@article{GottschollWagenhoeferKlimmeretal.2022, author = {Gottscholl, Andreas and Wagenh{\"o}fer, Maximilian and Klimmer, Manuel and Scherbel, Selina and Kasper, Christian and Baianov, Valentin and Astakhov, Georgy V. and Dyakonov, Vladimir and Sperlich, Andreas}, title = {Superradiance of spin defects in silicon carbide for maser applications}, series = {Frontiers in Photonics}, volume = {3}, journal = {Frontiers in Photonics}, issn = {2673-6853}, doi = {10.3389/fphot.2022.886354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284698}, year = {2022}, abstract = {Masers as telecommunication amplifiers have been known for decades, yet their application is strongly limited due to extreme operating conditions requiring vacuum techniques and cryogenic temperatures. Recently, a new generation of masers has been invented based on optically pumped spin states in pentacene and diamond. In this study, we pave the way for masers based on spin S = 3/2 silicon vacancy (V\(_{Si}\)) defects in silicon carbide (SiC) to overcome the microwave generation threshold and discuss the advantages of this highly developed spin hosting material. To achieve population inversion, we optically pump the V\(_{Si}\) into their m\(_S\) = ±1/2 spin sub-states and additionally tune the Zeeman energy splitting by applying an external magnetic field. In this way, the prerequisites for stimulated emission by means of resonant microwaves in the 10 GHz range are fulfilled. On the way to realising a maser, we were able to systematically solve a series of subtasks that improved the underlying relevant physical parameters of the SiC samples. Among others, we investigated the pump efficiency as a function of the optical excitation wavelength and the angle between the magnetic field and the defect symmetry axis in order to boost the population inversion factor, a key figure of merit for the targeted microwave oscillator. Furthermore, we developed a high-Q sapphire microwave resonator (Q ≈ 10\(^4\)-10\(^5\)) with which we find superradiant stimulated microwave emission. In summary, SiC with optimized spin defect density and thus spin relaxation rates is well on its way of becoming a suitable maser gain material with wide-ranging applications.}, language = {en} } @article{LodhaErhardDoelkenetal.2022, author = {Lodha, Manivel and Erhard, Florian and D{\"o}lken, Lars and Prusty, Bhupesh K.}, title = {The hidden enemy within: non-canonical peptides in virus-induced autoimmunity}, series = {Frontiers in Microbiology}, volume = {13}, journal = {Frontiers in Microbiology}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.840911}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263053}, year = {2022}, abstract = {Viruses play a key role in explaining the pathogenesis of various autoimmune disorders, whose underlying principle is defined by the activation of autoreactive T-cells. In many cases, T-cells escape self-tolerance due to the failure in encountering certain MHC-I self-peptide complexes at substantial levels, whose peptides remain invisible from the immune system. Over the years, contribution of unstable defective ribosomal products (DRiPs) in immunosurveillance has gained prominence. A class of unstable products emerge from non-canonical translation and processing of unannotated mammalian and viral ORFs and their peptides are cryptic in nature. Indeed, high throughput sequencing and proteomics have revealed that a substantial portion of our genomes comprise of non-canonical ORFs, whose generation is significantly modulated during disease. Many of these ORFs comprise short ORFs (sORFs) and upstream ORFs (uORFs) that resemble DRiPs and may hence be preferentially presented. Here, we discuss how such products, normally "hidden" from the immune system, become abundant in viral infections activating autoimmune T-cells, by discussing their emerging role in infection and disease. Finally, we provide a perspective on how these mechanisms can explain several autoimmune disorders in the wake of the COVID-19 pandemic.}, language = {en} } @article{SperlichAuthDyakonov2022, author = {Sperlich, Andreas and Auth, Michael and Dyakonov, Vladimir}, title = {Charge transfer in ternary solar cells employing two fullerene derivatives: where do electrons go?}, series = {Israel Journal of Chemistry}, volume = {62}, journal = {Israel Journal of Chemistry}, number = {7-8}, doi = {10.1002/ijch.202100064}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257506}, year = {2022}, abstract = {Earlier reports demonstrated that ternary organic solar cells (OSC) made of donor polymers (D) blended with different mixtures of fullerene acceptors (A : A) performed very similarly. This finding is surprising, as the corresponding fullerene LUMO levels are slightly different, which might result in decisive differences in the charge transfer step. We investigate ternary OSC (D : A : A) made of the donor polymer P3HT with stoichiometric mixtures of different fullerene derivatives, PC\(_{60}\)BM : PC\(_{70}\)BM and PC\(_{70}\)BM : IC\(_{60}\)BA, respectively. Using quantitative electron paramagnetic resonance (EPR) we can distinguish between positive and negative polarons, localized on the specific molecules. We found that after the initial charge transfer step, the electrons are re-distributed over two nearby acceptors in agreement with their stoichiometry and their relative LUMO energy difference. Remarkably, the measured ΔLUMO differences in fullerene mixtures are reduced by an order of magnitude compared to that of the pristine materials, i. e., below 1 meV for PC\(_{60}\)BM : PC\(_{70}\)BM and (20±5) meV for PC\(_{70}\)BM : IC\(_{60}\)BA. Furthermore, we found that this reduced ΔLUMO explains the shift in open circuit voltage for D : A : A organic solar cells. We attribute these findings to hybridization, leading to an effective fullerene LUMO. Consequently, multi-acceptor blends are indeed a viable option for photodetectors and solar cells, as they combine the best electron acceptor and light absorbing properties.}, language = {en} } @article{PozziPalmisanoReichetal.2022, author = {Pozzi, Nicol{\´o} G. and Palmisano, Chiara and Reich, Martin M. and Capetian, Philip and Pacchetti, Claudio and Volkmann, Jens and Isaias, Ioannis U.}, title = {Troubleshooting gait disturbances in Parkinson's disease with deep brain stimulation}, series = {Frontiers in Human Neuroscience}, volume = {16}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2022.806513}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-274007}, year = {2022}, abstract = {Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson's disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management.}, language = {en} } @article{SchickSchlegel2022, author = {Schick, Martin Alexander and Schlegel, Nicolas}, title = {Clinical implication of phosphodiesterase-4-inhibition}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms23031209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284511}, year = {2022}, abstract = {The pleiotropic function of 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent pathways in health and disease led to the development of pharmacological phosphodiesterase inhibitors (PDE-I) to attenuate cAMP degradation. While there are many isotypes of PDE, a predominant role of PDE4 is to regulate fundamental functions, including endothelial and epithelial barrier stability, modulation of inflammatory responses and cognitive and/or mood functions. This makes the use of PDE4-I an interesting tool for various therapeutic approaches. However, due to the presence of PDE4 in many tissues, there is a significant danger for serious side effects. Based on this, the aim of this review is to provide a comprehensive overview of the approaches and effects of PDE4-I for different therapeutic applications. In summary, despite many obstacles to use of PDE4-I for different therapeutic approaches, the current data warrant future research to utilize the therapeutic potential of phosphodiesterase 4 inhibition.}, language = {en} } @article{MihatschBeissertPomperetal.2022, author = {Mihatsch, Patrick W. and Beissert, Matthias and Pomper, Martin G. and Bley, Thorsten A. and Seitz, Anna K. and K{\"u}bler, Hubert and Buck, Andreas K. and Rowe, Steven P. and Serfling, Sebastian E. and Hartrampf, Philipp E. and Werner, Rudolf A.}, title = {Changing threshold-based segmentation has no relevant impact on semi-quantification in the context of structured reporting for PSMA-PET/CT}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers14020270}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254782}, year = {2022}, abstract = {Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50\%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50\% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.}, language = {en} } @article{HankirBruneauJr2022, author = {Hankir, Mohammed Khair and Bruneau Jr., Michael}, title = {Periphery-brain interactions and leptin in the regulation of whole-body energy metabolism}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {8}, issn = {2072-6643}, doi = {10.3390/nu14081594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270581}, year = {2022}, abstract = {No abstract available}, language = {en} } @phdthesis{Hofstetter2022, author = {Hofstetter, Julia Eva Ines}, title = {MYC shapes the composition of RNA polymerase II through direct recruitment of transcription elongation factors}, doi = {10.25972/OPUS-24035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240358}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The transcription factor MYC is a onco-protein, found to be deregulated in many human cancers. High MYC levels correlate with an aggressive tumor outcome and poor survival rates. Despite MYC being discovered as an oncogene already in the 1970s, how MYC regulates transcription of its target genes, which are involved in cellular growth and proliferation, is not fully understood yet. In this study, the question how MYC influences factors interacting with the RNA polymerase II ensuring productive transcription of its target genes was addressed using quantitative mass spectrometry. By comparing the interactome of RNA polymerase II under varying MYC levels, several potential factors involved in transcriptional elongation were identified. Furthermore, the question which of those factors interact with MYC was answered by employing quantitative mass spectrometry of MYC itself. Thereby, the direct interaction of MYC with the transcription elongation factor SPT5, a subunit of the DRB-sensitivity inducing factor, was discovered and analyzed in greater detail. SPT5 was shown to be recruited to chromatin by MYC. In addition, the interaction site of MYC on SPT5 was narrowed down to its evolutionary conserved NGN-domain, which is the known binding site for SPT4, the earlier characterized second subunit of the DRB-sensitivity inducing factor. This finding suggests a model in which MYC and SPT4 compete for binding the NGN-domain of SPT5. Investigations of the SPT5-interacting region on MYC showed binding of SPT5 to MYC's N-terminus including MYC-boxes 0, I and II. In order to analyze proteins interacting specifically with the N-terminal region of MYC, a truncated MYC-mutant was used for quantitative mass spectrometric analysis uncovering reduced binding for several proteins including the well-known interactor TRRAP and TRRAP-associated complexes. Summarized, ...}, subject = {Transkription }, language = {en} } @phdthesis{Vardapour2022, author = {Vardapour, Romina}, title = {Mutations in the DROSHA/DGCR8 microprocessor complex in high-risk blastemal Wilms tumor}, doi = {10.25972/OPUS-23140}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231404}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Wilms tumor (WT) or nephroblastoma is the most common kidney tumor in childhood. Several genetic alterations have been identified in WT over the past years. However, a clear-cut underlying genetic defect has remained elusive. Growing evidence suggests that miRNA processing genes play a major role in the formation of pediatric tumors, including WT. We and others have identified the microprocessor genes DROSHA and DGCR8 as key players in Wilms tumorigenesis. Exome sequence analysis of a cohort of blastemal-type WTs revealed the recurrent hotspot mutations DROSHA E1147K and DGCR8 E518K mapping to regions important for catalyic activity and RNA-binding. These alterations were expected to affect processing of miRNA precursors, ultimately leading to altered miRNA expression. Indeed, mutated tumor samples were characterized by distinct miRNA patterns. Notably, these mutations have been observed almost exclusively in WT, suggesting that they play a specific role in WT formation. The aim of the present work was to first examine the mutation frequency of DROSHA E1147K and DGCR8 E518K in a larger cohort of WTs, and to further characterize these microprocessor gene mutations as potential oncogenic drivers for WT formation. Screening of additional 700 WT samples by allele-specific PCR revealed a high frequency of DROSHA E1147K and DGCR8 E518K mutations, with the highest incidence found in tumors of high-risk histology. DROSHA E1147K was heterozygously expressed in all cases, which strongly implies a dominant negative effect. In contrast, DGCR8 E518K exclusively exhibited homozygous expression, suggestive for the mutation to act recessive. To functionally assess the mutations of the microprocessor complex in vitro, I generated stable HEK293T cell lines with inducible overexpression of DROSHA E1147K, and stable mouse embryonic stem cell (mESC) lines with inducible overexpression of DGCR8 E518K. To mimic the homozygous expression observed in WT, DGCR8 mESC lines were generated on a DGCR8 knockout background. Inducible overexpression of wild-type or mutant DROSHA in HEK293T cells showed that DROSHA E1147K leads to a global downregulation of miRNA expression. It has previously been shown that the knockout of DGCR8 in mESCs also results in a significant downregulation of canonical miRNAs. Inducible overexpression of wild type DGCR8 rescued this processing defect. DGCR8 E518K on the other hand, only led to a partial rescue. Differentially expressed miRNAs comprised members of the ESC cell cycle (ESCC) and let-7 miRNA families whose antagonism is known to play a pivotal role in the regulation of stem cell properties. Along with altered miRNA expression, DGCR8-E518K mESCs exhibited alterations in target gene expression potentially affecting various biological processes. We could observe decreased proliferation rates, most likely due to reduced cell viability. DGCR8-E518K seemed to be able to overcome the block of G1-S transition and to rescue the cell cycle defect in DGCR8-KO mESCs, albeit not to the full extent like DGCR8-wild-type. Moreover, DGCR8-E518K appeared to be unable to completely block epithelial-to-mesenchymal transition (EMT). Embryoid bodies (EBs) with the E518K mutation, however, were still able to silence the self-renewal program rescuing the differentiation defect in DGCR8-KO mESCs. Taken together, I could show that DROSHA E1147K and DGCR8 E518K are frequent events in WT with the highest incidence in high-risk tumor entities. Either mutation led to altered miRNA expression in vitro confirming our previous findings in tumor samples. While the DROSHA E1147K mutation resulted in a global downregulation of canonical miRNAs, DGCR8 E518K was able to retain significant activity of the microprocessor complex, suggesting that partial reduction of activity or altered specificity may be critical in Wilms tumorigenesis. Despite the significant differences found in the miRNA and mRNA profiles of DGCR8 E518K and DGCR8-wild-type mESCs, functional analysis showed that DGCR8 E518K could mostly restore important cellular functions in the knockout and only slightly differed from the wild-type situation. Further studies in a rather physiological environment, such as in a WT blastemal model system, may additionally help to better assess the subtle differences between DGCR8 E518K and DGCR8 wild-type observed in our mESC lines. Together with our findings, these model systems may thus contribute to better understand the role of these microprocessor mutations in the formation of WT.}, subject = {Nephroblastom}, language = {en} } @phdthesis{Berger2022, author = {Berger, Sarina Maria}, title = {Influence of Charge and Its Distribution on Biological Applications of Bis-Triarylboranes and Preliminary Investigations on H\(_2\)O\(_2\)-Cleavable Aryl Boronate Esters}, doi = {10.25972/OPUS-24314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243147}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {This dissertation describes the synthesis of an unsymmetrically-substituted triarylborane. This term describes a three-coordinate boron atom that is bound to three different aromatic systems, namely 2,6-dimethylphenyl, mesityl, and 4-(N,N-dimethylamino)-2,6-dimethylphenyl. It is also demonstrated that the amine functionality can be converted with methyl triflate into an ammonium moiety. The investigation of photophysical and electrochemical properties of this compound in comparison with the non-aminated and di-aminated analogues of the triarylborane is described besides other investigations of e. g. singlet oxygen sensitization, rotational barriers, and fundamental DFT calculations. Based on these investigations, selectively mono-, bis- and tris-dimethylamino- and trimethylammonium-substituted bis-triarylborane bithiophene chromophores were synthesized and their photophysical, and electrochemical properties were investigated together with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat1+, Cat2+, Cat(i)2+, and Cat3+. Comparing these properties with the results obtained for the mono-triarylboranes reveals a large influence of the bridging unit on the investigated properties of the bis-triarylboranes. In addition, the interaction of the cationic bis-triarylboranes with different polynucleotides were investigated in buffered solutions as well as the ability of these selectively charged compounds to enter and localize within organelles of human lung carcinoma and normal lung cells. All these investigations demonstrate that the number of charges and their distribution influences the interactions and staining properties as well as most of the other properties investigated. In addition, preliminary investigations on H2O2-cleavable boronate esters in the presence of stochiometric amounts of H2O2 are described for three different aryl boronate esters.}, subject = {Triarylborane}, language = {en} } @phdthesis{Youssef2022, author = {Youssef, Almoatazbellah}, title = {Fabrication of Micro-Engineered Scaffolds for Biomedical Application}, doi = {10.25972/OPUS-23545}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235457}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Thermoplastic polymers have a history of decades of safe and effective use in the clinic as implantable medical devices. In recent years additive manufacturing (AM) saw increased clinical interest for the fabrication of customizable and implantable medical devices and training models using the patients' own radiological data. However, approval from the various regulatory bodies remains a significant hurdle. A possible solution is to fabricate the AM scaffolds using materials and techniques with a clinical safety record, e.g. melt processing of polymers. Melt Electrowriting (MEW) is a novel, high resolution AM technique which uses thermoplastic polymers. MEW produces scaffolds with microscale fibers and precise fiber placement, allowing the control of the scaffold microarchitecture. Additionally, MEW can process medical-grade thermoplastic polymers, without the use of solvents paving the way for the production of medical devices for clinical applications. This pathway is investigated in this thesis, where the layout is designed to resemble the journey of a medical device produced via MEW from conception to early in vivo experiments. To do so, first, a brief history of the development of medical implants and the regenerative capability of the human body is given in Chapter 1. In Chapter 2, a review of the use of thermoplastic polymers in medicine, with a focus on poly(ε-caprolactone) (PCL), is illustrated, as this is the polymer used in the rest of the thesis. This review is followed by a comparison of the state of the art, regarding in vivo and clinical experiments, of three polymer melt AM technologies: melt-extrusion, selective laser sintering and MEW. The first two techniques already saw successful translation to the bedside, producing patient-specific, regulatory-approved AM implants. To follow in the footsteps of these two technologies, the MEW device parameters need to be optimized. The MEW process parameters and their interplay are further discussed in Chapter 3 focusing on the importance of a steady mass flow rate of the polymer during printing. MEW reaches a balance between polymer flow, the stabilizing electric field and moving collector to produce reproducible, high-resolution scaffolds. An imbalance creates phenomena like fiber pulsing or arcing which result in defective scaffolds and potential printer damage. Chapter 4 shows the use of X-ray microtomography (µCT) as a non-destructive method to characterize the pore-related features: total porosity and the pore size distribution. MEW scaffolds are three-dimensional (3D) constructs but have long been treated in the literature as two-dimensional (2D) ones and characterized mainly by microscopy, including stereo- and scanning electron microscopy, where pore size was simply reported as the distance between the fibers in a single layer. These methods, together with the trend of producing scaffolds with symmetrical pores in the 0/90° and 0/60/120° laydown patterns, disregarded the lateral connections between pores and the potential of MEW to be used for more complex 3D structures, mimicking the extracellular matrix. Here we characterized scaffolds in the aforementioned symmetrical laydown patterns, along with the more complex 0/45/90/135° and 0/30/60/90/120/150° ones. A 2D pore size estimation was done first using stereomicroscopy, followed by and compared to µCT scanning. The scaffolds with symmetrical laydown patterns resulted in the predominance of one pore size, while those with more complex patterns had a broader distribution, which could be better shown by µCT scans. Moreover, in the symmetrical scaffolds, the size of 3D pores was not able to reach the value of the fiber spacing due to a flattening effect of the scaffold, where the thickness of the scaffold was less than the fiber spacing, further restricting the pore size distribution in such scaffolds. This method could be used for quality assurance of fabricated scaffolds prior to use in in vitro or in vivo experiments and would be important for a clinical translation. Chapter 5 illustrates a proof of principle subcutaneous implantation in vivo experiment. MEW scaffolds were already featured in small animal in vivo experiments, but to date, no analysis of the foreign body reaction (FBR) to such implants was performed. FBR is an immune reaction to implanted foreign materials, including medical devices, aimed at protecting the host from potential adverse effects and can interfere with the function of some medical implants. Medical-grade PCL was used to melt electrowrite scaffolds with 50 and 60 µm fiber spacing for the 0/90° and 0/60/120° laydown patterns, respectively. These implants were implanted subcutaneously in immunocompetent, outbred mice, with appropriate controls, and explanted after 2, 4, 7 and 14 days. A thorough characterization of the scaffolds before implantation was done, followed by a full histopathological analysis of the FBR to the implants after excision. The scaffolds, irrespective of their pore geometry, induced an extensive FBR in the form of accumulation of foreign body giant cells around the fiber walls, in a manner that almost occluded available pore spaces with little to no neovascularization. This reaction was not induced by the material itself, as the same reaction failed to develop in the PCL solid film controls. A discussion of the results was given with special regard to the literature available on flat surgical meshes, as well as other hydrogel-based porous scaffolds with similar pore sizes. Finally, a general summary of the thesis in Chapter 6 recapitulates the most important points with a focus on future directions for MEW.}, language = {en} } @phdthesis{Schmeller2022, author = {Schmeller, Christof}, title = {Uniform distribution of zero ordinates of Epstein zeta-functions}, doi = {10.25972/OPUS-25199}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251999}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The dissertation investigates the wide class of Epstein zeta-functions in terms of uniform distribution modulo one of the ordinates of their nontrivial zeros. Main results are a proof of a Landau type theorem for all Epstein zeta-functions as well as uniform distribution modulo one for the zero ordinates of all Epstein zeta-functions asscoiated with binary quadratic forms.}, subject = {Zetafunktion}, language = {en} } @techreport{LhamoNguyenFitzek2022, type = {Working Paper}, author = {Lhamo, Osel and Nguyen, Giang T. and Fitzek, Frank H. P.}, title = {Virtual Queues for QoS Compliance of Haptic Data Streams in Teleoperation}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280762}, pages = {4}, year = {2022}, abstract = {Tactile Internet aims at allowing perceived real-time interactions between humans and machines. This requires satisfying a stringent latency requirement of haptic data streams whose data rates vary drastically as the results of perceptual codecs. This introduces a complex problem for the underlying network infrastructure to fulfill the pre-defined level of Quality of Service (QoS). However, novel networking hardware with data plane programming capability allows processing packets differently and opens up a new opportunity. For example, a dynamic and network-aware resource management strategy can help satisfy the QoS requirements of different priority flows without wasting precious bandwidth. This paper introduces virtual queues for service differentiation between different types of traffic streams, leveraging protocol independent switch architecture (PISA). We propose coordinating the management of all the queues and dynamically adapting their sizes to minimize packet loss and delay due to network congestion and ensure QoS compliance.}, subject = {Datennetz}, language = {en} } @article{HartrampfKrebsPeteretal.2022, author = {Hartrampf, Philipp E. and Krebs, Markus and Peter, Lea and Heinrich, Marieke and Ruffing, Julia and Kalogirou, Charis and Weinke, Maximilian and Brumberg, Joachim and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A. and Seitz, Anna Katharina}, title = {Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach}, series = {Biology}, volume = {11}, journal = {Biology}, number = {5}, issn = {2079-7737}, doi = {10.3390/biology11050660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271191}, year = {2022}, abstract = {Simple Summary The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT. Abstract (1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.}, language = {en} } @article{TucaBernardellideMattosFunketal.2022, author = {Tuca, Alexandru-Cristian and Bernardelli de Mattos, Ives and Funk, Martin and Winter, Raimund and Palackic, Alen and Groeber-Becker, Florian and Kruse, Daniel and Kukla, Fabian and Lemarchand, Thomas and Kamolz, Lars-Peter}, title = {Orchestrating the dermal/epidermal tissue ratio during wound healing by controlling the moisture content}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {6}, issn = {2227-9059}, doi = {10.3390/biomedicines10061286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275115}, year = {2022}, abstract = {A balanced and moist wound environment and surface increases the effect of various growth factors, cytokines, and chemokines, stimulating cell growth and wound healing. Considering this fact, we tested in vitro and in vivo water evaporation rates from the cellulose dressing epicite\(^{hydro}\) when combined with different secondary dressings as well as the resulting wound healing efficacy in a porcine donor site model. The aim of this study was to evaluate how the different rates of water evaporation affected wound healing efficacy. To this end, epicite\(^{hydro}\) primary dressing, in combination with different secondary dressing materials (cotton gauze, JELONET\(^◊\), AQUACEL\(^®\) Extra\(^™\), and OPSITE\(^◊\) Flexifix), was placed on 3 × 3 cm-sized dermatome wounds with a depth of 1.2 mm on the flanks of domestic pigs. The healing process was analyzed histologically and quantified by morphometry. High water evaporation rates by using the correct secondary dressing, such as cotton gauze, favored a better re-epithelialization in comparison with the low water evaporation resulting from an occlusive secondary dressing, which favored the formation of a new and intact dermal tissue that nearly fully replaced all the dermis that was removed during wounding. This newly available evidence may be of great benefit to clinical wound management.}, language = {en} } @article{NagaiFoersterDote2022, author = {Nagai, Michiaki and F{\"o}rster, Carola Yvette and Dote, Keigo}, title = {Sex hormone-specific neuroanatomy of Takotsubo syndrome: is the insular cortex a moderator?}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {1}, issn = {2218-273X}, doi = {10.3390/biom12010110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254776}, year = {2022}, abstract = {Takotsubo syndrome (TTS), a transient form of dysfunction in the heart's left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain-heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.}, language = {en} } @article{TrifaultMamontovaBurger2022, author = {Trifault, Barbara and Mamontova, Victoria and Burger, Kaspar}, title = {In vivo proximity labeling of nuclear and nucleolar proteins by a stably expressed, DNA damage-responsive NONO-APEX2 fusion protein}, series = {Frontiers in Molecular Biosciences}, volume = {9}, journal = {Frontiers in Molecular Biosciences}, issn = {2296-889X}, doi = {10.3389/fmolb.2022.914873}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276707}, year = {2022}, abstract = {Cellular stress can induce DNA lesions that threaten the stability of genes. The DNA damage response (DDR) recognises and repairs broken DNA to maintain genome stability. Intriguingly, components of nuclear paraspeckles like the non-POU domain containing octamer-binding protein (NONO) participate in the repair of DNA double-strand breaks (DSBs). NONO is a multifunctional RNA-binding protein (RBP) that facilitates the retention and editing of messenger (m)RNA as well as pre-mRNA processing. However, the role of NONO in the DDR is poorly understood. Here, we establish a novel human U2OS cell line that expresses NONO fused to the engineered ascorbate peroxidase 2 (U2OS:NONO-APEX2-HA). We show that NONO-APEX2-HA accumulates in the nucleolus in response to DNA damage. Combining viability assays, subcellular localisation studies, coimmunoprecipitation experiments and in vivo proximity labeling, we demonstrate that NONO-APEX2-HA is a stably expressed fusion protein that mimics endogenous NONO in terms of expression, localisation and bona fide interactors. We propose that in vivo proximity labeling in U2OS:NONO-APEX2-HA cells is capable for the assessment of NONO interactomes by downstream assays. U2OS:NONO-APEX2-HA cells will likely be a valuable resource for the investigation of NONO interactome dynamics in response to DNA damage and other stimuli.}, language = {en} } @incollection{LiaqatSednevHoebartner2022, author = {Liaqat, Anam and Sednev, Maksim V. and H{\"o}bartner, Claudia}, title = {In Vitro Selection of Deoxyribozymes for the Detection of RNA Modifications}, series = {Ribosome Biogenesis: Methods and Protocols}, booktitle = {Ribosome Biogenesis: Methods and Protocols}, publisher = {Humana Press}, isbn = {978-1-0716-2501-9}, doi = {10.1007/978-1-0716-2501-9_10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279208}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {167-179}, year = {2022}, abstract = {Deoxyribozymes are artificially evolved DNA molecules with catalytic abilities. RNA-cleaving deoxyribozymes have been recognized as an efficient tool for detection of modifications in target RNAs and provide an alternative to traditional and modern methods for detection of ribose or nucleobase methylation. However, there are only few examples of DNA enzymes that specifically reveal the presence of a certain type of modification, including N6-methyladenosine, and the knowledge about how DNA enzymes recognize modified RNAs is still extremely limited. Therefore, DNA enzymes cannot be easily engineered for the analysis of desired RNA modifications, but are instead identified by in vitro selection from random DNA libraries using synthetic modified RNA substrates. This protocol describes a general in vitro selection stagtegy to evolve new RNA-cleaving DNA enzymes that can efficiently differentiate modified RNA substrates from their unmodified counterpart.}, language = {en} } @article{EndresJungblutDivyapicigiletal.2022, author = {Endres, Leo M. and Jungblut, Marvin and Divyapicigil, Mustafa and Sauer, Markus and Stigloher, Christian and Christodoulides, Myron and Kim, Brandon J. and Schubert-Unkmeir, Alexandra}, title = {Development of a multicellular in vitro model of the meningeal blood-CSF barrier to study Neisseria meningitidis infection}, series = {Fluids and Barriers of the CNS}, volume = {19}, journal = {Fluids and Barriers of the CNS}, number = {1}, doi = {10.1186/s12987-022-00379-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300208}, year = {2022}, abstract = {Background Bacterial meningitis is a life-threatening disease that occurs when pathogens such as Neisseria meningitidis cross the meningeal blood cerebrospinal fluid barrier (mBCSFB) and infect the meninges. Due to the human-specific nature of N. meningitidis, previous research investigating this complex host-pathogen interaction has mostly been done in vitro using immortalized brain endothelial cells (BECs) alone, which often do not retain relevant barrier properties in culture. Here, we developed physiologically relevant mBCSFB models using BECs in co-culture with leptomeningeal cells (LMCs) to examine N. meningitidis interaction. Methods We used BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in co-culture with LMCs derived from tumor biopsies. We employed TEM and structured illumination microscopy to characterize the models as well as bacterial interaction. We measured TEER and sodium fluorescein (NaF) permeability to determine barrier tightness and integrity. We then analyzed bacterial adherence and penetration of the cell barrier and examined changes in host gene expression of tight junctions as well as chemokines and cytokines in response to infection. Results Both cell types remained distinct in co-culture and iBECs showed characteristic expression of BEC markers including tight junction proteins and endothelial markers. iBEC barrier function as determined by TEER and NaF permeability was improved by LMC co-culture and remained stable for seven days. BEC response to N. meningitidis infection was not affected by LMC co-culture. We detected considerable amounts of BEC-adherent meningococci and a relatively small number of intracellular bacteria. Interestingly, we discovered bacteria traversing the BEC-LMC barrier within the first 24 h post-infection, when barrier integrity was still high, suggesting a transcellular route for N. meningitidis into the CNS. Finally, we observed deterioration of barrier properties including loss of TEER and reduced expression of cell-junction components at late time points of infection. Conclusions Here, we report, for the first time, on co-culture of human iPSC derived BECs or hCMEC/D3 with meningioma derived LMCs and find that LMC co-culture improves barrier properties of iBECs. These novel models allow for a better understanding of N. meningitidis interaction at the mBCSFB in a physiologically relevant setting.}, language = {en} } @article{HerbertFickHeydarianetal.2022, author = {Herbert, Saskia-Laureen and Fick, Andrea and Heydarian, Motaharehsadat and Metzger, Marco and W{\"o}ckel, Achim and Rudel, Thomas and Kozjak-Pavlovic, Vera and Wulff, Christine}, title = {Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer}, series = {Journal of Tissue Engineering}, volume = {13}, journal = {Journal of Tissue Engineering}, issn = {2041-7314}, doi = {10.1177/20417314221088514}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301311}, pages = {1}, year = {2022}, abstract = {Ovarian cancer is the second most common gynecological malignancy in women. More than 70\% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40\%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer.}, language = {en} } @article{WangBachoferKoehleretal.2022, author = {Wang, Zhiyuan and Bachofer, Felix and Koehler, Jonas and Huth, Juliane and Hoeser, Thorsten and Marconcini, Mattia and Esch, Thomas and Kuenzer, Claudia}, title = {Spatial modelling and prediction with the spatio-temporal matrix: a study on predicting future settlement growth}, series = {Land}, volume = {11}, journal = {Land}, number = {8}, issn = {2073-445X}, doi = {10.3390/land11081174}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281856}, year = {2022}, abstract = {In the past decades, various Earth observation-based time series products have emerged, which have enabled studies and analysis of global change processes. Besides their contribution to understanding past processes, time series datasets hold enormous potential for predictive modeling and thereby meet the demands of decision makers on future scenarios. In order to further exploit these data, a novel pixel-based approach has been introduced, which is the spatio-temporal matrix (STM). The approach integrates the historical characteristics of a specific land cover at a high temporal frequency in order to interpret the spatial and temporal information for the neighborhood of a given target pixel. The provided information can be exploited with common predictive models and algorithms. In this study, this approach was utilized and evaluated for the prediction of future urban/built-settlement growth. Random forest and multi-layer perceptron were employed for the prediction. The tests have been carried out with training strategies based on a one-year and a ten-year time span for the urban agglomerations of Surat (India), Ho-Chi-Minh City (Vietnam), and Abidjan (Ivory Coast). The slope, land use, exclusion, urban, transportation, hillshade (SLEUTH) model was selected as a baseline indicator for the performance evaluation. The statistical results from the receiver operating characteristic curve (ROC) demonstrate a good ability of the STM to facilitate the prediction of future settlement growth and its transferability to different cities, with area under the curve (AUC) values greater than 0.85. Compared with SLEUTH, the STM-based model achieved higher AUC in all of the test cases, while being independent of the additional datasets for the restricted and the preferential development areas.}, language = {en} } @misc{Gross2022, type = {Master Thesis}, author = {Groß, Lennart}, title = {Point-spread function engineering for single-molecule localization microscopy in brain slices}, doi = {10.25972/OPUS-28259}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282596}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Single-molecule localization microscopy (SMLM) is the method of choice to study biological specimens on a nanoscale level. Advantages of SMLM imply its superior specificity due to targeted molecular fluorescence labeling and its enhanced tissue preservation compared to electron microscopy, while reaching similar resolution. To reveal the molecular organization of protein structures in brain tissue, SMLM moves to the forefront: Instead of investigating brain slices with a thickness of a few µm, measurements of intact neuronal assemblies (up to 100 µm in each dimension) are required. As proteins are distributed in the whole brain volume and can move along synapses in all directions, this method is promising in revealing arrangements of neuronal protein markers. However, diffraction-limited imaging still required for the localization of the fluorophores is prevented by sample-induced distortion of emission pattern due to optical aberrations in tissue slices from non-superficial planes. In particular, the sample causes wavefront dephasing, which can be described as a summation of Zernike polynomials. To recover an optimal point spread function (PSF), active shaping can be performed by the use of adaptive optics. The aim of this thesis is to establish a setup using a deformable mirror and a wavefront sensor to actively shape the PSF to correct the wavefront phases in a super-resolution microscope setup. Therefore, fluorescence-labeled proteins expressed in different anatomical regions in brain tissue will be used as experiment specimen. Resolution independent imaging depth in slices reaching tens of micrometers is aimed.}, subject = {Einzelmolek{\"u}lmikroskopie}, language = {en} } @article{WolfDoellingerMaletal.2022, author = {Wolf, Erik and D{\"o}llinger, Nina and Mal, David and Wenninger, Stephan and Bartl, Andrea and Botsch, Mario and Latoschik, Marc Erich and Wienrich, Carolin}, title = {Does distance matter? Embodiment and perception of personalized avatars in relation to the self-observation distance in virtual reality}, series = {Frontiers in Virtual Reality}, volume = {3}, journal = {Frontiers in Virtual Reality}, issn = {2673-4192}, doi = {10.3389/frvir.2022.1031093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299415}, year = {2022}, abstract = {Virtual reality applications employing avatar embodiment typically use virtual mirrors to allow users to perceive their digital selves not only from a first-person but also from a holistic third-person perspective. However, due to distance-related biases such as the distance compression effect or a reduced relative rendering resolution, the self-observation distance (SOD) between the user and the virtual mirror might influence how users perceive their embodied avatar. Our article systematically investigates the effects of a short (1 m), middle (2.5 m), and far (4 m) SOD between users and mirror on the perception of their personalized and self-embodied avatars. The avatars were photorealistic reconstructed using state-of-the-art photogrammetric methods. Thirty participants repeatedly faced their real-time animated self-embodied avatars in each of the three SOD conditions, where they were repeatedly altered in their body weight, and participants rated the 1) sense of embodiment, 2) body weight perception, and 3) affective appraisal towards their avatar. We found that the different SODs are unlikely to influence any of our measures except for the perceived body weight estimation difficulty. Here, the participants perceived the difficulty significantly higher for the farthest SOD. We further found that the participants' self-esteem significantly impacted their ability to modify their avatar's body weight to their current body weight and that it positively correlated with the perceived attractiveness of the avatar. Additionally, the participants' concerns about their body shape affected how eerie they perceived their avatars. The participants' self-esteem and concerns about their body shape influenced the perceived body weight estimation difficulty. We conclude that the virtual mirror in embodiment scenarios can be freely placed and varied at a distance of one to four meters from the user without expecting major effects on the perception of the avatar.}, language = {en} } @article{ForsterKohlmorgenHaasetal.2022, author = {Forster, Johannes and Kohlmorgen, Britta and Haas, Julian and Weis, Philipp and Breunig, Lukas and Turnwald, Doris and Mizaikoff, Boris and Schoen, Christoph}, title = {A streamlined method for the fast and cost-effective detection of bacterial pathogens from positive blood cultures for the BacT/ALERT blood culture system using the Vitek MS mass spectrometer}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0267669}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300213}, year = {2022}, abstract = {Background and objective Prompt pathogen identification of blood stream infections is essential to provide appropriate antibiotic treatment. Therefore, the objective of this prospective single centre study was to establish an inexpensive, fast and accurate protocol for bacterial species identification with SDS protein-extraction directly from BacT/Alert® blood culture (BC) bottles by VitekMS®. Results Correct species identification was obtained for 198/266 (74.4\%, 95\%-CI = [68.8\%, 79.6\%]) of pathogens. The protocol was more successful in identifying 87/96 (91.4\%, 95\%-CI = [83.8\%, 93.2\%]) gram-negative bacteria than 110/167 (65.9\%, 95\%-CI = [58.1\%, 73.0\%]) gram-positive bacteria. The hands-on time for sample preparation and measurement was about 15 min for up to five samples. This is shorter than for most other protocols using a similar lysis-centrifugation approach for the combination of BacT/Alert® BC bottles and the Vitek® MS mass spectrometer. The estimated costs per sample were approx. 1.80€ which is much cheaper than for commercial kits. Conclusion This optimized protocol allows for accurate identification of bacteria directly from blood culture bottles for laboratories equipped with BacT/Alert® blood culture bottles and VitekMS® mass spectrometer.}, language = {en} } @article{RoeschPlank2022, author = {R{\"o}sch, Moritz and Plank, Simon}, title = {Detailed mapping of lava and ash deposits at Indonesian volcanoes by means of VHR PlanetScope change detection}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {5}, issn = {2072-4292}, doi = {10.3390/rs14051168}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262232}, year = {2022}, abstract = {Mapping of lava flows in unvegetated areas of active volcanoes using optical satellite data is challenging due to spectral similarities of volcanic deposits and the surrounding background. Using very high-resolution PlanetScope data, this study introduces a novel object-oriented classification approach for mapping lava flows in both vegetated and unvegetated areas during several eruptive phases of three Indonesian volcanoes (Karangetang 2018/2019, Agung 2017, Krakatau 2018/2019). For this, change detection analysis based on PlanetScope imagery for mapping loss of vegetation due to volcanic activity (e.g., lava flows) is combined with the analysis of changes in texture and brightness, with hydrological runoff modelling and with analysis of thermal anomalies derived from Sentinel-2 or Landsat-8. Qualitative comparison of the mapped lava flows showed good agreement with multispectral false color time series (Sentinel-2 and Landsat-8). Reports of the Global Volcanism Program support the findings, indicating the developed lava mapping approach produces valuable results for monitoring volcanic hazards. Despite the lack of bands in infrared wavelengths, PlanetScope proves beneficial for the assessment of risk and near-real-time monitoring of active volcanoes due to its high spatial (3 m) and temporal resolution (mapping of all subaerial volcanoes on a daily basis).}, language = {en} } @article{BetzSegerNieding2022, author = {Betz, Ann-Katrin and Seger, Benedikt T. and Nieding, Gerhild}, title = {How can carbon labels and climate-friendly default options on restaurant menus contribute to the reduction of greenhouse gas emissions associated with dining?}, series = {PLOS Climate}, volume = {1}, journal = {PLOS Climate}, number = {5}, doi = {10.1371/journal.pclm.0000028}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301039}, year = {2022}, abstract = {In this study, we aimed to understand how restaurants can contribute to climate change mitigation via menu design. We investigated two types of interventions: changing the configuration of menu entries with variable side dishes so that the most climate-friendly option is set as the default and indicating the greenhouse gas emission of each dish via carbon labels. In an online simulation experiment, 265 participants were shown the menus of nine different restaurants and had to choose exactly one dish per menu. In six menus, the main dishes were presented with different default options: the side dish was associated either with the highest or with the lowest greenhouse gas emissions. The other three menus consisted of unitary dishes for which the default rules did not apply. All menus were presented either with or without carbon labels for each dish option. The results indicated that more climate-friendly dish choices resulting in lower greenhouse gas emissions were made with the low-emission than the high-emission default condition, and when carbon labels were present rather than absent. The effects of both interventions interacted, which indicates that the interventions partly overlap with regard to cognitive predecessors of choice behavior, such as attentional focus and social norms. The results suggest that the design of restaurant menus has a considerable effect on the carbon footprint of dining.}, language = {en} } @article{ChaianunpornHovestadt2022, author = {Chaianunporn, Thotsapol and Hovestadt, Thomas}, title = {Emergence of spatially structured populations by area-concentrated search}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {12}, doi = {10.1002/ece3.9528}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311939}, year = {2022}, abstract = {The idea that populations are spatially structured has become a very powerful concept in ecology, raising interest in many research areas. However, despite dispersal being a core component of the concept, it typically does not consider the movement behavior underlying any dispersal. Using individual-based simulations in continuous space, we explored the emergence of a spatially structured population in landscapes with spatially heterogeneous resource distribution and with organisms following simple area-concentrated search (ACS); individuals do not, however, perceive or respond to any habitat attributes per se but only to their foraging success. We investigated the effects of different resource clustering pattern in landscapes (single large cluster vs. many small clusters) and different resource density on the spatial structure of populations and movement between resource clusters of individuals. As results, we found that foraging success increased with increasing resource density and decreasing number of resource clusters. In a wide parameter space, the system exhibited attributes of a spatially structured populations with individuals concentrated in areas of high resource density, searching within areas of resources, and "dispersing" in straight line between resource patches. "Emigration" was more likely from patches that were small or of low quality (low resource density), but we observed an interaction effect between these two parameters. With the ACS implemented, individuals tended to move deeper into a resource cluster in scenarios with moderate resource density than in scenarios with high resource density. "Looping" from patches was more likely if patches were large and of high quality. Our simulations demonstrate that spatial structure in populations may emerge if critical resources are heterogeneously distributed and if individuals follow simple movement rules (such as ACS). Neither the perception of habitat nor an explicit decision to emigrate from a patch on the side of acting individuals is necessary for the emergence of such spatial structure.}, language = {en} } @article{WagenhaeuserRickertSommeretal.2022, author = {Wagenh{\"a}user, Laura and Rickert, Vanessa and Sommer, Claudia and Wanner, Christoph and Nordbeck, Peter and Rost, Simone and {\"U}{\c{c}}eyler, Nurcan}, title = {X-chromosomal inactivation patterns in women with Fabry disease}, series = {Molecular Genetics \& Genomic Medicine}, volume = {10}, journal = {Molecular Genetics \& Genomic Medicine}, number = {9}, doi = {10.1002/mgg3.2029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312795}, year = {2022}, abstract = {Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45\%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25\% distribution) in 6/87 (7\%) mouth epithelial cell samples, 31/88 (35\%) blood samples, and 9/27 (33\%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.}, language = {en} } @article{KaethnerEidelHaegeetal.2022, author = {K{\"a}thner, Ivo and Eidel, Matthias and H{\"a}ge, Anne-Sophie and Gram, Annika and Pauli, Paul}, title = {Observing physicians acting with different levels of empathy modulates later assessed pain tolerance}, series = {British Journal of Health Psychology}, volume = {27}, journal = {British Journal of Health Psychology}, number = {2}, doi = {10.1111/bjhp.12553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258368}, pages = {434-448}, year = {2022}, abstract = {Objectives The patient-physician relationship is essential for treatment success. Previous studies demonstrated that physicians who behave empathic in their interaction with patients have a positive effect on health outcomes. In this study, we investigated if the mere perception of physicians as empathic/not empathic modulates pain despite an emotionally neutral interaction with the patients. Methods N = 60 women took part in an experimental study that simulated a clinical interaction. In the paradigm, each participant watched two immersive 360° videos via a head-mounted display from a patient's perspective. The physicians in the videos behaved either empathic or not empathic towards a third person. Importantly, these physicians remained emotionally neutral in the subsequent virtual interaction with the participants. Finally, participants received a controlled, painful pressure stimulus within the narratives of the videos. Results The physicians in the high compared with the low empathy videos were rated as more empathic and more likable, indicating successful experimental manipulation. In spite of later neutral behaviour of physicians, this short observation of physicians' behaviour towards a third person was sufficient to modulate pain tolerance of the participants. Conclusions The finding of this study that the mere observation of physicians' behaviour towards a third person modulates pain, despite a neutral direct interaction with the participants, has important clinical implications. Further, the proposed paradigm enables investigating aspects of patient-physician communication that are difficult to examine in a clinical setting.}, language = {en} } @article{AchenbachLeHanneurCamenzindetal.2022, author = {Achenbach, Leonard and Le Hanneur, Malo and Camenzind, Roland S. and Bouyer, Michael and Pottecher, Pierre and Lafosse, Thibault}, title = {Systematic bifocal decompression for isolated long thoracic nerve paresis: A case series of 12 patients}, series = {Interdisciplinary Neurosurgery}, volume = {27}, journal = {Interdisciplinary Neurosurgery}, doi = {10.1016/j.inat.2021.101384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265085}, year = {2022}, abstract = {To date, no consensus exists regarding the best surgical management of isolated, micro-traumatic long thoracic nerve (LTN) paresis. Our hypothesis was that a combined decompression of the LTN at two potential locations for entrapment would be effective in the management of dynamic LTN paresis. We report on twelve patients with isolated LTN parersis, with tenderness at two entrapment sites, who underwent bifocal LTN decompression after undergoing unsuccessful conservative treatment for at least 6 months; all patients had preoperative electrodiagnostic studies that confirmed the paresis and ruled out peripheral neuritis. Clinical and electrical improvements were observed in eight patients (67\%) regarding shoulder flexion, shoulder abduction, and Quick-DASH scores. Four patients (33\%) did not improve after surgery. The results corroborate our hypothesis that a bifocal LTN decompression can be an effective and reliable therapeutic option in more than half of a very selective patient population suffering from serratus anterior muscle deficiency.}, language = {en} } @techreport{VomhoffGeisslerHossfeld2022, type = {Working Paper}, author = {Vomhoff, Viktoria and Geißler, Stefan and Hoßfeld, Tobias}, title = {Identification of Signaling Patterns in Mobile IoT Signaling Traffic}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280819}, pages = {4}, year = {2022}, abstract = {We attempt to identify sequences of signaling dialogs, to strengthen our understanding of the signaling behavior of IoT devices by examining a dataset containing over 270.000 distinct IoT devices whose signaling traffic has been observed over a 31-day period in a 2G network [4]. We propose a set of rules that allows the assembly of signaling dialogs into so-called sessions in order to identify common patterns and lay the foundation for future research in the areas of traffic modeling and anomaly detection.}, subject = {Datennetz}, language = {en} } @article{SpitzelWagnerBreyeretal.2022, author = {Spitzel, Marlene and Wagner, Elise and Breyer, Maximilian and Henniger, Dorothea and Bayin, Mehtap and Hofmann, Lukas and Mauceri, Daniela and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Dysregulation of immune response mediators and pain-related ion channels is associated with pain-like behavior in the GLA KO mouse model of Fabry disease}, series = {Cells}, volume = {11}, journal = {Cells}, number = {11}, issn = {2073-4409}, doi = {10.3390/cells11111730}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275186}, year = {2022}, abstract = {Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206\(^+\) macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1\(^+\) DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients.}, language = {en} } @article{DahlhoffManzSteinfattetal.2022, author = {Dahlhoff, Julia and Manz, Hannah and Steinfatt, Tim and Delgado-Tascon, Julia and Seebacher, Elena and Schneider, Theresa and Wilnit, Amy and Mokhtari, Zeinab and Tabares, Paula and B{\"o}ckle, David and Rasche, Leo and Martin Kort{\"u}m, K. and Lutz, Manfred B. and Einsele, Hermann and Brandl, Andreas and Beilhack, Andreas}, title = {Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression}, series = {Leukemia}, volume = {36}, journal = {Leukemia}, number = {3}, issn = {1476-5551}, doi = {10.1038/s41375-021-01422-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271787}, pages = {790-800}, year = {2022}, abstract = {Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4\(^{+}\)FoxP3\(^{+}\) regulatory T cells (Tregs) are highly abundant amongst CD4\(^{+}\) T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.}, language = {en} } @article{ForsterDichtlWagener2022, author = {Forster, Johannes and Dichtl, Karl and Wagener, Johannes}, title = {Lower beta-1,3-D-glucan testing cut-offs increase sensitivity for non-albicans Candida species bloodstream infections}, series = {Mycoses}, volume = {65}, journal = {Mycoses}, number = {5}, doi = {10.1111/myc.13421}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276515}, pages = {500 -- 507}, year = {2022}, abstract = {Purpose Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer-recommended cut-off for beta-1,3-D-glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\Serion) and anti-mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika). Methods Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital. Results Sensitivity of BDG testing (47\%) was higher than for Ag (17\%) or Ab (20\%). By combining Ag and Ab testing, sensitivity was raised to 32\%. Lowering the cut-off of BDG from 11 pg/ml to the newly recommended cut-off of 7 pg/ml resulted in a significant increase in sensitivity (47\% vs 58\%, p = .01 and 63\% vs 71\% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed. Conclusion BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut-off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non-albicans Candida species bloodstream infections.}, language = {en} } @article{FengZhouQiuetal.2022, author = {Feng, Yi and Zhou, Jiadong and Qiu, Honglin and Schnitzlein, Matthias and Hu, Jingtao and Liu, Linlin and W{\"u}rthner, Frank and Xie, Zengqi}, title = {Boron-Locked Starazine - A Soluble and Fluorescent Analogue of Starphene}, series = {Chemistry - A European Journal}, volume = {28}, journal = {Chemistry - A European Journal}, number = {29}, doi = {10.1002/chem.202200770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276423}, year = {2022}, abstract = {A starlike heterocyclic molecule containing an electron-deficient nonaaza-core structure and three peripheral isoquinolines locked by three tetracoordinate borons, namely isoquinoline-nona-starazine (QNSA), is synthesized by using readily available reactants through a rather straightforward approach. This new heteroatom-rich QNSA possesses a quasi-planar π-backbone structure, and bears phenyl substituents on borons which protrude on both sides of the π-backbones endowing it with good solubility in common organic solvents. Contrasting to its starphene analogue, QNSA shows intense fluorescence with a quantum yield (PLQY) of up to 62 \% in dilute solution.}, language = {en} } @article{KraemerSchuhmannVolkmannetal.2022, author = {Kr{\"a}mer, Stefanie D. and Schuhmann, Michael K. and Volkmann, Jens and Fluri, Felix}, title = {Deep brain stimulation in the subthalamic nucleus can improve skilled Forelimb movements and retune dynamics of striatal networks in a rat stroke model}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {24}, doi = {10.3390/ijms232415862}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312828}, year = {2022}, abstract = {Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single-pellet reaching (SPR) test after stroke and determined costimulated brain regions during STN-HFS using 2-[\(^{18}\)F]Fluoro-2-deoxyglucose-([\(^{18}\)F]FDG)-positron emission tomography (PET). After a 4-week training of SPR, photothrombotic stroke was induced in the sensorimotor cortex of the dominant hemisphere. Thereafter, an electrode was implanted in the STN ipsilateral to the infarction, followed by a continuous STN-HFS or sham stimulation for 7 days. On postinterventional day 2 and 7, an SPR test was performed during STN-HFS. Success rate of grasping was compared between these two time points. [\(^{18}\)F]FDG-PET was conducted on day 2 and 3 after stroke, without and with STN-HFS, respectively. STN-HFS resulted in a significant improvement of SPR compared to sham stimulation. During STN-HFS, a significantly higher [\(^{18}\)F]FDG-uptake was observed in the corticosubthalamic/pallidosubthalamic circuit, particularly ipsilateral to the stimulated side. Additionally, STN-HFS led to an increased glucose metabolism within the brainstem. These data demonstrate that STN-HFS supports rehabilitation of skilled forelimb movements, probably by retuning dysfunctional motor centers within the cerebral network.}, language = {en} } @article{Halbig Babu Gatter etal.2022, author = {Halbig , Andreas and Babu , Sooraj K. and Gatter , Shirin and Latoschik , Marc Erich and Brukamp, Kirsten and von Mammen , Sebastian}, title = {Opportunities and challenges of Virtual Reality in healthcare - a domain experts inquiry}, series = {Frontiers in Virtual Reality}, volume = {3}, journal = {Frontiers in Virtual Reality}, issn = {2673-4192}, doi = {10.3389/frvir.2022.837616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284752}, year = {2022}, abstract = {In recent years, the applications and accessibility of Virtual Reality (VR) for the healthcare sector have continued to grow. However, so far, most VR applications are only relevant in research settings. Information about what healthcare professionals would need to independently integrate VR applications into their daily working routines is missing. The actual needs and concerns of the people who work in the healthcare sector are often disregarded in the development of VR applications, even though they are the ones who are supposed to use them in practice. By means of this study, we systematically involve health professionals in the development process of VR applications. In particular, we conducted an online survey with 102 healthcare professionals based on a video prototype which demonstrates a software platform that allows them to create and utilise VR experiences on their own. For this study, we adapted and extended the Technology Acceptance Model (TAM). The survey focused on the perceived usefulness and the ease of use of such a platform, as well as the attitude and ethical concerns the users might have. The results show a generally positive attitude toward such a software platform. The users can imagine various use cases in different health domains. However, the perceived usefulness is tied to the actual ease of use of the platform and sufficient support for learning and working with the platform. In the discussion, we explain how these results can be generalized to facilitate the integration of VR in healthcare practice.}, language = {en} } @incollection{Kushch2022, author = {Kushch, Elina}, title = {The aphoristic potential of presidential rhetoric of G. Bush Jr.}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-25}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296456}, publisher = {W{\"u}rzburg University Press}, pages = {25-39}, year = {2022}, abstract = {This research paper concentrates on the analysis of the aphoristic potential of G. W. Bush's presidential rhetoric. Aphorisms are the most ancient laconic forms of expressing original and completed thoughts which reveal the peculiarity of their authors' world perception and worldview. From this perspective, these units can serve as the means of values codification. Repeatability and widespread use of aphorisms in various communications contribute to transmitting the values and ideas between the generations. Political aphorisms, which are a combination of aphoristic expressions from political communication and discourse, play an important role in this process. The authors of these expressions are not only politicians, but also philosophers, historians, writers, celebrities of different nationalities and generations. Presidential rhetoric is an integral and significant part of political discourse. The use of aphorisms as the means of codification of national and common human values in President G. W. Bush's formal addresses and speeches is intentional. It makes them concise and original, influential and convincing. Aphoristic expressions denoting common human values show the ideas and beliefs of their authors, as well as the politician, about life, justice, equality, freedom, faith, family. Aphorisms defining national values become the means of updating concepts of democracy, unity and diversity, freedom and security, success, and opportunity to fulfill one's potential in American society. The distinctive feature of G.W. Bush's rhetoric is the frequent use of aphorisms whose authors are the Founding Fathers.}, language = {en} } @incollection{Shtaltovna2022, author = {Shtaltovna, Yuliya}, title = {Linguistic Democratization of the Modern English Language: Functional Parameters of English Youth Slang Neologisms}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296514}, publisher = {W{\"u}rzburg University Press}, pages = {105-115}, year = {2022}, abstract = {No abstract available.}, language = {en} } @incollection{Kumar2022, author = {Kumar, Dinesh}, title = {A Brief Historical and Present Perspective of ELT in India}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-11}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296434}, publisher = {W{\"u}rzburg University Press}, pages = {11-17}, year = {2022}, abstract = {English language is being taught as a second foreign language in India. For most of the learners in India, English still a foreign language or target language. The study of this language is important to fulfill different kinds of academic and professional requirements. Still, there is a big gulf between demand and supply for which the failure of the system is largely responsible as its main emphasis on to adherence to the foreign curriculum. The government tries to impose this curriculum on English teachers, but, in fact, the curriculum is outdated.}, language = {en} } @incollection{Ali2022, author = {Ali, Zuraina}, title = {A Case Study of the Basic Learners' Struggles in Guessing from Context to Retain Words Learned}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296529}, publisher = {W{\"u}rzburg University Press}, pages = {117-124}, year = {2022}, abstract = {Guessing meaning from context is a challenging strategy for Second Language Learners (SLLs). In using the strategy, research found that poor students or low proficiency learners struggled in their attempts to use it. Mainly, it was reported that it was due to their vocabulary knowledge was limited. In another aspect, retaining vocabulary learnt is also important. Such is essential since learning vocabulary does not mean knowing the definition only. Yet, learners must also be able to use the vocabulary as they engage in language skills such as reading, writing, speaking and listening. The study aims at finding the hindrances faced among poor students' using contextual clues in retaining vocabulary. The study employed a case study to collect data from two basic students studying at a tertiary level. The study found that their hindrances in guessing meaning contexts were due to their being confused in guessing meaning when reading a sentence. Also, it was found that they were not able to find clues since they lacked vocabulary to guess correctly. The study implied that guessing meaning from context required sizeable vocabulary knowledge. Therefore, more training is necessary to assist basic learners in being successful in guessing from contexts.}, language = {en} } @incollection{KellenRibeiroWengDeToni2022, author = {Kellen Ribeiro Weng, Ana and De Toni, Plinio Marco}, title = {Differences and Similarities between the Fields of Bilingualism and Second Language Acquisition}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-19}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296447}, publisher = {W{\"u}rzburg University Press}, pages = {19-24}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{EnglmeiervonHoermannRiekeretal.2022, author = {Englmeier, Jana and von Hoermann, Christian and Rieker, Daniel and Benbow, Marc Eric and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Lackner, Tom{\´a}š and Mitesser, Oliver and Redlich, Sarah and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Salamon, J{\"o}rg-Alfred and Sommer, David and Steffan-Dewenter, Ingolf and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {10}, issn = {2045-7758}, doi = {10.1002/ece3.9386}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312846}, year = {2022}, abstract = {Dung beetles are important actors in the self-regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space-for-time approach to test the effects of land use and climate on α-diversity, local community specialization (H\(_2\)′) on dung resources, and γ-diversity of dung-visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land-use types: forests, grasslands, arable sites, and settlements, embedded in near-natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung-visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ-diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung-visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ-diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung-visiting beetle diversity and alter community networks. A decrease in dung-visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage.}, language = {en} } @article{HolzmannLittigFrankSchmadereretal.2022, author = {Holzmann-Littig, Christopher and Frank, Tamara and Schmaderer, Christoph and Braunisch, Matthias C. and Renders, Lutz and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Meerpohl, Joerg J. and Haller, Bernhard and Allwang, Christine}, title = {COVID-19 Vaccines: Fear of side effects among German health care workers}, series = {Vaccines}, volume = {10}, journal = {Vaccines}, number = {5}, issn = {2076-393X}, doi = {10.3390/vaccines10050689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270561}, year = {2022}, abstract = {(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.}, language = {en} } @article{KochPetzoldWesselyetal.2022, author = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus V.}, title = {Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {3}, issn = {2072-6694}, doi = {10.3390/cancers14030518}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254814}, year = {2022}, abstract = {Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95\% CI: 11.1-23.8) versus 9.4 months (cohort B, 95\% CI: 6.1-14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.}, language = {en} } @article{NoyaletIlgenBuerkleinetal.2022, author = {Noyalet, Laurent and Ilgen, Lukas and B{\"u}rklein, Miriam and Shehata-Dieler, Wafaa and Taeger, Johannes and Hagen, Rudolf and Neun, Tilmann and Zabler, Simon and Althoff, Daniel and Rak, Kristen}, title = {Vestibular aqueduct morphology and Meniere's disease - development of the vestibular aqueduct score by 3D analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.747517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312893}, year = {2022}, abstract = {Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.}, language = {en} } @article{GehrkeScherzadHagenetal.2022, author = {Gehrke, Thomas and Scherzad, Agmal and Hagen, Rudolf and Hackenberg, Stephan}, title = {Deep neck infections with and without mediastinal involvement: treatment and outcome in 218 patients}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {3}, issn = {1434-4726}, doi = {10.1007/s00405-021-06945-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266814}, pages = {1585-1592}, year = {2022}, abstract = {Purpose Infections of the deep neck, although becoming scarcer due to the widespread use of antibiotics, still represent a dangerous and possibly deadly disease, especially when descending into the mediastinum. Due to the different specialities involved in the treatment and the heterogenous presentation of the disease, therapeutic standard is still controversial. This study analyzes treatment and outcome in these patients based on a large retrospective review and proposes a therapeutic algorithm. Methods The cases of 218 adult patients treated with deep neck abscesses over a 10-year period at a tertiary university hospital were analyzed retrospectively. Clinical, radiological, microbiological and laboratory findings were compared between patients with and without mediastinal involvement. Results Forty-five patients (20.64\%) presented with abscess formation descending into the mediastinum. Those patients had significantly (all items p < 0.0001) higher rates of surgical interventions (4.27 vs. 1.11) and tracheotomies (82\% vs. 3.4\%), higher markers of inflammation (CRP 26.09 vs. 10.41 mg/dl), required more CT-scans (3.58 vs. 0.85), longer hospitalization (39.78 vs 9.79 days) and more frequently needed a change in antibiotic therapy (44.44\% vs. 6.40\%). Multi-resistant pathogens were found in 6.67\% vs. 1.16\%. Overall mortality rate was low with 1.83\%. Conclusion Despite of the high percentage of mediastinal involvement in the present patient collective, the proposed therapeutic algorithm resulted in a low mortality rate. Frequent CT-scans, regular planned surgical revisions with local drainage and lavage, as well as an early tracheotomy seem to be most beneficial regarding the outcome.}, language = {en} } @article{KrausHackenbergShehataDieleretal.2022, author = {Kraus, Fabian and Hackenberg, Stephan and Shehata-Dieler, Wafaa and Hagen, Rudolf}, title = {High-sensitivity FEES\(^{®}\) with the professional image enhancement technology "PIET"}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {1}, issn = {1434-4726}, doi = {10.1007/s00405-021-07067-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266822}, pages = {293-298}, year = {2022}, abstract = {Purpose Flexible endoscopic evaluation of swallowing (FEES\(^{®}\)) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the "professional image enhancement technique" (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES\(^{®}\) procedure. Methods Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES\(^{®}\) was performed and recorded with the two systems during daily routine. Results Performing an image enhancement during FEES\(^{®}\) is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected. Conclusion PIET proved to be non-inferior to NBI during image enhancement FEES\(^{®}\). So far, image enhancement FEES\(^{®}\) was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.}, language = {en} } @article{WunderPempCeciletal.2022, author = {Wunder, Juliane and Pemp, Daniela and Cecil, Alexander and Mahdiani, Maryam and Hauptstein, Ren{\´e} and Schmalbach, Katja and Geppert, Leo N. and Ickstadt, Katja and Esch, Harald L. and Dankekar, Thomas and Lehmann, Leane}, title = {Influence of breast cancer risk factors on proliferation and DNA damage in human breast glandular tissues: role of intracellular estrogen levels, oxidative stress and estrogen biotransformation}, series = {Archives of Toxicology}, volume = {96}, journal = {Archives of Toxicology}, number = {2}, issn = {1432-0738}, doi = {10.1007/s00204-021-03198-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265343}, pages = {673-687}, year = {2022}, abstract = {Breast cancer etiology is associated with both proliferation and DNA damage induced by estrogens. Breast cancer risk factors (BCRF) such as body mass index (BMI), smoking, and intake of estrogen-active drugs were recently shown to influence intratissue estrogen levels. Thus, the aim of the present study was to investigate the influence of BCRF on estrogen-induced proliferation and DNA damage in 41 well-characterized breast glandular tissues derived from women without breast cancer. Influence of intramammary estrogen levels and BCRF on estrogen receptor (ESR) activation, ESR-related proliferation (indicated by levels of marker transcripts), oxidative stress (indicated by levels of GCLC transcript and oxidative derivatives of cholesterol), and levels of transcripts encoding enzymes involved in estrogen biotransformation was identified by multiple linear regression models. Metabolic fluxes to adducts of estrogens with DNA (E-DNA) were assessed by a metabolic network model (MNM) which was validated by comparison of calculated fluxes with data on methoxylated and glucuronidated estrogens determined by GC- and UHPLC-MS/MS. Intratissue estrogen levels significantly influenced ESR activation and fluxes to E-DNA within the MNM. Likewise, all BCRF directly and/or indirectly influenced ESR activation, proliferation, and key flux constraints influencing E-DNA (i.e., levels of estrogens, CYP1B1, SULT1A1, SULT1A2, and GSTP1). However, no unambiguous total effect of BCRF on proliferation became apparent. Furthermore, BMI was the only BCRF to indeed influence fluxes to E-DNA (via congruent adverse influence on levels of estrogens, CYP1B1 and SULT1A2).}, language = {en} } @incollection{LazebnaPrykhodko2022, author = {Lazebna, Nataliia and Prykhodko, Anatoliy}, title = {English-language Digital Discourse of Human-Machine Communication}, series = {Studies in Modern English}, booktitle = {Studies in Modern English}, editor = {Lazebna, Nataliia and Kumar, Dinesh}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-199-0-41}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296468}, publisher = {W{\"u}rzburg University Press}, pages = {41-51}, year = {2022}, abstract = {The paper focuses on digital discourse. This is a speech-intellectual product of innovative information technologies, a phenomenon, which needs further interdisciplinary and linguistic interpretation. The English-language digital discourse shows how linguistic verbal communication is mediated by digits and to what extent these Signum and Verbum unity reigns over the world. The paper analyzes the ways and methods of integrated and differential use of verbal and non-verbal sign systems in the English language as compared to programming languages, considering the types of synchronous changes in the socio-cultural dimension of the sign. This research describes the processes of signs transformation during their functioning in programming languages and in the English language, common and distinctive features in the arrangement of grammatical, lexical-semantic, and graphic means of (natural) English and (artificial) programming languages in their projection on different modes of communication in the system Human ↔ Machine. Programming languages are constituted by verbal means of the English language with additional use of its own semiotic resources, which testifies to their integrative linguistic and mathematical nature. The specific representation of ElDD conveys its reciprocal nature when the English language using its own tools combines them with the elements of the programming languages thus creating an effective toolkit for self-process}, language = {en} }