@phdthesis{Reinhard2023, author = {Reinhard, Sebastian}, title = {Improving Super-Resolution Microscopy Data Reconstruction and Evaluation by Developing Advanced Processing Algorithms and Artifcial Neuronal Networks}, doi = {10.25972/OPUS-31695}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316959}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {The fusion of methods from several disciplines is a crucial component of scientific development. Artificial Neural Networks, based on the principle of biological neuronal networks, demonstrate how nature provides the best templates for technological advancement. These innovations can then be employed to solve the remaining mysteries of biology, including, in particular, processes that take place on microscopic scales and can only be studied with sophisticated techniques. For instance, direct Stochastic Optical Reconstruction Microscopy combines tools from chemistry, physics, and computer science to visualize biological processes at the molecular level. One of the key components is the computer-aided reconstruction of super-resolved images. Improving the corresponding algorithms increases the quality of the generated data, providing further insights into our biology. It is important, however, to ensure that the heavily processed images are still a reflection of reality and do not originate in random artefacts. Expansion microscopy is expanding the sample by embedding it in a swellable hydrogel. The method can be combined with other super-resolution techniques to gain additional resolution. We tested this approach on microtubules, a well-known filamentous reference structure, to evaluate the performance of different protocols and labelling techniques. We developed LineProfiler an objective tool for data collection. Instead of collecting perpendicular profiles in small areas, the software gathers line profiles from filamentous structures of the entire image. This improves data quantity, quality and prevents a biased choice of the evaluated regions. On the basis of the collected data, we deployed theoretical models of the expected intensity distribution across the filaments. This led to the conclusion that post-expansion labelling significantly reduces the labelling error and thus, improves the data quality. The software was further used to determine the expansion factor and arrangement of synaptonemal complex data. Automated Simple Elastix uses state-of-the-art image alignment to compare pre- and post-expansion images. It corrects linear distortions occurring under isotropic expansion, calculates a structural expansion factor and highlights structural mismatches in a distortion map. We used the software to evaluate expanded fungi and NK cells. We found that the expansion factor differs for the two structures and is lower than the overall expansion of the hydrogel. Assessing the fluorescence lifetime of emitters used for direct Stochastic Optical Reconstruction Microscopy can reveal additional information about the molecular environment or distinguish dyes emitting with a similar wavelength. The corresponding measurements require a confocal scanning of the sample in combination with the fluorescent switching of the underlying emitters. This leads to non-linear, interrupted Point Spread Functions. The software ReCSAI targets this problem by combining the classical algorithm of compressed sensing with modern methods of artificial intelligence. We evaluated several different approaches to combine these components and found, that unrolling compressed sensing into the network architecture yields the best performance in terms of reconstruction speed and accuracy. In addition to a deep insight into the functioning and learning of artificial intelligence in combination with classical algorithms, we were able to reconstruct the described non-linearities with significantly improved resolution, in comparison to other state-of-the-art architectures.}, subject = {Mikroskopie}, language = {en} } @phdthesis{Stoessel2023, author = {St{\"o}ßel, Anna}, title = {Auswirkungen zerebell{\"a}rer Gleichstromstimulation auf das motorische Lernen bei gesunden {\"a}lteren Probanden}, doi = {10.25972/OPUS-31793}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317930}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Sowohl neurologische Erkrankungen als auch der nat{\"u}rliche Alterungsprozess gehen regelhaft mit einem Untergang von Neuronen einher und bedingen neurologische Funktionsverluste. Diese mit Hilfe nicht-invasiver Techniken, beispielsweise tDCS, zu reduzieren, stellt ein wichtiges Ziel der neurowissenschaftlichen Forschung dar. Neben Arbeiten, die tDCS-Effekte auf das motorische Lernen bei Stimulation des motorischen Kortex nachweisen konnten, gibt es auch Hinweise f{\"u}r solche Effekte bei Stimulation des Kleinhirns. Allerdings besteht derzeit noch eine hohe Variabilit{\"a}t und damit einhergehend eine schlechte Vergleichbarkeit der Studien bez{\"u}glich ihrer Stimulationsbedingungen. Das Ansprechen unterschiedlicher Altersgruppen bleibt unklar. In der vorliegenden Arbeit wurden die Effekte zerebell{\"a}rer a-tDCS auf das motorische Lernen bei gesunden {\"a}lteren Probanden untersucht. Im Cross-over-Design wurde zu unterschiedlichen Zeitpunkten (vor bzw. nach der motorischen Aufgabe) stimuliert und im 24-Stunden-Verlauf die Langzeitwirkung evaluiert. Gruppe A erhielt vor einer motorischen {\"U}bungsaufgabe eine zerebell{\"a}re Stimulation, entweder als a-tDCS oder Scheinstimulation, Gruppe B nach der {\"U}bungsaufgabe. Zur {\"U}berpr{\"u}fung der Effekte auf das Sequenzlernen diente der Finger-Tapping-Task. Der Lernerfolg wurde anhand der Genauigkeit, der Sequenzdauer und des Skill-Index gemessen. Die Ergebnisse deuten darauf hin, dass eine zerebell{\"a}re a-tDCS vor einer {\"U}bungsaufgabe zu einer Verbesserung der Konsolidierung der F{\"a}higkeit, eine Zahlenfolge m{\"o}glichst schnell und gleichzeitig genau einzutippen, f{\"u}hrt, w{\"a}hrend die Stimulation nach einer {\"U}bungsaufgabe das motorische Lernen nicht zu beeinflussen scheint. Insgesamt st{\"u}tzen die Ergebnisse zum Teil die bisherigen Hinweise, dass eine zerebell{\"a}r applizierte a-tDCS das motorische Lernen verbessern kann. Aufgrund einiger Limitationen, besonders der geringen Gruppengr{\"o}ße, verbleibt dieses Ergebnis jedoch vorl{\"a}ufig und bedarf einer Best{\"a}tigung in gr{\"o}ßeren Probandengruppen. Es bleibt von hohem Interesse, die optimalen Bedingungen f{\"u}r die Anwendung von tDCS am Kleinhirn zu definieren, um motorische Lernprozesse positiv zu beeinflussen. Dies ist die Voraussetzung daf{\"u}r, zerebell{\"a}re tDCS mittelfristig auch zu therapeutischen Zwecken anwenden zu k{\"o}nnen.}, subject = {Motorisches Lernen}, language = {de} } @phdthesis{Ebner2023, author = {Ebner, Sebastian Manfred}, title = {Antimykotikaresistenzen bei deutschen \(Candida\) \(auris\) Isolaten}, doi = {10.25972/OPUS-31806}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318068}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Bei dem 2009 erstbeschriebenen Hefepilz C. auris handelt es sich um einen Keim, welcher aufgrund von nosokomialen Ausbr{\"u}chen und hohen Antimykotikaresistenzen Aufmerksamkeit erregte. Ziel dieser Arbeit war es in Deutschland gesammelte Isolate bez{\"u}glich vorhandener Resistenzen und Mutationen in Resistenzregionen zu testen und das epidemiologische Geschehen hierzulande mit dem globalen Auftreten des Keims zu vergleichen. Bez{\"u}glich der durchgef{\"u}hrten Resistenztestungen wiesen die CLSI-konformen Testarten (YO-Platten und E-Test-Verfahren) meist vergleichbare Ergebnisse auf. F{\"u}r das EUCAST-konforme Mikrodilutionstestverfahren kann aufgrund eines stark ausgepr{\"a}gten paradoxen Wachstumseffekts nur Anidulafungin, nicht jedoch Caspofungin, zur Testung empfohlen werden. Insgesamt erwiesen sich 25 \% der Isolate als Caspofungin-resistent. Zwei Isolate zeigten eine Resistenz gegen{\"u}ber allen getesteten Echinocandinen (16,7 \%). Die h{\"o}chsten Resistenzraten wurden gegen{\"u}ber Fluconazol (92 \%) beobachtet. Zwei der Isolate zeigten sich gegen{\"u}ber Voriconazol resistent (16,7 \%). F{\"u}r Amphotericin B konnte eine Resistenzrate von 33,3 \% festgestellt werden. F{\"u}r die Wirkstoffe Posaconazol und Itraconazol erwiesen sich alle untersuchten Isolate als sensitiv. Dies konnte auch mit Ausnahme eines Isolates f{\"u}r 5-Flucytosin beobachtet werden. Die durch eine Sanger-Sequenzierung erhaltenen Sequenzen der Gene FKS1 und ERG11 wurden auf Mutationen untersucht, welche zu Aminos{\"a}uresubstitutionen im Gesamtprotein f{\"u}hrten. Hierbei ergaben sich f{\"u}r zwei Isolate (16,7 \%) Mutationen im FKS1-Hot Spot 1 (Typ S639F und S639Y). Beide Isolate zeigten sich in den AFST Echinocandin-resistent. Bei allen untersuchten Isolaten lagen Mutationen im ERG11 Gen vor. So fand sich in 8 F{\"a}llen eine Mutation des Typen Y132F (66,7 \%), in 3 F{\"a}llen der Typ K143R (25 \%) und in einem Fall der Typ F126L (8,3 \%). Im Rahmen eines anderen Projekts wurde mit den hier gewonnenen PCR-Produkten ein WGS durchgef{\"u}hrt, um die Isolate durch SNPs-Vergleich mit Referenzst{\"a}mmen phylogenetischen Clades zuzuordnen. Dabei konnten 91,7 \% der Isolate dem s{\"u}dasiatischen Clade I und ein Isolat dem s{\"u}dafrikanischen Clade III zugeordnet werden. Aufgrund der geringen epidemiologischen Fallzahlen in Deutschland scheint gegenw{\"a}rtig keine Bedrohung von C. auris auszugehen. Berichte aus anderen L{\"a}ndern konnten allerdings eine rasche, ausbruchartige Zunahme von C. auris F{\"a}llen nachweisen. So kann nur angeraten werden das infektiologische Geschehen in Deutschland weiterhin zu beobachten.}, subject = {Candida}, language = {de} } @phdthesis{Rizzo2023, author = {Rizzo, Giuseppe}, title = {Determinants of macrophage and neutrophil heterogeneity in cardiac repair after myocardial infarction}, doi = {10.25972/OPUS-31068}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-310680}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Current therapeutic strategies efficiently improve survival in patients after myocardial infarction (MI). Nevertheless, long-term consequences such as heart failure development, are still one of the leading causes of death worldwide. Inflammation is critically involved in the cardiac healing process after MI and has a dual role, contributing to both tissue healing and tissue damage. In the last decade, a lot of attention was given to targeting inflammation as a potential therapeutic approach in MI, but the poor understanding of inflammatory cell heterogeneity and function is a limit to the development of immune modulatory strategies. The recent development of tools to profile immune cells with high resolution has provided a unique opportunity to better understand immune cell heterogeneity and dynamics in the ischemic heart. In this thesis, we employed single-cell RNA-sequencing combined with detection of epitopes by sequencing (CITE-seq) to refine our understanding of neutrophils and monocytes/macrophages heterogeneity and dynamic after experimental myocardial infarction. Neutrophils rapidly invade the infarcted heart shortly after ischemic damage and have previously been proposed to display time-dependent functional heterogeneity. At the single-cell level, we observed dynamic transcriptional heterogeneity in neutrophil populations during the acute post-MI phase and defined previously unknown cardiac neutrophil states. In particular, we identified a locally acquired SiglecFhi neutrophil state that displayed higher ROS production and phagocytic ability compared to newly recruited neutrophils, suggesting the acquisition of specific function in the infarcted heart. These findings highlight the importance of the tissue microenvironment in shaping neutrophil response. From the macrophage perspective, we characterized MI-associated monocyte-derived macrophage subsets, two with a pro-inflammatory gene signature (MHCIIhiIl1βhi) and three Trem2hi macrophage populations with a lipid associated macrophage (LAM) signature, also expressing pro-fibrotic and tissue repair genes. Combined analysis of blood monocytes and cardiac monocyte/macrophages indicated that the Trem2hi LAM signature is acquired in the infarcted heart. We furthermore characterized the role of TREM2, a surface protein expressed mainly in macrophages and involved in macrophage survival and function, in the post-MI macrophage response and cardiac repair. Using TREM2 deficient mice, we demonstrate that acquisition of the LAM signature in cardiac macrophages after MI is partially dependent on TREM2. While their cardiac function was not affected, TREM2 deficient mice showed reduced collagen deposition in the heart after MI. Thus, our data in Trem2-deficient mice highlight the role of TREM2 in promoting a macrophage pro-fibrotic phenotype, in line with the pro-fibrotic/tissue repair gene signature of the Trem2hi LAM-signature genes. Overall, our data provide a high-resolution characterization of neutrophils and macrophage heterogeneity and dynamics in the ischemic heart and can be used as a valuable resource to investigate how these cells modulate the healing processes after MI. Furthermore, our work identified TREM2 as a regulator of macrophage phenotype in the infarcted heart}, subject = {Makrophage}, language = {en} } @phdthesis{Yang2023, author = {Yang, Weiyue}, title = {Population Policy and Governance at the Local Level - A Qualitative Research of the Implementation of the Universal Two-Child Policy in China}, doi = {10.25972/OPUS-31305}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313052}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {The universal two-child policy was introduced by the central government of China in 2016 to respond to the country's deteriorating population problems, but it was soon replaced by a three-child policy in 2021 given that it failed to continuously boost fertility in Chinese society. This dissertation empirically investigates the implementation of universal two-child policy in three Chinese major cities. Based on the data collected through semi-structured interviews with leaders of local family planning agencies, it finds that local officials are primarily devoted to coping with the discontent of the bereaved single-child parents (shidu families), which is an unexpected consequence of the historical one-child policy, rather than working on the tasks regarding birth encouragement. The dissertation suggests understanding the implementation of China's population policy within the framework of both historical and rational choice institutionalism. The target responsibility system as an effective tool of the central authority drives local agents to fix their attention at tasks that have larger impact on their career. The shifted focus in the implementation of the universal two-child policy is a result of local officials' emphasis on the task of maintaining social stability. Shidu families are deemed as a salient threat to social order because their discontent with the state support has incurred continuous petitions at both the national and local level, which would severely undermine local officials' career advancement. However, in the meantime, stability maintenance is found to have become alienated as reflected by the rising costs and that it replaced birth support to be the focus of local family planning agents in the universal two-child policy era. Since the conflict between the shidu group and the state is unlikely to be resolved, the future population policy design and enforcement will continue to be constrained by the shidu problem.}, language = {en} } @phdthesis{CrespoVidal2023, author = {Crespo Vidal, Can Raphael}, title = {Spectroscopic investigation of the three-dimensional topological insulators (MnBi\(_2\)Te\(_4\))(Bi\(_2\)Te\(_3\))\(_n\) and HgTe: band structure, orbital symmetries, and influence of the cation \(d\)-states}, doi = {10.25972/OPUS-31293}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312931}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {This thesis examines the electronic properties of two materials that promise the realization and observation of novel exotic quantum phenomena. For this purpose, angle-resolved photoemission forms the experimental basis for the investigation of the electronic properties. Furthermore, the magnetic order is investigated utilizing X-ray dichroism measurements. First, the bulk and surface electronic structure of epitaxially grown HgTe in its three-dimensional topological insulator phase is investigated. In this study, synchrotron radiation is used to address the three-dimensional band structure and orbital composition of the bulk states by employing photon-energy-dependent and polarization-dependent measurements, respectively. In addition, the topological surface state is examined on in situ grown samples using a laboratory photon source. The resulting data provide a means to experimentally localize the bulk band inversion in momentum space and to evidence the momentum-dependent change in the orbital character of the inverted bulk states. Furthermore, a rather new series of van der Waals compounds, (MnBi\(_2\)Te\(_4\))(Bi\(_2\)Te\(_3\))\(_n\), is investigated. First, the magnetic properties of the first two members of the series, MnBi\(_2\)Te\(_4\) and MnBi\(_4\)Te\(_7\), are studied via X-ray absorption-based techniques. The topological surface state on the two terminations of MnBi\(_4\)Te\(_7\) is analyzed using circular dichroic, photon-energy-dependent, and spin-resolved photoemission. The topological state on the (MnBi\(_2\)Te\(_4\))-layer termination shows a free-standing Dirac cone with its Dirac point located in the bulk band gap. In contrast, on the (Bi\(_2\)Te\(_3\))-layer termination the surface state hybridizes with the bulk valences states, forming a spectral weight gap, and exhibits a Dirac point that is buried within the bulk continuum. Lastly, the lack of unambiguous evidence in the literature showing a temperature-dependent mass gap opening in these magnetic topological insulators is discussed through MnBi\(_2\)Te\(_4\).}, subject = {ARPES}, language = {en} } @phdthesis{Frackmann2023, author = {Frackmann, Kyra}, title = {In Vitro Analyse der Glukose- und Methionin-Restriktion im humanen Modellsystem HeLa sowie im Plattenepithelkarzinom HNSCC}, doi = {10.25972/OPUS-31156}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311565}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Krebserkrankung ist bis zum heutigen Zeitpunkt eine große Belastung in unserer Gesellschaft. Obwohl es stets Fortschritte in der Entwicklung neuer Therapiem{\"o}glichkeiten gibt, stellt die Behandlung auch in der modernen Medizin eine enorme Herausforderung dar. Darum besteht bis heute ein hoher Bedarf an neuen und weiterentwickelten Behandlungsm{\"o}glichkeiten. Um die Proliferation einer neoplastischen Zelle zu beeinflussen, stellen die Biomasse und die Energie einen grundlegenden Ansatz dar. Hier bieten sich vor allem die Aminos{\"a}uren als wesentlicher Baustein der Zellmasse und der Energietr{\"a}ger „Glukose" an, wodurch sich die beiden Ans{\"a}tze einer Protein- bzw. Aminos{\"a}ure-Restriktion und einer Glukose-Restriktion ergeben. Ziel ist es durch eine ver{\"a}nderte Stoffwechsellage einen Low-Energy-Metabolismus (LEM) zu induzieren, welcher die Zelle in einen sich selbst regenerierenden, antiproliferativen Zustand versetzt. Zus{\"a}tzlich sollte untersucht werden, ob sich die beiden Ans{\"a}tze grunds{\"a}tzlich als Therapieform gegen das Plattenepithelkarzinom (HNSCC) eignen. Zudem sollte ein Modell einer humanen Zelllinie erstellt werden, mit Hilfe dessen sich ein LEM auf metaboler Ebene charakterisieren l{\"a}sst. Die Ergebnisse zeigen, dass Zellen unter konstanter Glukose-Restriktion teils sensitiver auf Todesliganden reagieren. Außerdem wirken Kalorien-Restriktions-Mimetika antiproliferativ auf HNSCC Zellen. Hinzu kommt, dass eine Methionin-Restriktion Einfluss auf die Genexpression jener Gene hat, die mit der LEM-Signalkaskade in Zusammenhang stehen. Zuletzt lieferte die massenspektrometrische Analyse von mehr als 150 Metaboliten der humanen Zelllinie HeLa ein detailliertes Bild ihres Metabolismus unter Methionin-Restriktion. Durch die Definition eines charakteristischen Fingerabdrucks nach 72 h und eines kleinen Fußabdrucks aus wenigen Metaboliten, konnte ein humanes Modellsystem etabliert werden, dass zuk{\"u}nftig u.a. die schnelle Analyse von Kalorien-Restriktions-Mimetika erm{\"o}glicht.}, subject = {Methionin}, language = {de} } @phdthesis{Cetindere2023, author = {Cetindere, Rojan}, title = {Klinische und radiologische Ergebnisse nach offener Schultergelenksstabilisierung mittels Beckenkammspan}, doi = {10.25972/OPUS-31314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313148}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Im Rh{\"o}n-Klinikum wurden von 2012 bis 2015 49 Patient*innen wegen eines Glenoiddefektes mittels offenem Beckenkammspantransfer mit Kapselshift bei anteriorer Schulterinstabilit{\"a}t behandelt. 27 Patienten konnten in dieser Studie eingeschlossen werden (Einschlusskriterien: Follow-up von mindestens 12 Monaten, kompletter pr{\"a}operativer 3D-CT-Datensatz / Ausschlusskriterien: traumatische Schulterluxation oder Voroperation der kontralateralen Schulter). Ziel der Studie war es, das kurz- bis mittelfristige klinische Outcome dieser Kohorte zu erfassen, der Vergleich mit Ergebnissen anderer Arbeitsgruppen und der Vergleich von pr{\"a}operativ verwendeten Messmethoden (Chuang- bzw. Wambacher-Methode) f{\"u}r den Glenoiddefekt. Bei einem mittleren Follow-up von 27,11 Monaten zeigten sich {\"u}berwiegend gute bis exzellente kurz- bis mittelfristige OP-Ergebnisse (Rowe-Score: 84,81, Oxford-Shoulder-Score: 20,56, WOSI-Score: 371, Constant-Score: 86,74). Die OP-Methode eignet sich gut f{\"u}r Patient*innen, die mehrfach voroperiert sind, multiple Luxationsereignisse hatten sowie f{\"u}r diejenigen mit relevanter Hyperlaxizit{\"a}t, bei denen eine Latarjet-Operation kontraindiziert ist. Die OP-Methode ist gut anwendbar bei Patient*innen mit subkritischem Glenoidverlust < 20 \%, wenn zus{\"a}tzliche Sekund{\"a}rfaktoren vorliegen. Eine postoperative Omarthrose ist ein Risikofaktor f{\"u}r ein signifikant schlechteres Outcome. Die Gesamtkomplikationsrate lag bei 25,9\%, der Großteil hiervon (18,3\%) waren innerhalb kurzer Zeit reversibel. Die Reluxationsrate lag bei 3,7\%. Bei allen Studienteilnehmenden kam es zum Span-Remodelling ohne Schraubenlockerung oder Spanbruch. Eine {\"u}berm{\"a}ßige Spanresorbtion erfolgt antero-inferior, w{\"a}hrend um die Osteosyntheseschrauben eine {\"U}berkontur persistiert. Die Glenoiddefekte lagen bei 23,39 \% (Chuang) bzw. 22,06 \% (Wambacher). Es zeigte sich eine gute {\"U}bereinstimmung der Messergebnisse beider Methoden, allerdings lagen die Werte nach Chuang signifikant h{\"o}her.}, subject = {Orthop{\"a}die}, language = {de} } @phdthesis{Kreul2023, author = {Kreul, Lukas}, title = {Behandlungswechsel von Agalsidase beta zu Agalsidase alfa bei Morbus Fabry}, doi = {10.25972/OPUS-31311}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313113}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die lysosomale Speichererkrankung Morbus Fabry wird X-chromosomal rezessiv vererbt und f{\"u}hrt durch eine Mutation des α-Galactosidase A-Gens zu einer fehlerhaften Kodierung des α-Galactosidase A Enzyms. Die folgliche Akkumulation von Glykosphingolipiden, vorwiegend Gb-3 und Lyso-Gb-3 in den Lysosomen der Zellen verschiedener Organe sorgen dort f{\"u}r irreversible Sch{\"a}digungen. Klinisch werden von klassisch betroffenen M{\"a}nnern, bis zu nicht klassisch und teilweise v{\"o}llig asymptomatischen Frauen, eine Vielzahl an unterschiedlichen Ph{\"a}notypen detektiert. Insbesondere die Zellen des Herzens, der Niere, des Gef{\"a}ßsystems, des Nervensystems und auch der Cornea sind betroffen. Deshalb stellen die Krankheitsbilder der Herzinsuffizienz, fortschreitendes Nierenversagen und cerebrovaskul{\"a}re Ereignisse keine Seltenheit dar. Neben der im Jahr 2001 zugelassenen Enzymersatztherapie, besteht seit 2016 die M{\"o}glichkeit einer Chaperontherapie mit Migalastat f{\"u}r bestimmte Genotypen. Aktuell sind f{\"u}r die ERT die Produkte Agalsidase alfa (Replagal) mit einer Dosis von 0,2 mg/kg KG und Agalsidase beta (Fabrazyme) mit einer Dosis von 1,0 mg/kg KG beziehungsweise 0,3 mg/kg KG verf{\"u}gbar. Der perfekte Therapiebeginn und die optimale Dosis sind Gegenstand aktueller Forschung. Nachdem von 2009 bis 2012 ein Agalsidase beta Lieferengpass bestand, mussten viele Patienten unter Agalsidase beta Therapie auf Agalsidase alfa umgestellt werden. Bisherige Studien deuteten bei einem Wechsel zu Agalsidase alfa auf eine Abnahme der eGFR und eine Zunahme Fabry bezogener Schmerzen hin. Außerdem wurde bei einem Zur{\"u}ckwechseln zu Agalsidase beta ein Sinken der Plasma Lyso-Gb-3 Spiegel beobachtet. Da jedoch die Langzeiteffekte dieser Therapieumstellung noch unbeleuchtet waren, war es nun an der Zeit, mit dieser Arbeit Langzeitfolgen klinischer Stabilit{\"a}t und Sicherheit bei Patienten unter Dosisumstellung von Agalsidase alfa zu Agalsidase beta („switch") und solchen mit folgendem Zur{\"u}ckwechseln auf Agalsidase beta („re-switch") zu untersuchen. Von den 89 Studienteilnehmern aus drei verschiedenen Fabry Zentren in Deutschland zu Beginn konnten 78 Patienten am Ende des > 80 monatigen Bobachtungszeitraumes mit einer Baseline und zwei Follow-up Untersuchungen analysiert werden. Die Zuteilung zu den drei Gruppen „re-switch", „switch" und „regular Agalsidase beta" erfolgte je nach individuellem Therapieplan. Der Fokus der Studie lag auf den Langzeitdaten der Nierenfunktion, klinischen Symptomen und Ereignissen und der Plasma Lyso-Gb-3 Entwicklung. Patienten der „re-switch" Gruppe starteten zur Baseline mit den schlechtesten eGFR Werten. W{\"a}hrend die eGFR der Teilnehmer mit regul{\"a}rer Dosis stabil schien, verzeichnete sich in den „switch" und „re-switch" Gruppen eine signifikante Abnahme. Der eGFR-R{\"u}ckgang war dabei bei den „switch" Patienten am st{\"a}rksten. Im Geschlechtervergleich zeigten die M{\"a}nner aller drei Gruppen j{\"a}hrlich signifikante eGFR Einbußen zum zweiten Follow-up. Unterschiede in ernsthaften klinischen Ereignissen der Gruppen wurden nicht beobachtet. Gastrointestinale Beschwerden und Fabry bezogene Schmerzen verschlimmerten sich in der „re-switch" Gruppe nach Wechsel zu Agalsidase alfa und konnten durch Zur{\"u}ckwechseln zu Agalsidase beta wieder gebessert werden. Nachdem die Lyso-Gb-3 Spiegel der „switch" Gruppe konstant am h{\"o}chsten waren, konnten diese bei den „re-switch" Patienten nach einem Zur{\"u}ckwechseln zu Agalsidase beta signifikant gesenkt werden. Korrespondierend mit den vorherigen Studien konnte best{\"a}tigt werden, dass ein Wechsel von Agalsidase beta zu Agalsidase alfa im Allgemeinen sicher ist. Da aus den Daten nicht geschlussfolgert werden kann, dass Agalsidase beta das bessere Medikament ist, sollte die Wahl des Enzympr{\"a}parates nach wie vor auf individueller Basis erfolgen. Dennoch suggerieren die Daten eine bessere biochemische Antwort unter h{\"o}heren Enzymdosen, nach einem Zur{\"u}ckwechseln zu Agalsidase beta. Eine repr{\"a}sentative Optimierung der Nierenfunktion vor allem bei den M{\"a}nnern gelang nicht. Die Symptomverbesserung war am ehesten auf einen dosisabh{\"a}ngigen Enzymeffekt f{\"u}r die Beseitigung von Gb-3 Einschl{\"u}ssen zur{\"u}ckzuf{\"u}hren. Obwohl auch f{\"u}r die Reinigung von Gb-3 Einschl{\"u}ssen der Niere eine solche Wirkung nachgewiesen wurde, deutet der signifikante Verlust der Nierenfunktion der M{\"a}nner auf einen bereits gestarteten inflammatorischen Prozess hin, welcher auch durch h{\"o}here Dosen unbeeinflusst blieb. Eine L{\"o}sung k{\"o}nnte eine fr{\"u}here, noch vor dem Beginn der Inflammation startende ERT-Initiierung sein. Diese {\"U}berlegung und m{\"o}gliche anti-inflammatorische Therapiestrategien sollten mit zuk{\"u}nftigen Studien gekl{\"a}rt werden.}, subject = {Fabry-Krankheit}, language = {de} } @phdthesis{KlinnertVlachopoulou2023, author = {Klinnert Vlachopoulou, Cristina Maria}, title = {Comparison between Dual-Energy-CT perfusion imaging and perfusion-weighted SElf-gated Non-Contrast-Enhanced FUnctional MR imaging of the lung in patients with pulmonary artery embolism}, doi = {10.25972/OPUS-31303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313034}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Pulmonary artery embolism (PE) is a common condition and an even more common clinical suspect. The computed tomography pulmonary angiogram (CTPA) is the main medical imaging tool used to diagnose a suspected case of PE. To gain a better impression of the effects of a PE on the perfusion and hence the gas exchange, a functional imaging method is beneficial. One approach for functional imaging using radiation exposure is the generation of color-coded iodine perfusion maps acquired by Dual-Energy Computed Tomography (DECT), which enable the detection of perfusion defects in the pulmonary parenchyma. In contrast to the existing approach of DECT with iodine color-coded maps, the SElf-gated Non-Contrast-Enhanced FUnctional Lung (SENCEFUL) MRI technique offers the possibility to interpret perfusion maps without any radiation exposure or application of contrast agents. The measurement in SENCEFUL MRI can be performed during conditions of free breathing and without electrocardiogram triggering. The purpose of this study was to determine whether PE can be diagnosed on the basis of visible perfusion defects in the perfusion maps of SENCEFUL MRI and in the iodine-coded maps of DECT and to compare the diagnostic performance of these methods. Both SENCEFUL-MRI and iodine distribution maps from DECT have been compared with the CTPA of ten patients with PE. Additionally, the functional images were compared with each other on a per-patient basis. The iodine perfusion maps of DECT had a sensitivity of 84.2 \% and specificity of 65.2 \% for the diagnosis of PE. The SENCEFUL technique in MRI showed a sensitivity of 78.9 \% and a specificity of 26.1 \%. When comparing the whole lung depicted in both series of functional images, the main perfusion defect location matched in four of ten patients (40 \%). In conclusion, this work found that DECT iodine maps have higher sensitivity and specificity in the diagnosis of pulmonary embolism compared with SENCEFUL MRI.}, subject = {Lungenembolie}, language = {en} } @incollection{AckermannSnyderKoerber2023, author = {Ackermann, Zeno and Snyder-K{\"o}rber, MaryAnn}, title = {Series Foreword : JMU Cultural Studies - Strategies for Struggling with the Obvious}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-iii}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305801}, publisher = {W{\"u}rzburg University Press}, pages = {iii-v}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @article{AlpermannMalzer2023, author = {Alpermann, Bj{\"o}rn and Malzer, Michael}, title = {"In Other News": China's International Media Strategy on Xinjiang — CGTN and New China TV on YouTube}, series = {Modern China}, journal = {Modern China}, edition = {Online first}, issn = {1552-6836}, doi = {10.1177/00977004231169008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314173}, pages = {1-44}, year = {2023}, abstract = {In the Western world China stands accused of severe human rights violations regarding its treatment of the Uyghurs and other predominantly Muslim minorities in its northwestern Xinjiang Uyghur Autonomous Region. This is the first article to systematically analyze the response of China's international state media to these allegations. By studying the YouTube channels of two leading Chinese state media, China Global Television Network (CGTN) and New China TV (operated by Xinhua News Agency), it presents an indepth understanding of how China's foreign-facing propaganda works in a crucial case. The quantitative content analysis highlights how China reacted to increasing international (mostly United States) pressure regarding its Xinjiang policies by producing higher volumes of videos and putting out new counternarratives. The qualitative analysis that follows provides in-depth treatment of the most important discourses that Chinese media engage in to salvage the nation's international image, namely those on development, culture, nature, and terrorism. It finds several ways of countering criticism, ranging from presenting a positive image of China, in line with traditional propaganda guidelines and President Xi Jinping's assignment to state media to "tell the China story well," to more innovative approaches. Thus the development narrative becomes more personalized, the discourse on culture supports the "heritagization process" to incorporate minority cultures into a harmonized "Chinese civilization," representations of nature firmly tie Xinjiang into the discourse of "beautiful China," the "terror narrative" strategically employs shocking footage in an attempt to gain international "discourse power," etc. The article provides an up-to-date picture of China's state media strategy on a highly contentious international issue.}, language = {en} } @incollection{Jetter2023, author = {Jetter, Tobias}, title = {Afterword : Engaged Scholarship in Practice; or: How to Look Back into the Future}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305953}, publisher = {W{\"u}rzburg University Press}, pages = {183-187}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{OPUS4-31325, title = {Contributors}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-189}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313258}, publisher = {W{\"u}rzburg University Press}, pages = {189-192}, year = {2023}, abstract = {No abstract available.}, language = {en} } @techreport{NordEssHurtienneetal.2023, type = {Working Paper}, author = {Nord, Ilona and Ess, Charles and Hurtienne, J{\"o}rn and Schlag, Thomas}, title = {Robotics in Christian Religious Practice Reflections on initial experiments in this field}, doi = {10.25972/OPUS-30314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303149}, year = {2023}, abstract = {In this article we offer initial insights into the fairly new interdisciplinary and international domain of robotics in Christian religious practice. We are a group of scholars in media ethics, practical theology/religious education, and human computer interaction, who have been engaged in this discourse since 2017. A natural starting point is our study of BlessU2, a "blessing robot," a device which received considerable recognition from the global public at the Wittenberg 500th reformation anniversary in 2017. We thus begin with the results of this study. Secondly, we will briefly address the relevant theses from Gabriele Trovato et al., as presented in their 2019 article on so-called theomorphic robots - followed by our interdisciplinary discussion of their approach. Finally, we draw conclusions for further work on the field of "religious robots." Somewhat more carefully: Section 1 offers starting points within the perspectives of Christian religious practice: here, the blessing robot is both cause and occasion for doing religion and theologizing in the context of existential questions (1.1). We continue with perceptions in the field of religion regarding "Discursive Design Theory" (1.2). The interaction of humans with computers as posing questions for theological standardization of religious practice is focused upon in 1.3. Section 2 reconstructs the HRI/HCI-initiative to develop theomorphic robots in a twofold manner, i.e., the idea of developing theomorphic robots (2.1) and the concept of theomorphic robots: Questions and objections (2.2). In this part of the article we raise discussion points concerning the relationship between technology and religion and the need for sharpening the understanding of religion within the research field. Section 3 closes with propositions and alternatives.}, subject = {Soziale Robotik}, language = {en} } @incollection{Khapai2023, author = {Khapai, YS Sochuiwon Priscilla}, title = {Rethinking the Culture of Education with Raymond Williams}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-33}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305854}, publisher = {W{\"u}rzburg University Press}, pages = {33-44}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{Koch2023, author = {Koch, Louisa}, title = {Cultural Studies as a Question of Stance}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305845}, publisher = {W{\"u}rzburg University Press}, pages = {21-31}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{Jetter2023, author = {Jetter, Tobias}, title = {Introduction : Global Cultural Studies?}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305815}, publisher = {W{\"u}rzburg University Press}, pages = {1-3}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{JetterAckermannSnyderKoerber2023, author = {Jetter, Tobias and Ackermann, Zeno and Snyder-K{\"o}rber, MaryAnn}, title = {Acknowledgements}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-i}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305790}, publisher = {W{\"u}rzburg University Press}, pages = {i-ii}, year = {2023}, abstract = {No abstract available.}, language = {en} } @incollection{Saundarya2023, author = {Saundarya,}, title = {Food Cultures: Dynamics of Caste, Gender, Religion, and Class in India}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305901}, publisher = {W{\"u}rzburg University Press}, pages = {101-111}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{Mantraraj2023, author = {Mantraraj, Sudeeti Geeta}, title = {Strategies for Survival and Resources for Resistance}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-171}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305948}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {171-180}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @incollection{Doering2023, author = {D{\"o}ring, Adrian}, title = {A New International}, series = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, booktitle = {Global Cultural Studies? Engaged Scholarship between National and Transnational Frames}, editor = {Jetter, Tobias}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-207-2-87}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305898}, publisher = {W{\"u}rzburg University Press}, pages = {87-93}, year = {2023}, abstract = {No abstract available.}, subject = {Kulturwissenschaften}, language = {en} } @article{BrustNaglerShoyamaetal.2023, author = {Brust, Felix and Nagler, Oliver and Shoyama, Kazutaka and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Organic Light-Emitting Diodes Based on Silandiol-Bay-Bridged Perylene Bisimides}, series = {Advanced Optical Materials}, volume = {11}, journal = {Advanced Optical Materials}, number = {5}, doi = {10.1002/adom.202202676}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312599}, year = {2023}, abstract = {Perylene bisimides (PBIs) are among the best fluorophores but have to be enwrapped for optoelectronic applications by large and heavy substituents to prevent their ππ-stacking, which is known to accelerate non-radiative decay processes in the solid state. Here, light-weight di-tert-butylsilyl groups are introduced to bridge 1,12-dihydroxy and 1,6,7,12-tetrahydroxy PBIs to afford sublimable dyes for vacuum-processed optoelectronic devices. For both new compounds, this substitution provides a twisted and shielded perylene π-core whose, via OSiObridges, rigid structure affords well-resolved absorption and emission spectra with strong fluorescence in solution, as well as in the solid state. The usefulness of these dyes for vacuum-processed optoelectronic devices is demonstrated in organic light-emitting diodes (OLEDs) that show monomer-like emission spectra and high maximum external quantum efficiency (EQEmax) values of up to 3.1\% for the doubly silicon-bridged PBI.}, language = {en} } @article{DresenPimientoPateletal.2023, author = {Dresen, Ellen and Pimiento, Jose M. and Patel, Jayshil J. and Heyland, Daren K. and Rice, Todd W. and Stoppe, Christian}, title = {Overview of oxidative stress and the role of micronutrients in critical illness}, series = {Journal of Parenteral and Enteral Nutrition}, volume = {47}, journal = {Journal of Parenteral and Enteral Nutrition}, doi = {10.1002/jpen.2421}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318186}, pages = {S38 -- S49}, year = {2023}, abstract = {Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.}, language = {en} } @article{MoratinThoeleLangetal.2023, author = {Moratin, Helena and Th{\"o}le, Anna and Lang, Josephine and Ehret Kasemo, Totta and St{\"o}th, Manuel and Hagen, Rudolf and Scherzad, Agmal and Hackenberg, Stephan}, title = {Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {10}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15102506}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357403}, year = {2023}, abstract = {Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air-liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.}, language = {en} } @article{IsraelRiehlButtetal.2023, author = {Israel, Ina and Riehl, Gabriele and Butt, Elke and Buck, Andreas K. and Samnick, Samuel}, title = {Gallium-68-labeled KISS1-54 peptide for mapping KISS1 receptor via PET: initial evaluation in human tumor cell lines and in tumor-bearing mice}, series = {Pharmaceuticals}, volume = {17}, journal = {Pharmaceuticals}, number = {1}, issn = {1424-8247}, doi = {10.3390/ph17010044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355898}, year = {2023}, abstract = {Kisspeptins (KPs, KISS1) and their receptor (KISS1R) play a pivotal role as metastasis suppressor for many cancers. Low or lost KP expression is associated with higher tumor grade, increased metastatic potential, and poor prognosis. Therefore, KP expression has prognostic relevance and correlates with invasiveness in cancers. Furthermore, KISS1R represents a very promising target for molecular imaging and therapy for KISS1R-expressing tumors. The goal of this study was to evaluate the developed KISS1-54 derivative, [\(^{68}\)Ga]KISS1-54, as a PET-imaging probe for KISS1R-expressing tumors. The NODAGA-KISS1-54 peptide was labeled by Gallium-68, and the stability of the resulting [\(^{68}\)Ga]KISS1-54 evaluated in injection solution and human serum, followed by an examination in different KISS1R-expressing tumor cell lines, including HepG2, HeLa, MDA-MB-231, MCF7, LNCap, SK-BR-3, and HCT116. Finally, [\(^{68}\)Ga]KISS1-54 was tested in LNCap- and MDA-MB-231-bearing mice, using µ-PET, assessing its potential as an imaging probe for PET. [\(^{68}\)Ga]KISS1-54 was obtained in a 77 ± 7\% radiochemical yield and at a >99\% purity. The [\(^{68}\)Ga]KISS1-54 cell uptake amounted to 0.6-4.4\% per 100,000 cells. Moreover, the accumulation of [\(^{68}\)Ga]KISS1-54 was effectively inhibited by nonradioactive KISS1-54. In [\(^{68}\)Ga]KISS1-54-PET, KISS1R-positive LNCap-tumors were clearly visualized as compared to MDA-MB-231-tumor implant with predominantly intracellular KISS1R expression. Our first results suggest that [\(^{68}\)Ga]KISS1-54 is a promising candidate for a radiotracer for targeting KISS1R-expressing tumors via PET.}, language = {en} } @article{OdorferVolkmann2023, author = {Odorfer, Thorsten M. and Volkmann, Jens}, title = {Deep brain stimulation for focal or segmental craniocervical dystonia in patients who have failed botulinum neurotoxin therapy - a narrative review of the literature}, series = {Toxins}, volume = {15}, journal = {Toxins}, number = {10}, issn = {2072-6651}, doi = {10.3390/toxins15100606}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357707}, year = {2023}, abstract = {(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.}, language = {en} } @article{WatzlingKlausWeidemeieretal.2023, author = {Watzling, Martin and Klaus, Lorenz and Weidemeier, Tamara and Horder, Hannes and Ebert, Regina and Blunk, Torsten and Bauer-Kreisel, Petra}, title = {Three-dimensional breast cancer model to investigate CCL5/CCR1 expression mediated by direct contact between breast cancer cells and adipose-derived stromal cells or adipocytes}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {13}, issn = {2072-6694}, doi = {10.3390/cancers15133501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362502}, year = {2023}, abstract = {The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell-cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor-stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell-cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.}, language = {en} } @article{GuederReinFlohretal.2023, author = {G{\"u}der, G{\"u}lmisal and Rein, Eva von and Flohr, Thomas and Weismann, Dirk and Schmitt, Dominik and St{\"o}rk, Stefan and Frantz, Stefan and Kratzer, Vincent and Kendi, Christian}, title = {Motion detectors as additional monitoring devices in the intensive care unit — a proof-of-concept study}, series = {Applied Sciences}, volume = {13}, journal = {Applied Sciences}, number = {16}, issn = {2076-3417}, doi = {10.3390/app13169319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362404}, year = {2023}, abstract = {Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Gr{\"u}nwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes ("lying dead-still, with no or very shallow breathing"). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7\%) were rated correctly. Ratings were false negative (FN: "no movements detected, but recorded") in 7 out of 180 motion scenes (3.9\%). Ratings were false positive (FP: "movements detected, but not recorded") in 37 out of 150 scenes (24.7\%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p \< 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3\%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96\%) and acceptable specificity (75\%). Accuracy might increase further if activities are recorded continuously under real-world conditions.}, language = {en} } @article{HiewEibeckNguemenietal.2023, author = {Hiew, Shawn and Eibeck, Leila and Nguemeni, Carine and Zeller, Daniel}, title = {The influence of age and physical activity on locomotor adaptation}, series = {Brain Sciences}, volume = {13}, journal = {Brain Sciences}, number = {9}, issn = {2076-3425}, doi = {10.3390/brainsci13091266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362478}, year = {2023}, abstract = {Background: Aging increases individual susceptibility to falls and injuries, suggesting poorer adaptation of balance responses to perturbation during locomotion, which can be measured with the locomotor adaptation task (LAT). However, it is unclear how aging and lifestyle factors affect these responses during walking. Hence, the present study investigates the relationship between balance and lifestyle factors during the LAT in healthy individuals across the adult lifespan using a correlational design. Methods: Thirty participants aged 20-78 years performed an LAT on a split-belt treadmill (SBT). We evaluated the magnitude and rate of adaptation and deadaptation during the LAT. Participants reported their lifelong physical and cognitive activity. Results: Age positively correlated with gait-line length asymmetry at the late post-adaptation phase (p = 0.007). These age-related effects were mediated by recent physical activity levels (p = 0.040). Conclusion: Our results confirm that locomotor adaptive responses are preserved in aging, but the ability to deadapt newly learnt balance responses is compromised with age. Physical activity mediates these age-related effects. Therefore, gait symmetry post-adaptation could effectively measure the risk of falling, and maintaining physical activity could protect against declines in balance.}, language = {en} } @article{GryszelSchlossarekWuerthneretal.2023, author = {Gryszel, Maciej and Schlossarek, Tim and W{\"u}rthner, Frank and Natali, Mirco and Głowacki, Eric Daniel}, title = {Water-soluble cationic perylene diimide dyes as stable photocatalysts for H\(_2\)O\(_2\) evolution}, series = {ChemPhotoChem}, volume = {7}, journal = {ChemPhotoChem}, number = {9}, issn = {2367-0932}, doi = {10.1002/cptc.202300070}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370250}, year = {2023}, abstract = {Photocatalytic generation of hydrogen peroxide, H\(_2\)O\(_2\), has gained increasing attention in recent years, with applications ranging from solar energy conversion to biophysical research. While semiconducting solid-state materials are normally regarded as the workhorse for photogeneration of H\(_2\)O\(_2\), an intriguing alternative for on-demand H\(_2\)O\(_2\) is the use of photocatalytic organic dyes. Herein we report the use of water-soluble dyes based on perylene diimide molecules which behave as true molecular catalysts for the light-induced conversion of dissolved oxygen to hydrogen peroxide. In particular, we address how to obtain visible-light photocatalysts which are stable with respect to aggregation and photochemical degradation. We report on the factors affecting efficiency and stability, including variable electron donors, oxygen partial pressure, pH, and molecular catalyst structure. The result is a perylene diimide derivative with unprecedented peroxide evolution performance using a broad range of organic donor molecules and operating in a wide pH range.}, language = {en} } @article{OPUS4-37080, title = {Interview mit Prof. Dr. Marina Ortrud Hertrampf}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {9}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, editor = {Hesselbach, Robert}, issn = {2510-2613}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370808}, pages = {7-13}, year = {2023}, abstract = {Interview mit Prof. Dr. Marina Ortrud Hertrampf}, language = {de} }