirella A1 - Ankrett, Dyan A1 - Seufert, Florian A1 - Kirchner, Lukas A1 - Harmer, Nicholas J. A1 - Holzgrabe, Ulrike T1 - Fluorescent probe for the identification of potent inhibitors of the macrophage infectivity potentiator (Mip) protein of Burkholderia pseudomallei JF - SLAS Discovery N2 - Highlights • Synthesis of a new tracer molecule. • Robust and easy screening method for a broad range of compound activities. • FP assay validation considering limited use of starting material, DMSO tolerance, variation in incubation time and temperature. • Possibility of extension to HTP assay. Abstract The macrophage infectivity potentiator (Mip) protein belongs to the immunophilin superfamily. This class of enzymes catalyzes the interconversion between the cis and trans configuration of proline-containing peptide bonds. Mip has been shown to be important for the virulence of a wide range of pathogenic microorganisms, including the Gram-negative bacterium Burkholderia pseudomallei. Small molecules derived from the natural product rapamycin, lacking its immunosuppression-inducing moiety, inhibit Mip's peptidyl-prolyl cis-trans isomerase (PPIase) activity and lead to a reduction in pathogen load in vitro. Here, a fluorescence polarization assay (FPA) to enable the screening and effective development of BpMip inhibitors was established. A fluorescent probe was prepared, derived from previous pipecolic scaffold Mip inhibitors labeled with fluorescein. This probe showed moderate affinity for BpMip and enabled a highly robust FPA suitable for screening large compound libraries with medium- to high-throughput (Z factor ∼ 0.89) to identify potent new inhibitors. The FPA results are consistent with data from the protease-coupled PPIase assay. Analysis of the temperature dependence of the probe's binding highlighted that BpMip's ligand binding is driven by enthalpic rather than entropic effects. This has considerable consequences for the use of low-temperature kinetic assays. KW - PPIase KW - fluorescence polarization KW - anisotropy KW - high throughput screening KW - Burkholderia pseudomallei Mip KW - Mip inhibitor Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349784 VL - 28 IS - 5 ER - TY - JOUR A1 - Hampf, Chantal A1 - Scherf-Clavel, Maike A1 - Weiß, Carolin A1 - Klüpfel, Catherina A1 - Stonawski, Saskia A1 - Hommers, Leif A1 - Lichter, Katharina A1 - Erhardt-Lehmann, Angelika A1 - Unterecker, Stefan A1 - Domschke, Katharina A1 - Kittel-Schneider, Sarah A1 - Menke, Andreas A1 - Deckert, Jürgen A1 - Weber, Heike T1 - Effects of anxious depression on antidepressant treatment response JF - International Journal of Molecular Sciences N2 - Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually. KW - pharmacotherapy KW - depressive disorder KW - anxious depression KW - anxiety KW - therapy response Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355801 SN - 1422-0067 VL - 24 IS - 24 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Langhauser, Friederike A1 - Zimmermann, Lena A1 - Bellut, Maximilian A1 - Kleinschnitz, Christoph A1 - Fluri, Felix T1 - Dimethyl fumarate attenuates lymphocyte infiltration and reduces infarct size in experimental stroke JF - International journal of molecular sciences N2 - Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood–brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke. KW - experimental stroke KW - transient middle cerebral artery occlusion model KW - dimethyl fumarate KW - cerebral inflammation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357731 VL - 24 IS - 21 ER - TY - JOUR A1 - Eberl, Hanna A1 - Rebs, Sabine A1 - Hoppe, Stefanie A1 - Sedaghat-Hamedani, Farbod A1 - Kayvanpour, Elham A1 - Meder, Benjamin A1 - Streckfuss-Bömeke, Katrin T1 - Generation of an RBM20-mutation-associated left-ventricular non-compaction cardiomyopathy iPSC line (UMGi255-A) into a DCM genetic background to investigate monogenetic cardiomyopathies JF - Stem Cell Research N2 - RBM20 mutations account for 3 % of genetic cardiomypathies and manifest with high penetrance and arrhythmogenic effects. Numerous mutations in the conserved RS domain have been described as causing dilated cardiomyopathy (DCM), whereas a particular mutation (p.R634L) drives development of a different cardiac phenotype: left-ventricular non-compaction cardiomyopathy. We generated a mutation-induced pluripotent stem cell (iPSC) line in which the RBM20-LVNC mutation p.R634L was introduced into a DCM patient line with rescued RBM20-p.R634W mutation. These DCM-634L-iPSC can be differentiated into functional cardiomyocytes to test whether this RBM20 mutation induces development of the LVNC phenotype within the genetic context of a DCM patient. KW - cell biology KW - developmental biology KW - general medicine KW - RBM20 mutations KW - DCM genetic background KW - monogenetic cardiomyopathies Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350565 SN - 1873-5061 VL - 74 ER - TY - THES A1 - Friedrich, Anna-Lena T1 - FoxO3-mediated, inhibitory effects of CNP on the profibrotic activation of lung fibroblasts T1 - FoxO3-vermittelte, hemmende Wirkungen von CNP auf die profibrotische Aktivierung von Lungenfibroblasten N2 - Idiopathic Pulmonary Fibrosis (IPF) is a progressive parenchymal lung disease with limited therapeutic treatments. Pathologically altered lung fibroblasts, called myofibroblasts, exhibit increased proliferation, migration, and collagen production, and drive IPF development and progression. Fibrogenic factors such as Platelet derived growth factor-BB (PDGF-BB) contribute to these pathological alterations. Endogenous counter-regulating factors are barely known. Published studies have described a protective role of exogenously administered C-type Natriuretic Peptide (CNP) in pathological tissue remodeling, for example in heart and liver fibrosis. CNP and its cyclic GMP producing guanylyl cyclase B (GC-B) receptor are expressed in the lungs, but it is unknown whether CNP can attenuate lung fibrosis by this pathway. To address this question, we performed studies in primary cultured lung fibroblasts. To examine the effects of the CNP/GC-B pathway on PDGF-BB-induced collagen production, proliferation, and migration in vitro, lung fibroblasts were cultured from wildtype control and GC-B knockout mice. Human lung fibroblasts from patients with IPF and healthy controls were obtained from the UGMLC Biobank. In RIA experiments, CNP, at 10nM and 100nM, markedly and similarly increased cGMP levels in both the murine and human lung fibroblasts, demonstrating GC-B/cGMP signaling. CNP reduced PDGF-BB induced proliferation and migration of lung fibroblasts in BrdU incorporation and gap closure assays, respectively. CNP strongly decreased PDGF-BB-induced collagen 1/3 expression as measured by immunocytochemistry and immunoblotting. Importantly, the protective actions of CNP were preserved in IPF fibroblasts. It is known that the profibrotic actions of PDGF-BB are partly mediated by phosphorylation and nuclear export of Forkhead Box O3 (FoxO3), a transcription factor downregulated in IPF. CNP prevented PDGF-BB elicited FoxO3 phosphorylation and nuclear exclusion in both murine and human control and IPF fibroblasts. CNP signaling and functions were abolished in GC-B-deficient lung fibroblasts. Taken together, the results show that CNP moderates the PDGF-BB-induced activation and differentiation of human and murine lung fibroblasts to myofibroblasts. This effect is mediated CNP-dependent by GC-B/cGMP signaling and FoxO3 regulation. To follow up the patho-physiological relevance of these results, we are generating mice with fibroblast-restricted GC-B deletion for studies in the model of bleomycin-induced pulmonary fibrosis. N2 - Idiopathische pulmonale Fibrose (IPF) ist eine progressiv fortschreitende, parenchymale Lungenerkrankung mit beschränkten therapeutischen Behandlungsmöglichkeiten. Pathologisch veränderte Lungenfibroblasten, sogenannte Myofibroblasten, zeigen eine verstärkte Proliferation, Migration und Kollagenproduktion, die zu einem permanenten Fortschreiten der Erkrankung führen. Während fibrogene Faktoren wie Platelet derived growth factor-BB (PDGF-BB) zu dieser pathologischen Veränderung beitragen, sind endogene Faktoren, die diesem Wandel entgegenwirken, kaum bekannt. Allerdings konnten Studien bereits eine protektive Wirkung von exogen verabreichten C-typ natriuretischen Peptid (CNP) auf krankhaft verändertes Gewebe beschreiben, wie beispielsweise bei Herz- und Leberfibrose. Es ist bekannt, dass CNP und sein cGMP produzierender Rezeptor Guanylyl-Cyclase-B Rezeptor (GC-B) in der Lunge exprimiert werden. Allerdings konnte noch nicht nachgewiesen werden, ob CNP durch diesen Signalweg den Fortschritt einer Lungenfibrose verzögern kann. Um dies herauszufinden, wurden Experimente mit kultivierten, primären Lungenfibroblasten durchgeführt. Um die Effekte des CNP/ GC-B Signalwegs auf die PDGF-BB induzierte Kollagenproduktion, Proliferation und Migration in vitro zu überprüfen, wurden Lungenfibroblasten von Kontroll- und GC-B-Knock-Out Mäusen kultiviert. Weiterhin erhielten wir von der UGMLC Biobank menschliche Fibroblasten von IPF-erkrankten Patienten, sowie gesunde Kontrollfibroblasten. Zur Bestätigung der Funktionalität des GC-B/cGMP Weges, wurde in murinen und humanen Fibroblasten mithilfe eines RIAs ein durch CNP (10nM und 100nM) deutlich erhöhtes cGMP-Level gemessen. CNP reduzierte die durch PDGF-BB induzierte Beschleunigung von Proliferation und Migration der Lungenfibroblasten, was mit Hilfe von BrdU incorporation und Gap closure assay nachgewiesen wurde. Ebenfalls zeigten Immunocytochemistrie und -blotting, dass CNP den PDGF-BB induzierten Anstieg an Kollagenexpression verhindert. Somit wurde festgestellt, dass der schützende Effekt von CNP auch in IPF Fibroblasten erhalten bleibt. Weiterhin ist bekannt, dass die PDGF-BB-induzierten, profibrotischen Veränderungen durch Phosphorylierung und Export des Transkriptionsfaktors Forkhead Box O3 (FoxO3) aus dem Zellkern vermittelt werden, welcher in IPF Fibroblasten vermindert exprimiert ist. CNP verhindert diese PDGF-BB aktivierte Phosphorylierung und Translokation in murinen und humanen Kontroll- und IPF-Fibroblasten. In Lungenfibroblasten mit Deletion des GC-B- Rezeptors war das CNP-Signal und auch dessen Effekt ausgelöscht. Zusammengefasst zeigen die Ergebnisse, dass CNP die PDGF-BB induzierte Aktivierung und Differenzierung von menschlichen und murinen Lungenfibroblasten zu Myofibroblasten beeinflusst. Dieser Effekt wird CNP-abhängig durch den GC-B/cGMP Signalweg und durch die Regulierung von FoxO3 vermittelt. Um abschließend die pathophysiologische Relevanz dieser Erkenntnisse zu zeigen, werden zukünftig Mäuse mit einer fibroblasten-spezifischen Deletion des GC-B Rezeptors für Studien in Bleomycin-induzierter Lungenfibrose genutzt. KW - Idiopathische pulmonale Fibrose KW - Transkriptionsfaktor KW - Natriuretisches Hormon KW - C-type natriuretic peptide KW - FoxO3 Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359845 ER - TY - JOUR A1 - Schlecht, Sina A1 - Neubert, Sven A1 - Meng, Karin A1 - Rabe, Antonia A1 - Jentschke, Elisabeth T1 - Changes of symptoms of anxiety, depression, and fatigue in cancer patients 3 months after a video-based intervention JF - International journal of environmental research and public health N2 - During the COVID-19 pandemic, social distancing restricted psycho-oncological care. Therefore, this secondary analysis examines the changes in anxiety, fear of progression, fatigue, and depression in cancer patients after a video-based eHealth intervention. We used a prospective observational design with 155 cancer patients with mixed tumor entities. Data were assessed before and after the intervention and at a three-month follow-up using self-reported questionnaires (GAD-7, FOP-Q-SF, PHQ-8, and EORTC QLQ-FA12). The eight videos included psychoeducation, Acceptance and Commitment Therapy elements, and yoga and qigong exercises. The results showed that three months after finishing the video-based intervention, participants showed significantly reduced fear of progression (d = −0.23), depression (d = −0.27), and fatigue (d = −0.24) compared to the baseline. However, there was no change in anxiety (d = −0.09). Findings indicated marginal improvements in mental distress when using video-based intervention for cancer patients for up to three months, but long-term effectiveness must be confirmed using a controlled design. KW - cancer KW - psycho-oncology KW - eHealth KW - supportive care intervention KW - psychoeducation KW - mind–body intervention KW - distress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357294 VL - 20 IS - 20 ER - TY - JOUR A1 - Beierle, Felix A1 - Pryss, Rüdiger A1 - Aizawa, Akiko T1 - Sentiments about mental health on Twitter — before and during the COVID-19 pandemic JF - Healthcare N2 - During the COVID-19 pandemic, the novel coronavirus had an impact not only on public health but also on the mental health of the population. Public sentiment on mental health and depression is often captured only in small, survey-based studies, while work based on Twitter data often only looks at the period during the pandemic and does not make comparisons with the pre-pandemic situation. We collected tweets that included the hashtags #MentalHealth and #Depression from before and during the pandemic (8.5 months each). We used LDA (Latent Dirichlet Allocation) for topic modeling and LIWC, VADER, and NRC for sentiment analysis. We used three machine-learning classifiers to seek evidence regarding an automatically detectable change in tweets before vs. during the pandemic: (1) based on TF-IDF values, (2) based on the values from the sentiment libraries, (3) based on tweet content (deep-learning BERT classifier). Topic modeling revealed that Twitter users who explicitly used the hashtags #Depression and especially #MentalHealth did so to raise awareness. We observed an overall positive sentiment, and in tough times such as during the COVID-19 pandemic, tweets with #MentalHealth were often associated with gratitude. Among the three classification approaches, the BERT classifier showed the best performance, with an accuracy of 81% for #MentalHealth and 79% for #Depression. Although the data may have come from users familiar with mental health, these findings can help gauge public sentiment on the topic. The combination of (1) sentiment analysis, (2) topic modeling, and (3) tweet classification with machine learning proved useful in gaining comprehensive insight into public sentiment and could be applied to other data sources and topics. KW - COVID-19 KW - coronavirus KW - public health KW - sentiment analysis KW - topic modeling KW - machine learning Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355192 SN - 2227-9032 VL - 11 IS - 21 ER - TY - JOUR A1 - Meinert, Madlen A1 - Jessen, Christina A1 - Hufnagel, Anita A1 - Kreß, Julia Katharina Charlotte A1 - Burnworth, Mychal A1 - Däubler, Theo A1 - Gallasch, Till A1 - Da Xavier Silva, Thamara Nishida A1 - Dos Santos, Ancély Ferreira A1 - Ade, Carsten Patrick A1 - Schmitz, Werner A1 - Kneitz, Susanne A1 - Friedmann Angeli, José Pedro A1 - Meierjohann, Svenja T1 - Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner JF - Redox Biology N2 - The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf\(^{CA}\); Pten\(^{lox/+}\) melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell lines in vitro. RNA sequencing of human melanoma cells revealed a strong adaptive upregulation of NRF2 and ATF4 pathways, which orchestrated the compensatory upregulation of genes involved in antioxidant defence and de novo cysteine biosynthesis. In addition, the joint activation of ATF4 and NRF2 triggered a phenotypic switch characterized by a reduction of differentiation genes and induction of pro-invasive features, which was also observed after erastin treatment or the inhibition of glutathione synthesis. NRF2 alone was capable of inducing the phenotypic switch in a transient manner. Together, our data show that cystine or glutathione levels regulate the phenotypic plasticity of melanoma cells by elevating ATF4 and NRF2. KW - thiol starvation KW - ATF4 KW - NRF2 KW - melanoma Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350328 VL - 70 ER - TY - JOUR A1 - Bassler, Miriam C. A1 - Knoblich, Mona A1 - Gerhard-Hartmann, Elena A1 - Mukherjee, Ashutosh A1 - Youssef, Almoatazbellah A1 - Hagen, Rudolf A1 - Haug, Lukas A1 - Goncalves, Miguel A1 - Scherzad, Agmal A1 - Stöth, Manuel A1 - Ostertag, Edwin A1 - Steinke, Maria A1 - Brecht, Marc A1 - Hackenberg, Stephan A1 - Meyer, Till Jasper T1 - Differentiation of salivary gland and salivary gland tumor tissue via Raman imaging combined with multivariate data analysis JF - Diagnostics N2 - Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary. KW - salivary gland tumor KW - confocal Raman imaging KW - principal component analysis KW - discriminant analysis KW - multivariate data analysis KW - molecular diagnostics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355558 SN - 2075-4418 VL - 14 IS - 1 ER - TY - JOUR A1 - Kreß, Julia Katharina Charlotte A1 - Jessen, Christina A1 - Hufnagel, Anita A1 - Schmitz, Werner A1 - Da Xavier Silva, Thamara Nishida A1 - Ferreira Dos Santos, Ancély A1 - Mosteo, Laura A1 - Goding, Colin R. A1 - Friedmann Angeli, José Pedro A1 - Meierjohann, Svenja T1 - The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2 JF - Cell Reports N2 - Highlights • The integrated stress response leads to a general ATF4-dependent activation of NRF2 • ATF4 causes a CHAC1-dependent GSH depletion, resulting in NRF2 stabilization • An elevation of NRF2 transcript levels fosters this effect • NRF2 supports the ISR/ATF4 pathway by improving cystine and antioxidant supply Summary The redox regulator NRF2 becomes activated upon oxidative and electrophilic stress and orchestrates a response program associated with redox regulation, metabolism, tumor therapy resistance, and immune suppression. Here, we describe an unrecognized link between the integrated stress response (ISR) and NRF2 mediated by the ISR effector ATF4. The ISR is commonly activated after starvation or ER stress and plays a central role in tissue homeostasis and cancer plasticity. ATF4 increases NRF2 transcription and induces the glutathione-degrading enzyme CHAC1, which we now show to be critically important for maintaining NRF2 activation. In-depth analyses reveal that NRF2 supports ATF4-induced cells by increasing cystine uptake via the glutamate-cystine antiporter xCT. In addition, NRF2 upregulates genes mediating thioredoxin usage and regeneration, thus balancing the glutathione decrease. In conclusion, we demonstrate that the NRF2 response serves as second layer of the ISR, an observation highly relevant for the understanding of cellular resilience in health and disease. KW - NRF2 KW - ATF4 KW - integrated stress response KW - CHAC1 KW - melanoma KW - SLC7A11 KW - GSH Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350312 VL - 42 IS - 7 ER - TY - JOUR A1 - Hennes, Jan-Lucca A1 - Huflage, Henner A1 - Grunz, Jan-Peter A1 - Hartung, Viktor A1 - Augustin, Anne Marie A1 - Patzer, Theresa Sophie A1 - Pannenbecker, Pauline A1 - Petritsch, Bernhard A1 - Bley, Thorsten Alexander A1 - Gruschwitz, Philipp T1 - An intra-individual comparison of low-keV photon-counting CT versus energy-integrating-detector CT angiography of the aorta JF - Diagnostics N2 - This retrospective study aims to provide an intra-individual comparison of aortic CT angiographies (CTAs) using first-generation photon-counting-detector CT (PCD-CT) and third-generation energy-integrating-detector CT (EID-CT). High-pitch CTAs were performed with both scanners and equal contrast-agent protocols. EID-CT employed automatic tube voltage selection (90/100 kVp) with reference tube current of 434/350 mAs, whereas multi-energy PCD-CT scans were generated with fixed tube voltage (120 kVp), image quality level of 64, and reconstructed as 55 keV monoenergetic images. For image quality assessment, contrast-to-noise ratios (CNRs) were calculated, and subjective evaluation (overall quality, luminal contrast, vessel sharpness, blooming, and beam hardening) was performed independently by three radiologists. Fifty-seven patients (12 women, 45 men) were included with a median interval between examinations of 12.7 months (interquartile range 11.1 months). Using manufacturer-recommended scan protocols resulted in a substantially lower radiation dose in PCD-CT (size-specific dose estimate: 4.88 ± 0.48 versus 6.28 ± 0.50 mGy, p < 0.001), while CNR was approximately 50% higher (41.11 ± 8.68 versus 27.05 ± 6.73, p < 0.001). Overall image quality and luminal contrast were deemed superior in PCD-CT (p < 0.001). Notably, EID-CT allowed for comparable vessel sharpness (p = 0.439) and less pronounced blooming and beam hardening (p < 0.001). Inter-rater agreement was good to excellent (0.58–0.87). Concluding, aortic PCD-CTAs facilitate increased image quality with significantly lower radiation dose compared to EID-CTAs KW - CT angiography KW - aorta KW - photon-counting-detector CT KW - radiation dose reduction KW - spectral imaging Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355568 SN - 2075-4418 VL - 13 IS - 24 ER - TY - THES A1 - Adam, Pia Sophie T1 - Expression von PD-L1 und FGFR1-4 beim anaplastischen und gering differenzierten Schilddrüsenkarzinom - Evaluation als präklinische diagnostische Marker T1 - FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale N2 - Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and methods: Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results: PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation. N2 - Hintergrund: Die therapeutischen Optionen für das gering differenzierte (PDTC) und anaplastische (ATC) Schilddrüsenkarzinom sind limitiert, weshalb diese Erkrankungen überwiegend mit einer schlechten Prognose einhergehen. Lenvatinib (LEN) ist ein Multityrosinkinase-Inhibitor, der unter anderem die Fibroblasten-Wachstumsfaktor-Rezeptoren (FGFR) 1-4 inhibiert und zur Therapie des fortgeschrittenen radiojodrefraktären Schilddrüsenkarzinoms zugelassen ist. Es zeigt sich nur ein geringes Ansprechen auf die Monotherapie bei ATCs, wobei neuere Studien eine therapeutische Überlegenheit der Kombination aus LEN und dem PD-1-Inhibitor Pembrolizumab (PEM) beschreiben. Material und Methoden: Die Expression von PD-L1 wurde in ATC (n=93)- und PDTC (n=47)-Primärtumorgewebe von 1997-2019 aus fünf deutschen (Universitäts-)Kliniken mittels Immunhistochemie analysiert und mit dem Tumor Proportion Score (TPS) quantifiziert. Der Nachweis von FGFR1-4-mRNA wurde bei 31 ATC- und 14 PDTC-Gewebeproben mittels RNAscope In-situ-Hybridisierung quantifiziert. Als Kontrollgruppe wurde normales Schilddrüsengewebe (NT) und Gewebe von papillären Schilddrüsenkarzinomen (PTC) verwendet. Der primäre Endpunkt war das krankheitsspezifische Überleben (DSS). Ergebnisse: Eine PD-L1-Expression mit einem TPS ≥50% konnte in 42% der ATC- und in 26% der PDTC-Proben nachgewiesen werden. Die mediane PD-L1-Expression war in ATC-(TPS 30%) signifikant höher im Vergleich zu PDTC-Proben (5%; p<0,01) und NT (0%; p<0,001). 53% der PDTC-Proben zeigten eine PD-L1-Expression ≤5%. Die Expression von FGFR-mRNA war in allen Proben sehr gering, wobei die kombinierte FGFR1-4-Expression in PDTC- und ATC-Gewebe im Vergleich zu normalem Schilddrüsengewebe signifikant höher war (jeweils p<0,001). Es ergab sich keine Assoziation zwischen der PD-L1- und FGFR1-4-Expression mit dem krankheitsspezifischen Überleben. Schlussfolgerung: Eine hohe PD-L1-Expression in einem großen Anteil der ATCs und einem Viertel der PDTCs, könnte auf eine Rationale zur Therapieentscheidung für Immuncheckpoint-Inhibioren hinweisen. Die FGFR-Expression war in allen Schilddrüsenkarzinomen sehr gering. Der klinisch beobachtete Synergismus von PEM und LEN könnte durch immunmodulatorische Effekte hervorgerufen werden. KW - Schilddrüsenkrebs KW - Immun-Checkpoint KW - FGFR KW - PD-L1 KW - Immuncheckpointinhibitor KW - Tyrosinkinaseinhibitor KW - Anaplastisches Schilddrüsenkarzinom KW - Gering differenziertes Schilddrüsenkarzinom KW - Protein-Tyrosin-Kinasen KW - Immuntherapie KW - Tyrosinkinase Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359391 ER - TY - JOUR A1 - Pozzi, Nicoló Gabriele A1 - Bolzoni, Francesco A1 - Biella, Gabriele Eliseo Mario A1 - Pezzoli, Gianni A1 - Ip, Chi Wang A1 - Volkmann, Jens A1 - Cavallari, Paolo A1 - Asan, Esther A1 - Isaias, Ioannis Ugo T1 - Brain noradrenergic innervation supports the development of Parkinson’s tremor: a study in a reserpinized rat model JF - Cells N2 - The pathophysiology of tremor in Parkinson’s disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic–rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients. KW - Parkinson’s disease KW - tremor KW - locus coeruleus KW - noradrenaline KW - reserpinized rat model Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357721 SN - 2073-4409 VL - 12 IS - 21 ER - TY - THES A1 - Wilhelmi, Kai Alexander T1 - Untersuchung von Veränderungen der myelinisierten Nervenfasern durch Entmarkung in Haut- und Nervenbiopsien von Patienten mit Polyneuropathie T1 - Examination of changes in myelinated nerve fibers due to demyelination in skin and nerve biopsies of patients with polyneuropathy N2 - In dieser Arbeit wurde durch das immunhistochemische Anfärben von nodalen (Natriumkanäle, NF), paranodalen (Caspr, NF) und internodalen (MBP) Proteinen der in Fingerhautbiopsien vorhanden Nervenfasern untersucht, ob eine Veränderung der typischen Verteilungsmuster dieser Proteine, eine demyelinisierende Polyneuropathie anzeigen kann. Dazu wurden am Universitätsklinikum Würzburg prospektiv 93 Polyneuropathie-Patienten und 25 Kontrollpersonen rekrutiert. Bei allen Patienten wurden Hautstanzbiospien am Zeigefinger durchgeführt. Bei 35 Patienten mit schweren oder unklaren Verläufen, wurden konsiliarisch Nervus suralis Biopsien durchgeführt. Aus einem Abschnitt von 27 dieser Biopsien, konnten im Rahmen dieser Arbeit Zupfnervenpräparate angefertigt und analog zu den Hautbiopsien ausgewertet werden. Aus der Routinediagnostik der Klinik flossen weiterhin die Ergebnisse der elektrophysiologischen Routinediagnostik und der Histologiebefund der Nervus suralis Biopsien in die Auswertung ein. Zusammenfassend kamen veränderte Natriumkanalbanden in Fingerhautbiopsien signifikant häufiger bei Patienten mit elektrophysiologisch als demyelinisierend befundeten Polyneuropathien, als bei Patienten mit elektrophysiologisch als axonal befundeten Polyneuropathien vor. Vielfach fanden sich veränderte Natriumkanalbanden inmitten para- und internodal unauffälliger Schnürringe und umgekehrt. Diese Beobachtung stützt die bereits in Vorarbeiten vorgeschlagene und in der aktuellen Leitlinie zur Diagnostik für Polyneuropathien aufgegriffene Entität der Paranodopathien (Uncini, Susuki, & Yuki, 2013). Möglich wäre, dass eine veränderte Verteilung der Natriumkanäle die schnelle Leitfähigkeit beeinträchtigen und somit trotz intakter Bemarkung, elektrophysiologisch das Bild einer demyelinisierenden Neuropathie vermittelt. Ein direkter Zusammenhang zwischen dem Auftreten von doppelten und verlängerten Natriumkanalbanden und einzelnen Messwerten (z.B. Amplituden und Latenzzeiten) fand sich nicht. Auch in den Zupfnervenpräparaten der Nervus suralis Biopsien, konnten o.g. Verteilungsmuster untersucht werden. Deren Vorkommen zeigte sich als unabhängig vom elektrophysiologischen und histologischen Befund, von der Ätiologie der PNP und von den gefundenen Veränderungen in den Hautbiopsien des betreffenden Patienten. N2 - Myelinated nerve fibers in finger skin biopsies and sural nerve biopsies were examined using immunohistochemical staining to detect changes in the typical distribution patterns of nodal (voltage-gated sodium channels, neurofascin 186), paranodal (Caspr, neurofascin 155), and internodal (myelin basic protein) proteins, aiming to identify indicators for demyelinating polyneuropathies. A total of 93 polyneuropathy patients and 25 control subjects were prospectively recruited from the University Hospital Würzburg. Skin punch biopsies were conducted on all patients and control subjects. Additionally, sural nerve biopsies were performed on a consultative basis for 35 patients. Teased nerve fiber preparations were made from a section of 27 of these biopsies and evaluated similarly to the skin biopsies. In summary, altered sodium channel bands in myelinated nerve fibers from finger skin biopsies were significantly more prevalent in patients electrophysiologically diagnosed with demyelinating polyneuropathies. However, there was no significant difference in the means of individual electrophysiological measurements between patients with and without changes in the immunohistochemical stainings. Each of the investigated changes was significantly more common in the polyneuropathy group than in the control group. Further correlations, particularly in the comparison of results from skin and sural nerve biopsies, were not found KW - Polyneuropathie KW - Ranvier-Schnürring KW - Entmarkung KW - Elektrophysiologie KW - Caspr KW - Neurofascin KW - MBP KW - spannungsgesteuerter Natriumkanal Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-360046 ER - TY - THES A1 - Stratmann [geb. Hirster], Tizia T1 - Veränderung der gesundheitsbezogenen Lebensqualität nach leberchirurgischen Operationen T1 - Health-related Quality of Life after hepatic resection N2 - Es zeigte sich, dass die unmittelbare postoperative gesundheitsbezogene Lebensqualität erwartungsgemäß deutlich eingeschränkt, jedoch nach circa sechs Monaten wieder auf dem Ausgangsniveau der präoperativen Ebene angekommen war. Sowohl die Symptomskalen als auch die Funktionsskalen zeigten statistisch signifikante Unterschiede der erhobenen Werte bezüglich des Vergleichs der präoperativen zu den postoperativen Daten, dasselbe ließ sich über die Werte im Rahmen der Verlaufskontrolle nach circa sechs Monaten erheben. Eine kurzfristige Einbuße der Lebensqualität durch einen stationären Krankenhausaufenthalt sowie einer operativen Versorgung erscheint logisch. Für die zukünftige Entscheidung vor allem auch für Personen, welche aufgrund einer benignen Leberraumforderung eine operative Versorgung erhalten sollen, ist zu sagen, dass die globale gesundheitsbezogene Lebensqualität postoperativ nach circa sechs Monaten gleich bzw. etwas gebessert ausfiel und somit eine Rechtfertigung der operativen Versorgung auch bei benignen Erkrankungen darstellen kann. Ein wesentlicher Aspekt der Arbeit ist, dass gezeigt werden konnte, dass auch bei komplexen Lebereingriffen eine schnelle Rekonvaleszenz - mindestens auf das Niveau vor dem Eingriff - innerhalb der ersten sechs Monate zu erwarten ist. Die systematische Erfassung der Lebensqualität hilft die postoperativen Einschränkungen und die Rekonvaleszenz zu normieren. N2 - It has been shown that the immediate postoperative health-related quality of life was reduced significantly, as expected. After six months the health-related quality of life returned to the preoperative level. The data indicates that even in complex liver procedures, fast recovery - at least to the preoperative level - can be expected within six months. The systematic assessment of quality of life helps to objectify postoperative limitations and recovery. KW - Leberresektion KW - Lebensqualität KW - gesundheitsbezogene Lebensqualität KW - health-related quality of life KW - hrQOL KW - hepatic resection KW - hepatic surgery KW - Leberchirurgie Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359977 ER - TY - THES A1 - Menger, Kristina Rebekka T1 - Bauchlagerung für nicht-intubierte ARDS- und COVID-19 Patient/innen: eine systematische Übersichtsarbeit T1 - Prone Positioning for non-intubated ARDS and COVID-19 patients: a systematic review N2 - Die Bauchlagerung von intubierten ARDS-Patient/innen mit einer schlechten Oxygenierung wird laut Leitlinie seit mehreren Jahren als supportive Therapiemaßnahme empfohlen. Im Rahmen der COVID-19 Pandemie wurde nun erstmalig die Bauchlagerung auch bei hypoxämischen, nicht-intubierten Patient/innen untersucht. Diese Fragestellung wurde in der vorliegenden Arbeit mittels einer systematischen Übersichtsarbeit betrachtet. Aufgrund der aktuellen Pandemiesituation wurden neben ARDS-Patient/innen im Allgemeinen insbesondere COVID-19 Patient/innen mit einem akuten Lungenversagen als Subgruppe untersucht. Am 21.11.2020 wurde eine systematische Suche nach Studien in den Datenbanken MEDLINE, Cochrane COVID-19 Study Register und Living Overview of the Evidence platform durchgeführt. Die Ergebnisse wurden, wo möglich, in Form einer Meta-Analyse zusammengefasst, in Tabellen darstellt oder deskriptiv beschrieben. Das Risiko für Bias wurde jeweils für die eingeschlossenen kontrollierten Studien mittels ROBINS-I beurteilt. Die Vertrauenswürdigkeit der Evidenz der gesamten Arbeit wurde mit Hilfe des GRADE-Ansatzes untersucht. Insgesamt wurden 30 Studien eingeschlossen, davon 4 kontrollierte Studien, keine RCTs. In 3 der kontrollierten Studien wurde die Bauchlagerung bei COVID-19 Patient/innen untersucht, in einer bei Patient/innen mit einem anderweitig verursachten ARDS. Es ist unklar, ob die Bauchlagerung die Intubationsrate (RR = 0,92; 95% KI: 0,59 - 1,44; I² = 65%; sehr niedrige Vertrauenswürdigkeit der Evidenz), die Mortalität (RR = 0,55; 95% KI: 0,23 - 1,30; I² = 60%; sehr niedrige Vertrauenswürdigkeit der Evidenz) und die Wahrscheinlichkeit für eine Aufnahme auf die Intensivstation (RR = 0,94; 95% KI: 0,54 - 1,63; I2 = 71%; sehr niedrige Vertrauenswürdigkeit der Evidenz) verringern kann. Auch für die anderen betrachteten Endpunkte konnte kein signifikanter Effekt der Bauchlagerung nachgewiesen werden Im Vergleich der Subgruppen „Nicht-COVID-19“ (8 Studien) und „COVID-19“ (22 Studien) konnten in Bezug auf alle betrachteten Endpunkte keine relevanten Unterschiede festgestellt werden. Insgesamt ist die Evidenz nicht ausreichend, um Vor- und Nachteile der Bauchlagerung für nicht-intubierte ARDS Patient/innen gegenüber der üblichen Rückenlagerung aufzuzeigen und diese für die Praxis zu empfehlen. N2 - Prone positioning of intubated ARDS patients with poor oxygenation has been recommended as a supportive therapy for several years. In the context of the COVID-19 pandemic, prone positioning has now been investigated for the first time in hypoxemic, non-intubated patients. This issue was examined by our systematic review. Because of the current pandemic situation, we assessed the effects of prone positioning in COVID-19 patients with acute respiratory failure in particular as a subgroup in addition to ARDS patients in general. A systematic search for studies was performed in MEDLINE, Cochrane COVID-19 Study Register, and Living Overview of the Evidence platform databases on 21 November 2020. Where possible, results were analyzed in the form of meta-analysis, presented in tables, or described descriptively. Risk of bias was assessed for each of the included controlled studies using ROBINS-I. The quality of evidence for the entire systematic review was assessed using the GRADE approach. A total of 30 studies were included, 4 of which were controlled trials, but no RCTs. 3 of the controlled trials investigated prone positioning in COVID-19 patients, one trial in patients with ARDS caused by other means. It is unclear whether prone positioning can reduce intubation rate (RR =0.92; 95% CI: 0.59-1.44; I²=65%; very low quality evidence), mortality (RR =0.55; 95% CI: 0.23-1.30; I²=60%; very low quality evidence), and the likelihood of ICU admission (RR =0.94; 95% CI: 0.54-1.63; I2 =71%; very low quality evidence). No significant effect of prone positioning was demonstrated for the other outcomes considered either. When comparing the "non-COVID-19" (8 studies) and "COVID-19" (22 studies) subgroups, no relevant differences were found for all outcomes assessed. Overall, the evidence is insufficient to demonstrate benefits and harms of prone positioning for non-intubated ARDS patients compared with usual care and to translate the results into practice. KW - Bauchlage KW - ARDS KW - COVID-19 KW - Nicht-invasive Beatmung Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359865 ER - TY - RPRT ED - Nieswandt, Bernhard T1 - Platelets – Molecular, cellular and systemic functions in health and disease T1 - Thrombozyten – molekulare, zelluläre und systemische Funktionen unter physiologischen und pathologischen Bedingungen (SFB/TR240 - Abschlussbericht BT - Final Report (2018/2 - 2023/1) N2 - Besides their central role in haemostasis and thrombosis, platelets are increasingly recognised as versatile effector cells in inflammation, the innate and adaptive immune response, extracellular matrix reorganisation and fibrosis, maintenance of barrier and organ integrity, and host response to pathogens. These platelet functions, referred to as thrombo-inflammation and immunothrombosis, have gained major attention in the COVID-19 pandemic, where patients develop an inflammatory disease state with severe and life-threatening thromboembolic complications. In the CRC/TR 240, a highly interdisciplinary team of basic, translational and clinical scientists explored these emerging roles of platelets with the aim to develop novel treatment concepts for cardiovascular disorders and beyond. We have i) unravelled mechanisms leading to life-threatening thromboembolic complica-tions following vaccination against SARS-CoV-2 with adenoviral vector-based vaccines, ii) identified unrecognised functions of platelet receptors and their regulation, offering new potential targets for pharmacological intervention and iii) developed new methodology to study the biology of megakar-yocytes (MKs), the precursor cells of platelets in the bone marrow, which lay the foundation for the modulation of platelet biogenesis and function. The projects of the CRC/TR 240 built on the unique expertise of our research network and focussed on the following complementary fields: (A) Cell bi-ology of megakaryocytes and platelets and (B) Platelets as regulators and effectors in disease. To achieve this aim, we followed a comprehensive approach starting out from in vitro systems and animal models to clinical research with large prospective patient cohorts and data-/biobanking. Despite the comparably short funding period the CRC/TR 240 discovered basic new mechanisms of platelet biogenesis, signal transduction and effector function and identified potential MK/platelet-specific molecular targets for diagnosis and therapy of thrombotic, haemorrhagic and thrombo-inflammatory disease states. N2 - Thrombozyten sind von zentraler Bedeutung für die Hämostase, aber auch bei der Entstehung akuter thrombotischer Erkrankungen wie Herzinfarkt oder Schlaganfall. Darüber hinaus sind Thrombozyten aber auch vielseitige Effektorzellen von Entzündungsprozessen, der angeborenen Immunität, bei zellulären Abwehrmechanismen sowie bei der Aufrechterhaltung der Gefäß- und Organintegrität. Diese neuen, als Thrombo-Inflammation und Immunothrombose bezeichneten Funktionen haben im Rahmen der COVID-19 Pandemie große Aufmerksamkeit erlangt, da betroffene Patienten systemische Entzündungszustände in Verbindung mit thromboembolischen Komplikationen aufweisen, die oft auch tödlich verlaufen. Im SFB/TR 240 arbeitete ein interdisziplinäres Team von grundlagenorientierten, translationalen und klinischen Wissenschaftlern zusammen an der Erforschung dieser neuartigen Thrombozytenfunktionen mit dem Ziel, neue verbesserte Therapiemöglichkeiten für kardiovaskuläre, aber auch andere Erkrankungen zu entwickeln. Während der Förderphase haben wir i) die Mechanismen aufgeklärt, die in seltenen Fällen nach Impfung mit Adenovirus-basierten Vakzinen gegen Sars-CoV-2 zu lebensbedrohlichen thromboembolischen Komplikationen führten, ii) neue Funktionen und Regulationsmechanismen thrombozytärer Rezeptoren identifiziert, die Grundlage zur therapeutischen Intervention sein könnten und iii) neue Technologien entwickelt, die vertiefte Studien zur Biologie der Megakaryozyten, den Vorläuferzellen der Thrombozyten im Knochenmark, ermöglichen und den Weg zu einer gezielten Beeinflussung der Thrombozytenbiogenese und –funktion ebnen könnten. Die Projekte des TR 240 konzentrierten sich auf die folgenden komplementären Forschungsgebiete: (A) Zellbiologie der Megakaryozyten und Thrombozyten mit dem Ziel eines verbesserten Verständnisses der grundlegenden Funktionen beider Zelltypen und (B) Thrombozyten als Modulatoren und Effektoren bei Erkrankungen. Um dieses Ziel zu erreichen, wurde ein sehr umfassender Ansatz verfolgt, der sich von in vitro Systemen über Tiermodelle bis hin zur klinischen Forschung mit Biobanken und großen, prospektiven Patientenkohorten erstreckte. Der SFB/TR 240 konnte in der vergleichsweisen kurzen Zeit seiner Förderung grundlegend neue Erkenntnisse zu den Mechanismen der Thrombozytenbiogenese, Thrombozyten-Signaltransduktion und -Effektorfunktionen erarbeiten und neue MK/Thrombozyten-spezifische Angriffspunkte für Diag-nose und Therapie thrombotischer, hämorrhagischer und thrombo-inflammatorischer Erkrankungen identifizieren. KW - Thrombozyt KW - platelets KW - thrombo-inflammation KW - haemostasis KW - stroke KW - megakaryocytes KW - Sonderforschungsbereich Transregio 240 KW - Bericht KW - Collaborative Research Center KW - Experimental Biomedicine Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359636 ER - TY - THES A1 - Chen, Xinyu T1 - How natural walking changes occipital alpha oscillations and concurrently modulates cognitive processes T1 - Die Auswirkungen natürlichen Gehens auf okzipitale Alpha-Oszillationen bei gleichzeitiger Modulation kognitiver Prozesse N2 - Humans actively interact with the world through a wide range of body movements. To understand human cognition in its natural state, we need to incorporate ecologically relevant body movement into our account. One fundamental body movement during daily life is natural walking. Despite its ubiquity, the impact of natural walking on brain activity and cognition has remained a realm underexplored. In electrophysiology, previous studies have shown a robust reduction of ongoing alpha power in the parieto-occipital cortex during body movements. However, what causes the reduction of ongoing alpha, namely whether this is due to body movement or prevalent sensory input changes, was unknown. To clarify this, study 1 was performed to test if the alpha reduction is dependent on visual input. I compared the resting state alpha power during natural walking and standing, in both light and darkness. The results showed that natural walking led to decreased alpha activity over the occipital cortex compared to standing, regardless of the lighting condition. This suggests that the movement-induced modulation of occipital alpha activity is not driven by visual input changes during walking. I argue that the observed alpha power reduction reflects a change in the state of the subject based on disinhibition induced by walking. Accordingly, natural walking might enhance visual processing and other cognitive processes that involve occipital cortical activity. I first tested this hypothesis in vision. Study 2 was performed to examine the possible effects of natural walking across visual processing stages by assessing various neural markers during different movement states. The findings revealed an amplified early visual response, while a later visual response remain unaffected. A follow-up study 3 replicated the walking-induced enhancement of the early visual evoked potential and showed that the enhancement was dependent on specific stimulus-related parameters (eccentricity, laterality, distractor presence). Importantly, the results provided evidence that the enhanced early visual responses are indeed linked to the modulation of ongoing occipital alpha power. Walking also modulated the stimulus-induced alpha power. Specifically, it showed that when the target appeared in the fovea area without a distractor, walking exhibited a significantly reduced modulation of alpha power, and showed the largest difference to standing condition. This effect of eccentricity indicates that during later visual processing stages, the visual input in the fovea area is less processed than in peripheral areas while walking. The two visual studies showed that walking leads to an enhancement in temporally early visual processes which can be predicted by the walking-induced change in ongoing alpha oscillation likely marking disinhibition. However, while walking affects neural markers of early sensory processes, it does not necessarily lead to a change in the behavioural outcome of a sensory task. The two visual studies suggested that the behavioural outcome seems to be mainly based on later processing stages. To test the effects of walking outside the visual domain, I turned to audition in study 4. I investigated the influence of walking in a particular path vs. simply stepping on auditory processing. Specifically, the study tested whether enhanced processing due to natural walking can be found in primary auditory brain activity and whether the processing preferences are dependent on the walking path. In addition, I tested whether the changed spatial processing that was reported in previous visual studies can be seen in the auditory domain. The results showed enhanced sensory processing due to walking in the auditory domain, which was again linked to the modulation of occipital alpha oscillation. The auditory processing was further dependent on the walking path. Additionally, enhanced peripheral sensory processing, as found in vision, was also present in audition. The findings outside vision supported the idea of natural walking affecting cognition in a rather general way. Therefore in my study 5, I examined the effect of natural walking on higher cognitive processing, namely divergent thinking, and its correlation with the modulation of ongoing alpha oscillation. I analyzed alpha oscillations and behavioural performance during restricted and unrestricted movement conditions while subjects completed a Guilford's alternate uses test. The results showed that natural walking, as well as missing body restriction, reduces the occipital alpha ongoing power independent of the task phase which goes along with higher test scores. The occipital alpha power reduction can therefore be an indicator of a changed state that allows improved higher cognitive processes. In summary, the research presented in this thesis highlights that natural walking can change different processes in the visual and auditory domain as well as higher cognitive processes. The effect can be attributed to the movement of natural walking itself rather than to changes in sensory input during walking. The results further indicate that the walking-induced modulation of ongoing occipital alpha oscillations drives the cognitive effects. We therefore suggest that walking changes the inhibitory state which can influence awareness and attention. Such a mechanism could facilitate an adaptive enhancement in cognitive processes and thereby optimize movement-related behaviour such as navigation. N2 - Menschen interagieren aktiv mit der Welt durch eine breite Palette von Körperbewegungen. Um die menschliche Kognition in ihrem natürlichen Zustand zu verstehen, müssen wir ökologisch relevante Körperbewegungen in unsere Betrachtung einbeziehen. Eine grundlegende Körperbewegung im täglichen Leben ist das natürliche Gehen. Trotz seiner Allgegenwärtigkeit ist die Auswirkung des natürlichen Gehens auf die Gehirnaktivität und die Kognition weitgehend unerforscht geblieben. In der Elektrophysiologie haben frühere Studien eine robuste Reduktion der laufenden Alpha-Leistung im parieto-okzipitalen Cortex während Körperbewegungen gezeigt. Es war jedoch unbekannt, was die Reduktion des laufenden Alpha verursacht, nämlich ob dies auf Körperbewegung oder vorherrschende sensorische Eingangsänderungen zurückzuführen ist. Um dies zu klären, wurde Studie 1 durchgeführt, um zu testen, ob die Alpha-Reduktion von visuellem Input abhängig ist. Ich verglich die Alpha-Leistung im Ruhezustand beim natürlichen Gehen und Stehen, sowohl bei Licht als auch im Dunkeln. Die Ergebnisse zeigten, dass natürliches Gehen zu einer verminderten Alpha-Aktivität über dem okzipitalen Cortex im Vergleich zum Stehen führte, unabhängig von den Lichtverhältnissen. Dies legt nahe, dass die bewegungsinduzierte Modulation der okzipitalen Alpha-Aktivität nicht durch visuelle Veränderungen während des Gehens verursacht wird. Ich argumentiere, dass die beobachtete Reduktion der Alpha-Leistung eine Veränderung des Zustands der Versuchsperson aufgrund der durch das Gehen induzierten Hemmung widerspiegelt. Natürliches Gehen könnte daher die visuelle Verarbeitung und andere kognitive Prozesse, die die Aktivität des okzipitalen Cortex umfassen, verstärken. Ich habe diese Hypothese zuerst im Bereich der Vision getestet. Studie 2 wurde durchgeführt, um die möglichen Auswirkungen des natürlichen Gehens auf verschiedene neurale Marker in verschiedenen Bewegungszuständen zu untersuchen. Die Ergebnisse zeigten eine verstärkte frühe visuelle Reaktion, während eine spätere visuelle Reaktion unverändert blieb. Eine Nachfolgestudie 3 replizierte die durch das Gehen induzierte Verstärkung des frühen visuellen ereigniskorrelierten Potenzials und zeigte, dass die Verstärkung von spezifischen stimuliabhängigen Parametern abhängig war (Exzentrizität, Lateralität, Vorhandensein von Störreizen). Die Ergebnisse lieferten wichtige Hinweise darauf,dass die verstärkten frühen visuellen Reaktionen tatsächlich mit der Modulation der laufenden Alpha-Leistung im okzipitalen Cortex zusammenhängen. Das Gehen modulierte auch die stimuliinduzierte Alpha-Leistung. Insbesondere zeigte sich, dass bei Erscheinen des Ziels im fovealen Bereich ohne Störreiz das Gehen eine signifikant reduzierte Modulation der Alpha-Leistung aufwies und den größten Unterschied zum Stehzustand zeigte. Dieser Exzentrizitätseffekt deutet darauf hin, dass während späterer visueller Verarbeitungsstadien die visuelle Eingabe im Fovealbereich weniger verarbeitet wird als in peripheren Bereichen während des Gehens. Die beiden visuellen Studien zeigten, dass Gehen zu einer Verstärkung früher visueller Prozesse führt, die durch die durch das Gehen verursachte Veränderung der laufenden Alpha-Oszillation wahrscheinlich markiert werden. Allerdings beeinflusst Gehen zwar neuronale Marker früher sensorischer Prozesse, führt aber nicht zwangsläufig zu einer Veränderung des Verhaltensergebnisses einer sensorischen Aufgabe. Die beiden visuellen Studien legen nahe, dass das Verhaltensergebnis hauptsächlich auf späteren Verarbeitungsstadien beruht. Um die Auswirkungen des Gehens außerhalb des visuellen Bereichs zu testen, wandte ich mich in Studie 4 der Auditierung zu. Ich untersuchte den Einfluss des Gehens auf einen bestimmten Pfad im Vergleich zum einfachen Schritt auf die auditive Verarbeitung. Die Studie testete speziell, ob eine verbesserte Verarbeitung aufgrund des natürlichen Gehens in der primären auditorischen Hirnaktivität gefunden werden kann und ob die Verarbeitungspräferenzen vom Gehpfad abhängen. Darüber hinaus habe ich getestet, ob die in früheren visuellen Studien berichtete veränderte räumliche Verarbeitung auch im auditiven Bereich beobachtet werden kann. Die Ergebnisse zeigten eine verbesserte sensorische Verarbeitung aufgrund des Gehens im auditiven Bereich, die erneut mit der Modulation der okzipitalen Alpha-Oszillation in Verbindung stand. Die auditive Verarbeitung war auch vom Gehpfad abhängig. Darüber hinaus wurde eine verbesserte periphere sensorische Verarbeitung, wie sie in der Vision gefunden wurde, auch in der Auditierung beobachtet. Die außerhalb des visuellen Bereichs gefundenen Ergebnisse unterstützen die Idee, dass natürliches Gehen die Kognition auf eher allgemeine Weise beeinflusst. Daher habe ich in meiner Studie 5 die Wirkung des natürlichen Gehens auf höhere kognitive Prozesse untersucht, nämlich das divergente Denken, und seine Korrelation mit der Modulation der laufenden Alpha-Oszillation. Ich analysierte Alpha-Oszillationen und Verhaltensleistungen während eingeschränkter und uneingeschränkter Bewegungsbedingungen, während Versuchspersonen einen Guilford-Test für alternative Verwendungsmöglichkeiten absolvierten. Die Ergebnisse zeigten, dass natürliches Gehen sowie das Fehlen von Körperbeschränkungen die laufende Alpha-Leistung im okzipitalen Bereich unabhängig von der Aufgabenphase reduziert, was mit höheren Testergebnissen einhergeht. Die Reduktion der okzipitalen Alpha-Leistung kann daher ein Indikator für einen veränderten Zustand sein, der eine Verbesserung der höheren kognitiven Prozesse ermöglicht. Zusammenfassend hebt die in dieser Arbeit präsentierte Forschung hervor, dass natürliches Gehen verschiedene Prozesse im visuellen und auditiven Bereich sowie höhere kognitive Prozesse verändern kann. Die Wirkung kann auf die Bewegung des natürlichen Gehens selbst zurückgeführt werden, und nicht auf Veränderungen im sensorischen Input während des Gehens. Die Ergebnisse deuten weiterhin darauf hin, dass die durch das Gehen verursachte Modulation laufender Alpha-Oszillationen im okzipitalen Bereich die kognitiven Effekte antreibt. Daher schlagen wir vor, dass Gehen den hemmenden Zustand verändert, der das Bewusstsein und die Aufmerksamkeit beeinflussen kann. Ein solcher Mechanismus könnte eine adaptive Verbesserung in kognitiven Prozessen fördern und somit verhaltensbezogene Bewegungen wie die Navigation optimieren. KW - Walking KW - Alpha power KW - Mobie EEG KW - Body movement KW - Cognitive processing KW - Natural walking KW - Kognition KW - Cognition KW - Alpha Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-352958 ER - TY - CHAP A1 - Klein, Martin ED - Hochschild, Joshua P. ED - Nevitt, Turner C. ED - Wood, Adam ED - Borbély, Gábor T1 - Metaphors, Dead and Alive T2 - Metaphysics Through Semantics: The Philosophical Recovery of the Medieval Mind N2 - This paper examins how the medieval distinction between proper and improper signification can give a plausible explanation of both metaphorical use and the usual transformations a language can undergo. I will show how Thomas Aquinas distinguishes between ordinary ambiguous terms and metaphors, whereas William of Ockham and Walter Burley do not leave room for this distinction. I will argue that Ockham’s conception of transfer of sense through subsequent institution of words is best thought of as an explanation of how ordinary usage can contain ambiguities, whereas Burley’s conception of transfer of sense without new imposition is more plausible when it comes to explaining metaphors. If metaphorical use is lumped together with equivocation, the account of how they work cannot do full justice to either, an insight that we already find in Peter Abelard, if not in Boethius. KW - Aquinas KW - Ockham KW - Burley KW - metaphor KW - equivocation KW - signification KW - imposition KW - transference Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359678 UR - https://link.springer.com/chapter/10.1007/978-3-031-15026-5_8 N1 - Subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms). PB - Springer ER - TY - RPRT A1 - Kindermann, Katharina A1 - Fromm, Julia A1 - Theurer, Caroline A1 - Krüger, Nadine T1 - It's storytime: Ein digitales Märchenprojekt für den Englischunterricht in der Grundschule N2 - In diesem Beitrag wird zunächst das Konzept des digital storytelling mit dem Tablet im frühen Fremdsprachenunterricht methodisch-didaktisch gerahmt (Kapitel 1). Daran anschließend wird die Bedeutung lernunterstützender Maßnahmen in einem solchen digital gestützten und potenziell kreativitätsfördernden Unterrichtssetting erläutert (Kapitel 2). In Kapitel 3 folgt die Vorstellung der Unterrichtsreihe „It’s storytime – Let’s create our own digital fairy tale“. Im Verlauf dieser Unterrichtsreihe, die auch als Projektwoche angelegt werden kann, rezipieren die Schüler:innen zunächst eigenständig Märchen in englischer Sprache, die aus dem deutschen und angloamerikanischen Sprachraum bekannt sind. Die Märchen liegen für das Tablet multimedial aufbereitet vor. Anschließend entwickeln die Lernenden auf Grundlage des erarbeiteten gattungsspezifischen Wortschatzes ein eigenes multimediales Märchen. Alle für die Unterrichtsreihe benötigten digitalen und analogen Materialien stehen als Download zur Verfügung und können für den eigenen Unterricht genutzt und adaptiert werden. KW - Medienkompetenz KW - Digital Storytelling KW - Fremdsprachenlernen KW - Englischunterricht Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-353045 ER - TY - JOUR A1 - Maihoff, Fabienne A1 - Sahler, Simone A1 - Schoger, Simon A1 - Brenzinger, Kristof A1 - Kallnik, Katharina A1 - Sauer, Nikki A1 - Bofinger, Lukas A1 - Schmitt, Thomas A1 - Nooten, Sabine S. A1 - Classen, Alice T1 - Cuticular hydrocarbons of alpine bumble bees (Hymenoptera: Bombus) are species-specific, but show little evidence of elevation-related climate adaptation JF - Frontiers in Ecology and Evolution N2 - Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees’ CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species’ elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species’ ability to adapt to climatic changes. KW - pollinators KW - altitudinal gradient KW - cuticular hydrocarbon KW - desiccation KW - mountain KW - global change KW - translocation experiment KW - drought stress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304420 SN - 2296-701X VL - 11 ER - TY - JOUR A1 - Reinermann, Sophie A1 - Asam, Sarah A1 - Gessner, Ursula A1 - Ullmann, Tobias A1 - Kuenzer, Claudia T1 - Multi-annual grassland mowing dynamics in Germany BT - spatio-temporal patterns and the influence of climate, topographic and socio-political conditions JF - Frontiers in Environmental Science N2 - Introduction: Grasslands cover one third of the agricultural area in Germany and are mainly used for fodder production. However, grasslands fulfill many other ecosystem functions, like carbon storage, water filtration and the provision of habitats. In Germany, grasslands are mown and/or grazed multiple times during the year. The type and timing of management activities and the use intensity vary strongly, however co-determine grassland functions. Large-scale spatial information on grassland activities and use intensity in Germany is limited and not openly provided. In addition, the cause for patterns of varying mowing intensity are usually not known on a spatial scale as data on the incentives of farmers behind grassland management decisions is not available. Methods: We applied an algorithm based on a thresholding approach utilizing Sentinel-2 time series to detect grassland mowing events to investigate mowing dynamics in Germany in 2018–2021. The detected mowing events were validated with an independent dataset based on the examination of public webcam images. We analyzed spatial and temporal patterns of the mowing dynamics and relationships to climatic, topographic, soil or socio-political conditions. Results: We found that most intensively used grasslands can be found in southern/south-eastern Germany, followed by areas in northern Germany. This pattern stays the same among the investigated years, but we found variations on smaller scales. The mowing event detection shows higher accuracies in 2019 and 2020 (F1 = 0.64 and 0.63) compared to 2018 and 2021 (F1 = 0.52 and 0.50). We found a significant but weak (R2 of 0–0.13) relationship for a spatial correlation of mowing frequency and climate as well as topographic variables for the grassland areas in Germany. Further results indicate a clear value range of topographic and climatic conditions, characteristic for intensive grassland use. Extensive grassland use takes place everywhere in Germany and on the entire spectrum of topographic and climatic conditions in Germany. Natura 2000 grasslands are used less intensive but this pattern is not consistent among all sites. Discussion: Our findings on mowing dynamics and relationships to abiotic and socio-political conditions in Germany reveal important aspects of grassland management, including incentives of farmers. KW - remote sensing KW - Sentinel-2 KW - time series KW - cutting KW - management KW - pasture KW - meadow KW - Earth observation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320700 SN - 2296-665X VL - 11 ER - TY - JOUR A1 - Liu, Ruiqi A1 - Friedrich, Mike A1 - Hemmen, Katherina A1 - Jansen, Kerstin A1 - Adolfi, Mateus C. A1 - Schartl, Manfred A1 - Heinze, Katrin G. T1 - Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism JF - Frontiers in Endocrinology N2 - Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish. KW - fluorescence lifetime imaging microscopy KW - Förster Resonance Energy Transfer KW - Mc4r KW - puberty KW - Xiphophorus Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354261 SN - 1664-2392 VL - 14 ER - TY - JOUR A1 - Remde, Hanna A1 - Kranz, Stefanie A1 - Morell, Sarah Maria A1 - Altieri, Barbara A1 - Kroiss, Matthias A1 - Detomas, Mario A1 - Fassnacht, Martin A1 - Deutschbein, Timo T1 - Clinical course of patients with adrenal incidentalomas and cortisol autonomy BT - a German retrospective single center cohort study JF - Frontiers in Endocrinology N2 - Background Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Methods Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. Results A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing’s syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Conclusion Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy). KW - adrenal imaging KW - adrenal tumours KW - autonomous cortisol secretion KW - cardiovascular events KW - cardiovascular risk factors KW - dexamethasone suppression test KW - morbidity KW - mortality Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-316793 SN - 1664-2392 VL - 14 ER - TY - JOUR A1 - Then, Daniel A1 - Pohlmann-Rother, Sanna T1 - Adaptivity in the inclusive transition to school JF - Frontiers in Education N2 - The transition to school is a key juncture in an individual’s educational trajectory, with far-reaching effects on the development of children and their families. Successful transitions require flexibility in the design of the transition process, addressing the needs of the persons involved in an adaptive manner. Adaptivity is also considered crucial for the success of inclusive transitions. However, a systematic breakdown of the aspects that characterize the concept of adaptivity in the context of inclusive school entry is not available at this point. This article therefore provides a conceptualization of adaptivity in the inclusive transition to school as well as a review of the current literature focusing this topic. The goal is to develop a model that structures the various aspects of adaptivity at school entry and offers an overview of the way these aspects are important to design the transition successfully according to current findings of empirical research. Building on a concept of transitions informed by ecological systems theory, we are guided by the assumption that adaptivity at transition to school may occur in three forms: as a feature of the persons involved in the transition; as a feature of the processes that moderate the course of the transition; and as a feature of the structures that frame the transition. Based on this distinction, we develop a model that presents adaptivity in the inclusive transition to school. KW - adaptivity KW - adjustment KW - transition KW - preschool KW - school KW - inclusion Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354256 SN - 2504-284X VL - 8 ER - TY - JOUR A1 - Gerber, Sebastian A1 - Quarder, Jascha A1 - Greefrath, Gilbert A1 - Siller, Hans-Stefan T1 - Promoting adaptive intervention competence for teaching simulations and mathematical modelling with digital tools BT - theoretical background and empirical analysis of a university course in teacher education JF - Frontiers in Education N2 - Providing adaptive, independence-preserving and theory-guided support to students in dealing with real-world problems in mathematics lessons is a major challenge for teachers in their professional practice. This paper examines this challenge in the context of simulations and mathematical modelling with digital tools: in addition to mathematical difficulties when autonomously working out individual solutions, students may also experience challenges when using digital tools. These challenges need to be closely examined and diagnosed, and might – if necessary – have to be overcome by intervention in such a way that the students can subsequently continue working independently. Thus, if a difficulty arises in the working process, two knowledge dimensions are necessary in order to provide adapted support to students. For teaching simulations and mathematical modelling with digital tools, more specifically, these knowledge dimensions are: pedagogical content knowledge about simulation and modelling processes supported by digital tools (this includes knowledge about phases and difficulties in the working process) and pedagogical content knowledge about interventions during the mentioned processes (focussing on characteristics of suitable interventions as well as their implementation and effects on the students’ working process). The two knowledge dimensions represent cognitive dispositions as the basis for the conceptualisation and operationalisation of a so-called adaptive intervention competence for teaching simulations and mathematical modelling with digital tools. In our article, we present a domain-specific process model and distinguish different types of teacher interventions. Then we describe the design and content of a university course at two German universities aiming to promote this domain-specific professional adaptive intervention competence, among others. In a study using a quasi-experimental pre-post design (N = 146), we confirm that the structure of cognitive dispositions of adaptive intervention competence for teaching simulations and mathematical modelling with digital tools can be described empirically by a two-dimensional model. In addition, the effectiveness of the course is examined and confirmed quantitatively. Finally, the results are discussed, especially against the background of the sample and the research design, and conclusions are derived for possibilities of promoting professional adaptive intervention competence in university courses. KW - adaptive intervention competence KW - diagnosis KW - simulation KW - mathematical modelling KW - digital tools KW - teacher education KW - pedagogical content knowledge KW - technology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323701 SN - 2504-284X VL - 8 ER - TY - JOUR A1 - Zakaria, Nevine Nizar T1 - Assessing the working practices and the inclusive programs to students with disabilities in the Egyptian museums BT - challenges and possibilities for facilitating learning and promoting inclusion JF - Frontiers in Education N2 - Following the implementation of 2018’s laws on the rights of persons with disabilities (PWDs) in Egypt, students with disabilities (SWDs) have both legal and moral rights to meaningful learning opportunities and inclusive education. Despite that, SWDs still have very limited education resources which limit their career aspirations and quality of life. In this respect, education whether as part of formal education or lifelong learning is central to the museum’s mission. Museums, as part of non-formal education, are being acknowledged for their educative powers and investments in the development of quality formal, non-formal, and informal learning experiences. Further, phrases such as “inclusivity,” “accessibility,” and “diversity” were notably included in the newly approved museum definition by ICOM (2022) emphasizing museums’ obligations to embrace societal issues and shape a cultural attitude concerning disability rights, diversity, and equality together with overcoming exclusionary educational practices. The study seeks to investigate the existing resources and inclusive practices in Egyptian museums to achieve non-formal education for SWDs. Qualitative research approaches have been employed to answer a specific question: How can Egyptian museums work within their governing systems to support the learning of SWDs beyond their formal education system? The study aims to assess the potential of Egyptian museums in facilitating learning for SWDs. Further, it examines the capability of Egyptian museums in contributing to informal and non-formal learning for SWDs and striving for inclusive education inspired by the social model of disability that fosters inclusive educational programs and adopts a human rights-based approach. The results revealed that Egyptian museums contributed to the learning of SWDs, yet small-scale programs and individual efforts, but they are already engaged in active inclusive practices that address the learning of SWDs. The study suggests that they need to be acknowledged and supported by the government as state instruments and direct actors in advancing inclusive education and implementing appropriate pedagogies in favor of SWDs. KW - museum practice KW - social inclusion KW - students with disabilities KW - inclusive education KW - cultural diversity KW - people with disabilities Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319848 SN - 2504-284X VL - 8 ER - TY - JOUR A1 - Schreiber, Laura M. A1 - Lohr, David A1 - Baltes, Steffen A1 - Vogel, Ulrich A1 - Elabyad, Ibrahim A. A1 - Bille, Maya A1 - Reiter, Theresa A1 - Kosmala, Aleksander A1 - Gassenmaier, Tobias A1 - Stefanescu, Maria R. A1 - Kollmann, Alena A1 - Aures, Julia A1 - Schnitter, Florian A1 - Pali, Mihaela A1 - Ueda, Yuichiro A1 - Williams, Tatiana A1 - Christa, Martin A1 - Hofmann, Ulrich A1 - Bauer, Wolfgang A1 - Gerull, Brenda A1 - Zernecke, Alma A1 - Ergün, Süleyman A1 - Terekhov, Maxim T1 - Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research JF - Frontiers in Cardiovascular Medicine N2 - A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research. KW - ultrahigh-field MRI KW - large animal models KW - translational research KW - research infrastructure KW - heart KW - organoid KW - pig KW - cardiovascular MRI Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-317398 SN - 2297-055X VL - 10 ER - TY - JOUR A1 - Possler, Daniel A1 - Bowman, Nicholas David A1 - Daneels, Rowan T1 - Explaining the formation of eudaimonic gaming experiences: a theoretical overview and systemization based on interactivity and game elements JF - Frontiers in Communication N2 - Over the past years, scholars have explored eudaimonic video game experiences—profound entertainment responses that include meaningfulness, reflection, and others. In a comparatively short time, a plethora of explanations for the formation of such eudaimonic gaming experiences has been developed across multiple disciplines, making it difficult to keep track of the state of theory development. Hence, we present a theoretical overview of these explanations. We first provide a working definition of eudaimonic gaming experiences (i.e., experiences that reflect human virtues and encourage players to develop their potential as human beings fully) and outline four layers of video games—agency, narrative, sociality, and aesthetics—that form the basis for theorizing. Subsequently, we provide an overview of the theoretical approaches, categorizing them based on which of the four game layers their explanation mainly rests upon. Finally, we suggest the contingency of the different theoretical approaches for explaining eudaimonic experiences by describing how their usefulness varies as a function of interactivity. As different types of games offer players various levels of interactivity, our overview suggests which theories and which game layers should be considered when examining eudaimonic experiences for specific game types. KW - video games KW - interactivity KW - eudaimonia KW - theory KW - game layers Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328136 SN - 2297-900X VL - 8 ER - TY - JOUR A1 - Luther, Christian H. A1 - Brandt, Philipp A1 - Vylkova, Slavena A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Dittrich, Marcus T1 - Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans JF - Frontiers in Cellular and Infection Microbiology N2 - Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype. KW - sky kinases KW - kinase signaling KW - network analysis KW - transcriptome KW - transcriptional regulation KW - phosphoproteome KW - Candida albicans Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311771 SN - 2235-2988 VL - 13 ER - TY - JOUR A1 - Massih, Bita A1 - Veh, Alexander A1 - Schenke, Maren A1 - Mungwa, Simon A1 - Seeger, Bettina A1 - Selvaraj, Bhuvaneish T. A1 - Chandran, Siddharthan A1 - Reinhardt, Peter A1 - Sterneckert, Jared A1 - Hermann, Andreas A1 - Sendtner, Michael A1 - Lüningschrör, Patrick T1 - A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS JF - Frontiers in Cell and Developmental Biology N2 - The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND. KW - NMJ–neuromuscular junction KW - motoneuron (MN) KW - skeletal muscle KW - iPSC (induced pluripotent stem cells) KW - 3D cell culture Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304161 SN - 2296-634X VL - 11 ER - TY - JOUR A1 - Böck, Julia A1 - Maurus, Katja A1 - Gerhard-Hartmann, Elena A1 - Brändlein, Stephanie A1 - Kurz, Katrin S. A1 - Ott, German A1 - Anagnostopoulos, Ioannis A1 - Rosenwald, Andreas A1 - Zamò, Alberto T1 - Targeted panel sequencing in the routine diagnosis of mature T- and NK-cell lymphomas BT - report of 128 cases from two German reference centers JF - Frontiers in Oncology N2 - Diagnosing any of the more than 30 types of T-cell lymphomas is considered a challenging task for many pathologists and currently requires morphological expertise as well as the integration of clinical data, immunophenotype, flow cytometry and clonality analyses. Even considering all available information, some margin of doubt might remain using the current diagnostic procedures. In recent times, the genetic landscape of most T-cell lymphomas has been elucidated, showing a number of diagnostically relevant mutations. In addition, recent data indicate that some of these genetic alterations might bear prognostic and predictive value. Extensive genetic analyses, such as whole exome or large panel sequencing are still expensive and time consuming, therefore limiting their application in routine diagnostic. We therefore devoted our effort to develop a lean approach for genetic analysis of T-cell lymphomas, focusing on maximum efficiency rather than exhaustively covering all possible targets. Here we report the results generated with our small amplicon-based panel that could be used routinely on paraffin-embedded and even decalcified samples, on a single sample basis in parallel with other NGS-panels used in our routine diagnostic lab, in a relatively short time and with limited costs. We tested 128 available samples from two German reference centers as part of our routine work up (among which 116 T-cell lymphomas), which is the largest routine diagnostic series reported to date. Our results showed that this assay had a very high rate of technical success (97%) and could detect mutations in the majority (79%) of tested T-cell lymphoma samples. KW - T-cell lymphoma KW - panel-sequencing KW - NGS KW - diagnostics KW - mutation KW - FFPE Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-326478 SN - 2234-943X VL - 13 ER - TY - JOUR A1 - Ding, Hao A1 - Seusing, Nelly A1 - Nasseroleslami, Bahman A1 - Anwar, Abdul Rauf A1 - Strauss, Sebastian A1 - Lotze, Martin A1 - Grothe, Matthias A1 - Groppa, Sergiu A1 - Muthuraman, Muthuraman T1 - The role of ipsilateral motor network in upper limb movement JF - Frontiers in Physiology N2 - The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction. KW - ipsilateral motor network KW - upper limb KW - ipsilateral motor evoked potential KW - voluntary movement KW - bilateral motor network Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321805 SN - 1664-042X VL - 14 ER - TY - JOUR A1 - Leonhardt, Jonas A1 - Winkler, Marcela A1 - Kollikowski, Anne A1 - Schiffmann, Lisa A1 - Quenzer, Anne A1 - Einsele, Hermann A1 - Löffler, Claudia T1 - Mind–body-medicine in oncology—from patient needs to tailored programs and interventions BT - a cross-sectional study JF - Frontiers in Psychology N2 - Introduction: National and international guidelines recommend early integration of evidence-based multimodal interventions and programs, especially with a focus on relaxation techniques and other Mind–Body-based methods to maintain the quality of life of oncology patients, improve treatment tolerability, and promote healthy lifestyle behaviors. Consequently, we aim to understand what drives patients and how they navigate integrative medicine to best advise them. This study aimed to detect possible topics of particular interest to patients and identify the patient groups that could benefit most from further programs. Furthermore, we aimed to investigate if patients are open-minded toward integrative oncology concepts and learn about their motivational level to maintain or change behavior. Methods: Between August 2019 and October 2020 we surveyed patients undergoing oncological therapy in a university oncological outpatient center using a custom-developed questionnaire based on established Mind–Body Medicine concepts. Results: We included 294 patients with various cancers. More than half reported problems sleeping through (61%) and 42% felt stressed frequently, invariably rating this as detrimental to their health. Moreover, a slight majority (52%) felt physically limited due to their disease and only 30% performed defined exercise programs. Women were significantly more likely to feel stressed and reported with alarming frequency that they often feel “everything was up to them.” The 40–65-year-olds reported significantly less restful sleep, more stress and were more dissatisfied with their situation. However, this group already used natural remedies most frequently and was most often motivated to use relaxation techniques in the next 6 months. The lower the perceived individual energy level (EL), the less frequently patients did sport, the more frequently they felt their disease impaired their activity, mostly feeling stressed and tense. We also found significant associations between negative emotions/thoughts and the variables “sleep,” “use of relaxation techniques,” “personal stress perception,” and “successful lifestyle modification.” Conclusion: Mind–Body programs that focus on patient’s individual resources, with tools to explore impairing patterns of self-perception and cognitive biases, can be a valuable resource for oncology patients and should therefore be part of an integrative medical treatment concept. KW - lifestyle habits KW - symptom burden KW - individual mind state KW - motivational level KW - stress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321970 SN - 1664-1078 VL - 14 ER - TY - JOUR A1 - Hutmacher, Fabian T1 - Taking methodological pluralism seriously BT - considerations based on the work of Norbert Groeben JF - Frontiers in Psychology N2 - No abstract available. KW - methodological pluralism KW - quantitative methods KW - qualitative methods KW - replication crisis KW - Norbert Groeben Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328221 SN - 1664-1078 VL - 14 ER - TY - JOUR A1 - Lenhard, Alexandra A1 - Minten, Marie-Pierre A1 - Lenhard, Wolfgang T1 - When biology takes over: TV formats like The Bachelor and The Bachelorette confirm evolutionary theories of partner selection JF - Frontiers in Psychology N2 - Introduction: In this study, we investigated the impact of age on mate selection preferences in males and females, and explored how the formation and duration of committed relationships depend on the sex of the person making the selection. Methods: To this end, we utilized data from the television dating shows The Bachelor and The Bachelorette. In these programs, either a single man (“bachelor”) or a woman (“bachelorette”) has the opportunity to select a potential long-term partner from a pool of candidates. Our analysis encompassed a total of n = 169 seasons from 23 different countries, beginning with the first airing in 2002. Results: We found that the likelihood of the final couple continuing their relationship beyond the broadcast was higher in The Bachelorette than in The Bachelor, although the duration of these relationships was not significantly influenced by the type of show. On average, women were younger, both when selecting their partner and when being chosen. However, men exhibited a greater preference for larger age differences than women. Furthermore, the age of the chosen male partners significantly increased with the age of the “bachelorettes,” whereas “bachelors” consistently favored women around 25.5 years old, regardless of their own age. Discussion: We discuss these findings within the context of parental investment theory and sexual strategies theory. KW - mating strategies KW - parental investment theory KW - sex differences KW - relationship duration KW - Cox proportional regression analysis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325717 SN - 1664-1078 VL - 14 ER - TY - JOUR A1 - Simon, Johanna A1 - Parisi, Sandra A1 - Wabnitz, Katharina A1 - Simmenroth, Anne A1 - Schwienhorst-Stich, Eva-Maria T1 - Ten characteristics of high-quality planetary health education BT - results from a qualitative study with educators, students as educators and study deans at medical schools in Germany JF - Frontiers in Public Health N2 - Aim: The climate and ecological crises are considered fundamental threats to human health. Healthcare workers in general and doctors in particular can contribute as change agents in mitigation and adaptation. Planetary health education (PHE) aims to harness this potential. This study explores perspectives among stakeholders involved in PHE at German medical schools on the characteristics of high-quality PHE and compares them to existing PHE frameworks. Methods: In 2021, we conducted a qualitative interview study with stakeholders from German medical schools involved in PHE. Three different groups were eligible: faculty members, medical students actively involved in PHE, and study deans of medical schools. Recruitment was performed through national PHE networks and snowball sampling. Thematic qualitative text analysis according to Kuckartz was used for the analysis. Results were systematically compared to three existing PHE frameworks. Results: A total of 20 participants (13 female) from 15 different medical schools were interviewed. Participants covered a wide range of professional backgrounds and experience in PHE education. The analysis revealed ten key themes: (1) Complexity and systems thinking, (2) inter- and transdisciplinarity, (3) ethical dimension, (4) responsibility of health professionals, (5) transformative competencies including practical skills, (6) space for reflection and resilience building, (7) special role of students, (8) need for curricular integration, (9) innovative and proven didactic methods, and (10) education as a driver of innovation. Six of our themes showed substantial overlap with existing PHE frameworks. Two of our themes were only mentioned in one of the frameworks, and two others were not explicitly mentioned. Few important elements of the frameworks did not emerge from our data. Conclusions: In the light of increased attention regarding the connections of the climate and ecological crises and health, our results can be useful for anyone working toward the integration of planetary health into medical schools' and any health professions' curricula and should be considered when designing and implementing new educational activities. KW - climate change KW - climate resilience KW - planetary health KW - planetary health education KW - medical education KW - transformative education KW - education for sustainable healthcare KW - eco health Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313856 SN - 2296-2565 VL - 11 ER - TY - JOUR A1 - Müller, Christina A1 - Domokos, Bruno A1 - Amersbach, Tanja A1 - Hausmayer, Eva-Maria A1 - Roßmann, Christin A1 - Wallmann-Sperlich, Birgit A1 - Bucksch, Jens T1 - Development and reliability testing of an audit toolbox for the assessment of the physical activity friendliness of urban and rural environments in Germany JF - Frontiers in Public Health N2 - Background: According to socio-ecological theories, physical activity behaviors are linked to the physical and social neighborhood environment. Reliable and contextually adapted instruments are needed to assess environmental characteristics related to physical activity. This work aims to develop an audit toolbox adapted to the German context, to urban and rural settings, for different population groups, and different types of physical activity; and to evaluate its inter-rater reliability. Methods: We conducted a systematic literature search to collect existing audit tools and to identify the latest evidence of environmental factors influencing physical activity in general, as well as in German populations. The results guided the construction of a category system for the toolbox. Items were assigned to the categories based on their relevance to physical activity and to the German context as well as their comprehensibility. We piloted the toolbox in different urban and rural areas (100 street segments, 15 parks, and 21 playgrounds) and calculated inter-rater reliability by Cohen's Kappa. Results: The audit toolbox comprises a basic streetscape audit with seven categories (land use and destinations, traffic safety, pedestrian infrastructure, cycling infrastructure, attractiveness, social environment, and subjective assessment), as well as supplementary tools for children and adolescents, seniors and people with impaired mobility, parks and public open spaces, playgrounds, and rural areas. 76 % of all included items had moderate, substantial, or almost perfect inter-rater reliability (κ > 0.4). Conclusions: The audit toolbox is an innovative and reliable instrument for the assessment of the physical activity friendliness of urban and rural environments in Germany. KW - built environment KW - physical activity KW - reliability KW - rural KW - urban KW - walkability Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-326116 SN - 2296-2565 VL - 11 ER - TY - JOUR A1 - Schrader, Hanna A1 - Ruck, Jessica A1 - Borgulya, Gábor A1 - Parisi, Sandra A1 - Ehlers-Mondorf, Jana A1 - Kaduszkiewicz, Hanna A1 - Joos, Stefanie A1 - Grau, Anna A1 - Linde, Klaus A1 - Gágyor, Ildikó T1 - Stress experiences of healthcare assistants in family practice at the onset of the COVID-19 pandemic BT - a mixed methods study JF - Frontiers in Public Health N2 - Background: At the beginning of the pandemic in 2020, healthcare assistants in general practices were confronted with numerous new challenges. The aim of the study was to investigate the stress factors of healthcare assistants in March/April 2020 as well as in the further course of the pandemic in 2020. Methods: From August to December 2020, 6,300 randomly selected healthcare assistants in four German states were invited to participate in the study. We performed a mixed methods design using semi-structured telephone interviews and a cross-sectional survey with quantitative and open questions. The feeling of psychological burden was assessed on a 6-point likert-scale. We defined stress factors and categorized them in patient, non-patient and organizational stress factors. The results of the three data sets were compared within a triangulation protocol. Results: One thousand two hundred seventy-four surveys were analyzed and 28 interviews with 34 healthcare assistants were conducted. Of the participants, 29.5% reported experiences of a very high or high feeling of psychological burden in March/April 2020. Worries about the patients’ health and an uncertainty around the new disease were among the patient-related stress factors. Non-patient-related stress factors were problems with the compatibility of work and family, and the fear of infecting relatives with COVID-19. Organizational efforts and dissatisfaction with governmental pandemic management were reported as organizational stress factors. Support from the employer and team cohesion were considered as important resources. Discussion: It is necessary to reduce stress among healthcare assistants by improving their working conditions and to strengthen their resilience to ensure primary healthcare delivery in future health crises. KW - healthcare assistants KW - COVID-19 pandemic KW - psychological burden KW - stress factors KW - primary care Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-327427 SN - 2296-2565 VL - 11 ER - TY - JOUR A1 - Rack, Christian A1 - Fernando, Tamara A1 - Yalcin, Murat A1 - Hotho, Andreas A1 - Latoschik, Marc Erich T1 - Who is Alyx? A new behavioral biometric dataset for user identification in XR JF - Frontiers in Virtual Reality N2 - Introduction: This paper addresses the need for reliable user identification in Extended Reality (XR), focusing on the scarcity of public datasets in this area. Methods: We present a new dataset collected from 71 users who played the game “Half-Life: Alyx” on an HTC Vive Pro for 45 min across two separate sessions. The dataset includes motion and eye-tracking data, along with physiological data from a subset of 31 users. Benchmark performance is established using two state-of-the-art deep learning architectures, Convolutional Neural Networks (CNN) and Gated Recurrent Units (GRU). Results: The best model achieved a mean accuracy of 95% for user identification within 2 min when trained on the first session and tested on the second. Discussion: The dataset is freely available and serves as a resource for future research in XR user identification, thereby addressing a significant gap in the field. Its release aims to facilitate advancements in user identification methods and promote reproducibility in XR research. KW - dataset KW - behaviometric KW - deep learning KW - physiological dataset KW - user identification Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-353979 SN - 2673-4192 VL - 4 ER - TY - JOUR A1 - Winkler, Markus H. A1 - Li, Yonghui A1 - Pauli, Paul A1 - Mühlberger, Andreas T1 - Modulation of smoking cue reactivity by social context—Implications for exposure therapy in virtual reality JF - Frontiers in Virtual Reality N2 - Rationale: Social factors are considered important for the initiation and maintenance of drug abuse. Virtual reality (VR) research on cue reactivity and exposure frequently incorporates social stimuli as part of complex drug-intake scenarios. Attempts are rarely made to dissect the impact of the different components and their interactive effects. The present study critically extends this line of research by investigating the modulatory effects of social context on the reactivity evoked by proximal smoking cues. Methods: Thirty-two smokers and 33 never-smokers were presented in VR with proximal cues and neutral stimuli, embedded in a social context or a neutral context. A virtual hand model was used to translate real hand movements into VR. Each trial started with the presentation of the different stimulus–context combinations. Discrete stimuli were presented on the table in front of the participants, and contextual stimuli were presented at the end of the table. Afterward, participants were instructed to grasp the target stimulus (a cigarette vs. a pencil) in front of them. After successful contact, the stimulus appeared in the virtual hand. Modulation of cue reactivity by social context was assessed by self-report, physiological measures, and overt approach behavior. Results: The results revealed modulatory effects of social context on the responses to proximal smoking cues in smokers. In contrast to never-smokers, smoking cues evoked craving in smokers, which was attenuated in a social context. Furthermore, social context increased the latency to approach and contact the cigarette in the group of smokers but did not affect behavioral approach responses in never-smokers. Other data provided indications for interactive, but also main effects of cues and contexts. Interestingly, cue-evoked craving was increased after contact with the virtual cigarette. Conclusion: The present study critically extends previous research by providing evidence for the modulation of cue reactivity by social context. The results are particularly important given the well-established role of drug-associated environmental contexts in the stimulus control of addictive behaviors. Our results emphasize the need to address social context effects on cue reactivity in basic research and treatment and further suggest that changes in the perceived availability of smoking might enhance or inhibit cue-evoked reactivity. KW - cue reactivity KW - social context KW - cue exposure therapy KW - cue availability KW - smoking KW - substance use disorders KW - addiction KW - virtual reality Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-306199 VL - 4 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Saravi, Babak A1 - Breitenbuecher, Niko A1 - Mueller-Richter, Urs A1 - Straub, Anton A1 - Šimić, Luka A1 - Kübler, Alexander A1 - Vollmer, Michael A1 - Gubik, Sebastian A1 - Volland, Julian A1 - Hartmann, Stefan A1 - Brands, Roman C. T1 - Realizing in-house algorithm-driven free fibula flap set up within 24 hours BT - a pilot study evaluating accuracy with open-source tools JF - Frontiers in Surgery N2 - Objective: This study aims to critically evaluate the effectiveness and accuracy of a time safing and cost-efficient open-source algorithm for in-house planning of mandibular reconstructions using the free osteocutaneous fibula graft. The evaluation focuses on quantifying anatomical accuracy and assessing the impact on ischemia time. Methods: A pilot study was conducted, including patients who underwent in-house planned computer-aided design and manufacturing (CAD/CAM) of free fibula flaps between 2021 and 2023. Out of all patient cases, we included all with postoperative 3D imaging in the study. The study utilized open-source software tools for the planning step, and three-dimensional (3D) printing techniques. The Hausdorff distance and Dice coefficient metrics were used to evaluate the accuracy of the planning procedure. Results: The study assessed eight patients (five males and three females, mean age 61.75 ± 3.69 years) with different diagnoses such as osteoradionecrosis and oral squamous cell carcinoma. The average ischemia time was 68.38 ± 27.95 min. For the evaluation of preoperative planning vs. the postoperative outcome, the mean Hausdorff Distance was 1.22 ± 0.40. The Dice Coefficients yielded a mean of 0.77 ± 0.07, suggesting a satisfactory concordance between the planned and postoperative states. Dice Coefficient and Hausdorff Distance revealed significant correlations with ischemia time (Spearman's rho = −0.810, p = 0.015 and Spearman's rho = 0.762, p = 0.028, respectively). Linear regression models adjusting for disease type further substantiated these findings. Conclusions: The in-house planning algorithm not only achieved high anatomical accuracy, as reflected by the Dice Coefficients and Hausdorff Distance metrics, but this accuracy also exhibited a significant correlation with reduced ischemia time. This underlines the critical role of meticulous planning in surgical outcomes. Additionally, the algorithm's open-source nature renders it cost-efficient, easy to learn, and broadly applicable, offering promising avenues for enhancing both healthcare affordability and accessibility. KW - mandibular KW - reconstruction KW - preoperative KW - planning KW - ischemia KW - osteocutaneous KW - fibula KW - graft KW - computer-aided KW - design KW - manufacturing (CAD/CAM) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-353945 N1 - Funding The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. VL - 10 ER - TY - JOUR A1 - Diesendorf, Viktoria A1 - Roll, Valeria A1 - Geiger, Nina A1 - Fähr, Sofie A1 - Obernolte, Helena A1 - Sewald, Katherina A1 - Bodem, Jochen T1 - Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific JF - Frontiers in Cellular and Infection Microbiology N2 - Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication and phospholipidosis assays using the Calu-3 cells and PCLS as the patient-near system. Trimipramine and Chloroquine induced phospholipidosis but failed to inhibit SARS-CoV-2 replication in Calu-3 cells, which contradicts the reported findings and the proposed mechanism. Fluoxetine, only slightly induced phospholipidosis in Calu-3 cells but reduced viral replication by 2.7 orders of magnitude. Tilorone suppressed viral replication by 1.9 orders of magnitude in Calu-3 cells without causing phospholipidosis. Thus, induction of phospholipidosis is not correlated with the inhibition of SARS-CoV-2, and the compounds act via other mechanisms. However, we show that compounds, such as Amiodarone, Tamoxifen and Tilorone, with antiviral activity on Calu-3 cells, also inhibited viral replication in human PCLS. Our results indicate that antiviral assays against SARS-CoV-2 are cell-line specific. Data from Vero E6 can lead to non-transferable results, underlining the importance of an appropriate cell system for analysing antiviral compounds against SARS-CoV-2. We observed a correlation between the active compounds in Calu-3 cells and PCLS. KW - SARS-CoV-2 KW - phospholipidosis KW - Vero E6 KW - PCLS KW - Calu-3 KW - antivirals KW - Tamoxifen KW - cell line-specificity Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-326202 SN - 2235-2988 VL - 13 ER - TY - JOUR A1 - Siegmund, Daniela A1 - Zaitseva, Olena A1 - Wajant, Harald T1 - Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling JF - Frontiers in Cell and Developmental Biology N2 - Tumor necrosis factor (TNF) receptor 1 (TNFR1), TNFR2 and fibroblast growth factor-inducible 14 (Fn14) belong to the TNF receptor superfamily (TNFRSF). From a structural point of view, TNFR1 is a prototypic death domain (DD)-containing receptor. In contrast to other prominent death receptors, such as CD95/Fas and the two TRAIL death receptors DR4 and DR5, however, liganded TNFR1 does not instruct the formation of a plasma membrane-associated death inducing signaling complex converting procaspase-8 into highly active mature heterotetrameric caspase-8 molecules. Instead, liganded TNFR1 recruits the DD-containing cytoplasmic signaling proteins TRADD and RIPK1 and empowers these proteins to trigger cell death signaling by cytosolic complexes after their release from the TNFR1 signaling complex. The activity and quality (apoptosis versus necroptosis) of TNF-induced cell death signaling is controlled by caspase-8, the caspase-8 regulatory FLIP proteins, TRAF2, RIPK1 and the RIPK1-ubiquitinating E3 ligases cIAP1 and cIAP2. TNFR2 and Fn14 efficiently recruit TRAF2 along with the TRAF2 binding partners cIAP1 and cIAP2 and can thereby limit the availability of these molecules for other TRAF2/cIAP1/2-utilizing proteins including TNFR1. Accordingly, at the cellular level engagement of TNFR2 or Fn14 inhibits TNFR1-induced RIPK1-mediated effects reaching from activation of the classical NFκB pathway to induction of apoptosis and necroptosis. In this review, we summarize the effects of TNFR2- and Fn14-mediated depletion of TRAF2 and the cIAP1/2 on TNFR1 signaling at the molecular level and discuss the consequences this has in vivo. KW - apoptosis KW - Fn14 KW - necroptosis KW - TNF KW - TNFR1 KW - TNFR2 KW - TRAF2 KW - TWEAK Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354304 SN - 2296-634X VL - 11 ER - TY - JOUR A1 - Sammeth, Michael A1 - Ursache, Nicu-Cosmin A1 - Alboaie, Sînică T1 - OpenDSU: digital sovereignty in PharmaLedger JF - Frontiers in Blockchain N2 - Introduction: Distributed ledger networks, chiefly those based on blockchain technologies, currently are heralding a next-generation of computer systems that aims to suit modern users’ demands. Over the recent years, several technologies for blockchains, off-chaining strategies, as well as decentralised and respectively self-sovereign identity systems have shot up so fast that standardisation of the protocols is lagging behind, severely hampering the interoperability of different approaches. Moreover, most of the currently available solutions for distributed ledgers focus on either home users or enterprise use case scenarios, failing to provide integrative solutions addressing the needs of both. Methods: Herein, we introduce the OpenDSU platform that allows to interoperate generic blockchain technologies, organised–and possibly cascaded in a hierarchical fashion–in domains. To achieve this flexibility, we seamlessly integrated a set of well conceived components that orchestrate off-chain data and provide granularly resolved and cryptographically secure access levels, intrinsically nested with sovereign identities across the different domains. The source code and extensive documentation of all OpenDSU components described herein are publicly available under the MIT open-source licence at https://opendsu.com. Results: Employing our platform to PharmaLedger, an inter-European network for the standardisation of data handling in the pharmaceutical industry and in healthcare, we demonstrate that OpenDSU can cope with generic demands of heterogeneous use cases in both, performance and handling substantially different business policies. Discussion: Importantly, whereas available solutions commonly require a predefined and fixed set of components, no such vendor lock-in restrictions on the blockchain technology or identity system exist in OpenDSU, making systems built on it flexibly adaptable to new standards evolving in the future. KW - opendsu KW - blockchain interoperability KW - off-chain data KW - blockchain anchoring KW - self-sovereign identities KW - pharmaledger KW - blockchain in healthcare KW - blockchain in the pharmaceutical industry Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320458 SN - 2624-7852 VL - 6 ER - TY - JOUR A1 - Lisowski, Dominik A1 - Lutyj, Paul A1 - Abazari, Arya A1 - Weick, Stefan A1 - Traub, Jan A1 - Polat, Bülent A1 - Flentje, Michael A1 - Kraft, Johannes T1 - Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients JF - Cancers N2 - Purpose: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. Methods: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. Results: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0–64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0–3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0–1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2%). Depending on the national guidelines, 1–9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. Conclusion: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised. KW - battery depletion KW - cardiac implantable electronic devices (CIED) KW - cardiac resynchronization therapy (CRT) KW - implantable cardioverter defibrillator (ICD) KW - CIED malfunction; pacemaker (PM) KW - radiotherapy (RT) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358008 SN - 2072-6694 VL - 15 IS - 19 ER - TY - THES A1 - Karwen, Till T1 - Platelets promote insulin secretion of pancreatic β-cells T1 - Thrombozyten fördern die Insulinsekretion von pankreatischen β-Zellen N2 - The pancreas is the key organ for the maintenance of euglycemia. This is regulated in particular by α-cell-derived glucagon and β-cell-derived insulin, which are released in response to nutrient deficiency and elevated glucose levels, respectively. Although glucose is the main regulator of insulin secretion, it is significantly enhanced by various potentiators. Platelets are anucleate cell fragments in the bloodstream that are essential for hemostasis to prevent and stop bleeding events. Besides their classical role, platelets were implemented to be crucial for other physiological and pathophysiological processes, such as cancer progression, immune defense, and angiogenesis. Platelets from diabetic patients often present increased reactivity and basal activation. Interestingly, platelets store and release several substances that have been reported to potentiate insulin secretion by β-cells. For these reasons, the impact of platelets on β-cell functioning was investigated in this thesis. Here it was shown that both glucose and a β-cell-derived substance/s promote platelet activation and binding to collagen. Additionally, platelet adhesion specifically to the microvasculature of pancreatic islets was revealed, supporting the hypothesis of their influence on glucose homeostasis. Genetic or pharmacological ablation of platelet functioning and platelet depletion consistently resulted in reduced insulin secretion and associated glucose intolerance. Further, the platelet-derived lipid fraction was found to enhance glucose-stimulated insulin secretion, with 20-hydroxyeicosatetraenoic acid (20-HETE) and possibly also lyso-precursor of platelet-activating factor (lysoPAF) being identified as crucial factors. However, the acute platelet-stimulated insulin secretion was found to decline with age, as did the levels of platelet-derived 20-HETE. In addition to their direct stimulatory effect on insulin secretion, specific defects in platelet activation have also been shown to affect glucose homeostasis by potentially influencing islet vascular development. Taking together, the results of this thesis suggest a direct and indirect mechanism of platelets in the regulation of insulin secretion that ensures glucose homeostasis, especially in young individuals. N2 - Der Pankreas ist das Schlüsselorgan für die Aufrechterhaltung der Glukosehomöostase. Diese wird insbesondere durch das von α-Zellen stammende Glukagon und von β-Zellen stammende Insulin reguliert, die als Reaktion auf Nährstoffmangel beziehungsweise erhöhte Glukosespiegel freigesetzt werden. Obwohl Glukose der Hauptregulator der Insulinsekretion ist, wird sie durch verschiedene Potentiatoren erheblich gesteigert. Thrombozyten sind kernlose Zellfragmente im Blutkreislauf, die für die Hämostase unerlässlich sind. Neben ihrer klassischen Funktion sind sie auch an anderen physiologischen und pathophysiologischen Prozessen beteiligt, etwa an der Tumorentwicklung, der Immunabwehr und der Angiogenese. Thrombozyten von Diabetikern weisen häufig eine erhöhte Reaktivität und basale Aktivierung auf. Außerdem speichern und sekretieren sie Substanzen, von denen bekannt ist, dass sie die Insulinsekretion durch β-Zellen verstärken. Aus diesen Gründen wurde in dieser Arbeit der Einfluss von Thrombozyten auf die Funktion von β-Zellen untersucht. Es konnte gezeigt werden, dass sowohl Glukose als auch eine aus β-Zellen stammende Substanz/en die Thrombozytenaktivierung und die Bindung an Kollagen fördern. Darüber hinaus wurde eine spezifische Thrombozytenadhäsion an der Mikrovaskulatur der pankreatischen Inseln festgestellt, was die Hypothese ihres Einflusses auf die Glukosehomöostase unterstützt. Eine genetische oder pharmakologische Ablation der Thrombozytenfunktion sowie eine Depletion von Thrombozyten führten zu einer verminderten Insulinsekretion und einer damit verbundenen Glukoseintoleranz. Hierbei erwies sich die Lipidfraktion von Thrombozyten als essentieller Potentiator für die glukosestimulierte Insulinsekretion, wobei 20-Hydroxyeicosatetraensäure (20-HETE) und die Lyso-Vorstufe des Plättchen-Aktivierenden Faktors (LysoPAF) als entscheidende Faktoren identifiziert werden konnten. Weiterhin wurde festgestellt, dass sowohl der direkte stimulierende Effekt von Thrombozyten auf die Insulinsekretion, als auch deren 20-HETE Sekretion mit zunehmendem Alter abnimmt. Thrombozyten beeinflussten außerdem die Inselvaskularisierung, welche mutmaßlich zusätzlich zu Glukoseintoleranz führt. Insgesamt deuten die Ergebnisse dieser Arbeit auf einen direkten und indirekten Mechanismus der Thrombozyten bei der Regulierung der Insulinsekretion hin, der die Glukosehomöostase insbesondere bei jungen Menschen gewährleistet. KW - platelet KW - β cell KW - insulin KW - pancreas KW - diabetes KW - Thrombozyt KW - Insulinsekretion Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313933 ER - TY - THES A1 - Meyer-Sautter, Pascal Willy T1 - Evaluation der postoperativen empirischen antibiotischen Therapie intraabdomineller Infektionen aus Sicht des Antimicrobical Stewardships (AMS) T1 - Evaluation of postoperative empirical antibiotic therapy of intra-abdominal infections from the perspective of antimicrobial stewardship (AMS) N2 - Ziele: Das Ziel dieser Dissertation ist es, die empirischen antibiotische Therapien (PAT) bei komplizierten intraabdominellen Infektionen (cIAI) in den Jahren 2016 – 2018 in einem großen deutschen Maximalversorger zu evaluieren. Aktuelle Studien legen nahe, dass viele Patienten keine Nachteile durch kürzere Therapien mit schmaler wirksamen Antibiotika oder das vermeiden einer nicht notwendigen antibiotischen Therapie haben. Methoden: Es wurde eine retrospektive Kohortenstudie durch Analyse von elektronischen Patientenakten an einem 1500-Betten-Universitätsklinikum in Deutschland durchgeführt, bei der die Dauer der Antibiotikatherapie nach Notfalloperationen erhoben und mit antibiotischen Leitlinien durch die hausinterne Antibiotic-Stewardship-Abteilung (AMS) verglichen. Ergebnisse: 767 Patienten konnten eingeschlossen werden, davon erhielten 404 (52.7%) eine PAT. Die Gesamtanzahl der Therapietage pro 100 Patiententagen ging von 47,0 auf 42,2 Tage zurück (p = 0,035) ohne einen Anstieg an Komplikationen. Patienten ohne Sepsis, bei denen eine initiale chirurgischer Fokuskontrolle möglich war profitierten nicht von einer Therapiedauer über 4 Tage (160 vs 100 Patienten). Bei Patienten, bei denen diese Bedingungen nicht gegeben waren, zeigte sich ebenfalls kein Vorteil bei längeren Behandlungen (über >7 Tage, 74 lang vs. 32 kurz behandelte Patienten). Es zeigte sich ebenfalls kein Vorteil von empirischen Therapien mit Carbapenem statt mit Piperacillin-Tazobactam (n=51 C vs n=40 vs Pip/Taz). Schlussfolgerung: Die Reduktion unnötiger, zu breiter und zu langer antibiotischer Therapien bei cIAI ist ohne einen Anstieg der postoperativen Komplikationen möglich. Weitere RCTs sind notwendig, um das Wissen um sichere Behandlungen zu vergrößern. N2 - Objectives: The aim of this dissertation is to evaluate empirical antibiotic therapies (PAT) for complicated intra-abdominal infections (cIAI) in 2016 - 2018 in a large German maximum care hospital. Current studies suggest that many patients have no disadvantages due to shorter therapies with less effective antibiotics or the avoidance of unnecessary antibiotic therapy. Methods: A retrospective cohort study was conducted by analyzing electronic patient records at a 1500-bed university hospital in Germany, in which the duration of antibiotic therapy after emergency surgery was collected and compared with antibiotic guidelines by the in-house antibiotic stewardship department (AMS). Results: 767 patients were included, of which 404 (52.7%) received PAT. The total number of days of therapy per 100 patient days decreased from 47.0 to 42.2 days (p = 0.035) without an increase in complications. Patients without sepsis in whom initial surgical focus control was possible did not benefit from a treatment duration of more than 4 days (160 vs 100 patients). In patients who did not meet these conditions, there was also no advantage to longer treatments (over >7 days, 74 patients treated for a long time vs. 32 for a short time). There was also no advantage of empirical treatment with carbapenem instead of piperacillin-tazobactam (n=51 C vs n=40 vs Pip/Taz). Conclusion: The reduction of unnecessary, too broad and too long antibiotic therapies in cIAI is possible without an increase in postoperative complications. Further RCTs are needed to increase the knowledge of safe treatments. KW - Bakterielle Infektion KW - Antibiotikum KW - Bauchfellentzündung KW - Intraabdominelle Infektion KW - Antibiotic Stewardship Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359201 ER - TY - THES A1 - Kellner [geb. Friedel], Theresa T1 - Suizid durch Selbstverbrennung im Freien - Eine bildmorphologische Analyse der Intensität und Verteilung von Verbrennungen im Zusammenhang mit der Körperposition während des Brandgeschehens T1 - Suicide by self-immolation in the open air - A photo-based analysis of the intensity and distribution of burns in relation to body position during the burn event N2 - Ziel dieser Dissertation ist es, etwaige Gemeinsamkeiten und Unterschiede hinsichtlich der Distribution und Intensität von Brandverletzungen bei suizidaler Selbstverbrennung im Freien in Abhängigkeit von der jeweiligen Körperposition zum Auffindezeitpunkt anhand der Aktenlage herauszuarbeiten. Das Studienkollektiv umfasst 38 Fälle aus 9 deutschen rechtsmedizinischen Instituten, darunter 13 (34,2 %) weibliche und 25 (65,8 %) männliche Suizidenten/-innen im Alter von 18 – 77 Jahren. Neben einer deskriptiven visuellen Analyse erfolgt die Auswertung der Verteilung der Verbrennungen mittels der Software BurnCase 3D, die es ermöglicht, eine Sortierung der einzelnen Körperbereiche nach deren durchschnittlicher Verbrennungsintensität innerhalb verschiedener Cluster für die unterschiedlichen Auffindepositionen am Tatort (Rückenlage, Bauchlage, Seitenlage, Aufrecht, Sitzend) vorzunehmen. Am ehesten auf das in aufrechter Haltung beginnende Brandgeschehen zurückzuführen ist eine clusterübergreifend auftretende, intensive und nach kranial an Intensität abnehmende Verbrennung des Halses sowie der lateralen und perioralen Kopfbereiche. Geringe Verbrennungsfolgen weisen die distalen unteren Extremitäten sowie die Auflageflächen des Körpers auf dem Untergrund auf. Es zeigt sich eine Beeinflussung der lokalen Verbrennungstiefe durch ein hohes Fettgewebevorkommen. Ebenfalls clusterübergreifend können verstärkte Brandwirkungen an den Oberschenkelinnenseiten festgestellt werden. In Rücken- und Bauchlage liegt zudem eine höhere Verbrennungsintensität an den Flanken, den Arminnenseiten und im Unterbauchbereich vor. Bei in Seitenlage verbrannten Körpern ergeben sich Hinweise darauf, dass die nach oben gerichtete Körperseite vermehrt Verbrennungen aufweist. In aufrechter und sitzender Position konzentriert sich der Brandfokus überwiegend auf Torso, Hals und Kopf. Zusätzlich wurde eine Betrachtung des Entstehungsmusters kutaner Hitzerisse durchgeführt. Hier ergaben sich Übereinstimmungen u.a. mit dem Verlauf der Hautfaltlinien nach Pinkus. Ein Körperschema mit Abbildung der beobachteten Orientierungen der Risse wurde angefertigt. Die wichtigsten Limitationen ergeben sich aus einer geringen Fallzahl, einer fotografischen Dokumentation, die nicht alle Körperbereiche in ausreichender Qualität und Detailliertheit abdeckt, sowie dem subjektiven Bias hinsichtlich der Bewertung der Verbrennungsintensitäten. N2 - The aim of this dissertation is to identify any similarities and differences with regard to the distribution and intensity of burn injuries in suicidal self-immolation in the open air depending on the respective body position at the time of discovery on the basis of the records. The study collective comprises 38 cases from 9 German forensic medical institutes, including 13 (34.2 %) female and 25 (65.8 %) male suicides aged between 18 and 77 years. In addition to a descriptive visual analysis, the distribution of burns was evaluated using the BurnCase 3D software, which enables the individual body areas to be sorted according to their average burn intensity within different clusters for the different positions at the crime scene (supine, prone, lateral, upright, sitting). Burns to the neck and the lateral and perioral areas of the head are most likely to be due to the burns beginning in the upright position and occurring across all clusters. The distal lower extremities and the areas where the body rests on the ground show minor burn effects. The local burn depth is influenced by a high occurrence of fatty tissue. Increased burn effects on the inner thighs can also be observed across all clusters. In the supine and prone positions, there is also a higher intensity of burns on the flanks, inner sides of the arms and in the lower abdomen. In the case of bodies burned in the lateral position, there are indications that the upward-facing side of the body shows increased burns. In the upright and sitting position, the focus of the burn is predominantly on the torso, neck and head. In addition, the development pattern of cutaneous heat lacerations was examined. This revealed similarities with the course of the skin fold lines according to Pinkus, among others. A body diagram showing the observed orientations of the lacerations was drawn up. The most important limitations result from a small number of cases, photographic documentation that does not cover all areas of the body in sufficient quality and detail, and the subjective bias with regard to the assessment of burn intensities. KW - Selbstverbrennung KW - Hitzerisse KW - Suizid KW - Verbrennung Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359193 ER - TY - THES A1 - Englmeier, Jana T1 - Consequences of climate change and land-use intensification for decomposer communities and decomposition processes T1 - Folgen von Klimawandel und intensiver Landnutzung für Zersetzergemeinschaften und Abbauprozesse N2 - The increase in intensively used areas and climate change are direct and indirect consequences of anthropogenic actions, caused by a growing population and increasing greenhouse gas emissions. The number of research studies, investigating the effects of land use and climate change on ecosystems, including flora, fauna, and ecosystem services, is steadily growing. This thesis contributes to this research area by investigating land-use and climate effects on decomposer communities (arthropods and microbes) and the ecosystem service ‘decomposition of dead material’. Chapter II deals with consequences of intensified land use and climate change for the ecosystem service ‘decomposition of dead organic material’ (necromass). Considering the severe decline in insects, we experimentally excluded insects from half of the study objects. The decomposition of both dung and carrion was robust to land-use changes. Dung decomposition, moreover, was unaffected by temperature and the presence/ absence of insects. Along the altitudinal gradient, however, highest dung decomposition was observed at medium elevation between 600 and 700 m above sea level (although insignificant). As a consequence, we assume that at this elevation there is an ideal precipitation:temperature ratio for decomposing organisms, such as earthworms or collembolans. Carrion decomposition was accelerated by increasing elevation and by the presence of insects, indicating that increasing variability in climate and an ongoing decline in insects could modify decomposition processes and consequently natural nutrient cycles. Moreover, we show that different types of dead organic material respond differently to environmental factors and should be treated separately in future studies. In Chapter III, we investigated land-use and climate effects on dung-visiting beetles and their resource specialization. Here, all beetles that are preferentially found on dung, carrion or other rotten material were included. Both α- and γ-diversity were strongly reduced in agricultural and urban areas. High precipitation reduced dung-visiting beetle abundance, whereas γ-diversity was lowest in the warmest regions. Resource specialization decreased with increasing temperatures. The results give evidence that land use as well as climate can alter dung-visiting beetle diversity and resource specialization and may hence influence the natural balance of beetle communities and their contribution to the ecosystem service ‘decomposition of dead material’. The following chapter, Chapter IV, contributes to the findings in Chapter II. Here, carrion decomposition is not only explained by land-use intensity and climate but also by diversity and community composition of two taxonomic groups found on carrion, beetles and bacteria. The results revealed a strong correlation between bacteria diversity and community composition with temperature. Carrion decomposition was to a great extent directed by bacterial community composition and precipitation. The role of beetles was neglectable in carrion decomposition. With this study, I show that microbes, despite their microscopic size, direct carrion decomposition and may not be neglected in future decomposition studies. In Chapter V a third necromass type is investigated, namely deadwood. The aim was to assess climate and land-use effects on deadwood-inhabiting fungi and bacteria. Main driver for microbial richness (measured as number of OTUs) was climate, including temperature and precipitation. Warmer climates promoted the diversity of bacteria, whereas fungi richness was unaffected by temperature. In turn, fungi richness was lower in urban landscapes compared to near-natural landscapes and bacteria richness was higher on meadows than on forest sites. Fungi were extremely specialized on their host tree, independent of land use and climate. Bacteria specialization, however, was strongly directed by land use and climate. These results underpin previous studies showing that fungi are highly specialized in contrast to bacteria and add new insights into the robustness of fungi specialization to climate and land use. I summarize that climate as well as intensive land use influence biodiversity. Temperature and precipitation, however, had positive and negative effects on decomposer diversity, while anthropogenic land use had mostly negative effects on the diversity of decomposers. N2 - Die Zunahme intensiv genutzter Landschaften und der Klimawandel sind direkte und indirekte Folgen menschlichen Handelns, verursacht durch eine wachsende Weltbevölkerung und zunehmende Mengen an Treibhausgasen. Die Zahl der wissenschaftlichen Studien, die sich mit den Veränderungen der Umwelt und den Konsequenzen für Ökosysteme, einschließlich Flora, Fauna und Ökosystemleistungen auseinandersetzen, steigt stetig. Mit dieser Thesis möchte ich meinen Beitrag zu diesem wichtigen und aktuellen Forschungsgebiet leisten. Dazu untersuche ich die Auswirkungen von Landnutzung und Klima auf die Ökosystemleistung „Zersetzung toten organischen Materials“ (Nekromasse) und die Auswirkungen auf die daran beteiligten Arthropoden- und Mikrobengemeinschaften. Kapitel II dieser Thesis setzt sich mit den Konsequenzen von intensiver Landnutzung und Klimawandel für die Ökosystemleistung „Zersetzung toten Materials“ auseinander. Unter Anbetracht des globalen Insektenrückgangs, wurde dieser Aspekt anhand eines Insektenausschluss-Experimentes zusätzlich simuliert. Es stellt sich heraus, dass sowohl der Abbau von Dung als auch von Aas sehr robust gegenüber landschaftlicher Nutzung war. Zudem blieb der Abbau von Dung unberührt von Temperaturänderungen und dem Ausschluss von Insekten. Entlang eines Höhengradienten wurde hingegen ein Trend zu einem unimodalen Muster mit maximaler Zersetzung bei ca. 600-700 m ü.M. beobachtet. Dieser Trend lässt vermuten, dass in dieser Höhe das Verhältnis von Niederschlag und Temperatur ideal für Dung zersetzende Gemeinschaften ist. Aas hingegen wurde in zunehmender Höhe und unter der Beteiligung von Insekten schneller zersetzt, was verdeutlich, dass Klimaänderungen und ein ansteigender Insektenrückgang starke Auswirkungen auf die Zersetzung von Aas und somit auf Nährstoffkreisläufe haben können. Hierbei wurde zudem ersichtlich, dass verschiedene Typen von Nekromasse unterschiedlich auf Umweltparameter reagieren und daher in künftigen Studien und Auswertungen separat betrachtet werden sollten. Kapitel III behandelt die Auswirkungen von Landnutzung und Klima auf die Biodiversität und Spezialisierung von Käfergemeinschaften an Dung. Hierbei wurden sämtliche Käfer berücksichtigt, welche vor allem an Dung, Aas oder sonstigem faulenden Material gefunden werden können. Sowohl α- als auch γ-Diversität von diesen Käfern wurde durch Agrarlandschaften und urbane Gebiete stark reduziert. Hohe Niederschlagsmengen wirkten sich negativ auf die Abundanz von Dungkäfern aus, wohingegen die γ-Diversität in warmen Regionen am niedrigsten war. Der Grad der Spezialisierung von Käfergemeinschaften auf verschiedene Dungressourcen nahm mit abnehmenden Temperaturen zu. Aus den Ergebnissen geht hervor, dass sowohl intensive Landnutzung als auch Klimaveränderungen Auswirkungen auf die Diversität und den Spezialisierungsgrad von Käfergemeinschaften an Dung haben können und somit das ökologische Gleichgewicht der Dungkäfergemeinschaften und ihren Ökosystemfunktionen beeinflussen können. Das darauffolgende Kapitel IV stellt eine Ergänzung zu Kapitel II dar. Hier wird die Zersetzung von Aas nicht nur anhand von Landnutzung und Klima erklärt, sondern auch anhand der α-Diversität und der Artenzusammensetzung von Käfern und Bakterien an Aas diskutiert. Es zeigte sich, dass Abundanz und Artenzusammensetzung der Bakteriengemeinschaft an Aas vor allem von der Temperatur abhingen. Außerdem wurde die Zersetzungsgeschwindigkeit maßgeblich von der Bakteriengemeinschaft und der Niederschlagsmenge bestimmt. Mit dieser Studie konnte ich zeigen, dass Bakterien trotz ihrer mikroskopischen Größe maßgeblich an der Zersetzung von Aas beteiligt sind und diese in Zersetzungsversuchen nicht vernachlässigt werden sollten. Das letzte Kapitel, Kapitel V, befasst sich mit den Konsequenzen von intensiver Landnutzung und Klimawandel auf mikrobielle Gemeinschaften in Totholz. Untersucht wurden hier sowohl Bakterien- als auch Pilzgemeinschaften. Haupttreiber der Artenvielfalt für beide Gruppen (gemessen als Anzahl an OTUs) war das Klima (Niederschlag und Temperatur). Ein wärmeres Klima kam der Vielfalt von Bakterien zugute, wohingegen die Pilzvielfalt nicht tangiert wurde. Außerdem reagierten Pilze negativ auf urbane Landnutzung, Bakterienvielfalt in Totholz war auf Wiesen jedoch höher als im Wald. Vor allem Pilze zeigten eine sehr starke Bindung zu ihrem Wirtsbaum, welche auch von äußeren Einflüssen wie Landnutzung und Klima nicht beeinflusst werden konnte. Die Spezialisierung von Bakterien hingegen wurde stark von Landnutzung und Klima beeinflusst. Diese Ergebnisse untermauern frühere Studien, die besagen, dass Pilze hoch spezialisiert sind und geben neue Erkenntnisse zur Robustheit der Spezialisierung gegenüber Landnutzungsintensität und Klima. Zusammenfassend kann ich sagen, dass sowohl Klima als auch Landnutzung Auswirkungen auf die Biodiversität haben. Während Temperatur und Niederschlag jedoch positive so wie negative Effekte hatten, wirkte sich anthropogene Landnutzung überwiegend negativ auf die Diversität von Zersetzergemeinschaften aus. KW - Mikroorganismus KW - decomposition KW - Klimaänderung KW - Zersetzungsprozess KW - microbes KW - dead organic material KW - Mikroben Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313994 ER - TY - THES A1 - Blickle, Marc Manuel T1 - Das Zusammenspiel von Herz und Gehirn: Interozeptive Genauigkeit, Herzratenvariabilität und funktionelle Konnektivität kortikaler Netzwerke bei depressiven Patientinnen und Patienten T1 - The interplay of heart and brain: Interoceptive accuracy, heart rate variability, and functional connectivity of cortical networks in patients with depression N2 - Hintergrund: Depressionen zählen zu den häufigsten psychischen Erkrankungen. Depressive Symptome umfassen beeinträchtigte kognitive Funktionen, vegetative Beschwerden und ein verändertes emotionales Erleben. Die defizitäre Wahrnehmung interner körperlicher Signale wird sowohl mit der Pathogenese der Depression als auch mit Angststörungen in Verbindung gebracht. Interozeptive Genauigkeit (IAc) beschreibt dabei die Fähigkeit, körperliche Empfindungen wie den eigenen Herzschlag akkurat wahrzunehmen und wird mit einer Herzwahrnehmungsaufgabe erfasst. In bildgebenden Verfahren wie der funktionellen Magnetresonanztomografie (fMRT) war eine niedrigere IAc mit einer verringerten Inselaktivität assoziiert. Während der Ruhezustandsmessung des Gehirns (resting-state fMRT) kann in Abwesenheit einer Aufgabe die intrinsische Aktivität des Gehirns gemessen werden. Dies ermöglicht die Identifizierung von kortikalen Netzwerken. Depressive Patienten weisen eine veränderte funktionelle Konnektivität innerhalb und zwischen einzelnen Netzwerken wie dem Salience Network (SN), welchem die Insel zugerechnet wird, und dem Default Mode Network (DMN) auf. Bisherige Studien, in denen überwiegend jüngere depressive Patienten untersucht wurden, kamen jedoch hinsichtlich der IAc und den kortikalen Netzwerken zu inkonsistenten Ergebnissen. Insbesondere ist unklar, inwieweit sich die IAc nach einem Therapieansprechen verändert, von der Herzratenvariabilität (HRV) moduliert wird und welche Auswirkungen dies auf die funktionelle Konnektivität kortikaler Netzwerke hat. Ziele: Eine veränderte IAc und HRV wie auch funktionelle Konnektivitätsunterschiede im DMN und SN könnten Biomarker der Depression darstellen. Im Rahmen einer Längsschnittuntersuchung wurde getestet, ob ältere depressive Patienten über eine verringerte IAc, eine geringere HRV und über eine veränderte funktionelle Konnektivität im SN sowie DMN verfügen. Darüber hinaus sollte erforscht werden, in welchem Ausmaß sich Patienten, die auf die Behandlung ansprachen (Responder), von sogenannten Non-Respondern in Bezug auf die IAc, die HRV, das SN und das DMN unterschieden. Methoden: In Studie 1 (Baseline) wurden 30 größtenteils medizierte, schwer depressive Patienten (> 50 Jahre) und 30 gesunde Kontrollprobanden untersucht. Die IAc wurde in einer Herzwahrnehmungsaufgabe ermittelt und die HRV bestimmt. Zusätzlich wurde eine resting-state fMRT durchgeführt. Eine funktionelle Konnektivitätsanalyse für Saatregionen im SN und DMN wurde mit einem saatbasierten Ansatz (seed-to-voxel) durchgeführt. Für eine Subgruppenanalyse wurde die Patientengruppe in ängstlich-depressive und nicht-ängstlich depressive Patienten unterteilt. In Studie 2 (sechs Monate Follow-up) wurde die Studienkohorte nochmals untersucht. Es nahmen 21 Personen der Patientengruppe und 28 Probanden der Kontrollgruppe teil. Wiederum wurden die IAc und die HRV bestimmt. Außerdem fand eine resting-state fMRT-Messung statt. Die Patientengruppe wurde unterteilt in depressive Responder und Non-Responder. Ergebnisse: In Studie 1 zeigten depressive Patienten eine funktionelle Hypokonnektivität zwischen einzelnen Saatregionen der Insel (SN) und Teilen des superioren frontalen Gyrus, des supplementärmotorischen Cortex, des lateralen okzipitalen Cortex sowie des Okzipitalpols. Zudem wiesen depressive Patienten zwischen der Saatregion im anterioren Teil des DMN und der Insel sowie dem Operculum eine erhöhte funktionelle Konnektivität auf. Die Gruppen unterschieden sich nicht in der IAc und der HRV. Ängstlich-depressive Patienten zeigten eine höhere funktionelle Konnektivität innerhalb der Insel als nicht-ängstlich depressive Patienten, jedoch zeigten sich keine Unterschiede in der IAc und der HRV. In Studie 2 wiesen depressive Non-Responder im Vergleich zu Respondern eine Hyperkonnektivität zwischen dem posterioren DMN und dem Frontalpol sowie zwischen dem posterioren DMN und temporalen Arealen im SN auf. Keine funktionellen Konnektivitätsunterschiede zeigten sich für die Saatregionen im SN. Depressive Responder, Non-Responder und die Kontrollprobanden unterschieden sich in ihrer IAc und HRV nicht. Schlussfolgerungen: Die Ergebnisse der Studien unterstreichen, dass bei depressiven Patienten, Respondern und Non-Respondern Unterschiede in der intrinsischen Gehirnaktivität funktioneller Netzwerke bestehen, jedoch nicht in der akkuraten Wahrnehmung des eigenen Herzschlages und der HRV. Therapeutische Interventionen, die auf eine Verbesserung der IAc abzielen, könnten insbesondere für Non-Responder dennoch eine zusätzliche Behandlungsmöglichkeit darstellen. Für eine personalisierte Medizin könnte die weitere Erforschung von kortikalen Netzwerken einen wesentlichen Beitrag leisten, um ein individuelles Therapieansprechen zu prädizieren. N2 - Background: Major depressive disorder (MDD) is among the most prevalent psychiatric disorders. Symptoms include impaired cognitive functions, vegetative complaints, and altered emotional experience. The deficient perception of internal body signals is associated with the pathogenesis of depression and anxiety disorders. Interoceptive accuracy (IAc) refers to the ability to accurately perceive bodily sensations (e.g., own heartbeat) and is assessed via a heartbeat perception task. In neuroimaging studies using functional magnetic resonance imaging (fMRI) lower IAc was associated with reduced insula activity. Resting-state fMRI allows to measure intrinsic brain activity without performing a task. This enables the identification of cortical networks. Patients with depression exhibit altered functional connectivity within and between various networks: the salience network (SN), which comprises the insula, and the default mode network (DMN). Previous studies investigating IAc and cortical networks in predominantly younger patients with depression yielded inconsistent results. In particular it remains unclear to what extent IAc alters after treatment response and how it is modulated by heart rate variability (HRV). The impact of changed IAc on the functional connectivity of cortical networks is insufficiently understood. Objectives: Altered IAc and HRV as well as functional connectivity differences in DMN and SN could serve as biomarkers of MDD. In a longitudinal study it was investigated, whether middle-aged and older patients with depression exhibit lower IAc, reduced HRV, and altered functional connectivity in SN and DMN. Furthermore, differences between depressed responders and non-responders with regard to IAc, HRV, SN, and DMN were investigated. Methods: In Study 1 (baseline) 30 mostly medicated patients with depression (> 50 years) and 30 healthy controls were examined. IAc was measured by the heartbeat perception task and HRV was assessed. Additionally, all participants underwent resting-state fMRI. Seed-to-voxel resting-state functional connectivity analysis with seeds in the SN and the DMN was conducted. The patient group was divided into anxious and non-anxious depressed patients for a subgroup analysis. In Study 2 (six-month follow-up) participants were invited again. 21 persons from the former patient group and 28 healthy controls participated. IAc was measured, HRV assessed, and resting-state fMRI acquired. The former depressed patient group was split into responders and non-responders. Results: In Study 1 patients with depression showed functional hypoconnectivity between several seeds in the insula (SN) and parts of the superior frontal gyrus, the supplementary motor cortex, the lateral occipital cortex, and the occipital pole. Patients with depression exhibited higher functional connectivity between the seed region in the anterior DMN and the insula together with the operculum. Groups did not differ with regard to IAc and HRV. Patients with anxious depression showed higher functional connectivity within the insula than patients with non-anxious depression without alterations in IAc and HRV. In Study 2 non-responders exhibited hyperconnectivity between the posterior DMN and the frontal pole as well as between the posterior DMN and temporal areas in the SN compared to responders. No functional connectivity differences were found for seed regions in the SN. There were no group differences between responders, non-responders, and healthy controls with regard to IAc and HRV. Conclusions: The findings underscore differences in intrinsic functional connectivity between patients with depression, responders, and non-responders. However, patients with depression showed normal IAc and HRV. Yet, therapeutical interventions enhancing IAc could be a useful additional treatment option especially for non-responders. In terms of personal medicine, further research of functional connectivity of cortical networks might contribute to a prediction of treatment response. KW - Depression KW - Interozeption KW - Funktionelle Kernspintomografie KW - Interozeptive Genauigkeit KW - Herzratenvariabilität KW - resting-state fMRT KW - Herzfrequenzvariabilität Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-316762 ER - TY - THES A1 - Landmesser, Patricia Sophia T1 - Seroprävalenz von SARS-CoV-2 Antikörpern bei Medizinstudierenden im zweiten klinischen Semester von Juli 2020 bis Juni 2021 T1 - Seroprevalence of SARS-CoV-2 antibodies in medical students in the second clinical semester from July 2020 to June 2021 N2 - Im sechsten Semester des Medizinstudiums an der Julius-Maximilians-Universität Würzburg findet das verpflichtende Praktikum „Impfkurs“ statt. Im Rahmen dieses Kurses wurde vom Sommersemester 2020 bis zum Sommersemester 2021 ein standardisierter online Fragebogen erhoben, der unter anderem demographische Daten sowie Expositionsmöglichkeiten gegenüber SARS-CoV-2 im privaten, beruflichen und universitären Umfeld erfragte. Zusätzlich wurde im gleichen Zeitraum der SARS-CoV-2 Serostatus der Medizinstudierenden erhoben und ausgewertet und dieser mit den Daten des Fragebogens zusammengeführt. Dafür wurden Blutproben entnommen, welche im Labor des Instituts für Virologie der Universität Würzburg mittels Western Blot auf IgG/IgM/IgA Antikörper gegen SARS-CoV-2 untersucht wurden. N2 - In the sixth semester of medical studies at the Julius-Maximilians-Universität Würzburg, the compulsory internship “vaccination course” takes place. As part of this course, a standardized online questionnaire was collected from the summer semester 2020 to the summer semester 2021, which, among other things, collected demographic data and exposure to SARS-CoV-2 in the private, professional and university environment. In addition, the SARS-CoV-2 serostatus of the medical students was collected and evaluated during the same period and merged with the data from the questionnaire. For this purpose, blood samples were taken, which were tested for IgG/IgM/IgA antibodies against SARS-CoV-2 by Western blot. KW - SARS-CoV-2 KW - Medizinstudent Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359246 ER - TY - THES A1 - Kusan, Simon Ferdinand T1 - Keimspektrum und antibiotische Therapie bei Morbus Crohn-assoziierten Abszessen : Eine retrospektive monozentrische Analyse T1 - Microbial spectrum and antibiotic therapy in Crohn's disease-associated abscesses : A retrospective monocentric analysis N2 - In dieser monozentrischen retrospektiven Analyse wurde das Keimspektrum und die antibiotische Therapie bei Morbus Crohn- assoziierten Abszessen untersucht. N2 - In this monocentric retrospective analysis, the bacterial spectrum and antibiotic therapy in Crohn's disease-associated abscesses were investigated. KW - Antibiotikum KW - Abszess KW - Abszesse KW - Antibiotika KW - Morbus Crohn KW - Keimspektrum KW - Crohn-Krankheit Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359467 ER - TY - THES A1 - Reis, Stefanie T1 - Sicherheit und Wirksamkeit der halbtherapeutischen und therapeutischen Antikoagulation bei hospitalisierten Patientinnen und Patienten mit COVID-19: eine systematische Übersichtsarbeit und Meta-Analyse T1 - Safety and efficacy of intermediate and therapeutic dose anticoagulation in hospitalised patients with COVID-19: a systematic review and meta-analysis N2 - COVID-19 Patientinnen und Patienten haben ein hohes thrombotisches Risiko. Die Sicherheit und Wirksamkeit verschiedener Antikoagulationsschemata bei COVID-19 Patientinnen und Patienten sind unklar. Acht RCTs mit 5580 Patientinnen und Patienten wurden identifiziert, wovon zwei RCTs Antikoagulation in halbtherapeutischer und sechs RCTs Antikoagulation in therapeutischer Dosierung mit der Standard Thromboembolieprophylaxe verglichen haben. Die halbtherapeutische Antikoagulation kann wenig oder gar keinen Einfluss auf thrombotische Ereignisse oder Todesfälle haben (RR 1,03, 95% KI 0,86-1,24), kann aber schwere Blutungen (RR 1,48, 95% KI 0,53-4,15) bei mittelschweren bis schweren COVID-19 Patientinnen und Patienten verstärken. Therapeutische Antikoagulation kann thrombotische Ereignisse oder den Tod bei Patientinnen und Patienten mit mittelschwerem COVID-19 (RR 0,64, 95% KI 0,38-1,07) verringern, kann aber bei Patientinnen und Patienten mit schwerer Erkrankung (RR 0,98, 95% KI 0,86-1,12) wenig oder keine Wirkung haben. Das Risiko schwerer Blutungen kann unabhängig vom Schweregrad der Erkrankung zunehmen (RR 1,78, 95% KI 1,15-2,74). Die Evidenzsicherheit ist immer noch gering. Mäßig betroffene COVID-19 Patientinnen und Patienten können von einer therapeutischen Antikoagulation profitieren, jedoch ist das Blutungsrisiko erhöht. N2 - COVID-19 patients have a high risk of thrombotic disease. The safety and efficacy of various anticoagulation regimens in COVID-19 patients remains unclear. Eight RCTs with 5580 patients were identified, with two comparing anticoagulation in intermediate doses and six comparing therapeutic doses to standard thromboembolism prophylaxis. Intermediate anticoagulation may have little or no effect on thrombotic events or deaths (RR 1.03, 95% CI 0.86-1.24), but may increase major bleeding (RR 1.48, 95% CI 0.53-4.15) in moderate to severe COVID-19 patients. Therapeutic anticoagulation may reduce thrombotic events or death in patients with moderate COVID-19 (RR 0.64, 95% CI 0.38-1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95% CI 0.86-1.12). The risk of major bleeding may increase regardless of the severity of the disease (RR 1.78, 95% CI 1.15-2.74). The certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic anticoagulation, but the risk of bleeding is increased. KW - Metaanalyse KW - COVID-19 KW - Blutgerinnungshemmung KW - SARS-CoV-2 KW - Systematische Übersichtsarbeit KW - Antikoagulation Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359607 ER - TY - THES A1 - Staab, Monika T1 - International Teaching and Learning Settings in the Academic Professionalisation of Adult Education : An International and Comparative Study T2 - Studies on Adult Learning and Education ; 18 N2 - Academic education is seen as an important place for the development of professionalism of (future) adult educators. Since adult education academia, research, and practice is closely intertwined with global and international de- velopments, there is a need for adult education programmes to prepare their students for these interconnections. This can be examined in the context of international teaching and learning settings that integrate international, inter- cultural, or global perspectives into teaching and learning and are part of the internationalisation efforts of higher education. The focus of this international and comparative study is on how international teaching and learning settings contribute to the academic professionalisation in adult education in three mas- ter’s programmes with a focus on adult education at the University of Würzburg (Germany), University of Belgrade (Serbia) and University of Florence (Italy). International teaching and learning settings are examined on the structural and individual level of academic professionalisation. The aim is to explore the provision of international teaching and learning settings in the master’s pro- grammes on the one hand, and to analyse the contribution of international teach- ing and learning settings to the development of students’ professionalism on the other. For this purpose, three focus group interviews with programme heads, (academic) staff, and students as well as 22 guided interviews with graduates of the three master’s programmes at the three university locations are collected and analysed in an international and comparative study design. The study reveals similarities and differences in the forms, framework con- ditions, and goals of international teaching and learning settings between the three master’s programmes. Overarching contexts that guide the internationalisation of the master’s programmes become apparent (e.g. education and higher education policy, internationalisation of the university, programme structure). The triangulation of the interview data of the graduates shows that the interna- tional environment, the structural arrangement, and the practical relevance of the international teaching and learning settings support the development of the graduates’ professionalism. The results underline the relevance of international teaching and learning settings for the development of professionalism in adult education and point to the requirement for a systematic and comprehensive in- ternationalisation of adult education programmes. N2 - Die akademische Ausbildung wird als ein wichtiger Ort für die Professiona- litätsentwicklung von (zukünftigen) Erwachsenenbildner*innen angesehen. Da Wissenschaft, Forschung und Praxis der Erwachsenenbildung eng mit globalen und internationalen Entwicklungen verflochten sind, lässt sich an Studiengänge der Erwachsenenbildung der Bedarf herantragen, ihre Studierenden auf diese Verflechtungen vorzubereiten. Dies kann im Kontext internationaler Lehr- und Lernsettings untersucht werden, die internationale, interkulturelle oder globale Perspektiven in Lehre und Lernen integrieren und Teil der Internationalisie- rungsbemühungen der Hochschulbildung sind. Im Fokus dieser internationalen und vergleichenden Studie steht die Frage, wie internationale Lehr- und Lern- settings zur akademischen Professionalisierung in der Erwachsenenbildung in drei Masterstudiengängen mit Schwerpunkt Erwachsenenbildung an der Uni- versität Würzburg (Deutschland), der Universität Belgrad (Serbien) und der Universität Florenz (Italien) beitragen. Es werden internationale Lehr- und Lernsettings auf der strukturellen und der individuellen Ebene akademischer Professionalisierung untersucht. Ziel ist die Eruierung der Bereitstellung von internationalen Lehr- und Lernsettings in den Masterstudiengängen einerseits, sowie die Analyse des Beitrags internatio- naler Lehr- und Lernsettings zur Professionalitätsentwicklung von Studierenden andererseits. Hierzu werden drei Fokusgruppeninterviews mit Studiengangslei- tenden, (akademischem) Personal und Studierenden sowie 22 Leitfadeninter- views mit Absolvent*innen an den drei Hochschulstandorten erhoben und in einem internationalen und vergleichenden Studiendesign analysiert. Die Studie zeigt Gemeinsamkeiten und Unterschiede in den Formen, Rah- menbedingungen und Zielen internationaler Lehr- und Lernsettings zwi- schen den drei Masterstudiengängen auf. Es werden übergreifende Kontexte erkennbar, die die Internationalisierung der Masterstudiengänge leiten (z.B. Bildungs- und Hochschulpolitik, Internationalisierung der Universität, Pro- grammstruktur). Die Triangulation der Interviewdaten der Absolvent*innen zeigt, dass das internationale Umfeld, das strukturelle Arrangement und der Praxisbezug der internationalen Lehr- und Lernsettings die Professionalitäts- entwicklung der Absolvent*innen unterstützen. Die Ergebnisse unterstreichen die Relevanz internationaler Lehr- und Lernsettings für die Professionalitäts- entwicklung in der Erwachsenenbildung und verweisen auf die Anforderung an eine systematische und umfassende Internationalisierung von Studiengängen der Erwachsenenbildung. N2 - L’educazione accademica è considerata un luogo importante per lo sviluppo della professionalità dei (futuri) educatori degli adulti. Poiché il mondo accade- mico, la ricerca e la pratica dell’educazione degli adulti sono strettamente inter- connessi con gli sviluppi globali e internazionali, è necessario che i programmi di educazione degli adulti preparino i loro studenti a queste interconnessioni. Questo può essere esaminato nei contesti internazionali di insegnamento e ap- prendimento che integrano prospettive internazionali, interculturali o globali nell’insegnamento e nell’apprendimento e fanno parte dell’impegno di inter- nazionalizzazione dell’istruzione superiore. Questo studio internazionale e comparativo si concentra sul modo in cui i contesti internazionali di insegna- mento e apprendimento contribuiscono alla professionalizzazione accademica nell’educazione degli adulti in tre programmi di master incentrati sull’educa- zione degli adulti presso l’Università di Würzburg (Germania), l’Università di Belgrado (Serbia) e l’Università di Firenze (Italia). I contesti internazionali di insegnamento e apprendimento sono esaminati a livello strutturale e individuale della professionalizzazione accademica. L’o- biettivo è esplorare l’offerta di contesti internazionali di insegnamento e ap- prendimento nei programmi di master, da un lato, e analizzare il contributo dei contesti internazionali di insegnamento e apprendimento allo sviluppo della professionalità degli studenti, dall’altro. A tal fine, sono state raccolte e analiz- zate tre focus group con responsabili di programma, personale (accademico) e studenti, nonché 22 interviste guidate a laureati nelle tre sedi universitarie, se- condo un disegno di studio internazionale e comparativo. Lo studio rivela somiglianze e differenze nelle forme, nelle condizioni quadro e negli obiettivi dei contesti internazionali di insegnamento e apprendimento tra i tre programmi di master. I contesti generali che guidano l’internaziona- lizzazione dei programmi di master diventano evidenti (ad esempio, la politica dell’istruzione e dell’istruzione superiore, l’internazionalizzazione dell’uni- versità, la struttura del programma). La triangolazione dei dati delle interviste con i laureati mostra che l’ambiente internazionale, l’assetto strutturale e la ri- levanza pratica dei contesti internazionali di insegnamento e apprendimento sostengono lo sviluppo della professionalità dei laureati. I risultati sottolinea- no l’importanza dei contesti internazionali di insegnamento e apprendimento per lo sviluppo della professionalità nell’educazione degli adulti e indicano la necessità di un’internazionalizzazione sistematica e completa dei programmi di educazione degli adulti. KW - Erwachsenenbildung KW - Professionalisierung KW - Academic Professionalisation KW - Adult Education KW - Learning Settings Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359613 SN - 979-12-215-0287-9 N1 - erscheint auch als gedruckte Ausgabe im Verlag "Firneze University Press", ISBN 979-12-215-0286-2 PB - Firenze University Press CY - Firenze ER - TY - THES A1 - Zillig, Anna-Lena Christina T1 - Einfluss von Sicherheit auf die Schmerzverarbeitung T1 - The influence of safety on pain perception N2 - Im Rahmen des interdisziplinären Promotionsschwerpunkts Resilienzfaktoren der Schmerzverarbeitung des evangelischen Studienwerks in Zusammenarbeit mit der Julius-Maximilians-Universität Würzburg und der Otto-Friedrich-Universität Bamberg untersuche ich in diesem Promotionsprojekt den Einfluss von Sicherheit auf die Schmerzverarbeitung. Es ist bekannt, dass die Schmerzverarbeitung durch Emotionen moduliert werden kann. Man geht davon aus, dass negative Emotionen den Schmerz in der Regel verstärken, während positive Emotionen zu einer Schmerzreduktion führen. Frühere Studien fanden heraus, dass die Erwartung eines aversiven Ereignisses zu Bedrohung und stärkeren Schmerzen führt. Es stellt sich die Frage, ob das Gegenteil von Bedrohung, nämlich Sicherheit, zu einer Verringerung der Schmerzen führen kann. Um diese Hypothese zu untersuchen, habe ich drei Experimente an gesunden ProbandInnen durchgeführt. N2 - I am investigating the influence of safety on pain processing in the present dissertation project as part of the interdisciplinary doctoral program on resilience factors of pain processing of the Evangelisches Studienwerk in cooperation with the Julius-Maximilians-University of Würzburg and the Otto-Friedrich-University of Bamberg. It is known that pain processing is susceptible to an individual’s emotional state, such that negative emotions mostly increase pain while positive emotions lead to a pain decrease. Previous studies found that the anticipation of an aversive event induces threat and elevated pain. The question arises whether the exact opposite, namely safety, can lead to a reduction in pain. To investigate this hypothesis, I conducted three experiments in healthy volunteers. KW - Sicherheit KW - Schmerzverarbeitung Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359282 ER - TY - THES A1 - Drobczyk, Martin T1 - Ultra-Wideband Wireless Network for Enhanced Intra-Spacecraft Communication T1 - Drahtloses Ultra-Breitband-Netzwerk für verbesserte Intra-Spacecraft-Kommunikation N2 - Wireless communication networks already comprise an integral part of both the private and industrial sectors and are successfully replacing existing wired networks. They enable the development of novel applications and offer greater flexibility and efficiency. Although some efforts are already underway in the aerospace sector to deploy wireless communication networks on board spacecraft, none of these projects have yet succeeded in replacing the hard-wired state-of-the-art architecture for intra-spacecraft communication. The advantages are evident as the reduction of the wiring harness saves time, mass, and costs, and makes the whole integration process more flexible. It also allows for easier scaling when interconnecting different systems. This dissertation deals with the design and implementation of a wireless network architecture to enhance intra-spacecraft communications by breaking with the state-of-the-art standards that have existed in the space industry for decades. The potential and benefits of this novel wireless network architecture are evaluated, an innovative design using ultra-wideband technology is presented. It is combined with a Medium Access Control (MAC) layer tailored for low-latency and deterministic networks supporting even mission-critical applications. As demonstrated by the Wireless Compose experiment on the International Space Station (ISS), this technology is not limited to communications but also enables novel positioning applications. To adress the technological challenges, extensive studies have been carried out on electromagnetic compatibility, space radiation, and data robustness. The architecture was evaluated from various perspectives and successfully demonstrated in space. Overall, this research highlights how a wireless network can improve and potentially replace existing state-of-the-art communication systems on board spacecraft in future missions. And it will help to adapt and ultimately accelerate the implementation of wireless networks in space systems. N2 - Drahtlose Kommunikationsnetzwerke sind sowohl im privaten als auch im industriellen Bereich bereits ein fester Bestandteil und ersetzen erfolgreich bestehende drahtgebundene Netzwerke. Sie ermöglichen die Entwicklung neuer Anwendungen und bieten mehr Flexibilität und Effizienz. Obwohl in der Raumfahrt bereits einige Anstrengungen unternommen wurden, um drahtlose Kommunikationsnetzwerke an Bord von Raumfahrzeugen einzusetzen, ist es bisher noch keinem dieser Projekte gelungen, die moderne drahtgebundene Architektur für die Kommunikation innerhalb von Raumfahrzeugen zu ersetzen. Die Vorteile liegen auf der Hand: Die Reduzierung des Kabelbaums spart Zeit, Masse und Kosten und macht den gesamten Integrationsprozess flexibler. Außerdem ist eine einfachere Skalierung möglich, wenn verschiedene Systeme miteinander verbunden werden. Diese Dissertation befasst sich mit dem Entwurf und der Implementierung einer drahtlosen Netzwerkarchitektur zur Verbesserung der Kommunikation innerhalb von Raumfahrzeugen, indem mit den seit Jahrzehnten in der Raumfahrtindustrie bestehenden Standards gebrochen wird. Das Potential und die Vorteile dieser neuartigen drahtlosen Netzwerkarchitektur werden bewertet und ein innovatives Design mit Ultrabreitbandtechnologie wird vorgestellt. Es wird mit einer Medium Access Control (MAC) Schicht kombiniert, die für Netzwerke mit niedriger Latenz und Determinismus ausgelegt ist und sogar missionskritische Anwendungen unterstützt. Wie das Wireless Compose-Experiment auf der Internationalen Raumstation ISS gezeigt hat, ist diese Technologie nicht auf Kommunikation beschränkt, sondern ermöglicht auch neuartige Positionierungsanwendung. Um die technologischen Herausforderungen zu meistern, wurden umfangreiche Studien zur elektromagnetischen Verträglichkeit, Weltraumstrahlung und Robustheit der Daten durchgeführt. Die Architektur wurde aus verschiedenen Blickwinkeln bewertet und erfolgreich im Weltraum demonstriert. Insgesamt zeigt diese Forschung, wie ein drahtloses Netzwerk die bestehenden hochmodernen Kommunikationssysteme an Bord von Raumfahrzeugen bei zukünftigen Missionen verbessern und möglicherweise ersetzen kann. Darüber hinaus wird sie dazu beitragen, die Implementierung von drahtlosen Netzwerken in Raumfahrtsystemen an die jeweiligen Gegebenheiten anzupassen und damit letztlich die Integration dieser Systeme zu beschleunigen. KW - Raumfahrttechnik KW - ISS KW - Funktechnik KW - Ultraweitband KW - Avionik KW - Intra-Spacecraft Communication KW - Localization KW - Wireless Network KW - In-Orbit demonstration Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359564 ER - TY - THES A1 - Biersack, Florian T1 - Topological Properties of Quasiconformal Automorphism Groups T1 - Topologische Eigenschaften quasikonformer Automorphismengruppen N2 - The goal of this thesis is to study the topological and algebraic properties of the quasiconformal automorphism groups of simply and multiply connected domains in the complex plain, in which the quasiconformal automorphism groups are endowed with the supremum metric on the underlying domain. More precisely, questions concerning central topological properties such as (local) compactness, (path)-connectedness and separability and their dependence on the boundary of the corresponding domains are studied, as well as completeness with respect to the supremum metric. Moreover, special subsets of the quasiconformal automorphism group of the unit disk are investigated, and concrete quasiconformal automorphisms are constructed. Finally, a possible application of quasiconformal unit disk automorphisms to symmetric cryptography is presented, in which a quasiconformal cryptosystem is defined and studied. N2 - Das Ziel dieser Arbeit ist es, die topologischen und algebraischen Eigenschaften der quasikonformen Automorphismengruppen von einfach und mehrfach zusammenhängenden Gebieten in der komplexen Zahlenebene zu untersuchen, in denen die quasikonformen Automorphismengruppen mit der Supremum-Metrik auf dem zugrunde liegenden Gebiet versehen sind. Die Arbeit befasst sich mit Fragen zu zentralen topologischen Eigenschaften wie (lokaler) Kompaktheit, (Weg-)Zusammenhang und Separabilität sowie deren Abhängigkeit der Ränder der entsprechenden Gebiete, sowie mit der Vollständigkeit bezüglich der betrachteten Supremums-Metrik. Darüber hinaus werden spezielle Teilmengen der quasikonformen Automorphismengruppe des Einheitskreises untersucht und konkrete quasikonforme Automorphismen konstruiert. Schließlich wird eine mögliche Anwendung von quasikonformen Einheitskreis-Automorphismen auf symmetrische Kryptographie vorgestellt, bei der ein quasikonformes Kryptosystem definiert und untersucht wird. KW - Quasikonforme Abbildung KW - Automorphismengruppe KW - Quasiconformal automorphism KW - Uniform topology Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359177 ER - TY - THES A1 - Müller, Saskia T1 - The Influence of Personality and Trust on Information Processing and Decision Making in the Specific Context of Online Marketing T1 - Der Einfluss von Persönlichkeit und Vertrauen auf Informationsverarbeitung und Entscheidungsfindung im spezifischen Kontext des Online-Marketings N2 - Trust carries the capacity to shift the focus from risks to opportunities of a situation. Scientific studies from the field of trust research point out that besides situation-specific factors (i.e., stimuli of the environment), cross-situationally stable interindividual differences (i.e., personality) are involved in the emergence of trust. Stable interindividual differences are particularly influential to the subjective experience of situational conditions when crucial information is incomplete. The online shopping environment classifies as a prime example of markets with asymmetric information. Research has examined online consumer trust in the light of signaling theory to understand the effects of trust-enhancing signals. Previous research largely neglects interindividual differences in the perception, processing and reaction to these signals. Against this background, this scientific work has two primary objectives: the investigation of (1) interindividual differences in the evaluation of trust-enhancing signals and (2) a personality-based personalization of trust-enhancing signals in its effect on cognition and behavior. For this purpose, an interactive online shop setup was created, which served as realistic environmental framework. First, the results show a trust-enhancing effect of both objective and subjective personalization, with a superiority of subjective over objective personalization. Second, results suggest a particular susceptibility of the beliefs component of trust. Third, the results suggest that personalization exerts a specifically strong effect in what is, by definition, the particularly uncertain environment of credence goods. Fourth, results indicate that while the trust-enhancing effects of personalization operate (largely) independently of personality, the effect of personality on trust seems to depend on the condition of signal presentation. Taken together, the present work makes a contribution to understanding the effect of personality-adapted signaling environments on the emergence of trust and decision making in the specific context of B2C e-commerce. N2 - Vertrauen verlagert den Fokus von Risiken auf Chancen einer Situation. Studien aus dem Bereich der Vertrauensforschung weisen darauf hin, dass neben situationsspezifischen Faktoren (d.h. Stimuli der Umwelt) auch situationsübergreifende interindividuelle Unterschiede (d.h. die Persönlichkeit) an der Entstehung von Vertrauen beteiligt sind. Stabile interindividuelle Unterschiede sind besonders einflussreich für das subjektive Erleben, wenn entscheidende Informationen unvollständig sind. Das Online-Einkaufsumfeld gilt als Paradebeispiel für Märkte mit asymmetrischen Informationen. Die bisherige Forschung in diesem Bereich hat das Vertrauen im Lichte der Signaltheorie untersucht, um die Auswirkungen vertrauensfördernder Signale zu verstehen. Dabei wurden jedoch weitgehend interindividuelle Unterschiede in der Wahrnehmung, Verarbeitung und Reaktion auf diese Signale vernachlässigt. Diese Arbeit verfolgt daher zwei primäre Ziele: die Untersuchung von (1) interindividuellen Unterschieden in der Bewertung vertrauensfördernder Signale und (2) einer persönlichkeitsbasierten Personalisierung vertrauensfördernder Signale. Zu diesem Zweck wurde ein interaktiver Online-Shop konzipiert, der als realistischer Umweltrahmen diente. Erstens zeigen die Ergebnisse eine vertrauensfördernde Wirkung sowohl von objektiver als auch von subjektiver Personalisierung mit einer Überlegenheit der subjektiven Personalisierung. Zweitens deuten die Ergebnisse auf eine besondere Suszeptibilität der Einstellungskomponente des Vertrauens hin. Drittens legen die Ergebnisse nahe, dass die Personalisierung eine besonders starke Wirkung im Bereich der per Definition besonders unsicherheitsbehafteten Vertrauensgüter ausübt. Viertens zeigen die Ergebnisse, dass die vertrauensfördernden Effekte der Personalisierung zwar (weitgehend) unabhängig von der Persönlichkeit wirken, der Effekt der Persönlichkeit auf das Vertrauen jedoch von den Bedingungen der Signalpräsentation abzuhängen scheint. Insgesamt leistet die vorliegende Arbeit einen Beitrag zum Verständnis der Wirkung von persönlichkeitsangepassten Signalisierungsumgebungen auf die Entstehung von Vertrauen und die Entscheidungsfindung im spezifischen Kontext des B2C-E-Commerce. KW - Persönlichkeit KW - Vertrauen KW - Personalisierung KW - Personality KW - Trust KW - Personalization Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359526 ER - TY - JOUR A1 - Kraemer, Markus A1 - Becker, Jana A1 - Bley, Thorsten Alexander A1 - Steinbrecher, Andreas A1 - Minnerup, Jens A1 - Hellmich, Bernhard T1 - Diagnostik und Therapie der Riesenzellarteriitis T1 - Diagnostics and treatment of giant cell arteritis JF - Der Nervenarzt N2 - Die Riesenzellarteriitis (RZA) ist in der Altersgruppe der über 50-Jährigen die häufigste idiopathische systemische Vaskulitis. Die Erkrankung bedarf einer zeitnahen Diagnostik und Therapie, um schwere Komplikationen wie eine Erblindung oder einen Schlaganfall zu vermeiden. Die Rezidivneigung erfordert eine mehrjährige, zum Teil lebenslange Glukokortikoid(GC)-Therapie, was das Risiko GC-induzierter Langzeitnebenwirkungen erhöht. Daher wird bei der Mehrzahl der Patienten eine additive GC-einsparende Therapie empfohlen. Hierzu steht der Anti-IL-6-Rezeptor-Antikörper Tocilizumab in subkutaner Applikation als zugelassene Substanz zur Verfügung, alternativ kann Methotrexat (MTX) eingesetzt werden (off-label). N2 - Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis in the age group over 50 years. It requires prompt diagnostics and treatment to avoid severe complications, such as visual loss or stroke. The tendency to relapse makes a glucocorticoid (GC) treatment necessary for several years and sometimes lifelong, which increases the risk of GC-induced long-term side effects. Therefore, additive GC-sparing treatment is recommended in the majority of patients. For this purpose, the anti-IL‑6 receptor antibody tocilizumab is available as an approved substance for subcutaneous application; alternatively, methotrexate (MTX) can be used (off-label). KW - Riesenzellarteriitis KW - Diagnose KW - Therapie KW - Glukokortikoide KW - Glukokortikoideinsparende Therapie KW - Tocilizumab KW - Methotrexat KW - giant cell arteritis KW - diagnosis KW - therapy KW - glucocorticoids KW - glucocorticoid-sparing agents KW - Tocilizumab KW - Methotrexate Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307771 SN - 0028-2804 SN - 1433-0407 VL - 93 IS - 8 ER - TY - JOUR A1 - Barlinn, J. A1 - Winzer, S. A1 - Worthmann, H. A1 - Urbanek, C. A1 - Häusler, K. G. A1 - Günther, A. A1 - Erdur, H. A1 - Görtler, M. A1 - Busetto, L. A1 - Wojciechowski, C. A1 - Schmitt, J. A1 - Shah, Y. A1 - Büchele, B. A1 - Sokolowski, P. A1 - Kraya, T. A1 - Merkelbach, S. A1 - Rosengarten, B. A1 - Stangenberg-Gliss, K. A1 - Weber, J. A1 - Schlachetzki, F. A1 - Abu-Mugheisib, M. A1 - Petersen, M. A1 - Schwartz, A. A1 - Palm, F. A1 - Jowaed, A. A1 - Volbers, B. A1 - Zickler, P. A1 - Remi, J. A1 - Bardutzky, J. A1 - Bösel, J. A1 - Audebert, H. J. A1 - Hubert, G. J. A1 - Gumbinger, C. T1 - Telemedizin in der Schlaganfallversorgung – versorgungsrelevant für Deutschland T1 - Telemedicine in stroke—pertinent to stroke care in Germany JF - Der Nervenarzt N2 - Hintergrund und Ziel Telemedizinische Schlaganfall-Netzwerke tragen dazu bei, die Schlaganfallversorgung und insbesondere den Zugang zu zeitkritischen Schlaganfalltherapien in vorrangig strukturschwachen, ländlichen Regionen zu gewährleisten. Ziel ist eine Darstellung der Nutzungsfrequenz und regionalen Verteilung dieser Versorgungsstruktur. Methoden Die Kommission „Telemedizinische Schlaganfallversorgung“ der Deutschen Schlaganfall-Gesellschaft führte eine Umfragestudie in allen Schlaganfall-Netzwerken durch. Ergebnisse In Deutschland sind 22 telemedizinische Schlaganfall-Netzwerke aktiv, welche insgesamt 43 Zentren (pro Netzwerk: Median 1,5, Interquartilsabstand [IQA] 1–3) sowie 225 Kooperationskliniken (pro Netzwerk: Median 9, IQA 4–17) umfassen und an einem unmittelbaren Zugang zur Schlaganfallversorgung für 48 Mio. Menschen teilhaben. Im Jahr 2018 wurden 38.211 Telekonsile (pro Netzwerk: Median 1340, IQA 319–2758) durchgeführt. Die Thrombolyserate betrug 14,1 % (95 %-Konfidenzintervall 13,6–14,7 %), eine Verlegung zur Thrombektomie wurde bei 7,9 % (95 %-Konfidenzintervall 7,5–8,4 %) der ischämischen Schlaganfallpatienten initiiert. Das Finanzierungssystem ist uneinheitlich mit einem Vergütungssystem für die Zentrumsleistungen in nur drei Bundesländern. Diskussion Etwa jeder 10. Schlaganfallpatient wird telemedizinisch behandelt. Die telemedizinischen Schlaganfall-Netzwerke erreichen vergleichbar hohe Lyseraten und Verlegungen zur Thrombektomie wie neurologische Stroke-Units und tragen zur Sicherstellung einer flächendeckenden Schlaganfallversorgung bei. Eine netzwerkübergreifende Sicherstellung der Finanzierung und einheitliche Erhebung von Qualitätssicherungsdaten haben das Potenzial diese Versorgungsstruktur zukünftig weiter zu stärken. N2 - Background and objective Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. Methods The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. Results Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1–3) as well as 225 cooperating hospitals (per network: median 9, IQR 4–17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319–2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6–14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5–8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. Conclusion Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future. KW - Schlaganfall KW - Stroke-Unit KW - Telemedizin KW - Schlaganfall-Netzwerk KW - Umfragestudie KW - stroke KW - stroke unit KW - telemedicine KW - stroke networks KW - survey Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307752 SN - 0028-2804 SN - 1433-0407 VL - 92 IS - 6 ER - TY - JOUR A1 - Wagner, N. A1 - Crippa, L. A1 - Amaricci, A. A1 - Hansmann, P. A1 - Klett, M. A1 - König, E. J. A1 - Schäfer, T. A1 - Di Sante, D. A1 - Cano, J. A1 - Millis, A. J. A1 - Georges, A. A1 - Sangiovanni, G. T1 - Mott insulators with boundary zeros JF - Nature Communications N2 - The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green’s function zeros defining the “Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of “topological antimatter” annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green’s function zeros. KW - electronic properties and materials KW - topological insulators Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358150 VL - 14 ER - TY - JOUR A1 - Wu, Hao A1 - Zhao, Xiufeng A1 - Hochrein, Sophia M. A1 - Eckstein, Miriam A1 - Gubert, Gabriela F. A1 - Knöpper, Konrad A1 - Mansilla, Ana Maria A1 - Öner, Arman A1 - Doucet-Ladevèze, Remi A1 - Schmitz, Werner A1 - Ghesquière, Bart A1 - Theurich, Sebastian A1 - Dudek, Jan A1 - Gasteiger, Georg A1 - Zernecke, Alma A1 - Kobold, Sebastian A1 - Kastenmüller, Wolfgang A1 - Vaeth, Martin T1 - Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming JF - Nature Communications N2 - T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy. KW - cytotoxic T cells KW - infection KW - lymphocyte differentiation KW - translational research Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358052 VL - 14 ER - TY - JOUR A1 - Groh, Janos A1 - Abdelwahab, Tassnim A1 - Kattimani, Yogita A1 - Hörner, Michaela A1 - Loserth, Silke A1 - Gudi, Viktoria A1 - Adalbert, Robert A1 - Imdahl, Fabian A1 - Saliba, Antoine-Emmanuel A1 - Coleman, Michael A1 - Stangel, Martin A1 - Simons, Mikael A1 - Martini, Rudolf T1 - Microglia-mediated demyelination protects against CD8\(^+\) T cell-driven axon degeneration in mice carrying PLP defects JF - Nature Communications N2 - Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8\(^+\) T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation. KW - diseases of the nervous system KW - myelin biology and repair KW - neuroimmunology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357641 VL - 14 ER - TY - JOUR A1 - Sendell-Price, Ashley T. A1 - Tulenko, Frank J. A1 - Pettersson, Mats A1 - Kang, Du A1 - Montandon, Margo A1 - Winkler, Sylke A1 - Kulb, Kathleen A1 - Naylor, Gavin P. A1 - Phillippy, Adam A1 - Fedrigo, Olivier A1 - Mountcastle, Jacquelyn A1 - Balacco, Jennifer R. A1 - Dutra, Amalia A1 - Dale, Rebecca E. A1 - Haase, Bettina A1 - Jarvis, Erich D. A1 - Myers, Gene A1 - Burgess, Shawn M. A1 - Currie, Peter D. A1 - Andersson, Leif A1 - Schartl, Manfred T1 - Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks JF - Nature Communications N2 - Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10\(^{−10}\) per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate. KW - evolutionary genetics KW - genomics KW - molecular evolution Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357827 VL - 14 ER - TY - JOUR A1 - Karunakaran, Mohindar M. A1 - Subramanian, Hariharan A1 - Jin, Yiming A1 - Mohammed, Fiyaz A1 - Kimmel, Brigitte A1 - Juraske, Claudia A1 - Starick, Lisa A1 - Nöhren, Anna A1 - Länder, Nora A1 - Willcox, Carrie R. A1 - Singh, Rohit A1 - Schamel, Wolfgang W. A1 - Nikolaev, Viacheslav O. A1 - Kunzmann, Volker A1 - Wiemer, Andrew J. A1 - Willcox, Benjamin E. A1 - Herrmann, Thomas T1 - A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing JF - Nature Communications N2 - Butyrophilin (BTN)–3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members. KW - gammadelta T cells KW - immunosurveillance Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358179 VL - 14 ER - TY - JOUR A1 - Müller, Jörg A1 - Mitesser, Oliver A1 - Schaefer, H. Martin A1 - Seibold, Sebastian A1 - Busse, Annika A1 - Kriegel, Peter A1 - Rabl, Dominik A1 - Gelis, Rudy A1 - Arteaga, Alejandro A1 - Freile, Juan A1 - Leite, Gabriel Augusto A1 - de Melo, Tomaz Nascimento A1 - LeBien, Jack A1 - Campos-Cerqueira, Marconi A1 - Blüthgen, Nico A1 - Tremlett, Constance J. A1 - Böttger, Dennis A1 - Feldhaar, Heike A1 - Grella, Nina A1 - Falconí-López, Ana A1 - Donoso, David A. A1 - Moriniere, Jerome A1 - Buřivalová, Zuzana T1 - Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests JF - Nature Communications N2 - Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures – an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data. KW - animal behaviour KW - conservation biology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358130 VL - 14 ER - TY - JOUR A1 - Beetz, M. Jerome A1 - Kraus, Christian A1 - el Jundi, Basil T1 - Neural representation of goal direction in the monarch butterfly brain JF - Nature Communications N2 - Neural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals. KW - animal behaviour KW - navigation KW - neuroscience Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358073 VL - 14 ER - TY - JOUR A1 - Djakovic, Lara A1 - Hennig, Thomas A1 - Reinisch, Katharina A1 - Milić, Andrea A1 - Whisnant, Adam W. A1 - Wolf, Katharina A1 - Weiß, Elena A1 - Haas, Tobias A1 - Grothey, Arnhild A1 - Jürges, Christopher S. A1 - Kluge, Michael A1 - Wolf, Elmar A1 - Erhard, Florian A1 - Friedel, Caroline C. A1 - Dölken, Lars T1 - The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes JF - Nature Communications N2 - Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection. KW - herpes virus KW - transcription Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358161 VL - 14 ER - TY - JOUR A1 - Haake, Markus A1 - Haack, Beatrice A1 - Schäfer, Tina A1 - Harter, Patrick N. A1 - Mattavelli, Greta A1 - Eiring, Patrick A1 - Vashist, Neha A1 - Wedekink, Florian A1 - Genssler, Sabrina A1 - Fischer, Birgitt A1 - Dahlhoff, Julia A1 - Mokhtari, Fatemeh A1 - Kuzkina, Anastasia A1 - Welters, Marij J. P. A1 - Benz, Tamara M. A1 - Sorger, Lena A1 - Thiemann, Vincent A1 - Almanzar, Giovanni A1 - Selle, Martina A1 - Thein, Klara A1 - Späth, Jacob A1 - Gonzalez, Maria Cecilia A1 - Reitinger, Carmen A1 - Ipsen-Escobedo, Andrea A1 - Wistuba-Hamprecht, Kilian A1 - Eichler, Kristin A1 - Filipski, Katharina A1 - Zeiner, Pia S. A1 - Beschorner, Rudi A1 - Goedemans, Renske A1 - Gogolla, Falk Hagen A1 - Hackl, Hubert A1 - Rooswinkel, Rogier W. A1 - Thiem, Alexander A1 - Romer Roche, Paula A1 - Joshi, Hemant A1 - Pühringer, Dirk A1 - Wöckel, Achim A1 - Diessner, Joachim E. A1 - Rüdiger, Manfred A1 - Leo, Eugen A1 - Cheng, Phil F. A1 - Levesque, Mitchell P. A1 - Goebeler, Matthias A1 - Sauer, Markus A1 - Nimmerjahn, Falk A1 - Schuberth-Wagner, Christine A1 - Felten, Stefanie von A1 - Mittelbronn, Michel A1 - Mehling, Matthias A1 - Beilhack, Andreas A1 - van der Burg, Sjoerd H. A1 - Riedel, Angela A1 - Weide, Benjamin A1 - Dummer, Reinhard A1 - Wischhusen, Jörg T1 - Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment JF - Nature Communications N2 - Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development. KW - cancer microenvironment KW - immunotherapy KW - T cells KW - tumour immunology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357333 VL - 14 ER - TY - JOUR A1 - Salehi, Saeede A1 - Zare, Abdolhossein A1 - Prezza, Gianluca A1 - Bader, Jakob A1 - Schneider, Cornelius A1 - Fischer, Utz A1 - Meissner, Felix A1 - Mann, Matthias A1 - Briese, Michael A1 - Sendtner, Michael T1 - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr JF - Nature Communications N2 - The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3’ UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein. KW - molecular neuroscience KW - RNA-binding proteins KW - RNA transport Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357639 VL - 14 ER - TY - JOUR A1 - Gunkel, Sarah A1 - Schötzau, Andreas A1 - Fluri, Felix T1 - Burden of cerebral small vessel disease and changes of diastolic blood pressure affect clinical outcome after acute ischemic stroke JF - Scientific Reports N2 - Elevated and low blood pressure (BP) may lead to poor functional outcome after ischemic stroke, which is conflicting. Hence, there must be another factor—such as cerebral small vessel disease (cSVD) -interacting with BP and thus, affecting outcome. Here, we investigate the relationship between BP and cSVD regarding outcome after stroke. Data of 423/503 stroke patients were prospectively analyzed. Diastolic (DBP) and systolic BP (SBP) were collected on hospital admission (BP\(_{ad}\)) and over the first 72 h (BP\(_{72h}\)). cSVD-burden was determined on MR-scans. Good functional outcome was defined as a modified Rankin Scale score ≤ 2 at hospital discharge and 12 months thereafter. cSVD was a predictor of poor outcome (OR 2.8; p < 0.001). SBPad, DBP\(_{ad}\) and SBP\(_{72h}\) were not significantly associated with outcome at any time. A significant relationship was found between DBP\(_{72h}\), (p < 0.01), cSVD (p = 0.013) and outcome at discharge. At 12 months, we found a relationship between outcome and DBP\(_{72h}\) (p = 0.018) and a statistical tendency regarding cSVD (p = 0.08). Changes in DBP72h were significantly related with outcome. There was a U-shaped relationship between DBP\(_{72h}\) and outcome at discharge. Our results suggest an individualized stroke care by either lowering or elevating DBP depending on cSVD-burden in order to influence functional outcome. KW - cerebrovascular disorders KW - neurological disorders KW - stroke KW - white matter disease Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357669 VL - 13 ER - TY - JOUR A1 - Weismann, Dirk A1 - Möckel, Martin A1 - Paeth, Heiko A1 - Slagman, Anna T1 - Modelling variations of emergency attendances using data on community mobility, climate and air pollution JF - Scientific Reports N2 - Air pollution is associated with morbidity and mortality worldwide. We investigated the impact of improved air quality during the economic lockdown during the SARS-Cov2 pandemic on emergency room (ER) admissions in Germany. Weekly aggregated clinical data from 33 hospitals were collected in 2019 and 2020. Hourly concentrations of nitrogen and sulfur dioxide (NO2, SO2), carbon and nitrogen monoxide (CO, NO), ozone (O3) and particulate matter (PM10, PM2.5) measured by ground stations and meteorological data (ERA5) were selected from a 30 km radius around the corresponding ED. Mobility was assessed using aggregated cell phone data. A linear stepwise multiple regression model was used to predict ER admissions. The average weekly emergency numbers vary from 200 to over 1600 cases (total n = 2,216,217). The mean maximum decrease in caseload was 5 standard deviations. With the enforcement of the shutdown in March, the mobility index dropped by almost 40%. Of all air pollutants, NO2 has the strongest correlation with ER visits when averaged across all departments. Using a linear stepwise multiple regression model, 63% of the variation in ER visits is explained by the mobility index, but still 6% of the variation is explained by air quality and climate change. KW - cardiovascular diseases KW - environmental health KW - environmental impact KW - preclinical research KW - preventive medicine KW - reproductive disorders KW - respiratory signs and symptoms Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357578 VL - 13 ER - TY - JOUR A1 - Huestegge, Lynn A1 - Pieczykolan, Aleks A1 - Koch, Iring T1 - A Gestalt account of human behavior is supported by evidence from switching between single and dual actions JF - Scientific Reports N2 - The question of how behavior is represented in the mind lies at the core of psychology as the science of mind and behavior. While a long-standing research tradition has established two opposing fundamental views of perceptual representation, Structuralism and Gestalt psychology, we test both accounts with respect to action representation: Are multiple actions (characterizing human behavior in general) represented as the sum of their component actions (Structuralist view) or holistically (Gestalt view)? Using a single-/dual-response switch paradigm, we analyzed switches between dual ([A + B]) and single ([A], [B]) responses across different effector systems and revealed comparable performance in partial repetitions and full switches of behavioral requirements (e.g., in [A + B] → [A] vs. [B] → [A], or [A] → [A + B] vs. [B] → [A + B]), but only when the presence of dimensional overlap between responses allows for Gestalt formation. This evidence for a Gestalt view of behavior in our paradigm challenges some fundamental assumptions in current (tacitly Structuralist) action control theories (in particular the idea that all actions are represented compositionally with reference to their components), provides a novel explanatory angle for understanding complex, highly synchronized human behavior (e.g., dance), and delimitates the degree to which complex behavior can be analyzed in terms of its basic components. KW - cognitive neuroscience KW - human behaviour KW - learning and memory Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357862 VL - 13 ER - TY - JOUR A1 - Stebani, Jannik A1 - Blaimer, Martin A1 - Zabler, Simon A1 - Neun, Tilmann A1 - Pelt, Daniël M. A1 - Rak, Kristen T1 - Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework JF - Scientific Reports N2 - Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability. KW - anatomy KW - bone imaging KW - diagnosis KW - medical imaging KW - software KW - three-dimensional imaging KW - tomography Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357411 VL - 13 ER - TY - JOUR A1 - Kirsch, Wladimir A1 - Kunde, Wilfried T1 - Human perception of spatial frequency varies with stimulus orientation and location in the visual field JF - Scientific Reports N2 - Neuroanatomical variations across the visual field of human observers go along with corresponding variations of the perceived coarseness of visual stimuli. Here we show that horizontal gratings are perceived as having lower spatial frequency than vertical gratings when occurring along the horizontal meridian of the visual field, whereas gratings occurring along the vertical meridian show the exact opposite effect. This finding indicates a new peculiarity of processes operating along the cardinal axes of the visual field. KW - neuroscience KW - psychology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357888 VL - 13 ER - TY - JOUR A1 - Gruschwitz, Philipp A1 - Hartung, Viktor A1 - Kleefeldt, Florian A1 - Ergün, Süleyman A1 - Lichthardt, Sven A1 - Huflage, Henner A1 - Hendel, Robin A1 - Kunz, Andreas Steven A1 - Pannenbecker, Pauline A1 - Kuhl, Philipp Josef A1 - Augustin, Anne Marie A1 - Bley, Thorsten Alexander A1 - Petritsch, Bernhard A1 - Grunz, Jan-Peter T1 - Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model JF - Scientific Reports N2 - This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall’s concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability. KW - experimental models of disease KW - preclinical research KW - translational research Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357912 VL - 13 ER - TY - JOUR A1 - Weiß, Martin A1 - Gründahl, Marthe A1 - Deckert, Jürgen A1 - Eichner, Felizitas A. A1 - Kohls, Mirjam A1 - Störk, Stefan A1 - Heuschmann, Peter U. A1 - Hein, Grit T1 - Differential network interactions between psychosocial factors, mental health, and health-related quality of life in women and men JF - Scientific Reports N2 - Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the “Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)” cohort study, a representative age- and gender-stratified sample of the general population of Würzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis. KW - anxiety KW - depression KW - human behaviour KW - quality of life Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357858 VL - 13 ER - TY - JOUR A1 - Vogel, P. A1 - Rückert, M. A. A1 - Greiner, C. A1 - Günther, J. A1 - Reichl, T. A1 - Kampf, T. A1 - Bley, T. A. A1 - Behr, V. C. A1 - Herz, S. T1 - iMPI: portable human-sized magnetic particle imaging scanner for real-time endovascular interventions JF - Scientific Reports N2 - Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model. KW - biomedical engineering KW - electrical and electronic engineering KW - imaging KW - three-dimensional imaging Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357794 VL - 13 ER - TY - JOUR A1 - Gründahl, Marthe A1 - Weiß, Martin A1 - Stenzel, Kilian A1 - Deckert, Jürgen A1 - Hein, Grit T1 - The effects of everyday-life social interactions on anxiety-related autonomic responses differ between men and women JF - Scientific Reports N2 - Social buffering, a phenomenon where social presence can reduce anxiety and fear-related autonomic responses, has been studied in numerous laboratory settings. The results suggest that the familiarity of the interaction partner influences social buffering while also providing some evidence for gender effects. In the laboratory, however, it is difficult to mimic the complexity of real-life social interactions. Consequently, the social modulation of anxiety and related autonomic responses in everyday life remains poorly understood. We used smartphone-based Ecological Momentary Assessment (EMA) combined with wearable electrocardiogram sensors to investigate how everyday-life social interactions affect state anxiety and related cardiac changes in women and men. On five consecutive days, 96 healthy young participants (53% women) answered up to six EMA surveys per day, indicating characteristics of their most recent social interaction and the respective interaction partner(s). In women, our results showed lower heart rate in the presence of a male interaction partner. Men showed the same effect with female interaction partners. Moreover, only women showed decreased heart rate and increased heart rate variability with increasing interaction partner familiarity. These findings specify the conditions under which social interactions reduce anxiety-related responses in women and men. KW - physiology KW - psychology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357840 VL - 13 ER - TY - JOUR A1 - Bachert, Antonia A1 - Scheiner, Ricarda T1 - The ant’s weapon improves honey bee learning performance JF - Scientific Reports N2 - Formic acid is the main component of the ant’s major weapon against enemies. Being mainly used as a chemical defense, the acid is also exploited for recruitment and trail marking. The repelling effect of the organic acid is used by some mammals and birds which rub themselves in the acid to eliminate ectoparasites. Beekeepers across the world rely on this effect to control the parasitic mite Varroa destructor. Varroa mites are considered the most destructive pest of honey bees worldwide and can lead to the loss of entire colonies. Formic acid is highly effective against Varroa mites but can also kill the honeybee queen and worker brood. Whether formic acid can also affect the behavior of honey bees is unknown. We here study the effect of formic acid on sucrose responsiveness and cognition of honey bees treated at different live stages in field-relevant doses. Both behaviors are essential for survival of the honey bee colony. Rather unexpectedly, formic acid clearly improved the learning performance of the bees in appetitive olfactory conditioning, while not affecting sucrose responsiveness. This exciting side effect of formic acid certainly deserves further detailed investigations. KW - animal behaviour KW - animal physiology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358064 VL - 13 ER - TY - JOUR A1 - Patzer, Theresa Sophie A1 - Kunz, Andreas Steven A1 - Huflage, Henner A1 - Luetkens, Karsten Sebastian A1 - Conrads, Nora A1 - Gruschwitz, Philipp A1 - Pannenbecker, Pauline A1 - Ergün, Süleyman A1 - Bley, Thorsten Alexander A1 - Grunz, Jan-Peter T1 - Quantitative and qualitative image quality assessment in shoulder examinations with a first-generation photon-counting detector CT JF - Scientific Reports N2 - Photon-counting detector (PCD) CT allows for ultra-high-resolution (UHR) examinations of the shoulder without requiring an additional post-patient comb filter to narrow the detector aperture. This study was designed to compare the PCD performance with a high-end energy-integrating detector (EID) CT. Sixteen cadaveric shoulders were examined with both scanners using dose-matched 120 kVp acquisition protocols (low-dose/full-dose: CTDI\(_{vol}\) = 5.0/10.0 mGy). Specimens were scanned in UHR mode with the PCD-CT, whereas EID-CT examinations were conducted in accordance with the clinical standard as “non-UHR”. Reconstruction of EID data employed the sharpest kernel available for standard-resolution scans (ρ\(_{50}\) = 12.3 lp/cm), while PCD data were reconstructed with both a comparable kernel (11.8 lp/cm) and a sharper dedicated bone kernel (16.5 lp/cm). Six radiologists with 2–9 years of experience in musculoskeletal imaging rated image quality subjectively. Interrater agreement was analyzed by calculation of the intraclass correlation coefficient in a two-way random effects model. Quantitative analyses comprised noise recording and calculating signal-to-noise ratios based on attenuation measurements in bone and soft tissue. Subjective image quality was higher in UHR-PCD-CT than in EID-CT and non-UHR-PCD-CT datasets (all p < 0.001). While low-dose UHR-PCD-CT was considered superior to full-dose non-UHR studies on either scanner (all p < 0.001), ratings of low-dose non-UHR-PCD-CT and full-dose EID-CT examinations did not differ (p > 0.99). Interrater reliability was moderate, indicated by a single measures intraclass correlation coefficient of 0.66 (95% confidence interval: 0.58–0.73; p < 0.001). Image noise was lowest and signal-to-noise ratios were highest in non-UHR-PCD-CT reconstructions at either dose level (p < 0.001). This investigation demonstrates that superior depiction of trabecular microstructure and considerable denoising can be realized without additional radiation dose by employing a PCD for shoulder CT imaging. Allowing for UHR scans without dose penalty, PCD-CT appears as a promising alternative to EID-CT for shoulder trauma assessment in clinical routine. KW - bone KW - musculoskeletal system Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357925 VL - 13 ER - TY - JOUR A1 - Kirsch, Wladimir A1 - Kunde, Wilfried T1 - Changes in body perception following virtual object manipulation are accompanied by changes of the internal reference scale JF - Scientific Reports N2 - Changes in body perception often arise when observers are confronted with related yet discrepant multisensory signals. Some of these effects are interpreted as outcomes of sensory integration of various signals, whereas related biases are ascribed to learning-dependent recalibration of coding individual signals. The present study explored whether the same sensorimotor experience entails changes in body perception that are indicative of multisensory integration and those that indicate recalibration. Participants enclosed visual objects by a pair of visual cursors controlled by finger movements. Then either they judged their perceived finger posture (indicating multisensory integration) or they produced a certain finger posture (indicating recalibration). An experimental variation of the size of the visual object resulted in systematic and opposite biases of the perceived and produced finger distances. This pattern of results is consistent with the assumption that multisensory integration and recalibration had a common origin in the task we used. KW - human behaviour KW - perception Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357876 VL - 13 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Müller, Kerstin A1 - Notz, Quirin A1 - Hübsch, Martha A1 - Haas, Kirsten A1 - Horn, Anna A1 - Schmidt, Julia A1 - Heuschmann, Peter A1 - Maschmann, Jens A1 - Frosch, Matthias A1 - Deckert, Jürgen A1 - Einsele, Hermann A1 - Ertl, Georg A1 - Frantz, Stefan A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients JF - Scientific Reports N2 - Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87% and 80% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24% of non-ICU and 3% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5% of non-ICU and 10% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19. KW - health care KW - public health KW - quality of life Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357174 VL - 13 ER - TY - JOUR A1 - Odorfer, Thorsten M. A1 - Yabe, Marie A1 - Hiew, Shawn A1 - Volkmann, Jens A1 - Zeller, Daniel T1 - Topological differences and confounders of mental rotation in cervical dystonia and blepharospasm JF - Scientific Reports N2 - Mental rotation (mR) bases on imagination of actual movements. It remains unclear whether there is a specific pattern of mR impairment in focal dystonia. We aimed to investigate mR in patients with cervical dystonia (CD) and blepharospasm (BS) and to assess potential confounders. 23 CD patients and 23 healthy controls (HC) as well as 21 BS and 19 hemifacial spasm (HS) patients were matched for sex, age, and education level. Handedness, finger dexterity, general reaction time, and cognitive status were assessed. Disease severity was evaluated by clinical scales. During mR, photographs of body parts (head, hand, or foot) and a non-corporal object (car) were displayed at different angles rotated within their plane. Subjects were asked to judge laterality of the presented image by keystroke. Both speed and correctness were evaluated. Compared to HC, CD and HS patients performed worse in mR of hands, whereas BS group showed comparable performance. There was a significant association of prolonged mR reaction time (RT) with reduced MoCA scores and with increased RT in an unspecific reaction speed task. After exclusion of cognitively impaired patients, increased RT in the mR of hands was confined to CD group, but not HS. While the question of whether specific patterns of mR impairment reliably define a dystonic endophenotype remains elusive, our findings point to mR as a useful tool, when used carefully with control measures and tasks, which may be capable of identifying specific deficits that distinguish between subtypes of dystonia. KW - neurology KW - neuroscience Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357713 VL - 13 ER - TY - JOUR A1 - Kárpáti, Zsolt A1 - Deutsch, Ferenc A1 - Kiss, Balázs A1 - Schmitt, Thomas T1 - Seasonal changes in photoperiod and temperature lead to changes in cuticular hydrocarbon profiles and affect mating success in Drosophila suzukii JF - Scientific Reports N2 - Seasonal plasticity in insects is often triggered by temperature and photoperiod changes. When climatic conditions become sub-optimal, insects might undergo reproductive diapause, a form of seasonal plasticity delaying the development of reproductive organs and activities. During the reproductive diapause, the cuticular hydrocarbon (CHC) profile, which covers the insect body surface, might also change to protect insects from desiccation and cold temperature. However, CHCs are often important cues and signals for mate recognition and changes in CHC composition might affect mate recognition. In the present study, we investigated the CHC profile composition and the mating success of Drosophila suzukii in 1- and 5-day-old males and females of summer and winter morphs. CHC compositions differed with age and morphs. However, no significant differences were found between the sexes of the same age and morph. The results of the behavioral assays show that summer morph pairs start to mate earlier in their life, have a shorter mating duration, and have more offspring compared to winter morph pairs. We hypothesize that CHC profiles of winter morphs are adapted to survive winter conditions, potentially at the cost of reduced mate recognition cues. KW - ecology KW - zoology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358095 VL - 13 ER - TY - JOUR A1 - Rudloff, Jan Philipp A1 - Hutmacher, Fabian A1 - Appel, Markus T1 - Post-truth epistemic beliefs rooted in the Dark Factor of Personality are associated with higher COVID-19 vaccination refusal JF - Scientific Reports N2 - A substantial number of people refused to get vaccinated against COVID-19, which prompts the question as to why. We focus on the role of individual worldviews about the nature and generation of knowledge (epistemic beliefs). We propose a model that includes epistemic beliefs, their relationship to the Dark Factor of Personality (D), and their mutual effect on the probability of having been vaccinated against COVID-19. Based on a US nationally representative sample (N = 1268), we show that stronger endorsement of post-truth epistemic beliefs was associated with a lower probability of having been vaccinated against COVID-19. D was also linked to a lower probability of having been vaccinated against COVID-19, which can be explained by post-truth epistemic beliefs. Our results indicate that the more individuals deliberately refrain from adhering to the better argument, the less likely they are vaccinated. More generally, post-truth epistemic beliefs pose a challenge for rational communication. KW - diseases KW - psychology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357619 VL - 13 ER - TY - JOUR A1 - Kuzkina, A. A1 - Rößle, J. A1 - Seger, A. A1 - Panzer, C. A1 - Kohl, A. A1 - Maltese, V. A1 - Musacchio, T. A1 - Blaschke, S. J. A1 - Tamgüney, G. A1 - Kaulitz, S. A1 - Rak, K. A1 - Scherzad, A. A1 - Zimmermann, P. H. A1 - Klussmann, J. P. A1 - Hackenberg, S. A1 - Volkmann, J. A1 - Sommer, C. A1 - Sommerauer, M. A1 - Doppler, K. T1 - Combining skin and olfactory α-synuclein seed amplification assays (SAA)—towards biomarker-driven phenotyping in synucleinopathies JF - npj Parkinson’s Disease N2 - Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson’s disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients. KW - diagnostic markers KW - Parkinson's disease Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357687 SN - 2373-8057 VL - 9 ER - TY - JOUR A1 - Frank, Erik T. A1 - Kesner, Lucie A1 - Liberti, Joanito A1 - Helleu, Quentin A1 - LeBoeuf, Adria C. A1 - Dascalu, Andrei A1 - Sponsler, Douglas B. A1 - Azuma, Fumika A1 - Economo, Evan P. A1 - Waridel, Patrice A1 - Engel, Philipp A1 - Schmitt, Thomas A1 - Keller, Laurent T1 - Targeted treatment of injured nestmates with antimicrobial compounds in an ant society JF - Nature Communications N2 - Infected wounds pose a major mortality risk in animals. Injuries are common in the ant Megaponera analis, which raids pugnacious prey. Here we show that M. analis can determine when wounds are infected and treat them accordingly. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds, workers reduce the mortality of infected individuals by 90%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile, thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that M. analis ant societies use antimicrobial compounds produced in the metapleural glands to treat infected wounds and reduce nestmate mortality. KW - animal behaviour KW - chemical ecology KW - entomology KW - microbial ecology KW - proteomics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358081 VL - 14 ER -