@article{StebaniBlaimerZableretal.2023,
  author    = {Stebani, Jannik and Blaimer, Martin and Zabler, Simon and Neun, Tilmann and Pelt, Dani{\"e}l M. and Rak, Kristen},
  title     = {Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-45466-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357411},
  year      = {2023},
  abstract  = {Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.},
  language  = {en}
}
@article{GruendahlWeissStenzeletal.2023,
  author    = {Gr{\"u}ndahl, Marthe and Weiß, Martin and Stenzel, Kilian and Deckert, J{\"u}rgen and Hein, Grit},
  title     = {The effects of everyday-life social interactions on anxiety-related autonomic responses differ between men and women},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-36118-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357840},
  year      = {2023},
  abstract  = {Social buffering, a phenomenon where social presence can reduce anxiety and fear-related autonomic responses, has been studied in numerous laboratory settings. The results suggest that the familiarity of the interaction partner influences social buffering while also providing some evidence for gender effects. In the laboratory, however, it is difficult to mimic the complexity of real-life social interactions. Consequently, the social modulation of anxiety and related autonomic responses in everyday life remains poorly understood. We used smartphone-based Ecological Momentary Assessment (EMA) combined with wearable electrocardiogram sensors to investigate how everyday-life social interactions affect state anxiety and related cardiac changes in women and men. On five consecutive days, 96 healthy young participants (53\% women) answered up to six EMA surveys per day, indicating characteristics of their most recent social interaction and the respective interaction partner(s). In women, our results showed lower heart rate in the presence of a male interaction partner. Men showed the same effect with female interaction partners. Moreover, only women showed decreased heart rate and increased heart rate variability with increasing interaction partner familiarity. These findings specify the conditions under which social interactions reduce anxiety-related responses in women and men.},
  language  = {en}
}
@article{WeissGruendahlDeckertetal.2023,
  author    = {Weiß, Martin and Gr{\"u}ndahl, Marthe and Deckert, J{\"u}rgen and Eichner, Felizitas A. and Kohls, Mirjam and St{\"o}rk, Stefan and Heuschmann, Peter U. and Hein, Grit},
  title     = {Differential network interactions between psychosocial factors, mental health, and health-related quality of life in women and men},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  organization    = {STAAB-COVID Study Group},
  doi       = {10.1038/s41598-023-38525-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357858},
  year      = {2023},
  abstract  = {Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)" cohort study, a representative age- and gender-stratified sample of the general population of W{\"u}rzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis.},
  language  = {en}
}
@article{HuesteggePieczykolanKoch2023,
  author    = {Huestegge, Lynn and Pieczykolan, Aleks and Koch, Iring},
  title     = {A Gestalt account of human behavior is supported by evidence from switching between single and dual actions},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-47788-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357862},
  year      = {2023},
  abstract  = {The question of how behavior is represented in the mind lies at the core of psychology as the science of mind and behavior. While a long-standing research tradition has established two opposing fundamental views of perceptual representation, Structuralism and Gestalt psychology, we test both accounts with respect to action representation: Are multiple actions (characterizing human behavior in general) represented as the sum of their component actions (Structuralist view) or holistically (Gestalt view)? Using a single-/dual-response switch paradigm, we analyzed switches between dual ([A + B]) and single ([A], [B]) responses across different effector systems and revealed comparable performance in partial repetitions and full switches of behavioral requirements (e.g., in [A + B] → [A] vs. [B] → [A], or [A] → [A + B] vs. [B] → [A + B]), but only when the presence of dimensional overlap between responses allows for Gestalt formation. This evidence for a Gestalt view of behavior in our paradigm challenges some fundamental assumptions in current (tacitly Structuralist) action control theories (in particular the idea that all actions are represented compositionally with reference to their components), provides a novel explanatory angle for understanding complex, highly synchronized human behavior (e.g., dance), and delimitates the degree to which complex behavior can be analyzed in terms of its basic components.},
  language  = {en}
}
@article{VogelRueckertGreineretal.2023,
  author    = {Vogel, P. and R{\"u}ckert, M. A. and Greiner, C. and G{\"u}nther, J. and Reichl, T. and Kampf, T. and Bley, T. A. and Behr, V. C. and Herz, S.},
  title     = {iMPI: portable human-sized magnetic particle imaging scanner for real-time endovascular interventions},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-37351-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357794},
  year      = {2023},
  abstract  = {Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model.},
  language  = {en}
}
@article{BachertScheiner2023,
  author    = {Bachert, Antonia and Scheiner, Ricarda},
  title     = {The ant's weapon improves honey bee learning performance},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-35540-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358064},
  year      = {2023},
  abstract  = {Formic acid is the main component of the ant's major weapon against enemies. Being mainly used as a chemical defense, the acid is also exploited for recruitment and trail marking. The repelling effect of the organic acid is used by some mammals and birds which rub themselves in the acid to eliminate ectoparasites. Beekeepers across the world rely on this effect to control the parasitic mite Varroa destructor. Varroa mites are considered the most destructive pest of honey bees worldwide and can lead to the loss of entire colonies. Formic acid is highly effective against Varroa mites but can also kill the honeybee queen and worker brood. Whether formic acid can also affect the behavior of honey bees is unknown. We here study the effect of formic acid on sucrose responsiveness and cognition of honey bees treated at different live stages in field-relevant doses. Both behaviors are essential for survival of the honey bee colony. Rather unexpectedly, formic acid clearly improved the learning performance of the bees in appetitive olfactory conditioning, while not affecting sucrose responsiveness. This exciting side effect of formic acid certainly deserves further detailed investigations.},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Erg{\"u}n, S{\"u}leyman and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Kunz, Andreas Steven and Pannenbecker, Pauline and Kuhl, Philipp Josef and Augustin, Anne Marie and Bley, Thorsten Alexander and Petritsch, Bernhard and Grunz, Jan-Peter},
  title     = {Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-39063-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357912},
  year      = {2023},
  abstract  = {This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall's concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.},
  language  = {en}
}
@article{KirschKunde2023,
  author    = {Kirsch, Wladimir and Kunde, Wilfried},
  title     = {Human perception of spatial frequency varies with stimulus orientation and location in the visual field},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-44673-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357888},
  year      = {2023},
  abstract  = {Neuroanatomical variations across the visual field of human observers go along with corresponding variations of the perceived coarseness of visual stimuli. Here we show that horizontal gratings are perceived as having lower spatial frequency than vertical gratings when occurring along the horizontal meridian of the visual field, whereas gratings occurring along the vertical meridian show the exact opposite effect. This finding indicates a new peculiarity of processes operating along the cardinal axes of the visual field.},
  language  = {en}
}
@article{KronerWeiglChuRudertetal.2023,
  author    = {Kroner-Weigl, Niklas and Chu, Jin and Rudert, Maximilian and Alt, Volker and Shukunami, Chisa and Docheva, Denitsa},
  title     = {Dexamethasone is not sufficient to facilitate tenogenic differentiation of dermal fibroblasts in a 3D organoid model},
  series = {Biomedicines},
  volume    = {11},
  journal   = {Biomedicines},
  number    = {3},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines11030772},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311234},
  year      = {2023},
  abstract  = {Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating functional tendon-like tissue. The glucocorticoid dexamethasone (DEX) has been shown to regulate cell proliferation and facilitate differentiation towards other mesenchymal lineages. Therefore, we hypothesized that the administration of DEX could reduce excessive DF proliferation and thus, facilitate the tenogenic differentiation of DFs using a previously established 3D organoid model combined with dose-dependent application of DEX. Interestingly, the results demonstrated that DEX, in all tested concentrations, was not sufficient to notably induce the tenogenic differentiation of human DFs and DEX-treated organoids did not have clear advantages over untreated control organoids. Moreover, high concentrations of DEX exerted a negative impact on the organoid phenotype. Nevertheless, the expression profile of tendon-related genes of untreated and 10 nM DEX-treated DF organoids was largely comparable to organoids formed by tendon-derived cells, which is encouraging for further investigations on utilizing DFs for tendon tissue engineering.},
  language  = {en}
}
@article{GriebelSegebarthSteinetal.2023,
  author    = {Griebel, Matthias and Segebarth, Dennis and Stein, Nikolai and Schukraft, Nina and Tovote, Philip and Blum, Robert and Flath, Christoph M.},
  title     = {Deep learning-enabled segmentation of ambiguous bioimages with deepflash2},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-36960-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357286},
  year      = {2023},
  abstract  = {Bioimages frequently exhibit low signal-to-noise ratios due to experimental conditions, specimen characteristics, and imaging trade-offs. Reliable segmentation of such ambiguous images is difficult and laborious. Here we introduce deepflash2, a deep learning-enabled segmentation tool for bioimage analysis. The tool addresses typical challenges that may arise during the training, evaluation, and application of deep learning models on ambiguous data. The tool's training and evaluation pipeline uses multiple expert annotations and deep model ensembles to achieve accurate results. The application pipeline supports various use-cases for expert annotations and includes a quality assurance mechanism in the form of uncertainty measures. Benchmarked against other tools, deepflash2 offers both high predictive accuracy and efficient computational resource usage. The tool is built upon established deep learning libraries and enables sharing of trained model ensembles with the research community. deepflash2 aims to simplify the integration of deep learning into bioimage analysis projects while improving accuracy and reliability.},
  language  = {en}
}
@article{HaederSchaeubleGehlenetal.2023,
  author    = {H{\"a}der, Antje and Sch{\"a}uble, Sascha and Gehlen, Jan and Thielemann, Nadja and Buerfent, Benedikt C. and Sch{\"u}ller, Vitalia and Hess, Timo and Wolf, Thomas and Schr{\"o}der, Julia and Weber, Michael and H{\"u}nniger, Kerstin and L{\"o}ffler, J{\"u}rgen and Vylkova, Slavena and Panagiotou, Gianni and Schumacher, Johannes and Kurzai, Oliver},
  title     = {Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-38994-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357441},
  year      = {2023},
  abstract  = {Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.},
  language  = {en}
}
@article{WehShoyamaWuerthner2023,
  author    = {Weh, Manuel and Shoyama, Kazutaka and W{\"u}rthner, Frank},
  title     = {Preferential molecular recognition of heterochiral guests within a cyclophane receptor},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-35851-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357750},
  year      = {2023},
  abstract  = {The discrimination of enantiomers by natural receptors is a well-established phenomenon. In contrast the number of synthetic receptors with the capability for enantioselective molecular recognition of chiral substrates is scarce and for chiral cyclophanes indicative for a preferential binding of homochiral guests. Here we introduce a cyclophane composed of two homochiral core-twisted perylene bisimide (PBI) units connected by p-xylylene spacers and demonstrate its preference for the complexation of [5]helicene of opposite helicity compared to the PBI units of the host. The pronounced enantio-differentiation of this molecular receptor for heterochiral guests can be utilized for the enrichment of the P-PBI-M-helicene-P-PBI epimeric bimolecular complex. Our experimental results are supported by DFT calculations, which reveal that the sterically demanding bay substituents attached to the PBI chromophores disturb the helical shape match of the perylene core and homochiral substrates and thereby enforce the formation of syndiotactic host-guest complex structures. Hence, the most efficient substrate binding is observed for those aromatic guests, e. g. perylene, [4]helicene, phenanthrene and biphenyl, that can easily adapt in non-planar axially chiral conformations due to their inherent conformational flexibility. In all cases the induced chirality for the guest is opposed to those of the embedding PBI units, leading to heterochiral host-guest structures.},
  language  = {en}
}
@article{HaerterichMatlerDewhurstetal.2023,
  author    = {H{\"a}rterich, Marcel and Matler, Alexander and Dewhurst, Rian D. and Sachs, Andreas and Oppel, Kai and Stoy, Andreas and Braunschweig, Holger},
  title     = {A step-for-step main-group replica of the Fischer carbene synthesis at a borylene carbonyl},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-36251-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357270},
  year      = {2023},
  abstract  = {The Fischer carbene synthesis, involving the conversion of a transition metal (TM)-bound CO ligand to a carbene ligand of the form [=C(OR')R] (R, R' = organyl groups), is one of the seminal reactions in the history of organometallic chemistry. Carbonyl complexes of p-block elements, of the form [E(CO)n] (E = main-group fragment), are much less abundant than their TM cousins; this scarcity and the general instability of low-valent p-block species means that replicating the historical reactions of TM carbonyls is often very difficult. Here we present a step-for-step replica of the Fischer carbene synthesis at a borylene carbonyl involving nucleophilic attack at the carbonyl carbon followed by electrophilic quenching at the resultant acylate oxygen atom. These reactions provide borylene acylates and alkoxy-/silyloxy-substituted alkylideneboranes, main-group analogues of the archetypal transition metal acylate and Fischer carbene families, respectively. When either the incoming electrophile or the boron center has a modest steric profile, the electrophile instead attacks at the boron atom, leading to carbene-stabilized acylboranes - boron analogues of the well-known transition metal acyl complexes. These results constitute faithful main-group replicas of a number of historical organometallic processes and pave the way to further advances in the field of main-group metallomimetics.},
  language  = {en}
}
@article{NishidaXavierdaSilvaSchulteNunesAlvesetal.2023,
  author    = {Nishida Xavier da Silva, Thamara and Schulte, Clemens and Nunes Alves, Ariane and Maric, Hans Michael and Friedmann Angeli, Jos{\´e} Pedro},
  title     = {Molecular characterization of AIFM2/FSP1 inhibition by iFSP1-like molecules},
  series = {Cell Death \& Disease},
  volume    = {14},
  journal   = {Cell Death \& Disease},
  doi       = {10.1038/s41419-023-05787-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357943},
  year      = {2023},
  abstract  = {Ferroptosis is a form of cell death characterized by phospholipid peroxidation, where numerous studies have suggested that the induction of ferroptosis is a therapeutic strategy to target therapy refractory cancer entities. Ferroptosis suppressor protein 1 (FSP1), an NAD(P)H-ubiquinone reductase, is a key determinant of ferroptosis vulnerability, and its pharmacological inhibition was shown to strongly sensitize cancer cells to ferroptosis. A first generation of FSP1 inhibitors, exemplified by the small molecule iFSP1, has been reported; however, the molecular mechanisms underlying inhibition have not been characterized in detail. In this study, we explore the species-specific inhibition of iFSP1 on the human isoform to gain insights into its mechanism of action. Using a combination of cellular, biochemical, and computational methods, we establish a critical contribution of a species-specific aromatic architecture that is essential for target engagement. The results described here provide valuable insights for the rational development of second-generation FSP1 inhibitors combined with a tracer for screening the druggable pocket. In addition, we pose a cautionary notice for using iFSP1 in animal models, specifically murine models.},
  language  = {en}
}
@article{MaichlKirnerBecketal.2023,
  author    = {Maichl, Daniela Simone and Kirner, Julius Arthur and Beck, Susanne and Cheng, Wen-Hui and Krug, Melanie and Kuric, Martin and Ade, Carsten Patrick and Bischler, Thorsten and Jakob, Franz and Hose, Dirk and Seckinger, Anja and Ebert, Regina and Jundt, Franziska},
  title     = {Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival},
  series = {Blood Cancer Journal},
  volume    = {13},
  journal   = {Blood Cancer Journal},
  doi       = {10.1038/s41408-023-00907-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357598},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{IpWischhusen2023,
  author    = {Ip, Chi Wang and Wischhusen, J{\"o}rg},
  title     = {Versatile guardians: regenerative regulatory T cells in Parkinson's disease rodent models},
  series = {Signal Transduction and Targeted Therapy},
  volume    = {8},
  journal   = {Signal Transduction and Targeted Therapy},
  doi       = {10.1038/s41392-023-01681-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357674},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{RodriguezRozadaFrantzTovote2023,
  author    = {Rodriguez-Rozada, Silvia and Frantz, Stefan and Tovote, Philip},
  title     = {Cardiac optogenetics: regulating brain states via the heart},
  series = {Signal Transduction and Targeted Therapy},
  volume    = {8},
  journal   = {Signal Transduction and Targeted Therapy},
  doi       = {10.1038/s41392-023-01582-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357625},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{HaakeHaackSchaeferetal.2023,
  author    = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg},
  title     = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-39817-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333},
  year      = {2023},
  abstract  = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.},
  language  = {en}
}
@article{SalehiZarePrezzaetal.2023,
  author    = {Salehi, Saeede and Zare, Abdolhossein and Prezza, Gianluca and Bader, Jakob and Schneider, Cornelius and Fischer, Utz and Meissner, Felix and Mann, Matthias and Briese, Michael and Sendtner, Michael},
  title     = {Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-39787-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357639},
  year      = {2023},
  abstract  = {The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3' UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.},
  language  = {en}
}
@article{DjakovicHennigReinischetal.2023,
  author    = {Djakovic, Lara and Hennig, Thomas and Reinisch, Katharina and Milić, Andrea and Whisnant, Adam W. and Wolf, Katharina and Weiß, Elena and Haas, Tobias and Grothey, Arnhild and J{\"u}rges, Christopher S. and Kluge, Michael and Wolf, Elmar and Erhard, Florian and Friedel, Caroline C. and D{\"o}lken, Lars},
  title     = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-40217-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358161},
  year      = {2023},
  abstract  = {Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.},
  language  = {en}
}
@article{MuellerMitesserSchaeferetal.2023,
  author    = {M{\"u}ller, J{\"o}rg and Mitesser, Oliver and Schaefer, H. Martin and Seibold, Sebastian and Busse, Annika and Kriegel, Peter and Rabl, Dominik and Gelis, Rudy and Arteaga, Alejandro and Freile, Juan and Leite, Gabriel Augusto and de Melo, Tomaz Nascimento and LeBien, Jack and Campos-Cerqueira, Marconi and Bl{\"u}thgen, Nico and Tremlett, Constance J. and B{\"o}ttger, Dennis and Feldhaar, Heike and Grella, Nina and Falcon{\´i}-L{\´o}pez, Ana and Donoso, David A. and Moriniere, Jerome and Buřivalov{\´a}, Zuzana},
  title     = {Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-41693-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358130},
  year      = {2023},
  abstract  = {Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures - an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data.},
  language  = {en}
}
@article{BeetzKrauselJundi2023,
  author    = {Beetz, M. Jerome and Kraus, Christian and el Jundi, Basil},
  title     = {Neural representation of goal direction in the monarch butterfly brain},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-41526-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358073},
  year      = {2023},
  abstract  = {Neural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals.},
  language  = {en}
}
@article{WeismannMoeckelPaethetal.2023,
  author    = {Weismann, Dirk and M{\"o}ckel, Martin and Paeth, Heiko and Slagman, Anna},
  title     = {Modelling variations of emergency attendances using data on community mobility, climate and air pollution},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-47857-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357578},
  year      = {2023},
  abstract  = {Air pollution is associated with morbidity and mortality worldwide. We investigated the impact of improved air quality during the economic lockdown during the SARS-Cov2 pandemic on emergency room (ER) admissions in Germany. Weekly aggregated clinical data from 33 hospitals were collected in 2019 and 2020. Hourly concentrations of nitrogen and sulfur dioxide (NO2, SO2), carbon and nitrogen monoxide (CO, NO), ozone (O3) and particulate matter (PM10, PM2.5) measured by ground stations and meteorological data (ERA5) were selected from a 30 km radius around the corresponding ED. Mobility was assessed using aggregated cell phone data. A linear stepwise multiple regression model was used to predict ER admissions. The average weekly emergency numbers vary from 200 to over 1600 cases (total n = 2,216,217). The mean maximum decrease in caseload was 5 standard deviations. With the enforcement of the shutdown in March, the mobility index dropped by almost 40\%. Of all air pollutants, NO2 has the strongest correlation with ER visits when averaged across all departments. Using a linear stepwise multiple regression model, 63\% of the variation in ER visits is explained by the mobility index, but still 6\% of the variation is explained by air quality and climate change.},
  language  = {en}
}
@article{BellKleinRieseretal.2023,
  author    = {Bell, Alexandra and Klein, Doris and Rieser, Jakob and Kraus, Tanja and Thiel, Michael and Dech, Stefan},
  title     = {Scientific evidence from space — a review of spaceborne remote sensing applications at the science-policy interface},
  series = {Remote Sensing},
  volume    = {15},
  journal   = {Remote Sensing},
  number    = {4},
  issn      = {2072-4292},
  doi       = {10.3390/rs15040940},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303925},
  year      = {2023},
  abstract  = {On a daily basis, political decisions are made, often with their full extent of impact being unclear. Not seldom, the decisions and policy measures implemented result in direct or indirect unintended negative impacts, such as on the natural environment, which can vary in time, space, nature, and severity. To achieve a more sustainable world with equitable societies requires fundamental rethinking of our policymaking. It calls for informed decision making and a monitoring of political impact for which evidence-based knowledge is necessary. The most powerful tool to derive objective and systematic spatial information and, thus, add to transparent decisions is remote sensing (RS). This review analyses how spaceborne RS is used by the scientific community to provide evidence for the policymaking process. We reviewed 194 scientific publications from 2015 to 2020 and analysed them based on general insights (e.g., study area) and RS application-related information (e.g., RS data and products). Further, we classified the studies according to their degree of science-policy integration by determining their engagement with the political field and their potential contribution towards four stages of the policy cycle: problem identification/knowledge building, policy formulation, policy implementation, and policy monitoring and evaluation. Except for four studies, we found that studies had not directly involved or informed the policy field or policymaking process. Most studies contributed to the stage problem identification/knowledge building, followed by ex post policy impact assessment. To strengthen the use of RS for policy-relevant studies, the concept of the policy cycle is used to showcase opportunities of RS application for the policymaking process. Topics gaining importance and future requirements of RS at the science-policy interface are identified. If tackled, RS can be a powerful complement to provide policy-relevant evidence to shed light on the impact of political decisions and thus help promote sustainable development from the core.},
  language  = {en}
}
@article{DhillonDahmsKuebertFlocketal.2023,
  author    = {Dhillon, Maninder Singh and Dahms, Thorsten and K{\"u}bert-Flock, Carina and Liepa, Adomas and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias},
  title     = {Impact of STARFM on crop yield predictions: fusing MODIS with Landsat 5, 7, and 8 NDVIs in Bavaria Germany},
  series = {Remote Sensing},
  volume    = {15},
  journal   = {Remote Sensing},
  number    = {6},
  issn      = {2072-4292},
  doi       = {10.3390/rs15061651},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311092},
  year      = {2023},
  abstract  = {Rapid and accurate yield estimates at both field and regional levels remain the goal of sustainable agriculture and food security. Hereby, the identification of consistent and reliable methodologies providing accurate yield predictions is one of the hot topics in agricultural research. This study investigated the relationship of spatiotemporal fusion modelling using STRAFM on crop yield prediction for winter wheat (WW) and oil-seed rape (OSR) using a semi-empirical light use efficiency (LUE) model for the Free State of Bavaria (70,550 km\(^2\)), Germany, from 2001 to 2019. A synthetic normalised difference vegetation index (NDVI) time series was generated and validated by fusing the high spatial resolution (30 m, 16 days) Landsat 5 Thematic Mapper (TM) (2001 to 2012), Landsat 7 Enhanced Thematic Mapper Plus (ETM+) (2012), and Landsat 8 Operational Land Imager (OLI) (2013 to 2019) with the coarse resolution of MOD13Q1 (250 m, 16 days) from 2001 to 2019. Except for some temporal periods (i.e., 2001, 2002, and 2012), the study obtained an R\(^2\) of more than 0.65 and a RMSE of less than 0.11, which proves that the Landsat 8 OLI fused products are of higher accuracy than the Landsat 5 TM products. Moreover, the accuracies of the NDVI fusion data have been found to correlate with the total number of available Landsat scenes every year (N), with a correlation coefficient (R) of +0.83 (between R\(^2\) of yearly synthetic NDVIs and N) and -0.84 (between RMSEs and N). For crop yield prediction, the synthetic NDVI time series and climate elements (such as minimum temperature, maximum temperature, relative humidity, evaporation, transpiration, and solar radiation) are inputted to the LUE model, resulting in an average R\(^2\) of 0.75 (WW) and 0.73 (OSR), and RMSEs of 4.33 dt/ha and 2.19 dt/ha. The yield prediction results prove the consistency and stability of the LUE model for yield estimation. Using the LUE model, accurate crop yield predictions were obtained for WW (R\(^2\) = 0.88) and OSR (R\(^2\) = 0.74). Lastly, the study observed a high positive correlation of R = 0.81 and R = 0.77 between the yearly R\(^2\) of synthetic accuracy and modelled yield accuracy for WW and OSR, respectively.},
  language  = {en}
}
@article{TutovChenWerneretal.2023,
  author    = {Tutov, Anna and Chen, Xinyu and Werner, Rudolf A. and M{\"u}hlig, Saskia and Zimmermann, Thomas and Nose, Naoko and Koshino, Kazuhiro and Lapa, Constantin and Decker, Michael and Higuchi, Takahiro},
  title     = {Rationalizing the binding modes of PET radiotracers targeting the norepinephrine transporter},
  series = {Pharmaceutics},
  volume    = {15},
  journal   = {Pharmaceutics},
  number    = {2},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics15020690},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303949},
  year      = {2023},
  abstract  = {Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped π-π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.},
  language  = {en}
}
@article{GreubelAndresHennecke2023,
  author    = {Greubel, Andr{\´e} and Andres, Daniela and Hennecke, Martin},
  title     = {Analyzing reporting on ransomware incidents: a case study},
  series = {Social Sciences},
  volume    = {12},
  journal   = {Social Sciences},
  number    = {5},
  issn      = {2076-0760},
  doi       = {10.3390/socsci12050265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313746},
  year      = {2023},
  abstract  = {Knowledge about ransomware is important for protecting sensitive data and for participating in public debates about suitable regulation regarding its security. However, as of now, this topic has received little to no attention in most school curricula. As such, it is desirable to analyze what citizens can learn about this topic outside of formal education, e.g., from news articles. This analysis is both relevant to analyzing the public discourse about ransomware, as well as to identify what aspects of this topic should be included in the limited time available for this topic in formal education. Thus, this paper was motivated both by educational and media research. The central goal is to explore how the media reports on this topic and, additionally, to identify potential misconceptions that could stem from this reporting. To do so, we conducted an exploratory case study into the reporting of 109 media articles regarding a high-impact ransomware event: the shutdown of the Colonial Pipeline (located in the east of the USA). We analyzed how the articles introduced central terminology, what details were provided, what details were not, and what (mis-)conceptions readers might receive from them. Our results show that an introduction of the terminology and technical concepts of security is insufficient for a complete understanding of the incident. Most importantly, the articles may lead to four misconceptions about ransomware that are likely to lead to misleading conclusions about the responsibility for the incident and possible political and technical options to prevent such attacks in the future.},
  language  = {en}
}
@article{ScheinerSeisKleindienstetal.2023,
  author    = {Scheiner, Christin and Seis, Christian and Kleindienst, Nikolaus and Buerger, Arne},
  title     = {Psychopathology, protective factors, and COVID-19 among adolescents: a structural equation model},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {20},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {3},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph20032493},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304475},
  year      = {2023},
  abstract  = {Since the outbreak of the COVID-19 pandemic in December 2019 and the associated restrictions, mental health in children and adolescents has been increasingly discussed in the media. Negative impacts of the pandemic, including a sharp increase in psychopathology and, consequently, reduced quality of life, appear to have particularly affected children and young people, who may be especially vulnerable to the adverse effects of isolation. Nevertheless, many children and adolescents have managed to cope well with the restrictions, without deterioration of their mental health. The present study therefore explored the links between COVID-19 infection (in oneself or a family member, as well as the death of a family member due to the virus), protective factors such as self-efficacy, resilience, self-esteem, and health-related quality of life, and measures of psychopathology such as depression scores, internalizing/externalizing problems, emotion dysregulation, and victimization. For this purpose, we examined data from 2129 adolescents (mean age = 12.31, SD = 0.67; 51\% male; 6\% born outside of Germany) using a structural equation model. We found medium to high loadings of the manifest variables with the latent variables (COVID-19, protective factors, and psychopathology). Protective factors showed a significant negative correlation with psychopathology. However, COVID-19 had a weak connection with psychopathology in our sample. External pandemic-related factors (e.g., restrictions) and their interaction with existing psychopathology or individual protective factors appear to have a greater influence on young people's mental health than the impact of the virus per se. Sociopolitical efforts should be undertaken to foster prevention and promote individual resilience, especially in adolescence.},
  language  = {en}
}
@article{GarciaFernandezReinholdUeceyleretal.2023,
  author    = {Garc{\´i}a-Fern{\´a}ndez, Patricia and Reinhold, Colette and {\"U}{\c{c}}eyler, Nurcan and Sommer, Claudia},
  title     = {Local inflammatory mediators involved in neuropathic pain},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24097814},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313613},
  year      = {2023},
  abstract  = {Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50\% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.},
  language  = {en}
}
@article{BrennerGeigerSchlegeletal.2023,
  author    = {Brenner, Daniela and Geiger, Nina and Schlegel, Jan and Diesendorf, Viktoria and Kersting, Louise and Fink, Julian and Stelz, Linda and Schneider-Schaulies, Sibylle and Sauer, Markus and Bodem, Jochen and Seibel, J{\"u}rgen},
  title     = {Azido-ceramides, a tool to analyse SARS-CoV-2 replication and inhibition — SARS-CoV-2 is inhibited by ceramides},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {8},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24087281},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313581},
  year      = {2023},
  abstract  = {Recently, we have shown that C6-ceramides efficiently suppress viral replication by trapping the virus in lysosomes. Here, we use antiviral assays to evaluate a synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) and to confirm the biological activity of C6-ceramides inhibiting SARS-CoV-2. Click-labeling with a fluorophore demonstrated that AKS461 accumulates in lysosomes. Previously, it has been shown that suppression of SARS-CoV-2 replication can be cell-type specific. Thus, AKS461 inhibited SARS-CoV-2 replication in Huh-7, Vero, and Calu-3 cells up to 2.5 orders of magnitude. The results were confirmed by CoronaFISH, indicating that AKS461 acts comparable to the unmodified C6-ceramide. Thus, AKS461 serves as a tool to study ceramide-associated cellular and viral pathways, such as SARS-CoV-2 infections, and it helped to identify lysosomes as the central organelle of C6-ceramides to inhibit viral replication.},
  language  = {en}
}
@article{PatzerKunzHuflageetal.2023,
  author    = {Patzer, Theresa Sophie and Kunz, Andreas Steven and Huflage, Henner and Conrads, Nora and Luetkens, Karsten Sebastian and Pannenbecker, Pauline and Paul, Mila Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Ultrahigh-resolution photon-counting CT in cadaveric fracture models: spatial frequency is not everything},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {10},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13101677},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319281},
  year      = {2023},
  abstract  = {In this study, the impact of reconstruction sharpness on the visualization of the appendicular skeleton in ultrahigh-resolution (UHR) photon-counting detector (PCD) CT was investigated. Sixteen cadaveric extremities (eight fractured) were examined with a standardized 120 kVp scan protocol (CTDI\(_{vol}\) 10 mGy). Images were reconstructed with the sharpest non-UHR kernel (Br76) and all available UHR kernels (Br80 to Br96). Seven radiologists evaluated image quality and fracture assessability. Interrater agreement was assessed with the intraclass correlation coefficient. For quantitative comparisons, signal-to-noise-ratios (SNRs) were calculated. Subjective image quality was best for Br84 (median 1, interquartile range 1-3; p ≤ 0.003). Regarding fracture assessability, no significant difference was ascertained between Br76, Br80 and Br84 (p > 0.999), with inferior ratings for all sharper kernels (p < 0.001). Interrater agreement for image quality (0.795, 0.732-0.848; p < 0.001) and fracture assessability (0.880; 0.842-0.911; p < 0.001) was good. SNR was highest for Br76 (3.4, 3.0-3.9) with no significant difference to Br80 and Br84 (p > 0.999). Br76 and Br80 produced higher SNRs than all kernels sharper than Br84 (p ≤ 0.026). In conclusion, PCD-CT reconstructions with a moderate UHR kernel offer superior image quality for visualizing the appendicular skeleton. Fracture assessability benefits from sharp non-UHR and moderate UHR kernels, while ultra-sharp reconstructions incur augmented image noise.},
  language  = {en}
}
@article{HeinzEidmannJakuscheitetal.2023,
  author    = {Heinz, Tizian and Eidmann, Annette and Jakuscheit, Axel and Laux, Tino and Rudert, Maximilian and Stratos, Ioannis},
  title     = {Demographics and trends for inbound medical tourism in Germany for orthopedic patients before and during the COVID-19 pandemic},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {20},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {2},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph20021209},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304955},
  year      = {2023},
  abstract  = {Medical tourism is a rapidly growing sector of economic growth and diversification. However, data on the demographics and characteristics of the traveling patients are sparse. In this study, we analyzed the common demographic properties and characteristics of the inbound medical tourists seeking orthopedic medical care in Germany for the years 2010 to 2019 compared to a domestic group. At the same time, we examined how the COVID-19 pandemic outbreak of 2020 changed the field of medical tourism in Germany. Calculations were performed using administrative hospital data provided by the Federal Statistical Department of Germany. Data were analyzed from the years 2010 to 2020. A total of six elective orthopedic surgery codes (bone biopsy, knee arthroplasty, foot surgery, osteotomy, hardware removal, and arthrodesis) were identified as key service indicators for medical tourism and further analyzed. Factors including residence, sex, year, and type of elective surgery were modeled using linear regression analysis. Age and sex distributions were compared between patients living inside Germany (DE) or outside Germany (non-DE). Between 2010 and 2020, 6,261,801 orthopedic procedures were coded for the DE group and 27,420 key procedures were identified for the non-DE group. Medical tourists were predominantly male and significantly younger than the domestic population. The linear regression analysis of the OPS codes over the past years showed a significantly different slope between the DE and non-DE groups only for the OPS code "hardware removal". With the COVID-19 pandemic, an overall decline in performed orthopedic procedures was observed for the non-DE and the DE group. A significant reduction below the 95\% prediction bands for the year 2020 could be shown for hardware removal and foot surgery (for DE), and for hardware removal, knee arthroplasty, foot surgery, and osteotomy (for non-DE). This study is the first to quantify inbound medical tourism in elective orthopedic surgery in Germany. The COVID-19 pandemic negatively affected many — but not all — areas of orthopedic surgery. It has to be seen how this negative trend will develop in the future.},
  language  = {en}
}
@article{HuflageKunzHendeletal.2023,
  author    = {Huflage, Henner and Kunz, Andreas Steven and Hendel, Robin and Kraft, Johannes and Weick, Stefan and Razinskas, Gary and Sauer, Stephanie Tina and Pennig, Lenhard and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Obesity-related pitfalls of virtual versus true non-contrast imaging — an intraindividual comparison in 253 oncologic patients},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {9},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13091558},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313519},
  year      = {2023},
  abstract  = {Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m\(^2\)) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m\(^2\) (n = 110), pre-obese: 25-29.9 kg/m\(^2\) (n = 73), and obese: >30 kg/m\(^2\) (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDI\(_{vol}\) than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R\(^2\) = 0.738) and SECT (R\(^2\) = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1\%) compared with non-obese (0\%) and pre-obese patients (4.1\%). Conclusion: DECT facilitates a 30.8\% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.},
  language  = {en}
}
@article{HuflageGrunzPatzeretal.2023,
  author    = {Huflage, Henner and Grunz, Jan-Peter and Patzer, Theresa Sophie and Pannenbecker, Pauline and Feldle, Philipp and Sauer, Stephanie Tina and Petritsch, Bernhard and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Kunz, Andreas Steven},
  title     = {Potential of unenhanced ultra-low-dose abdominal photon-counting CT with tin filtration: a cadaveric study},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {4},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13040603},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304122},
  year      = {2023},
  abstract  = {Objectives: This study investigated the feasibility and image quality of ultra-low-dose unenhanced abdominal CT using photon-counting detector technology and tin prefiltration. Materials and Methods: Employing a first-generation photon-counting CT scanner, eight cadaveric specimens were examined both with tin prefiltration (Sn 100 kVp) and polychromatic (120 kVp) scan protocols matched for radiation dose at three different levels: standard-dose (3 mGy), low-dose (1 mGy) and ultra-low-dose (0.5 mGy). Image quality was evaluated quantitatively by means of contrast-to-noise-ratios (CNR) with regions of interest placed in the renal cortex and subcutaneous fat. Additionally, three independent radiologists performed subjective evaluation of image quality. The intraclass correlation coefficient was calculated as a measure of interrater reliability. Results: Irrespective of scan mode, CNR in the renal cortex decreased with lower radiation dose. Despite similar mean energy of the applied x-ray spectrum, CNR was superior for Sn 100 kVp over 120 kVp at standard-dose (17.75 ± 3.51 vs. 14.13 ± 4.02), low-dose (13.99 ± 2.6 vs. 10.68 ± 2.17) and ultra-low-dose levels (8.88 ± 2.01 vs. 11.06 ± 1.74) (all p ≤ 0.05). Subjective image quality was highest for both standard-dose protocols (score 5; interquartile range 5-5). While no difference was ascertained between Sn 100 kVp and 120 kVp examinations at standard and low-dose levels, the subjective image quality of tin-filtered scans was superior to 120 kVp with ultra-low radiation dose (p < 0.05). An intraclass correlation coefficient of 0.844 (95\% confidence interval 0.763-0.906; p < 0.001) indicated good interrater reliability. Conclusions: Photon-counting detector CT permits excellent image quality in unenhanced abdominal CT with very low radiation dose. Employment of tin prefiltration at 100 kVp instead of polychromatic imaging at 120 kVp increases the image quality even further in the ultra-low-dose range of 0.5 mGy.},
  language  = {en}
}
@article{GeigerDiesendorfRolletal.2023,
  author    = {Geiger, Nina and Diesendorf, Viktoria and Roll, Valeria and K{\"o}nig, Eva-Maria and Obernolte, Helena and Sewald, Katherina and Breidenbach, Julian and Pillaiyar, Thanigaimalai and G{\"u}tschow, Michael and M{\"u}ller, Christa E. and Bodem, Jochen},
  title     = {Cell type-specific anti-viral effects of novel SARS-CoV-2 main protease inhibitors},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24043972},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304034},
  year      = {2023},
  abstract  = {Recently, we have described novel pyridyl indole esters and peptidomimetics as potent inhibitors of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) main protease. Here, we analysed the impact of these compounds on viral replication. It has been shown that some antivirals against SARS-CoV-2 act in a cell line-specific way. Thus, the compounds were tested in Vero, Huh-7, and Calu-3 cells. We showed that the protease inhibitors at 30 µM suppress viral replication by up to 5 orders of magnitude in Huh-7 cells, while in Calu-3 cells, suppression by 2 orders of magnitude was achieved. Three pyridin-3-yl indole-carboxylates inhibited viral replication in all cell lines, indicating that they might repress viral replication in human tissue as well. Thus, we investigated three compounds in human precision-cut lung slices and observed donor-dependent antiviral activity in this patient-near system. Our results provide evidence that even direct-acting antivirals may act in a cell line-specific manner.},
  language  = {en}
}
@article{KrenzerBanckMakowskietal.2023,
  author    = {Krenzer, Adrian and Banck, Michael and Makowski, Kevin and Hekalo, Amar and Fitting, Daniel and Troya, Joel and Sudarevic, Boban and Zoller, Wolfgang G. and Hann, Alexander and Puppe, Frank},
  title     = {A real-time polyp-detection system with clinical application in colonoscopy using deep convolutional neural networks},
  series = {Journal of Imaging},
  volume    = {9},
  journal   = {Journal of Imaging},
  number    = {2},
  issn      = {2313-433X},
  doi       = {10.3390/jimaging9020026},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304454},
  year      = {2023},
  abstract  = {Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. The best method to prevent CRC is with a colonoscopy. During this procedure, the gastroenterologist searches for polyps. However, there is a potential risk of polyps being missed by the gastroenterologist. Automated detection of polyps helps to assist the gastroenterologist during a colonoscopy. There are already publications examining the problem of polyp detection in the literature. Nevertheless, most of these systems are only used in the research context and are not implemented for clinical application. Therefore, we introduce the first fully open-source automated polyp-detection system scoring best on current benchmark data and implementing it ready for clinical application. To create the polyp-detection system (ENDOMIND-Advanced), we combined our own collected data from different hospitals and practices in Germany with open-source datasets to create a dataset with over 500,000 annotated images. ENDOMIND-Advanced leverages a post-processing technique based on video detection to work in real-time with a stream of images. It is integrated into a prototype ready for application in clinical interventions. We achieve better performance compared to the best system in the literature and score a F1-score of 90.24\% on the open-source CVC-VideoClinicDB benchmark.},
  language  = {en}
}
@article{EngertSpahnBieniussaetal.2023,
  author    = {Engert, Jonas and Spahn, Bjoern and Bieniussa, Linda and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes},
  title     = {Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body},
  series = {Life},
  volume    = {13},
  journal   = {Life},
  number    = {5},
  issn      = {2075-1729},
  doi       = {10.3390/life13051188},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319387},
  year      = {2023},
  abstract  = {The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.},
  language  = {en}
}
@article{PaulMiedenLeferingetal.2023,
  author    = {Paul, Mila M. and Mieden, Hannah J. and Lefering, Rolf and Kupczyk, Eva K. and Jordan, Martin C. and Gilbert, Fabian and Meffert, Rainer H. and Sir{\´e}n, Anna-Leena and Hoelscher-Doht, Stefanie},
  title     = {Impact of a femoral fracture on outcome after traumatic brain injury — a matched-pair analysis of the TraumaRegister DGU\(^®\)},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {11},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12113802},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319363},
  year      = {2023},
  abstract  = {Traumatic brain injury (TBI) is the leading cause of death and disability in polytrauma and is often accompanied by concomitant injuries. We conducted a retrospective matched-pair analysis of data from a 10-year period from the multicenter database TraumaRegister DGU\(^®\) to analyze the impact of a concomitant femoral fracture on the outcome of TBI patients. A total of 4508 patients with moderate to critical TBI were included and matched by severity of TBI, American Society of Anesthesiologists (ASA) risk classification, initial Glasgow Coma Scale (GCS), age, and sex. Patients who suffered combined TBI and femoral fracture showed increased mortality and worse outcome at the time of discharge, a higher chance of multi-organ failure, and a rate of neurosurgical intervention. Especially those with moderate TBI showed enhanced in-hospital mortality when presenting with a concomitant femoral fracture (p = 0.037). The choice of fracture treatment (damage control orthopedics vs. early total care) did not impact mortality. In summary, patients with combined TBI and femoral fracture have higher mortality, more in-hospital complications, an increased need for neurosurgical intervention, and inferior outcome compared to patients with TBI solely. More investigations are needed to decipher the pathophysiological consequences of a long-bone fracture on the outcome after TBI.},
  language  = {en}
}
@article{HeinzEidmannAndersonetal.2023,
  author    = {Heinz, Tizian and Eidmann, Annette and Anderson, Philip and Weißenberger, Manuel and Jakuscheit, Axel and Rudert, Maximilian and Stratos, Ioannis},
  title     = {Trends in computer-assisted surgery for total knee arthroplasty in Germany: an analysis based on the operative procedure classification system between 2010 to 2021},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {2},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12020549},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304879},
  year      = {2023},
  abstract  = {Alignment strategies for primary total knee arthroplasty (TKA) have changed significantly over time with a shift towards a more individualized alignment goal. At the same time, computer-assisted surgery (CAS) has gained interest for intraoperative control and accuracy in implant positioning and limb alignment. Despite the often discussed benefits and drawbacks of robotics and navigation for TKA, the routine use of these new devices on a day-to-day basis remains obscure. Therefore, nationwide hospital billing data based on the Operation Procedure Classification System (OPS) were retrieved from the Federal Statistical Office of Germany for the period from 2010 to 2021. OPS codes for primary total knee arthroplasty (OPS code: 5-822*) were further analyzed regarding the usage of computer navigation (additional OPS code: 5-988) or robotic devices (additional OPS code: 5-987). Gender and age at the time of surgery were also assessed. The results show a total of 2,226,559 primary TKAs were implanted between 2010 and 2021, of which 2,044,914 were performed conventionally (91.84\% of all TKAs). A total of 170,276 TKAs were performed using navigation technique (7.65\% of all TKAs) and another 11,369 TKAs were performed using robotics (0.51\% of all TKAs). For the period from 2018 to 2021, a substantial increase in robot-assisted TKA (R-TKA) was observed, with an average increase rate of 84.74\% per year, while the number of navigated TKAs declined (-3.67\% per year). Computer-assisted surgery, and particularly robotics for TKA, are seeing growing popularity and stepwise translation into routine clinical use in Germany, with a steep increase rate of more than 80\% per year since 2018. Nevertheless, the majority of TKAs are still performed using manual instrumentation, rendering conventional TKA the currently unchanged gold standard.},
  language  = {en}
}
@article{DomokosBeerReutheretal.2023,
  author    = {Domokos, Bruno and Beer, Lisa and Reuther, Stefanie and Raschka, Christoph and Spang, Christoph},
  title     = {Immediate effects of isolated lumbar extension resistance exercise (ILEX) on spine posture and mobility measured with the IDIAG Spinal Mouse System},
  series = {Journal of Functional Morphology and Kinesiology},
  volume    = {8},
  journal   = {Journal of Functional Morphology and Kinesiology},
  number    = {2},
  issn      = {2411-5142},
  doi       = {10.3390/jfmk8020060},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319334},
  year      = {2023},
  abstract  = {Posture and mobility are important aspects for spinal health. In the context of low back pain, strategies to alter postural anomalies (e.g., hyper/hypolordosis, hyper/hypokyphosis) and mobility deficits (e.g., bending restrictions) have been of interest to researchers and clinicians. Machine-based isolated lumbar extension resistance exercise (ILEX) has been used successfully for rehabilitation of patients suffering from low back pain. The aim of this study was to analyse the immediate effects of ILEX on spinal posture and mobility. In this interventional cohort study, the posture and mobility measures of 33 healthy individuals (m = 17, f = 16; mean age 30.0 years) were taken using the surface-based Spinal Mouse system (IDIAG M360©, Fehraltdorf, Switzerland). Individuals performed one exercise set to full exhaustion with an ILEX-device (Powerspine, Wuerzburg, Germany) in a standardized setup, including uniform range of motion and time under tension. Scans were made immediately before and after the exercise. There was an immediate significant decrease in standing lumbar lordosis and thoracic kyphosis. No change could be observed in standing pelvic tilt. Mobility measures showed a significant decrease in the lumbar spine and an increase in the sacrum. The results show that ILEX alters spine posture and mobility in the short-term, which may benefit certain patient groups.},
  language  = {en}
}
@article{EidmannKamawalLuedemannetal.2023,
  author    = {Eidmann, Annette and Kamawal, Yama and Luedemann, Martin and Raab, Peter and Rudert, Maximilian and Stratos, Ioannis},
  title     = {Demographics and etiology for lower extremity amputations — experiences of an university orthopaedic center in Germany},
  series = {Medicina},
  volume    = {59},
  journal   = {Medicina},
  number    = {2},
  issn      = {1648-9144},
  doi       = {10.3390/medicina59020200},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304856},
  year      = {2023},
  abstract  = {Background and Objectives: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods: We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results: A total of 114 amputations of the lower extremity were performed, of which 60.5\% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9\%) and implant-associated complications (25.4\%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions: Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation.},
  language  = {en}
}
@article{FrankKesnerLibertietal.2023,
  author    = {Frank, Erik T. and Kesner, Lucie and Liberti, Joanito and Helleu, Quentin and LeBoeuf, Adria C. and Dascalu, Andrei and Sponsler, Douglas B. and Azuma, Fumika and Economo, Evan P. and Waridel, Patrice and Engel, Philipp and Schmitt, Thomas and Keller, Laurent},
  title     = {Targeted treatment of injured nestmates with antimicrobial compounds in an ant society},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-43885-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358081},
  year      = {2023},
  abstract  = {Infected wounds pose a major mortality risk in animals. Injuries are common in the ant Megaponera analis, which raids pugnacious prey. Here we show that M. analis can determine when wounds are infected and treat them accordingly. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds, workers reduce the mortality of infected individuals by 90\%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile, thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that M. analis ant societies use antimicrobial compounds produced in the metapleural glands to treat infected wounds and reduce nestmate mortality.},
  language  = {en}
}
@article{KuzkinaRoessleSegeretal.2023,
  author    = {Kuzkina, A. and R{\"o}ßle, J. and Seger, A. and Panzer, C. and Kohl, A. and Maltese, V. and Musacchio, T. and Blaschke, S. J. and Tamg{\"u}ney, G. and Kaulitz, S. and Rak, K. and Scherzad, A. and Zimmermann, P. H. and Klussmann, J. P. and Hackenberg, S. and Volkmann, J. and Sommer, C. and Sommerauer, M. and Doppler, K.},
  title     = {Combining skin and olfactory α-synuclein seed amplification assays (SAA)—towards biomarker-driven phenotyping in synucleinopathies},
  series = {npj Parkinson's Disease},
  volume    = {9},
  journal   = {npj Parkinson's Disease},
  issn      = {2373-8057},
  doi       = {10.1038/s41531-023-00519-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357687},
  year      = {2023},
  abstract  = {Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.},
  language  = {en}
}
@article{HerrmannMuellerNotzetal.2023,
  author    = {Herrmann, Johannes and M{\"u}ller, Kerstin and Notz, Quirin and H{\"u}bsch, Martha and Haas, Kirsten and Horn, Anna and Schmidt, Julia and Heuschmann, Peter and Maschmann, Jens and Frosch, Matthias and Deckert, J{\"u}rgen and Einsele, Hermann and Ertl, Georg and Frantz, Stefan and Meybohm, Patrick and Lotz, Christopher},
  title     = {Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-33783-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357174},
  year      = {2023},
  abstract  = {Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87\% and 80\% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24\% of non-ICU and 3\% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5\% of non-ICU and 10\% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19.},
  language  = {en}
}
@article{RudloffHutmacherAppel2023,
  author    = {Rudloff, Jan Philipp and Hutmacher, Fabian and Appel, Markus},
  title     = {Post-truth epistemic beliefs rooted in the Dark Factor of Personality are associated with higher COVID-19 vaccination refusal},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-31079-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357619},
  year      = {2023},
  abstract  = {A substantial number of people refused to get vaccinated against COVID-19, which prompts the question as to why. We focus on the role of individual worldviews about the nature and generation of knowledge (epistemic beliefs). We propose a model that includes epistemic beliefs, their relationship to the Dark Factor of Personality (D), and their mutual effect on the probability of having been vaccinated against COVID-19. Based on a US nationally representative sample (N = 1268), we show that stronger endorsement of post-truth epistemic beliefs was associated with a lower probability of having been vaccinated against COVID-19. D was also linked to a lower probability of having been vaccinated against COVID-19, which can be explained by post-truth epistemic beliefs. Our results indicate that the more individuals deliberately refrain from adhering to the better argument, the less likely they are vaccinated. More generally, post-truth epistemic beliefs pose a challenge for rational communication.},
  language  = {en}
}
@article{OdorferYabeHiewetal.2023,
  author    = {Odorfer, Thorsten M. and Yabe, Marie and Hiew, Shawn and Volkmann, Jens and Zeller, Daniel},
  title     = {Topological differences and confounders of mental rotation in cervical dystonia and blepharospasm},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-33262-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357713},
  year      = {2023},
  abstract  = {Mental rotation (mR) bases on imagination of actual movements. It remains unclear whether there is a specific pattern of mR impairment in focal dystonia. We aimed to investigate mR in patients with cervical dystonia (CD) and blepharospasm (BS) and to assess potential confounders. 23 CD patients and 23 healthy controls (HC) as well as 21 BS and 19 hemifacial spasm (HS) patients were matched for sex, age, and education level. Handedness, finger dexterity, general reaction time, and cognitive status were assessed. Disease severity was evaluated by clinical scales. During mR, photographs of body parts (head, hand, or foot) and a non-corporal object (car) were displayed at different angles rotated within their plane. Subjects were asked to judge laterality of the presented image by keystroke. Both speed and correctness were evaluated. Compared to HC, CD and HS patients performed worse in mR of hands, whereas BS group showed comparable performance. There was a significant association of prolonged mR reaction time (RT) with reduced MoCA scores and with increased RT in an unspecific reaction speed task. After exclusion of cognitively impaired patients, increased RT in the mR of hands was confined to CD group, but not HS. While the question of whether specific patterns of mR impairment reliably define a dystonic endophenotype remains elusive, our findings point to mR as a useful tool, when used carefully with control measures and tasks, which may be capable of identifying specific deficits that distinguish between subtypes of dystonia.},
  language  = {en}
}
@article{KirschKunde2023,
  author    = {Kirsch, Wladimir and Kunde, Wilfried},
  title     = {Changes in body perception following virtual object manipulation are accompanied by changes of the internal reference scale},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-34311-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357876},
  year      = {2023},
  abstract  = {Changes in body perception often arise when observers are confronted with related yet discrepant multisensory signals. Some of these effects are interpreted as outcomes of sensory integration of various signals, whereas related biases are ascribed to learning-dependent recalibration of coding individual signals. The present study explored whether the same sensorimotor experience entails changes in body perception that are indicative of multisensory integration and those that indicate recalibration. Participants enclosed visual objects by a pair of visual cursors controlled by finger movements. Then either they judged their perceived finger posture (indicating multisensory integration) or they produced a certain finger posture (indicating recalibration). An experimental variation of the size of the visual object resulted in systematic and opposite biases of the perceived and produced finger distances. This pattern of results is consistent with the assumption that multisensory integration and recalibration had a common origin in the task we used.},
  language  = {en}
}
@article{KarpatiDeutschKissetal.2023,
  author    = {K{\´a}rp{\´a}ti, Zsolt and Deutsch, Ferenc and Kiss, Bal{\´a}zs and Schmitt, Thomas},
  title     = {Seasonal changes in photoperiod and temperature lead to changes in cuticular hydrocarbon profiles and affect mating success in Drosophila suzukii},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-32652-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358095},
  year      = {2023},
  abstract  = {Seasonal plasticity in insects is often triggered by temperature and photoperiod changes. When climatic conditions become sub-optimal, insects might undergo reproductive diapause, a form of seasonal plasticity delaying the development of reproductive organs and activities. During the reproductive diapause, the cuticular hydrocarbon (CHC) profile, which covers the insect body surface, might also change to protect insects from desiccation and cold temperature. However, CHCs are often important cues and signals for mate recognition and changes in CHC composition might affect mate recognition. In the present study, we investigated the CHC profile composition and the mating success of Drosophila suzukii in 1- and 5-day-old males and females of summer and winter morphs. CHC compositions differed with age and morphs. However, no significant differences were found between the sexes of the same age and morph. The results of the behavioral assays show that summer morph pairs start to mate earlier in their life, have a shorter mating duration, and have more offspring compared to winter morph pairs. We hypothesize that CHC profiles of winter morphs are adapted to survive winter conditions, potentially at the cost of reduced mate recognition cues.},
  language  = {en}
}
@article{PatzerKunzHuflageetal.2023,
  author    = {Patzer, Theresa Sophie and Kunz, Andreas Steven and Huflage, Henner and Luetkens, Karsten Sebastian and Conrads, Nora and Gruschwitz, Philipp and Pannenbecker, Pauline and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Quantitative and qualitative image quality assessment in shoulder examinations with a first-generation photon-counting detector CT},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-35367-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357925},
  year      = {2023},
  abstract  = {Photon-counting detector (PCD) CT allows for ultra-high-resolution (UHR) examinations of the shoulder without requiring an additional post-patient comb filter to narrow the detector aperture. This study was designed to compare the PCD performance with a high-end energy-integrating detector (EID) CT. Sixteen cadaveric shoulders were examined with both scanners using dose-matched 120 kVp acquisition protocols (low-dose/full-dose: CTDI\(_{vol}\) = 5.0/10.0 mGy). Specimens were scanned in UHR mode with the PCD-CT, whereas EID-CT examinations were conducted in accordance with the clinical standard as "non-UHR". Reconstruction of EID data employed the sharpest kernel available for standard-resolution scans (ρ\(_{50}\) = 12.3 lp/cm), while PCD data were reconstructed with both a comparable kernel (11.8 lp/cm) and a sharper dedicated bone kernel (16.5 lp/cm). Six radiologists with 2-9 years of experience in musculoskeletal imaging rated image quality subjectively. Interrater agreement was analyzed by calculation of the intraclass correlation coefficient in a two-way random effects model. Quantitative analyses comprised noise recording and calculating signal-to-noise ratios based on attenuation measurements in bone and soft tissue. Subjective image quality was higher in UHR-PCD-CT than in EID-CT and non-UHR-PCD-CT datasets (all p < 0.001). While low-dose UHR-PCD-CT was considered superior to full-dose non-UHR studies on either scanner (all p < 0.001), ratings of low-dose non-UHR-PCD-CT and full-dose EID-CT examinations did not differ (p > 0.99). Interrater reliability was moderate, indicated by a single measures intraclass correlation coefficient of 0.66 (95\% confidence interval: 0.58-0.73; p < 0.001). Image noise was lowest and signal-to-noise ratios were highest in non-UHR-PCD-CT reconstructions at either dose level (p < 0.001). This investigation demonstrates that superior depiction of trabecular microstructure and considerable denoising can be realized without additional radiation dose by employing a PCD for shoulder CT imaging. Allowing for UHR scans without dose penalty, PCD-CT appears as a promising alternative to EID-CT for shoulder trauma assessment in clinical routine.},
  language  = {en}
}
@article{WuZhaoHochreinetal.2023,
  author    = {Wu, Hao and Zhao, Xiufeng and Hochrein, Sophia M. and Eckstein, Miriam and Gubert, Gabriela F. and Kn{\"o}pper, Konrad and Mansilla, Ana Maria and {\"O}ner, Arman and Doucet-Ladev{\`e}ze, Remi and Schmitz, Werner and Ghesqui{\`e}re, Bart and Theurich, Sebastian and Dudek, Jan and Gasteiger, Georg and Zernecke, Alma and Kobold, Sebastian and Kastenm{\"u}ller, Wolfgang and Vaeth, Martin},
  title     = {Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-42634-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358052},
  year      = {2023},
  abstract  = {T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.},
  language  = {en}
}
@article{GrohAbdelwahabKattimanietal.2023,
  author    = {Groh, Janos and Abdelwahab, Tassnim and Kattimani, Yogita and H{\"o}rner, Michaela and Loserth, Silke and Gudi, Viktoria and Adalbert, Robert and Imdahl, Fabian and Saliba, Antoine-Emmanuel and Coleman, Michael and Stangel, Martin and Simons, Mikael and Martini, Rudolf},
  title     = {Microglia-mediated demyelination protects against CD8\(^+\) T cell-driven axon degeneration in mice carrying PLP defects},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-42570-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357641},
  year      = {2023},
  abstract  = {Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8\(^+\) T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.},
  language  = {en}
}
@article{KarunakaranSubramanianJinetal.2023,
  author    = {Karunakaran, Mohindar M. and Subramanian, Hariharan and Jin, Yiming and Mohammed, Fiyaz and Kimmel, Brigitte and Juraske, Claudia and Starick, Lisa and N{\"o}hren, Anna and L{\"a}nder, Nora and Willcox, Carrie R. and Singh, Rohit and Schamel, Wolfgang W. and Nikolaev, Viacheslav O. and Kunzmann, Volker and Wiemer, Andrew J. and Willcox, Benjamin E. and Herrmann, Thomas},
  title     = {A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-41938-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358179},
  year      = {2023},
  abstract  = {Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.},
  language  = {en}
}
@article{SendellPriceTulenkoPetterssonetal.2023,
  author    = {Sendell-Price, Ashley T. and Tulenko, Frank J. and Pettersson, Mats and Kang, Du and Montandon, Margo and Winkler, Sylke and Kulb, Kathleen and Naylor, Gavin P. and Phillippy, Adam and Fedrigo, Olivier and Mountcastle, Jacquelyn and Balacco, Jennifer R. and Dutra, Amalia and Dale, Rebecca E. and Haase, Bettina and Jarvis, Erich D. and Myers, Gene and Burgess, Shawn M. and Currie, Peter D. and Andersson, Leif and Schartl, Manfred},
  title     = {Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-42238-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357827},
  year      = {2023},
  abstract  = {Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10\(^{-10}\) per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.},
  language  = {en}
}
@article{GunkelSchoetzauFluri2023,
  author    = {Gunkel, Sarah and Sch{\"o}tzau, Andreas and Fluri, Felix},
  title     = {Burden of cerebral small vessel disease and changes of diastolic blood pressure affect clinical outcome after acute ischemic stroke},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-49502-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357669},
  year      = {2023},
  abstract  = {Elevated and low blood pressure (BP) may lead to poor functional outcome after ischemic stroke, which is conflicting. Hence, there must be another factor—such as cerebral small vessel disease (cSVD) -interacting with BP and thus, affecting outcome. Here, we investigate the relationship between BP and cSVD regarding outcome after stroke. Data of 423/503 stroke patients were prospectively analyzed. Diastolic (DBP) and systolic BP (SBP) were collected on hospital admission (BP\(_{ad}\)) and over the first 72 h (BP\(_{72h}\)). cSVD-burden was determined on MR-scans. Good functional outcome was defined as a modified Rankin Scale score ≤ 2 at hospital discharge and 12 months thereafter. cSVD was a predictor of poor outcome (OR 2.8; p < 0.001). SBPad, DBP\(_{ad}\) and SBP\(_{72h}\) were not significantly associated with outcome at any time. A significant relationship was found between DBP\(_{72h}\), (p < 0.01), cSVD (p = 0.013) and outcome at discharge. At 12 months, we found a relationship between outcome and DBP\(_{72h}\) (p = 0.018) and a statistical tendency regarding cSVD (p = 0.08). Changes in DBP72h were significantly related with outcome. There was a U-shaped relationship between DBP\(_{72h}\) and outcome at discharge. Our results suggest an individualized stroke care by either lowering or elevating DBP depending on cSVD-burden in order to influence functional outcome.},
  language  = {en}
}
@article{WagnerCrippaAmariccietal.2023,
  author    = {Wagner, N. and Crippa, L. and Amaricci, A. and Hansmann, P. and Klett, M. and K{\"o}nig, E. J. and Sch{\"a}fer, T. and Di Sante, D. and Cano, J. and Millis, A. J. and Georges, A. and Sangiovanni, G.},
  title     = {Mott insulators with boundary zeros},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-42773-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358150},
  year      = {2023},
  abstract  = {The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green's function zeros defining the "Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of "topological antimatter" annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green's function zeros.},
  language  = {en}
}
@article{CaliskanCaliskanRasbachetal.2023,
  author    = {Caliskan, Aylin and Caliskan, Deniz and Rasbach, Lauritz and Yu, Weimeng and Dandekar, Thomas and Breitenbach, Tim},
  title     = {Optimized cell type signatures revealed from single-cell data by combining principal feature analysis, mutual information, and machine learning},
  series = {Computational and Structural Biotechnology Journal},
  volume    = {21},
  journal   = {Computational and Structural Biotechnology Journal},
  issn      = {2001-0370},
  doi       = {10.1016/j.csbj.2023.06.002},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349989},
  pages     = {3293-3314},
  year      = {2023},
  abstract  = {Machine learning techniques are excellent to analyze expression data from single cells. These techniques impact all fields ranging from cell annotation and clustering to signature identification. The presented framework evaluates gene selection sets how far they optimally separate defined phenotypes or cell groups. This innovation overcomes the present limitation to objectively and correctly identify a small gene set of high information content regarding separating phenotypes for which corresponding code scripts are provided. The small but meaningful subset of the original genes (or feature space) facilitates human interpretability of the differences of the phenotypes including those found by machine learning results and may even turn correlations between genes and phenotypes into a causal explanation. For the feature selection task, the principal feature analysis is utilized which reduces redundant information while selecting genes that carry the information for separating the phenotypes. In this context, the presented framework shows explainability of unsupervised learning as it reveals cell-type specific signatures. Apart from a Seurat preprocessing tool and the PFA script, the pipeline uses mutual information to balance accuracy and size of the gene set if desired. A validation part to evaluate the gene selection for their information content regarding the separation of the phenotypes is provided as well, binary and multiclass classification of 3 or 4 groups are studied. Results from different single-cell data are presented. In each, only about ten out of more than 30000 genes are identified as carrying the relevant information. The code is provided in a GitHub repository at https://github.com/AC-PHD/Seurat_PFA_pipeline.},
  language  = {en}
}
@article{CaliskanDangwalDandekar2023,
  author    = {Caliskan, Aylin and Dangwal, Seema and Dandekar, Thomas},
  title     = {Metadata integrity in bioinformatics: bridging the gap between data and knowledge},
  series = {Computational and Structural Biotechnology Journal},
  volume    = {21},
  journal   = {Computational and Structural Biotechnology Journal},
  issn      = {2001-0370},
  doi       = {10.1016/j.csbj.2023.10.006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349990},
  pages     = {4895-4913},
  year      = {2023},
  abstract  = {In the fast-evolving landscape of biomedical research, the emergence of big data has presented researchers with extraordinary opportunities to explore biological complexities. In biomedical research, big data imply also a big responsibility. This is not only due to genomics data being sensitive information but also due to genomics data being shared and re-analysed among the scientific community. This saves valuable resources and can even help to find new insights in silico. To fully use these opportunities, detailed and correct metadata are imperative. This includes not only the availability of metadata but also their correctness. Metadata integrity serves as a fundamental determinant of research credibility, supporting the reliability and reproducibility of data-driven findings. Ensuring metadata availability, curation, and accuracy are therefore essential for bioinformatic research. Not only must metadata be readily available, but they must also be meticulously curated and ideally error-free. Motivated by an accidental discovery of a critical metadata error in patient data published in two high-impact journals, we aim to raise awareness for the need of correct, complete, and curated metadata. We describe how the metadata error was found, addressed, and present examples for metadata-related challenges in omics research, along with supporting measures, including tools for checking metadata and software to facilitate various steps from data analysis to published research. Highlights • Data awareness and data integrity underpins the trustworthiness of results and subsequent further analysis. • Big data and bioinformatics enable efficient resource use by repurposing publicly available RNA-Sequencing data. • Manual checks of data quality and integrity are insufficient due to the overwhelming volume and rapidly growing data. • Automation and artificial intelligence provide cost-effective and efficient solutions for data integrity and quality checks. • FAIR data management, various software solutions and analysis tools assist metadata maintenance.},
  language  = {en}
}
@article{DaeullaryImdahlDietrichetal.2023,
  author    = {D{\"a}ullary, Thomas and Imdahl, Fabian and Dietrich, Oliver and Hepp, Laura and Krammer, Tobias and Fey, Christina and Neuhaus, Winfried and Metzger, Marco and Vogel, J{\"o}rg and Westermann, Alexander J. and Saliba, Antoine-Emmanuel and Zdzieblo, Daniela},
  title     = {A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection},
  series = {Gut Microbes},
  volume    = {15},
  journal   = {Gut Microbes},
  number    = {1},
  doi       = {10.1080/19490976.2023.2186109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350451},
  year      = {2023},
  abstract  = {Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.},
  language  = {en}
}
@article{EngstlerBeneke2023,
  author    = {Engstler, Markus and Beneke, Tom},
  title     = {Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit},
  series = {eLife},
  volume    = {12},
  journal   = {eLife},
  doi       = {10.7554/eLife.85605},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350002},
  year      = {2023},
  abstract  = {CRISPR/Cas9 gene editing has revolutionised loss-of-function experiments in Leishmania, the causative agent of leishmaniasis. As Leishmania lack a functional non-homologous DNA end joining pathway however, obtaining null mutants typically requires additional donor DNA, selection of drug resistance-associated edits or time-consuming isolation of clones. Genome-wide loss-of-function screens across different conditions and across multiple Leishmania species are therefore unfeasible at present. Here, we report a CRISPR/Cas9 cytosine base editor (CBE) toolbox that overcomes these limitations. We employed CBEs in Leishmania to introduce STOP codons by converting cytosine into thymine and created http://www.leishbaseedit.net/ for CBE primer design in kinetoplastids. Through reporter assays and by targeting single- and multi-copy genes in L. mexicana, L. major, L. donovani, and L. infantum, we demonstrate how this tool can efficiently generate functional null mutants by expressing just one single-guide RNA, reaching up to 100\% editing rate in non-clonal populations. We then generated a Leishmania-optimised CBE and successfully targeted an essential gene in a plasmid library delivered loss-of-function screen in L. mexicana. Since our method does not require DNA double-strand breaks, homologous recombination, donor DNA, or isolation of clones, we believe that this enables for the first time functional genetic screens in Leishmania via delivery of plasmid libraries.},
  language  = {en}
}
@article{KunzUllmannKneiseletal.2023,
  author    = {Kunz, Julius and Ullmann, T. and Kneisel, C. and Baumhauer, R.},
  title     = {Three-dimensional subsurface architecture and its influence on the spatiotemporal development of a retrogressive thaw slump in the Richardson Mountains, Northwest Territories, Canada},
  series = {Arctic, Antarctic, and Alpine Research},
  volume    = {55},
  journal   = {Arctic, Antarctic, and Alpine Research},
  number    = {1},
  issn      = {1523-0430},
  doi       = {10.1080/15230430.2023.2167358},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350147},
  year      = {2023},
  abstract  = {The development of retrogressive thaw slumps (RTS) is known to be strongly influenced by relief-related parameters, permafrost characteristics, and climatic triggers. To deepen the understanding of RTS, this study examines the subsurface characteristics in the vicinity of an active thaw slump, located in the Richardson Mountains (Western Canadian Arctic). The investigations aim to identify relationships between the spatiotemporal slump development and the influence of subsurface structures. Information on these were gained by means of electrical resistivity tomography (ERT) and ground-penetrating radar (GPR). The spatiotemporal development of the slump was revealed by high-resolution satellite imagery and unmanned aerial vehicle-based digital elevation models (DEMs). The analysis indicated an acceleration of slump expansion, especially since 2018. The comparison of the DEMs enabled the detailed balancing of erosion and accumulation within the slump area between August 2018 and August 2019. In addition, manual frost probing and GPR revealed a strong relationship between the active layer thickness, surface morphology, and hydrology. Detected furrows in permafrost table topography seem to affect the active layer hydrology and cause a canalization of runoff toward the slump. The three-dimensional ERT data revealed a partly unfrozen layer underlying a heterogeneous permafrost body. This may influence the local hydrology and affect the development of the RTS. The results highlight the complex relationships between slump development, subsurface structure, and hydrology and indicate a distinct research need for other RTSs.},
  language  = {en}
}
@article{MeistervonSuchodoletzZeeden2023,
  author    = {Meister, Julia and von Suchodoletz, Hans and Zeeden, Christian},
  title     = {Preface: Quaternary research from and inspired by the first virtual DEUQUA conference},
  series = {E\&G Quaternary Science Journal},
  volume    = {72},
  journal   = {E\&G Quaternary Science Journal},
  number    = {2},
  doi       = {10.5194/egqsj-72-185-2023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350157},
  pages     = {185-187},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{RamirezZavalaKruegerWollneretal.2023,
  author    = {Ram{\´i}rez-Zavala, Bernardo and Kr{\"u}ger, Ines and Wollner, Andreas and Schwanfelder, Sonja and Morschh{\"a}user, Joachim},
  title     = {The Ypk1 protein kinase signaling pathway is rewired and not essential for viability in \(Candida\) \(albicans\)},
  series = {PLoS Genetics},
  volume    = {19},
  journal   = {PLoS Genetics},
  number    = {8},
  doi       = {10.1371/journal.pgen.1010890},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350076},
  year      = {2023},
  abstract  = {Abstract Protein kinases are central components of almost all signaling pathways that control cellular activities. In the model organism Saccharomyces cerevisiae, the paralogous protein kinases Ypk1 and Ypk2, which control membrane lipid homeostasis, are essential for viability, and previous studies strongly indicated that this is also the case for their single ortholog Ypk1 in the pathogenic yeast Candida albicans. Here, using FLP-mediated inducible gene deletion, we reveal that C. albicans ypk1Δ mutants are viable but slow-growing, explaining prior failures to obtain null mutants. Phenotypic analyses of the mutants showed that the functions of Ypk1 in regulating sphingolipid biosynthesis and cell membrane lipid asymmetry are conserved, but the consequences of YPK1 deletion are milder than in S. cerevisiae. Mutational studies demonstrated that the highly conserved PDK1 phosphorylation site T548 in its activation loop is essential for Ypk1 function, whereas the TORC2 phosphorylation sites S687 and T705 at the C-terminus are important for Ypk1-dependent resistance to membrane stress. Unexpectedly, Pkh1, the single C. albicans orthologue of Pkh1/Pkh2, which mediate Ypk1 phosphorylation at the PDK1 site in S. cerevisiae, was not required for normal growth of C. albicans under nonstressed conditions, and Ypk1 phosphorylation at T548 was only slightly reduced in pkh1Δ mutants. We found that another protein kinase, Pkh3, whose ortholog in S. cerevisiae cannot substitute Pkh1/2, acts redundantly with Pkh1 to activate Ypk1 in C. albicans. No phenotypic effects were observed in cells lacking Pkh3 alone, but pkh1Δ pkh3Δ double mutants had a severe growth defect and Ypk1 phosphorylation at T548 was completely abolished. These results establish that Ypk1 is not essential for viability in C. albicans and that, despite its generally conserved function, the Ypk1 signaling pathway is rewired in this pathogenic yeast and includes a novel upstream kinase to activate Ypk1 by phosphorylation at the PDK1 site. Author summary Protein kinases are key components of cellular signaling pathways, and elucidating the specific roles of individual kinases is important to understand how organisms adapt to changes in their environment. The protein kinase Ypk1 is highly conserved in eukaryotic organisms and crucial for the maintenance of cell membrane homeostasis. It was previously thought that Ypk1 is essential for viability in the pathogenic yeast Candida albicans, as in the model organism Saccharomyces cerevisiae. Here, by using forced, inducible gene deletion, we reveal that C. albicans mutants lacking Ypk1 are viable but have a strong growth defect. The phenotypes of the mutants indicate that the known functions of Ypk1 are conserved in C. albicans, but loss of this kinase has less severe consequences than in S. cerevisiae. We also unravel the puzzling previous observation that C. albicans mutants lacking the Ypk1-activating kinase Pkh1, which is essential in S. cerevisiae, have no obvious growth defects. We show that the protein kinase Pkh3, which has not previously been implicated in the Ypk1 signaling pathway, can substitute Pkh1 and activate Ypk1 in C. albicans. These findings provide novel insights into this conserved signaling pathway and how it is rewired in a human-pathogenic fungus.},
  language  = {en}
}
@article{HombergerHaywardBarquistetal.2023,
  author    = {Homberger, Christina and Hayward, Regan J. and Barquist, Lars and Vogel, J{\"o}rg},
  title     = {Improved bacterial single-cell RNA-seq through automated MATQ-seq and Cas9-based removal of rRNA reads},
  series = {mBio},
  volume    = {14},
  journal   = {mBio},
  number    = {2},
  doi       = {10.1128/mbio.03557-22},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350059},
  year      = {2023},
  abstract  = {Bulk RNA sequencing technologies have provided invaluable insights into host and bacterial gene expression and associated regulatory networks. Nevertheless, the majority of these approaches report average expression across cell populations, hiding the true underlying expression patterns that are often heterogeneous in nature. Due to technical advances, single-cell transcriptomics in bacteria has recently become reality, allowing exploration of these heterogeneous populations, which are often the result of environmental changes and stressors. In this work, we have improved our previously published bacterial single-cell RNA sequencing (scRNA-seq) protocol that is based on multiple annealing and deoxycytidine (dC) tailing-based quantitative scRNA-seq (MATQ-seq), achieving a higher throughput through the integration of automation. We also selected a more efficient reverse transcriptase, which led to reduced cell loss and higher workflow robustness. Moreover, we successfully implemented a Cas9-based rRNA depletion protocol into the MATQ-seq workflow. Applying our improved protocol on a large set of single Salmonella cells sampled over different growth conditions revealed improved gene coverage and a higher gene detection limit compared to our original protocol and allowed us to detect the expression of small regulatory RNAs, such as GcvB or CsrB at a single-cell level. In addition, we confirmed previously described phenotypic heterogeneity in Salmonella in regard to expression of pathogenicity-associated genes. Overall, the low percentage of cell loss and high gene detection limit makes the improved MATQ-seq protocol particularly well suited for studies with limited input material, such as analysis of small bacterial populations in host niches or intracellular bacteria. IMPORTANCE: Gene expression heterogeneity among isogenic bacteria is linked to clinically relevant scenarios, like biofilm formation and antibiotic tolerance. The recent development of bacterial single-cell RNA sequencing (scRNA-seq) enables the study of cell-to-cell variability in bacterial populations and the mechanisms underlying these phenomena. Here, we report a scRNA-seq workflow based on MATQ-seq with increased robustness, reduced cell loss, and improved transcript capture rate and gene coverage. Use of a more efficient reverse transcriptase and the integration of an rRNA depletion step, which can be adapted to other bacterial single-cell workflows, was instrumental for these improvements. Applying the protocol to the foodborne pathogen Salmonella, we confirmed transcriptional heterogeneity across and within different growth phases and demonstrated that our workflow captures small regulatory RNAs at a single-cell level. Due to low cell loss and high transcript capture rates, this protocol is uniquely suited for experimental settings in which the starting material is limited, such as infected tissues.},
  language  = {en}
}
@article{HossfeldHeegaardKellerer2023,
  author    = {Hossfeld, Tobias and Heegaard, Poul E. and Kellerer, Wolfgang},
  title     = {Comparing the scalability of communication networks and systems},
  series = {IEEE Access},
  volume    = {11},
  journal   = {IEEE Access},
  doi       = {10.1109/ACCESS.2023.3314201},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349403},
  pages     = {101474-101497},
  year      = {2023},
  abstract  = {Scalability is often mentioned in literature, but a stringent definition is missing. In particular, there is no general scalability assessment which clearly indicates whether a system scales or not or whether a system scales better than another. The key contribution of this article is the definition of a scalability index (SI) which quantifies if a system scales in comparison to another system, a hypothetical system, e.g., linear system, or the theoretically optimal system. The suggested SI generalizes different metrics from literature, which are specialized cases of our SI. The primary target of our scalability framework is, however, benchmarking of two systems, which does not require any reference system. The SI is demonstrated and evaluated for different use cases, that are (1) the performance of an IoT load balancer depending on the system load, (2) the availability of a communication system depending on the size and structure of the network, (3) scalability comparison of different location selection mechanisms in fog computing with respect to delays and energy consumption; (4) comparison of time-sensitive networking (TSN) mechanisms in terms of efficiency and utilization. Finally, we discuss how to use and how not to use the SI and give recommendations and guidelines in practice. To the best of our knowledge, this is the first work which provides a general SI for the comparison and benchmarking of systems, which is the primary target of our scalability analysis.},
  language  = {en}
}
@article{SchreiberLohrBaltesetal.2023,
  author    = {Schreiber, Laura M. and Lohr, David and Baltes, Steffen and Vogel, Ulrich and Elabyad, Ibrahim A. and Bille, Maya and Reiter, Theresa and Kosmala, Aleksander and Gassenmaier, Tobias and Stefanescu, Maria R. and Kollmann, Alena and Aures, Julia and Schnitter, Florian and Pali, Mihaela and Ueda, Yuichiro and Williams, Tatiana and Christa, Martin and Hofmann, Ulrich and Bauer, Wolfgang and Gerull, Brenda and Zernecke, Alma and Erg{\"u}n, S{\"u}leyman and Terekhov, Maxim},
  title     = {Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {10},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2023.1068390},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317398},
  year      = {2023},
  abstract  = {A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.},
  language  = {en}
}
@article{SimonParisiWabnitzetal.2023,
  author    = {Simon, Johanna and Parisi, Sandra and Wabnitz, Katharina and Simmenroth, Anne and Schwienhorst-Stich, Eva-Maria},
  title     = {Ten characteristics of high-quality planetary health education},
  series = {Frontiers in Public Health},
  volume    = {11},
  journal   = {Frontiers in Public Health},
  issn      = {2296-2565},
  doi       = {10.3389/fpubh.2023.1143751},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313856},
  year      = {2023},
  abstract  = {Aim: The climate and ecological crises are considered fundamental threats to human health. Healthcare workers in general and doctors in particular can contribute as change agents in mitigation and adaptation. Planetary health education (PHE) aims to harness this potential. This study explores perspectives among stakeholders involved in PHE at German medical schools on the characteristics of high-quality PHE and compares them to existing PHE frameworks. Methods: In 2021, we conducted a qualitative interview study with stakeholders from German medical schools involved in PHE. Three different groups were eligible: faculty members, medical students actively involved in PHE, and study deans of medical schools. Recruitment was performed through national PHE networks and snowball sampling. Thematic qualitative text analysis according to Kuckartz was used for the analysis. Results were systematically compared to three existing PHE frameworks. Results: A total of 20 participants (13 female) from 15 different medical schools were interviewed. Participants covered a wide range of professional backgrounds and experience in PHE education. The analysis revealed ten key themes: (1) Complexity and systems thinking, (2) inter- and transdisciplinarity, (3) ethical dimension, (4) responsibility of health professionals, (5) transformative competencies including practical skills, (6) space for reflection and resilience building, (7) special role of students, (8) need for curricular integration, (9) innovative and proven didactic methods, and (10) education as a driver of innovation. Six of our themes showed substantial overlap with existing PHE frameworks. Two of our themes were only mentioned in one of the frameworks, and two others were not explicitly mentioned. Few important elements of the frameworks did not emerge from our data. Conclusions: In the light of increased attention regarding the connections of the climate and ecological crises and health, our results can be useful for anyone working toward the integration of planetary health into medical schools' and any health professions' curricula and should be considered when designing and implementing new educational activities.},
  language  = {en}
}
@article{Zakaria2023,
  author    = {Zakaria, Nevine Nizar},
  title     = {Assessing the working practices and the inclusive programs to students with disabilities in the Egyptian museums},
  series = {Frontiers in Education},
  volume    = {8},
  journal   = {Frontiers in Education},
  issn      = {2504-284X},
  doi       = {10.3389/feduc.2023.1111695},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319848},
  year      = {2023},
  abstract  = {Following the implementation of 2018's laws on the rights of persons with disabilities (PWDs) in Egypt, students with disabilities (SWDs) have both legal and moral rights to meaningful learning opportunities and inclusive education. Despite that, SWDs still have very limited education resources which limit their career aspirations and quality of life. In this respect, education whether as part of formal education or lifelong learning is central to the museum's mission. Museums, as part of non-formal education, are being acknowledged for their educative powers and investments in the development of quality formal, non-formal, and informal learning experiences. Further, phrases such as "inclusivity," "accessibility," and "diversity" were notably included in the newly approved museum definition by ICOM (2022) emphasizing museums' obligations to embrace societal issues and shape a cultural attitude concerning disability rights, diversity, and equality together with overcoming exclusionary educational practices. The study seeks to investigate the existing resources and inclusive practices in Egyptian museums to achieve non-formal education for SWDs. Qualitative research approaches have been employed to answer a specific question: How can Egyptian museums work within their governing systems to support the learning of SWDs beyond their formal education system? The study aims to assess the potential of Egyptian museums in facilitating learning for SWDs. Further, it examines the capability of Egyptian museums in contributing to informal and non-formal learning for SWDs and striving for inclusive education inspired by the social model of disability that fosters inclusive educational programs and adopts a human rights-based approach. The results revealed that Egyptian museums contributed to the learning of SWDs, yet small-scale programs and individual efforts, but they are already engaged in active inclusive practices that address the learning of SWDs. The study suggests that they need to be acknowledged and supported by the government as state instruments and direct actors in advancing inclusive education and implementing appropriate pedagogies in favor of SWDs.},
  language  = {en}
}
@article{MaihoffSahlerSchogeretal.2023,
  author    = {Maihoff, Fabienne and Sahler, Simone and Schoger, Simon and Brenzinger, Kristof and Kallnik, Katharina and Sauer, Nikki and Bofinger, Lukas and Schmitt, Thomas and Nooten, Sabine S. and Classen, Alice},
  title     = {Cuticular hydrocarbons of alpine bumble bees (Hymenoptera: Bombus) are species-specific, but show little evidence of elevation-related climate adaptation},
  series = {Frontiers in Ecology and Evolution},
  volume    = {11},
  journal   = {Frontiers in Ecology and Evolution},
  issn      = {2296-701X},
  doi       = {10.3389/fevo.2023.1082559},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304420},
  year      = {2023},
  abstract  = {Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees' CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species' elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species' ability to adapt to climatic changes.},
  language  = {en}
}
@article{LiuFriedrichHemmenetal.2023,
  author    = {Liu, Ruiqi and Friedrich, Mike and Hemmen, Katherina and Jansen, Kerstin and Adolfi, Mateus C. and Schartl, Manfred and Heinze, Katrin G.},
  title     = {Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism},
  series = {Frontiers in Endocrinology},
  volume    = {14},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2023.1267590},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-354261},
  year      = {2023},
  abstract  = {Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by F{\"o}rster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.},
  language  = {en}
}
@article{ReinermannAsamGessneretal.2023,
  author    = {Reinermann, Sophie and Asam, Sarah and Gessner, Ursula and Ullmann, Tobias and Kuenzer, Claudia},
  title     = {Multi-annual grassland mowing dynamics in Germany},
  series = {Frontiers in Environmental Science},
  volume    = {11},
  journal   = {Frontiers in Environmental Science},
  issn      = {2296-665X},
  doi       = {10.3389/fenvs.2023.1040551},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320700},
  year      = {2023},
  abstract  = {Introduction: Grasslands cover one third of the agricultural area in Germany and are mainly used for fodder production. However, grasslands fulfill many other ecosystem functions, like carbon storage, water filtration and the provision of habitats. In Germany, grasslands are mown and/or grazed multiple times during the year. The type and timing of management activities and the use intensity vary strongly, however co-determine grassland functions. Large-scale spatial information on grassland activities and use intensity in Germany is limited and not openly provided. In addition, the cause for patterns of varying mowing intensity are usually not known on a spatial scale as data on the incentives of farmers behind grassland management decisions is not available. Methods: We applied an algorithm based on a thresholding approach utilizing Sentinel-2 time series to detect grassland mowing events to investigate mowing dynamics in Germany in 2018-2021. The detected mowing events were validated with an independent dataset based on the examination of public webcam images. We analyzed spatial and temporal patterns of the mowing dynamics and relationships to climatic, topographic, soil or socio-political conditions. Results: We found that most intensively used grasslands can be found in southern/south-eastern Germany, followed by areas in northern Germany. This pattern stays the same among the investigated years, but we found variations on smaller scales. The mowing event detection shows higher accuracies in 2019 and 2020 (F1 = 0.64 and 0.63) compared to 2018 and 2021 (F1 = 0.52 and 0.50). We found a significant but weak (R2 of 0-0.13) relationship for a spatial correlation of mowing frequency and climate as well as topographic variables for the grassland areas in Germany. Further results indicate a clear value range of topographic and climatic conditions, characteristic for intensive grassland use. Extensive grassland use takes place everywhere in Germany and on the entire spectrum of topographic and climatic conditions in Germany. Natura 2000 grasslands are used less intensive but this pattern is not consistent among all sites. Discussion: Our findings on mowing dynamics and relationships to abiotic and socio-political conditions in Germany reveal important aspects of grassland management, including incentives of farmers.},
  language  = {en}
}
@article{RemdeKranzMorelletal.2023,
  author    = {Remde, Hanna and Kranz, Stefanie and Morell, Sarah Maria and Altieri, Barbara and Kroiss, Matthias and Detomas, Mario and Fassnacht, Martin and Deutschbein, Timo},
  title     = {Clinical course of patients with adrenal incidentalomas and cortisol autonomy},
  series = {Frontiers in Endocrinology},
  volume    = {14},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2023.1123132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316793},
  year      = {2023},
  abstract  = {Background Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Methods Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. Results A total of 260 patients were enrolled (147 women (56.5\%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0\%) and PACS (21.9\%) than in NFA (8.1\%). Over time, 40/124 (32.3\%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9\%; PACS, 24.0\%; ACS, 39.0\%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3\% vs. 81.9\% and 92.0\%; p<0.05), diabetes (23.8\% vs. 35.6\% and 40.0\%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95\%-CI 0.89-13.29; ACS: HR 5.96, 95\%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95\%-CI 0.94-5.32; ACS: HR 2.60, 95\%-CI 0.87-7.79; p=0.1). Twenty-five (12.6\%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95\%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95\%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0\% at diagnosis to 61.7\% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Conclusion Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30\% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).},
  language  = {en}
}
@article{GerberQuarderGreefrathetal.2023,
  author    = {Gerber, Sebastian and Quarder, Jascha and Greefrath, Gilbert and Siller, Hans-Stefan},
  title     = {Promoting adaptive intervention competence for teaching simulations and mathematical modelling with digital tools},
  series = {Frontiers in Education},
  volume    = {8},
  journal   = {Frontiers in Education},
  issn      = {2504-284X},
  doi       = {10.3389/feduc.2023.1141063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323701},
  year      = {2023},
  abstract  = {Providing adaptive, independence-preserving and theory-guided support to students in dealing with real-world problems in mathematics lessons is a major challenge for teachers in their professional practice. This paper examines this challenge in the context of simulations and mathematical modelling with digital tools: in addition to mathematical difficulties when autonomously working out individual solutions, students may also experience challenges when using digital tools. These challenges need to be closely examined and diagnosed, and might - if necessary - have to be overcome by intervention in such a way that the students can subsequently continue working independently. Thus, if a difficulty arises in the working process, two knowledge dimensions are necessary in order to provide adapted support to students. For teaching simulations and mathematical modelling with digital tools, more specifically, these knowledge dimensions are: pedagogical content knowledge about simulation and modelling processes supported by digital tools (this includes knowledge about phases and difficulties in the working process) and pedagogical content knowledge about interventions during the mentioned processes (focussing on characteristics of suitable interventions as well as their implementation and effects on the students' working process). The two knowledge dimensions represent cognitive dispositions as the basis for the conceptualisation and operationalisation of a so-called adaptive intervention competence for teaching simulations and mathematical modelling with digital tools. In our article, we present a domain-specific process model and distinguish different types of teacher interventions. Then we describe the design and content of a university course at two German universities aiming to promote this domain-specific professional adaptive intervention competence, among others. In a study using a quasi-experimental pre-post design (N = 146), we confirm that the structure of cognitive dispositions of adaptive intervention competence for teaching simulations and mathematical modelling with digital tools can be described empirically by a two-dimensional model. In addition, the effectiveness of the course is examined and confirmed quantitatively. Finally, the results are discussed, especially against the background of the sample and the research design, and conclusions are derived for possibilities of promoting professional adaptive intervention competence in university courses.},
  language  = {en}
}
@article{PosslerBowmanDaneels2023,
  author    = {Possler, Daniel and Bowman, Nicholas David and Daneels, Rowan},
  title     = {Explaining the formation of eudaimonic gaming experiences: a theoretical overview and systemization based on interactivity and game elements},
  series = {Frontiers in Communication},
  volume    = {8},
  journal   = {Frontiers in Communication},
  issn      = {2297-900X},
  doi       = {10.3389/fcomm.2023.1215960},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328136},
  year      = {2023},
  abstract  = {Over the past years, scholars have explored eudaimonic video game experiences—profound entertainment responses that include meaningfulness, reflection, and others. In a comparatively short time, a plethora of explanations for the formation of such eudaimonic gaming experiences has been developed across multiple disciplines, making it difficult to keep track of the state of theory development. Hence, we present a theoretical overview of these explanations. We first provide a working definition of eudaimonic gaming experiences (i.e., experiences that reflect human virtues and encourage players to develop their potential as human beings fully) and outline four layers of video games—agency, narrative, sociality, and aesthetics—that form the basis for theorizing. Subsequently, we provide an overview of the theoretical approaches, categorizing them based on which of the four game layers their explanation mainly rests upon. Finally, we suggest the contingency of the different theoretical approaches for explaining eudaimonic experiences by describing how their usefulness varies as a function of interactivity. As different types of games offer players various levels of interactivity, our overview suggests which theories and which game layers should be considered when examining eudaimonic experiences for specific game types.},
  language  = {en}
}
@article{LutherBrandtVylkovaetal.2023,
  author    = {Luther, Christian H. and Brandt, Philipp and Vylkova, Slavena and Dandekar, Thomas and M{\"u}ller, Tobias and Dittrich, Marcus},
  title     = {Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {13},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2023.1108235},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311771},
  year      = {2023},
  abstract  = {Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.},
  language  = {en}
}
@article{SchraderRuckBorgulyaetal.2023,
  author    = {Schrader, Hanna and Ruck, Jessica and Borgulya, G{\´a}bor and Parisi, Sandra and Ehlers-Mondorf, Jana and Kaduszkiewicz, Hanna and Joos, Stefanie and Grau, Anna and Linde, Klaus and G{\´a}gyor, Ildik{\´o}},
  title     = {Stress experiences of healthcare assistants in family practice at the onset of the COVID-19 pandemic},
  series = {Frontiers in Public Health},
  volume    = {11},
  journal   = {Frontiers in Public Health},
  issn      = {2296-2565},
  doi       = {10.3389/fpubh.2023.1238144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327427},
  year      = {2023},
  abstract  = {Background: At the beginning of the pandemic in 2020, healthcare assistants in general practices were confronted with numerous new challenges. The aim of the study was to investigate the stress factors of healthcare assistants in March/April 2020 as well as in the further course of the pandemic in 2020. Methods: From August to December 2020, 6,300 randomly selected healthcare assistants in four German states were invited to participate in the study. We performed a mixed methods design using semi-structured telephone interviews and a cross-sectional survey with quantitative and open questions. The feeling of psychological burden was assessed on a 6-point likert-scale. We defined stress factors and categorized them in patient, non-patient and organizational stress factors. The results of the three data sets were compared within a triangulation protocol. Results: One thousand two hundred seventy-four surveys were analyzed and 28 interviews with 34 healthcare assistants were conducted. Of the participants, 29.5\% reported experiences of a very high or high feeling of psychological burden in March/April 2020. Worries about the patients' health and an uncertainty around the new disease were among the patient-related stress factors. Non-patient-related stress factors were problems with the compatibility of work and family, and the fear of infecting relatives with COVID-19. Organizational efforts and dissatisfaction with governmental pandemic management were reported as organizational stress factors. Support from the employer and team cohesion were considered as important resources. Discussion: It is necessary to reduce stress among healthcare assistants by improving their working conditions and to strengthen their resilience to ensure primary healthcare delivery in future health crises.},
  language  = {en}
}
@article{LeonhardtWinklerKollikowskietal.2023,
  author    = {Leonhardt, Jonas and Winkler, Marcela and Kollikowski, Anne and Schiffmann, Lisa and Quenzer, Anne and Einsele, Hermann and L{\"o}ffler, Claudia},
  title     = {Mind-body-medicine in oncology—from patient needs to tailored programs and interventions},
  series = {Frontiers in Psychology},
  volume    = {14},
  journal   = {Frontiers in Psychology},
  issn      = {1664-1078},
  doi       = {10.3389/fpsyg.2023.1140693},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321970},
  year      = {2023},
  abstract  = {Introduction: National and international guidelines recommend early integration of evidence-based multimodal interventions and programs, especially with a focus on relaxation techniques and other Mind-Body-based methods to maintain the quality of life of oncology patients, improve treatment tolerability, and promote healthy lifestyle behaviors. Consequently, we aim to understand what drives patients and how they navigate integrative medicine to best advise them. This study aimed to detect possible topics of particular interest to patients and identify the patient groups that could benefit most from further programs. Furthermore, we aimed to investigate if patients are open-minded toward integrative oncology concepts and learn about their motivational level to maintain or change behavior. Methods: Between August 2019 and October 2020 we surveyed patients undergoing oncological therapy in a university oncological outpatient center using a custom-developed questionnaire based on established Mind-Body Medicine concepts. Results: We included 294 patients with various cancers. More than half reported problems sleeping through (61\%) and 42\% felt stressed frequently, invariably rating this as detrimental to their health. Moreover, a slight majority (52\%) felt physically limited due to their disease and only 30\% performed defined exercise programs. Women were significantly more likely to feel stressed and reported with alarming frequency that they often feel "everything was up to them." The 40-65-year-olds reported significantly less restful sleep, more stress and were more dissatisfied with their situation. However, this group already used natural remedies most frequently and was most often motivated to use relaxation techniques in the next 6 months. The lower the perceived individual energy level (EL), the less frequently patients did sport, the more frequently they felt their disease impaired their activity, mostly feeling stressed and tense. We also found significant associations between negative emotions/thoughts and the variables "sleep," "use of relaxation techniques," "personal stress perception," and "successful lifestyle modification." Conclusion: Mind-Body programs that focus on patient's individual resources, with tools to explore impairing patterns of self-perception and cognitive biases, can be a valuable resource for oncology patients and should therefore be part of an integrative medical treatment concept.},
  language  = {en}
}
@article{DingSeusingNasseroleslamietal.2023,
  author    = {Ding, Hao and Seusing, Nelly and Nasseroleslami, Bahman and Anwar, Abdul Rauf and Strauss, Sebastian and Lotze, Martin and Grothe, Matthias and Groppa, Sergiu and Muthuraman, Muthuraman},
  title     = {The role of ipsilateral motor network in upper limb movement},
  series = {Frontiers in Physiology},
  volume    = {14},
  journal   = {Frontiers in Physiology},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2023.1199338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321805},
  year      = {2023},
  abstract  = {The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction.},
  language  = {en}
}
@article{MassihVehSchenkeetal.2023,
  author    = {Massih, Bita and Veh, Alexander and Schenke, Maren and Mungwa, Simon and Seeger, Bettina and Selvaraj, Bhuvaneish T. and Chandran, Siddharthan and Reinhardt, Peter and Sterneckert, Jared and Hermann, Andreas and Sendtner, Michael and L{\"u}ningschr{\"o}r, Patrick},
  title     = {A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {11},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2023.996952},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304161},
  year      = {2023},
  abstract  = {The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.},
  language  = {en}
}
@article{BoeckMaurusGerhardHartmannetal.2023,
  author    = {B{\"o}ck, Julia and Maurus, Katja and Gerhard-Hartmann, Elena and Br{\"a}ndlein, Stephanie and Kurz, Katrin S. and Ott, German and Anagnostopoulos, Ioannis and Rosenwald, Andreas and Zam{\`o}, Alberto},
  title     = {Targeted panel sequencing in the routine diagnosis of mature T- and NK-cell lymphomas},
  series = {Frontiers in Oncology},
  volume    = {13},
  journal   = {Frontiers in Oncology},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2023.1231601},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326478},
  year      = {2023},
  abstract  = {Diagnosing any of the more than 30 types of T-cell lymphomas is considered a challenging task for many pathologists and currently requires morphological expertise as well as the integration of clinical data, immunophenotype, flow cytometry and clonality analyses. Even considering all available information, some margin of doubt might remain using the current diagnostic procedures. In recent times, the genetic landscape of most T-cell lymphomas has been elucidated, showing a number of diagnostically relevant mutations. In addition, recent data indicate that some of these genetic alterations might bear prognostic and predictive value. Extensive genetic analyses, such as whole exome or large panel sequencing are still expensive and time consuming, therefore limiting their application in routine diagnostic. We therefore devoted our effort to develop a lean approach for genetic analysis of T-cell lymphomas, focusing on maximum efficiency rather than exhaustively covering all possible targets. Here we report the results generated with our small amplicon-based panel that could be used routinely on paraffin-embedded and even decalcified samples, on a single sample basis in parallel with other NGS-panels used in our routine diagnostic lab, in a relatively short time and with limited costs. We tested 128 available samples from two German reference centers as part of our routine work up (among which 116 T-cell lymphomas), which is the largest routine diagnostic series reported to date. Our results showed that this assay had a very high rate of technical success (97\%) and could detect mutations in the majority (79\%) of tested T-cell lymphoma samples.},
  language  = {en}
}
@article{Hutmacher2023,
  author    = {Hutmacher, Fabian},
  title     = {Taking methodological pluralism seriously},
  series = {Frontiers in Psychology},
  volume    = {14},
  journal   = {Frontiers in Psychology},
  issn      = {1664-1078},
  doi       = {10.3389/fpsyg.2023.1215737},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328221},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KressJessenHufnageletal.2023,
  author    = {Kreß, Julia Katharina Charlotte and Jessen, Christina and Hufnagel, Anita and Schmitz, Werner and Da Xavier Silva, Thamara Nishida and Ferreira Dos Santos, Anc{\´e}ly and Mosteo, Laura and Goding, Colin R. and Friedmann Angeli, Jos{\´e} Pedro and Meierjohann, Svenja},
  title     = {The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2},
  series = {Cell Reports},
  volume    = {42},
  journal   = {Cell Reports},
  number    = {7},
  doi       = {10.1016/j.celrep.2023.112724},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350312},
  year      = {2023},
  abstract  = {Highlights • The integrated stress response leads to a general ATF4-dependent activation of NRF2 • ATF4 causes a CHAC1-dependent GSH depletion, resulting in NRF2 stabilization • An elevation of NRF2 transcript levels fosters this effect • NRF2 supports the ISR/ATF4 pathway by improving cystine and antioxidant supply Summary The redox regulator NRF2 becomes activated upon oxidative and electrophilic stress and orchestrates a response program associated with redox regulation, metabolism, tumor therapy resistance, and immune suppression. Here, we describe an unrecognized link between the integrated stress response (ISR) and NRF2 mediated by the ISR effector ATF4. The ISR is commonly activated after starvation or ER stress and plays a central role in tissue homeostasis and cancer plasticity. ATF4 increases NRF2 transcription and induces the glutathione-degrading enzyme CHAC1, which we now show to be critically important for maintaining NRF2 activation. In-depth analyses reveal that NRF2 supports ATF4-induced cells by increasing cystine uptake via the glutamate-cystine antiporter xCT. In addition, NRF2 upregulates genes mediating thioredoxin usage and regeneration, thus balancing the glutathione decrease. In conclusion, we demonstrate that the NRF2 response serves as second layer of the ISR, an observation highly relevant for the understanding of cellular resilience in health and disease.},
  language  = {en}
}
@article{BasslerKnoblichGerhardHartmannetal.2023,
  author    = {Bassler, Miriam C. and Knoblich, Mona and Gerhard-Hartmann, Elena and Mukherjee, Ashutosh and Youssef, Almoatazbellah and Hagen, Rudolf and Haug, Lukas and Goncalves, Miguel and Scherzad, Agmal and St{\"o}th, Manuel and Ostertag, Edwin and Steinke, Maria and Brecht, Marc and Hackenberg, Stephan and Meyer, Till Jasper},
  title     = {Differentiation of salivary gland and salivary gland tumor tissue via Raman imaging combined with multivariate data analysis},
  series = {Diagnostics},
  volume    = {14},
  journal   = {Diagnostics},
  number    = {1},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics14010092},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355558},
  year      = {2023},
  abstract  = {Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90\% and validated by predicting model-unknown Raman spectra, of which 93\% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.},
  language  = {en}
}
@article{SchlechtNeubertMengetal.2023,
  author    = {Schlecht, Sina and Neubert, Sven and Meng, Karin and Rabe, Antonia and Jentschke, Elisabeth},
  title     = {Changes of symptoms of anxiety, depression, and fatigue in cancer patients 3 months after a video-based intervention},
  series = {International journal of environmental research and public health},
  volume    = {20},
  journal   = {International journal of environmental research and public health},
  number    = {20},
  doi       = {10.3390/ijerph20206933},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357294},
  year      = {2023},
  abstract  = {During the COVID-19 pandemic, social distancing restricted psycho-oncological care. Therefore, this secondary analysis examines the changes in anxiety, fear of progression, fatigue, and depression in cancer patients after a video-based eHealth intervention. We used a prospective observational design with 155 cancer patients with mixed tumor entities. Data were assessed before and after the intervention and at a three-month follow-up using self-reported questionnaires (GAD-7, FOP-Q-SF, PHQ-8, and EORTC QLQ-FA12). The eight videos included psychoeducation, Acceptance and Commitment Therapy elements, and yoga and qigong exercises. The results showed that three months after finishing the video-based intervention, participants showed significantly reduced fear of progression (d = -0.23), depression (d = -0.27), and fatigue (d = -0.24) compared to the baseline. However, there was no change in anxiety (d = -0.09). Findings indicated marginal improvements in mental distress when using video-based intervention for cancer patients for up to three months, but long-term effectiveness must be confirmed using a controlled design.},
  language  = {en}
}
@article{BeierlePryssAizawa2023,
  author    = {Beierle, Felix and Pryss, R{\"u}diger and Aizawa, Akiko},
  title     = {Sentiments about mental health on Twitter — before and during the COVID-19 pandemic},
  series = {Healthcare},
  volume    = {11},
  journal   = {Healthcare},
  number    = {21},
  issn      = {2227-9032},
  doi       = {10.3390/healthcare11212893},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355192},
  year      = {2023},
  abstract  = {During the COVID-19 pandemic, the novel coronavirus had an impact not only on public health but also on the mental health of the population. Public sentiment on mental health and depression is often captured only in small, survey-based studies, while work based on Twitter data often only looks at the period during the pandemic and does not make comparisons with the pre-pandemic situation. We collected tweets that included the hashtags \#MentalHealth and \#Depression from before and during the pandemic (8.5 months each). We used LDA (Latent Dirichlet Allocation) for topic modeling and LIWC, VADER, and NRC for sentiment analysis. We used three machine-learning classifiers to seek evidence regarding an automatically detectable change in tweets before vs. during the pandemic: (1) based on TF-IDF values, (2) based on the values from the sentiment libraries, (3) based on tweet content (deep-learning BERT classifier). Topic modeling revealed that Twitter users who explicitly used the hashtags \#Depression and especially \#MentalHealth did so to raise awareness. We observed an overall positive sentiment, and in tough times such as during the COVID-19 pandemic, tweets with \#MentalHealth were often associated with gratitude. Among the three classification approaches, the BERT classifier showed the best performance, with an accuracy of 81\% for \#MentalHealth and 79\% for \#Depression. Although the data may have come from users familiar with mental health, these findings can help gauge public sentiment on the topic. The combination of (1) sentiment analysis, (2) topic modeling, and (3) tweet classification with machine learning proved useful in gaining comprehensive insight into public sentiment and could be applied to other data sources and topics.},
  language  = {en}
}
@article{HennesHuflageGrunzetal.2023,
  author    = {Hennes, Jan-Lucca and Huflage, Henner and Grunz, Jan-Peter and Hartung, Viktor and Augustin, Anne Marie and Patzer, Theresa Sophie and Pannenbecker, Pauline and Petritsch, Bernhard and Bley, Thorsten Alexander and Gruschwitz, Philipp},
  title     = {An intra-individual comparison of low-keV photon-counting CT versus energy-integrating-detector CT angiography of the aorta},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {24},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13243645},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355568},
  year      = {2023},
  abstract  = {This retrospective study aims to provide an intra-individual comparison of aortic CT angiographies (CTAs) using first-generation photon-counting-detector CT (PCD-CT) and third-generation energy-integrating-detector CT (EID-CT). High-pitch CTAs were performed with both scanners and equal contrast-agent protocols. EID-CT employed automatic tube voltage selection (90/100 kVp) with reference tube current of 434/350 mAs, whereas multi-energy PCD-CT scans were generated with fixed tube voltage (120 kVp), image quality level of 64, and reconstructed as 55 keV monoenergetic images. For image quality assessment, contrast-to-noise ratios (CNRs) were calculated, and subjective evaluation (overall quality, luminal contrast, vessel sharpness, blooming, and beam hardening) was performed independently by three radiologists. Fifty-seven patients (12 women, 45 men) were included with a median interval between examinations of 12.7 months (interquartile range 11.1 months). Using manufacturer-recommended scan protocols resulted in a substantially lower radiation dose in PCD-CT (size-specific dose estimate: 4.88 ± 0.48 versus 6.28 ± 0.50 mGy, p < 0.001), while CNR was approximately 50\% higher (41.11 ± 8.68 versus 27.05 ± 6.73, p < 0.001). Overall image quality and luminal contrast were deemed superior in PCD-CT (p < 0.001). Notably, EID-CT allowed for comparable vessel sharpness (p = 0.439) and less pronounced blooming and beam hardening (p < 0.001). Inter-rater agreement was good to excellent (0.58-0.87). Concluding, aortic PCD-CTAs facilitate increased image quality with significantly lower radiation dose compared to EID-CTAs},
  language  = {en}
}
@article{HampfScherfClavelWeissetal.2023,
  author    = {Hampf, Chantal and Scherf-Clavel, Maike and Weiß, Carolin and Kl{\"u}pfel, Catherina and Stonawski, Saskia and Hommers, Leif and Lichter, Katharina and Erhardt-Lehmann, Angelika and Unterecker, Stefan and Domschke, Katharina and Kittel-Schneider, Sarah and Menke, Andreas and Deckert, J{\"u}rgen and Weber, Heike},
  title     = {Effects of anxious depression on antidepressant treatment response},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {24},
  issn      = {1422-0067},
  doi       = {10.3390/ijms242417128},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355801},
  year      = {2023},
  abstract  = {Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50\%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.},
  language  = {en}
}
@article{SchuhmannLanghauserZimmermannetal.2023,
  author    = {Schuhmann, Michael K. and Langhauser, Friederike and Zimmermann, Lena and Bellut, Maximilian and Kleinschnitz, Christoph and Fluri, Felix},
  title     = {Dimethyl fumarate attenuates lymphocyte infiltration and reduces infarct size in experimental stroke},
  series = {International journal of molecular sciences},
  volume    = {24},
  journal   = {International journal of molecular sciences},
  number    = {21},
  doi       = {10.3390/ijms242115540},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357731},
  year      = {2023},
  abstract  = {Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood-brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke.},
  language  = {en}
}
@article{TessmerMargison2023,
  author    = {Tessmer, Ingrid and Margison, Geoffrey P.},
  title     = {The DNA alkyltransferase family of DNA repair proteins: common mechanisms, diverse functions},
  series = {International Journal of Molecular Sciences},
  volume    = {25},
  journal   = {International Journal of Molecular Sciences},
  number    = {1},
  issn      = {1422-0067},
  doi       = {10.3390/ijms25010463},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355790},
  year      = {2023},
  abstract  = {DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O\(^6\)-alkylguanine and O\(^4\)-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O\(^6\)-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms. Nevertheless, between species, subtle as well as more extensive differences that affect target lesion preferences and/or introduce additional protein functions have evolved. Examining these differences and their functional consequences is intricately entwined with understanding the details of their DNA repair mechanism(s) and their biological roles. In this review, we will present and discuss various aspects of the current status of knowledge on this intriguing protein family.},
  language  = {en}
}
@article{ScheupleinLohrVivoliVegaetal.2023,
  author    = {Scheuplein, Nicolas Julian and Lohr, Theresa and Vivoli Vega, Mirella and Ankrett, Dyan and Seufert, Florian and Kirchner, Lukas and Harmer, Nicholas J. and Holzgrabe, Ulrike},
  title     = {Fluorescent probe for the identification of potent inhibitors of the macrophage infectivity potentiator (Mip) protein of Burkholderia pseudomallei},
  series = {SLAS Discovery},
  volume    = {28},
  journal   = {SLAS Discovery},
  number    = {5},
  doi       = {10.1016/j.slasd.2023.03.004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349784},
  pages     = {211-222},
  year      = {2023},
  abstract  = {Highlights • Synthesis of a new tracer molecule. • Robust and easy screening method for a broad range of compound activities. • FP assay validation considering limited use of starting material, DMSO tolerance, variation in incubation time and temperature. • Possibility of extension to HTP assay. Abstract The macrophage infectivity potentiator (Mip) protein belongs to the immunophilin superfamily. This class of enzymes catalyzes the interconversion between the cis and trans configuration of proline-containing peptide bonds. Mip has been shown to be important for the virulence of a wide range of pathogenic microorganisms, including the Gram-negative bacterium Burkholderia pseudomallei. Small molecules derived from the natural product rapamycin, lacking its immunosuppression-inducing moiety, inhibit Mip's peptidyl-prolyl cis-trans isomerase (PPIase) activity and lead to a reduction in pathogen load in vitro. Here, a fluorescence polarization assay (FPA) to enable the screening and effective development of BpMip inhibitors was established. A fluorescent probe was prepared, derived from previous pipecolic scaffold Mip inhibitors labeled with fluorescein. This probe showed moderate affinity for BpMip and enabled a highly robust FPA suitable for screening large compound libraries with medium- to high-throughput (Z factor ∼ 0.89) to identify potent new inhibitors. The FPA results are consistent with data from the protease-coupled PPIase assay. Analysis of the temperature dependence of the probe's binding highlighted that BpMip's ligand binding is driven by enthalpic rather than entropic effects. This has considerable consequences for the use of low-temperature kinetic assays.},
  language  = {en}
}
@article{SchuergerEngel2023,
  author    = {Sch{\"u}rger, Peter and Engel, Volker},
  title     = {On the relation between nodal structures in quantum wave functions and particle correlation},
  series = {AIP Advances},
  volume    = {13},
  journal   = {AIP Advances},
  number    = {12},
  doi       = {10.1063/5.0180004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350361},
  year      = {2023},
  abstract  = {We study the influence of nodal structures in two-dimensional quantum mechanical densities on wave packet entanglement. This is motivated by our recent study [Entropy, 25, 970 (2023)], which showed that the mutual information derived from the momentum-space probability density of a coupled two-particle system exhibits an unusual time dependence, which is not encountered if the position-space density is employed in the calculation. In studying a model density, here, we identify cases where the mutual information increases with the number of nodes in the wave function and approaches a finite value, whereas in this limit, the linear correlation vanishes. The results of the analytical model are then applied to interpret the correlation measures for coupled electron-nuclear dynamics, which are treated by numerically solving the time-dependent Schr{\"o}dinger equation.},
  language  = {en}
}
@article{SchadeBaderHuberetal.2023,
  author    = {Schade, A. and Bader, A. and Huber, T. and Kuhn, S. and Czyszanowski, T. and Pfenning, A. and Rygała, M. and Smołka, T. and Motyka, M. and Sęk, G. and Hartmann, F. and H{\"o}fling, S.},
  title     = {Monolithic high contrast grating on GaSb/AlAsSb based epitaxial structures for mid-infrared wavelength applications},
  series = {Optics Express},
  volume    = {31},
  journal   = {Optics Express},
  number    = {10},
  doi       = {10.1364/OE.487119},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350346},
  pages     = {16025-16034},
  year      = {2023},
  abstract  = {We demonstrate monolithic high contrast gratings (MHCG) based on GaSb/AlAs0.08Sb0.92 epitaxial structures with sub-wavelength gratings enabling high reflection of unpolarized mid-infrared radiation at the wavelength range from 2.5 to 5 µm. We study the reflectivity wavelength dependence of MHCGs with ridge widths ranging from 220 to 984 nm and fixed 2.6 µm grating period and demonstrate that peak reflectivity of above 0.7 can be shifted from 3.0 to 4.3 µm for ridge widths from 220 to 984 nm, respectively. Maximum reflectivity of up to 0.9 at 4 µm can be achieved. The experiments are in good agreement with numerical simulations, confirming high process flexibility in terms of peak reflectivity and wavelength selection. MHCGs have hitherto been regarded as mirrors enabling high reflection of selected light polarization. With this work, we show that thoughtfully designed MHCG yields high reflectivity for both orthogonal polarizations simultaneously. Our experiment demonstrates that MHCGs are promising candidates to replace conventional mirrors like distributed Bragg reflectors to realize resonator based optical and optoelectronic devices such as resonant cavity enhanced light emitting diodes and resonant cavity enhanced photodetectors in the mid-infrared spectral region, for which epitaxial growth of distributed Bragg reflectors is challenging.},
  language  = {en}
}
@article{PozziBolzoniBiellaetal.2023,
  author    = {Pozzi, Nicol{\´o} Gabriele and Bolzoni, Francesco and Biella, Gabriele Eliseo Mario and Pezzoli, Gianni and Ip, Chi Wang and Volkmann, Jens and Cavallari, Paolo and Asan, Esther and Isaias, Ioannis Ugo},
  title     = {Brain noradrenergic innervation supports the development of Parkinson's tremor: a study in a reserpinized rat model},
  series = {Cells},
  volume    = {12},
  journal   = {Cells},
  number    = {21},
  issn      = {2073-4409},
  doi       = {10.3390/cells12212529},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357721},
  year      = {2023},
  abstract  = {The pathophysiology of tremor in Parkinson's disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (\% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic-rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.},
  language  = {en}
}
@article{SteinerZacharyBaueretal.2023,
  author    = {Steiner, Thomas and Zachary, Marie and Bauer, Susanne and M{\"u}ller, Martin J. and Krischke, Markus and Radziej, Sandra and Klepsch, Maximilian and Huettel, Bruno and Eisenreich, Wolfgang and Rudel, Thomas and Beier, Dagmar},
  title     = {Central Role of Sibling Small RNAs NgncR_162 and NgncR_163 in Main Metabolic Pathways of Neisseria gonorrhoeae},
  series = {mBio},
  volume    = {14},
  journal   = {mBio},
  doi       = {10.1128/mbio.03093-22},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313323},
  year      = {2023},
  abstract  = {Small bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in a very few cases has the role in metabolism been demonstrated. Here, we performed a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 (NgncR_162/163) and their impact on the metabolism of Neisseria gonorrhoeae. These sRNAs have been reported to control genes of the citric acid and methylcitric acid cycles by posttranscriptional negative regulation. By transcriptome analysis, we now expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially in the uptake of glycine, phenylalanine, and branched-chain amino acids. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and, hence, probably affect biosyntheses of nucleotides, vitamins, and other amino acids via the supply of one-carbon (C\(_1\)) units. Indeed, these roles were confirmed by metabolomics and metabolic flux analysis, which revealed a bipartite metabolic network with glucose degradation for the supply of anabolic pathways and the usage of amino acids via the citric acid cycle for energy metabolism. Thus, by combined deep RNA sequencing (RNA-seq) and metabolomics, we significantly extended the regulon of NgncR_162/163 and demonstrated the role of NgncR_162/163 in the regulation of central metabolic pathways of the gonococcus.},
  language  = {en}
}
@article{LibandaPaeth2023,
  author    = {Libanda, Brigadier and Paeth, Heiko},
  title     = {Modelling wind speed across Zambia: Implications for wind energy},
  series = {International Journal of Climatology},
  volume    = {43},
  journal   = {International Journal of Climatology},
  number    = {2},
  doi       = {10.1002/joc.7826},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312134},
  pages     = {772 -- 786},
  year      = {2023},
  abstract  = {Wind energy is a key option in global dialogues about climate change mitigation. Here, we combined observations from surface wind stations, reanalysis datasets, and state-of-the-art regional climate models from the Coordinated Regional Climate Downscaling Experiment (CORDEX Africa) to study the current and future wind energy potential in Zambia. We found that winds are dominated by southeasterlies and are rarely strong with an average speed of 2.8 m·s\(^{-1}\). When we converted the observed surface wind speed to a turbine hub height of 100 m, we found a ~38\% increase in mean wind speed for the period 1981-2000. Further, both simulated and observed wind speed data show statistically significant increments across much of the country. The only areas that divert from this upward trend of wind speeds are the low land terrains of the Eastern Province bordering Malawi. Examining projections of wind power density (WPD), we found that although wind speed is increasing, it is still generally too weak to support large-scale wind power generation. We found a meagre projected annual average WPD of 46.6 W·m\(^{-2}\). The highest WPDs of ~80 W·m\(^{-2}\) are projected in the northern and central parts of the country while the lowest are to be expected along the Luangwa valley in agreement with wind speed simulations. On average, Zambia is expected to experience minor WPD increments of 0.004 W·m\(^{-2}\) per year from 2031 to 2050. We conclude that small-scale wind turbines that accommodate cut-in wind speeds of 3.8 m·s\(^{-1}\) are the most suitable for power generation in Zambia. Further, given the limitations of small wind turbines, they are best suited for rural and suburban areas of the country where obstructions are few, thus making them ideal for complementing the government of the Republic of Zambia's rural electrification efforts.},
  language  = {en}
}
@article{LambergerZainuddinScheibeletal.2023,
  author    = {Lamberger, Zan and Zainuddin, Shakir and Scheibel, Thomas and Lang, Gregor},
  title     = {Polymeric Janus Fibers},
  series = {ChemPlusChem},
  volume    = {88},
  journal   = {ChemPlusChem},
  number    = {2},
  doi       = {10.1002/cplu.202200371},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318516},
  year      = {2023},
  abstract  = {Janus fibers are a class of composite materials comprising mechanical and chemical to biological functionality. Combining different materials and functionalities in one micro- or even nanoscale fiber enables otherwise unreachable synergistic physicochemical effects with unprecedented opportunities for technical or biomedical applications. Here, recent developments of processing technologies and applications of polymeric Janus fibers will be reviewed. Various examples in the fields of textiles, catalysis, sensors as well as medical applications, like drug delivery systems, tissue engineering and antimicrobial materials, are presented to illuminate the outstanding potential of such high-end functional materials for novel applications in the upcoming future.},
  language  = {en}
}
@article{DhillonDahmsKuebertFlocketal.2023,
  author    = {Dhillon, Maninder Singh and Dahms, Thorsten and Kuebert-Flock, Carina and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias},
  title     = {Integrating random forest and crop modeling improves the crop yield prediction of winter wheat and oil seed rape},
  series = {Frontiers in Remote Sensing},
  volume    = {3},
  journal   = {Frontiers in Remote Sensing},
  issn      = {2673-6187},
  doi       = {10.3389/frsen.2022.1010978},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301462},
  year      = {2023},
  abstract  = {The fast and accurate yield estimates with the increasing availability and variety of global satellite products and the rapid development of new algorithms remain a goal for precision agriculture and food security. However, the consistency and reliability of suitable methodologies that provide accurate crop yield outcomes still need to be explored. The study investigates the coupling of crop modeling and machine learning (ML) to improve the yield prediction of winter wheat (WW) and oil seed rape (OSR) and provides examples for the Free State of Bavaria (70,550 km2), Germany, in 2019. The main objectives are to find whether a coupling approach [Light Use Efficiency (LUE) + Random Forest (RF)] would result in better and more accurate yield predictions compared to results provided with other models not using the LUE. Four different RF models [RF1 (input: Normalized Difference Vegetation Index (NDVI)), RF2 (input: climate variables), RF3 (input: NDVI + climate variables), RF4 (input: LUE generated biomass + climate variables)], and one semi-empiric LUE model were designed with different input requirements to find the best predictors of crop monitoring. The results indicate that the individual use of the NDVI (in RF1) and the climate variables (in RF2) could not be the most accurate, reliable, and precise solution for crop monitoring; however, their combined use (in RF3) resulted in higher accuracies. Notably, the study suggested the coupling of the LUE model variables to the RF4 model can reduce the relative root mean square error (RRMSE) from -8\% (WW) and -1.6\% (OSR) and increase the R 2 by 14.3\% (for both WW and OSR), compared to results just relying on LUE. Moreover, the research compares models yield outputs by inputting three different spatial inputs: Sentinel-2(S)-MOD13Q1 (10 m), Landsat (L)-MOD13Q1 (30 m), and MOD13Q1 (MODIS) (250 m). The S-MOD13Q1 data has relatively improved the performance of models with higher mean R 2 [0.80 (WW), 0.69 (OSR)], and lower RRMSE (\%) (9.18, 10.21) compared to L-MOD13Q1 (30 m) and MOD13Q1 (250 m). Satellite-based crop biomass, solar radiation, and temperature are found to be the most influential variables in the yield prediction of both crops.},
  language  = {en}
}
@article{Ibebuchi2023,
  author    = {Ibebuchi, Chibuike Chiedozie},
  title     = {On the representation of atmospheric circulation modes in regional climate models over Western Europe},
  series = {International Journal of Climatology},
  volume    = {43},
  journal   = {International Journal of Climatology},
  number    = {1},
  doi       = {10.1002/joc.7807},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312424},
  pages     = {668 -- 682},
  year      = {2023},
  abstract  = {Atmospheric circulation is a key driver of climate variability, and the representation of atmospheric circulation modes in regional climate models (RCMs) can enhance the credibility of regional climate projections. This study examines the representation of large-scale atmospheric circulation modes in Coupled Model Inter-comparison Project phase 5 RCMs once driven by ERA-Interim, and by two general circulation models (GCMs). The study region is Western Europe and the circulation modes are classified using the Promax rotated T-mode principal component analysis. The results indicate that the RCMs can replicate the classified atmospheric modes as obtained from ERA5 reanalysis, though with biases dependent on the data providing the lateral boundary condition and the choice of RCM. When the boundary condition is provided by ERA-Interim that is more consistent with observations, the simulated map types and the associating time series match well with their counterparts from ERA5. Further, on average, the multi-model ensemble mean of the analysed RCMs, driven by ERA-Interim, indicated a slight improvement in the representation of the modes obtained from ERA5. Conversely, when the RCMs are driven by the GCMs that are models without assimilation of observational data, the representation of the atmospheric modes, as obtained from ERA5, is relatively less accurate compared to when the RCMs are driven by ERA-Interim. This suggests that the biases stem from the GCMs. On average, the representation of the modes was not improved in the multi-model ensemble mean of the five analysed RCMs driven by either of the GCMs. However, when the best-performed RCMs were selected on average the ensemble mean indicated a slight improvement. Moreover, the presence of the North Atlantic Oscillation (NAO) in the simulated modes depends also on the lateral boundary conditions. The relationship between the modes and the NAO was replicated only when the RCMs were driven by reanalysis. The results indicate that the forcing model is the main factor in reproducing the atmospheric circulation.},
  language  = {en}
}
@article{MenekseMahlAlbertetal.2023,
  author    = {Menekse, Kaan and Mahl, Magnus and Albert, Julius and Niyas, M. A. and Shoyama, Kazutaka and Stolte, Matthias and W{\"u}rthner, Frank},
  title     = {Supramolecularly Engineered Bulk-Heterojunction Solar Cells with Self-Assembled Non-Fullerene Nanographene Tetraimide Acceptors},
  series = {Solar RRL},
  volume    = {7},
  journal   = {Solar RRL},
  number    = {2},
  doi       = {10.1002/solr.202200895},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312099},
  year      = {2023},
  abstract  = {A series of novel imide-functionalized C\(_{64}\) nanographenes is investigated as acceptor components in organic solar cells (OSCs) in combination with donor polymer PM6. These electron-poor molecules either prevail as a monomer or self-assemble into dimers in the OSC active layer depending on the chosen imide substituents. This allows for the controlled stacking of electron-poor and electron-rich π-scaffolds to establish a novel class of non-fullerene acceptor materials to tailor the bulk-heterojunction morphology of the OSCs. The best performance is observed for derivatives that are able to self-assemble into dimers, reaching power conversion efficiencies of up to 7.1\%.},
  language  = {en}
}
@article{MaihoffFriessHoissetal.2023,
  author    = {Maihoff, Fabienne and Friess, Nicolas and Hoiss, Bernhard and Schmid-Egger, Christian and Kerner, Janika and Neumayer, Johann and Hopfenm{\"u}ller, Sebastian and B{\"a}ssler, Claus and M{\"u}ller, J{\"o}rg and Classen, Alice},
  title     = {Smaller, more diverse and on the way to the top: Rapid community shifts of montane wild bees within an extraordinary hot decade},
  series = {Diversity and Distributions},
  volume    = {29},
  journal   = {Diversity and Distributions},
  number    = {2},
  doi       = {10.1111/ddi.13658},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312126},
  pages     = {272-288},
  year      = {2023},
  abstract  = {Aim Global warming is assumed to restructure mountain insect communities in space and time. Theory and observations along climate gradients predict that insect abundance and richness, especially of small-bodied species, will increase with increasing temperature. However, the specific responses of single species to rising temperatures, such as spatial range shifts, also alter communities, calling for intensive monitoring of real-world communities over time. Location German Alps and pre-alpine forests in south-east Germany. Methods We empirically examined the temporal and spatial change in wild bee communities and its drivers along two largely well-protected elevational gradients (alpine grassland vs. pre-alpine forest), each sampled twice within the last decade. Results We detected clear abundance-based upward shifts in bee communities, particularly in cold-adapted bumble bee species, demonstrating the speed with which mobile organisms can respond to climatic changes. Mean annual temperature was identified as the main driver of species richness in both regions. Accordingly, and in large overlap with expectations under climate warming, we detected an increase in bee richness and abundance, and an increase in small-bodied species in low- and mid-elevations along the grassland gradient. Community responses in the pre-alpine forest gradient were only partly consistent with community responses in alpine grasslands. Main Conclusion In well-protected temperate mountain regions, small-bodied bees may initially profit from warming temperatures, by getting more abundant and diverse. Less severe warming, and differences in habitat openness along the forested gradient, however, might moderate species responses. Our study further highlights the utility of standardized abundance data for revealing rapid changes in bee communities over only one decade.},
  language  = {en}
}
@article{WeiWangYangetal.2023,
  author    = {Wei, Yuxiang and Wang, Junyi and Yang, Weiguang and Lin, Zhenyang and Ye, Qing},
  title     = {Boosting Ring Strain and Lewis Acidity of Borirane: Synthesis, Reactivity and Density Functional Theory Studies of an Uncoordinated Arylborirane Fused to o-Carborane},
  series = {Chemistry - A European Journal},
  volume    = {29},
  journal   = {Chemistry - A European Journal},
  number    = {5},
  doi       = {10.1002/chem.202203265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312089},
  year      = {2023},
  abstract  = {Among the parent borirane, benzoborirene and ortho-dicarbadodecaborane-fused borirane, the latter possesses the highest ring strain and the highest Lewis acidity according to our density functional theory (DFT) studies. The synthesis of this class of compounds is thus considerably challenging. The existing examples require either a strong π-donating group or an extra ligand for B-coordination, which nevertheless suppresses or completely turns off the Lewis acidity. The title compound, which possesses both features, not only allows the 1,2-insertion of P=O, C=O or C≡N to proceed under milder conditions, but also enables the heretofore unknown dearomative 1,4-insertion of Ar-(C=O)- into a B-C bond. The fusion of strained molecular systems to an o-carborane cage shows great promise for boosting both the ring strain and acidity.},
  language  = {en}
}