@phdthesis{Dehmer2024,
  author    = {Dehmer, Markus},
  title     = {A novel USP11-TCEAL1-mediated mechanism protects transcriptional elongation by RNA Polymerase II},
  doi       = {10.25972/OPUS-36054},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360544},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Deregulated expression of MYC oncoproteins is a driving event in many human cancers. Therefore, understanding and targeting MYC protein-driven mechanisms in tumor biology remain a major challenge. Oncogenic transcription in MYCN-amplified neuroblastoma leads to the formation of the MYCN-BRCA1-USP11 complex that terminates transcription by evicting stalling RNAPII from chromatin. This reduces cellular stress and allows reinitiation of new rounds of transcription. Basically, tumors with amplified MYC genes have a high demand on well orchestration of transcriptional processes-dependent and independent from MYC proteins functions in gene regulation. To date, the cooperation between promoter-proximal termination and transcriptional elongation in cancer cells remains still incomplete in its understanding. In this study the putative role of the dubiquitinase Ubiquitin Specific Protease 11 (USP11) in transcription regulation was further investigated. First, several USP11 interaction partners involved in transcriptional regulation in neuroblastoma cancer cells were identified. In particular, the transcription elongation factor A like 1 (TCEAL1) protein, which assists USP11 to engage protein-protein interactions in a MYCN-dependent manner, was characterized. The data clearly show that TCEAL1 acts as a pro-transcriptional factor for RNA polymerase II (RNAPII)-medi- ated transcription. In detail, TCEAL1 controls the transcription factor S-II (TFIIS), a factor that assists RNAPII to escape from paused sites. The findings claim that TCEAL1 outcompetes the transcription elongation factor TFIIS in a non-catalytic manner on chromatin of highly expressed genes. This is reasoned by the need regulating TFIIS function in transcription. TCEAL1 equili- brates excessive backtracking and premature termination of transcription caused by TFIIS. Collectively, the work shed light on the stoichiometric control of TFIIS demand in transcriptional regulation via the USP11-TCEAL1-USP7 complex. This complex protects RNAPII from TFIIS-mediated termination helping to regulate productive transcription of highly active genes in neuroblastoma.},
  subject      = {Transkription},
  language  = {en}
}
@phdthesis{Zhang2024,
  author    = {Zhang, Tengyu},
  title     = {Development of Modified polylysine based antibody conjugated nanoparticles with tumor-restricted, FcγR-independent stimulatory activity by targeting Fn14},
  doi       = {10.25972/OPUS-35865},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358650},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In this study, we developed an innovative nanoparticle formulation to facilitate the delivery of antitumor antibodies to tumor sites. The study commenced with the utilization of 13 bispecific antibody fusion proteins, which targeted the Fn14 receptor, thereby validating the pivotal role of crosslinking in Fn14 receptor activation. Subsequently, gold nanoparticles were activated using COOH-PEG-SH in combination with EDC/NHS, and subsequently conjugated with two Fn14-targeting antibodies, PDL192 and 5B6. Following this, a pH-sensitive shell was generated on the outer layer of the antibody-coupled gold nanoparticles through the application of chemically modified polylysine. The resultant complexes, termed MPL-antibody-AuNP, demonstrated a release profile reminiscent of the tumor microenvironment (TME). Notably, these complexes released antibody-AuNPs only in slightly acidic conditions while remaining intact in neutral or basic environments. Functionality analysis further affirmed the pH-sensitive property of MPL-antibody-AuNPs, demonstrating that the antibodies only initiated potent Fn14 activation in slightly acidic environments. This formulation holds potential for applicability to antibodies or ligands targeting the 80 TNFRSF family, given that gold nanoparticles successfully served as platforms for antibody crosslinking, thereby transforming these antibodies into potent agonists. Moreover, the TME disintegration profile of MPL mitigates the potential cytotoxic effects of antibodies, thereby circumventing associated adverse side effects. This study not only showcases the potential of nanoparticle formulations in targeted therapy, but also provides a solid foundation for further investigations on their clinical application in the context of targeting category II TNFRSF receptors with antibodies or ligands.},
  subject      = {Immuntherapie},
  language  = {en}
}
@phdthesis{Schwebs2024,
  author    = {Schwebs, Marie},
  title     = {Structure and dynamics of the plasma membrane: a single-molecule study in \(Trypanosoma\) \(brucei\)},
  doi       = {10.25972/OPUS-27569},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275699},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The unicellular, flagellated parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and nagana in livestock. In the last decades, it has become an established eukaryotic model organism in the field of biology, as well as in the interdisciplinary field of biophysics. For instance, the dense variant surface glycoprotein (VSG) coat offers the possibility to study the dynamics of GPI-anchored proteins in the plasma membrane of living cells. The fluidity of the VSG coat is not only an interesting object of study for its own sake, but is critically important for the survival of the parasite in the mammalian host. In order to maintain the integrity of the coat, the entire VSG coat is recycled within a few minutes. This is surprisingly fast for a purely diffusive process with the flagellar pocket (FP) as the sole site for endo- and exocytosis. Previous studies characterising VSG dynamics using FRAP reported diffusion coefficients that were not sufficient to to enable fast turnover based on passive VSG randomisation on the trypanosome surface. In this thesis, live-cell single-molecule fluorescence microscopy (SMFM) was employed to elucidate whether VSG diffusion coefficients were priorly underestimated or whether directed forces could be involved to bias VSGs towards the entrance of the FP. Embedding the highly motile trypanosomes in thermo-stable hydrogels facilitated the investigation of VSG dynamics on living trypanosomes at the mammalian host's temperature of 37°C. To allow for a spatial correlation of the VSG dynamics to the FP entrance, a cell line was employed harbouring a fluorescently labelled structure as a reference. Sequential two-colour SMFM was then established to allow for recording and registration of the dynamic and static single-molecule information. In order to characterise VSG dynamics, an algorithm to obtain reliable information from short trajectories was adapted (shortTrAn). It allowed for the quantification of the local dynamics in two distinct scenarios: diffusion and directed motion. The adaptation of the algorithm to the VSG data sets required the introduction of an additional projection filter. The algorithm was further extended to take into account the localisation errors inherent to single-particle tracking. The results of the quantification of diffusion and directed motion were presented in maps of the trypanosome surface, including an outline generated from a super-resolved static structure as a reference. Information on diffusion was displayed in one map, an ellipse plot. The colour code represented the local diffusion coefficient, while the shape of the ellipses provided an indication of the diffusion behaviour (aniso- or isotropic diffusion). The eccentricity of the ellipses was used to quantify deviations from isotropic diffusion. Information on directed motion was shown in three maps: A velocity map, representing the amplitude of the local velocities in a colour code. A quiver plot, illustrating the orientation of directed motion, and a third map which indicated the relative standard error of the local velocities colour-coded. Finally, a guideline based on random walk simulations was used to identify which of the two motion scenarios dominated locally. Application of the guideline to the VSG dynamics analysed by shortTrAn yielded supermaps that showed the locally dominant motion mode colour-coded. I found that VSG dynamics are dominated by diffusion, but several times faster than previously determined. The diffusion behaviour was additionally characterised by spatial heterogeneity. Moreover, isolated regions exhibiting the characteristics of round and elongated traps were observed on the cell surface. Additionally, VSG dynamics were studied with respect to the entrance of the FP. VSG dynamics in this region displayed similar characteristics compared to the remainder of the cell surface and forces biasing VSGs into the FP were not found. Furthermore, I investigated a potential interference of the attachment of the cytoskeleton to the plasma membrane with the dynamics of VSGs which are anchored to the outer leaflet of the membrane. Preliminary experiments were conducted on osmotically swollen trypanosomes and trypanosomes depleted for a microtubule-associated protein anchoring the subpellicular microtubule cytoskeleton to the plasma membrane. The measurements revealed a trend that detachment of the cytoskeleton could be associated with a reduction in the VSG diffusion coefficient and a loss of elongated traps. The latter could be an indication that these isolated regions were caused by underlying structures associated with the cytoskeleton. The measurements on cells with an intact cytoskeleton were complemented by random walk simulations of VSG dynamics with the newly determined diffusion coefficient on long time scales not accessible in experiments. Simulations showed that passive VSG randomisation is fast enough to allow for a turnover of the full VSG coat within a few minutes. According to an estimate based on the known rate of endocytosis and the newly determined VSG diffusion coefficient, the majority of exocytosed VSGs could escape from the FP to the cell surface without being immediately re-endocytosed.},
  subject      = {Trypanosoma brucei},
  language  = {en}
}
@article{PfisterSchwarzHolzmannetal.2023,
  author    = {Pfister, Roland and Schwarz, Katharina A. and Holzmann, Patricia and Reis, Moritz and Yogeeswaran, Kumar and Kunde, Wilfried},
  title     = {Headlines win elections: mere exposure to fictitious news media alters voting behavior},
  series = {PloS One},
  volume    = {18},
  journal   = {PloS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0289341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349845},
  year      = {2023},
  abstract  = {Repeatedly encountering a stimulus biases the observer's affective response and evaluation of the stimuli. Here we provide evidence for a causal link between mere exposure to fictitious news reports and subsequent voting behavior. In four pre-registered online experiments, participants browsed through newspaper webpages and were tacitly exposed to names of fictitious politicians. Exposure predicted voting behavior in a subsequent mock election, with a consistent preference for frequent over infrequent names, except when news items were decidedly negative. Follow-up analyses indicated that mere media presence fuels implicit personality theories regarding a candidate's vigor in political contexts. News outlets should therefore be mindful to cover political candidates as evenly as possible.},
  language  = {en}
}
@article{KollmannBuerkertMeiretal.2023,
  author    = {Kollmann, Catherine and Buerkert, Hannah and Meir, Michael and Richter, Konstantin and Kretzschmar, Kai and Flemming, Sven and Kelm, Matthias and Germer, Christoph-Thomas and Otto, Christoph and Burkard, Natalie and Schlegel, Nicolas},
  title     = {Human organoids are superior to cell culture models for intestinal barrier research},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {11},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2023.1223032},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357317},
  year      = {2023},
  abstract  = {Loss of intestinal epithelial barrier function is a hallmark in digestive tract inflammation. The detailed mechanisms remain unclear due to the lack of suitable cell-based models in barrier research. Here we performed a detailed functional characterization of human intestinal organoid cultures under different conditions with the aim to suggest an optimized ex-vivo model to further analyse inflammation-induced intestinal epithelial barrier dysfunction. Differentiated Caco2 cells as a traditional model for intestinal epithelial barrier research displayed mature barrier functions which were reduced after challenge with cytomix (TNFα, IFN-γ, IL-1ß) to mimic inflammatory conditions. Human intestinal organoids grown in culture medium were highly proliferative, displayed high levels of LGR5 with overall low rates of intercellular adhesion and immature barrier function resembling conditions usually found in intestinal crypts. WNT-depletion resulted in the differentiation of intestinal organoids with reduced LGR5 levels and upregulation of markers representing the presence of all cell types present along the crypt-villus axis. This was paralleled by barrier maturation with junctional proteins regularly distributed at the cell borders. Application of cytomix in immature human intestinal organoid cultures resulted in reduced barrier function that was accompanied with cell fragmentation, cell death and overall loss of junctional proteins, demonstrating a high susceptibility of the organoid culture to inflammatory stimuli. In differentiated organoid cultures, cytomix induced a hierarchical sequence of changes beginning with loss of cell adhesion, redistribution of junctional proteins from the cell border, protein degradation which was accompanied by loss of epithelial barrier function. Cell viability was observed to decrease with time but was preserved when initial barrier changes were evident. In summary, differentiated intestinal organoid cultures represent an optimized human ex-vivo model which allows a comprehensive reflection to the situation observed in patients with intestinal inflammation. Our data suggest a hierarchical sequence of inflammation-induced intestinal barrier dysfunction starting with loss of intercellular adhesion, followed by redistribution and loss of junctional proteins resulting in reduced barrier function with consecutive epithelial death.},
  language  = {en}
}
@article{KrauseHerbort2023,
  author    = {Krause, Lisa-Marie and Herbort, Oliver},
  title     = {Just visual context or part of the gesture? The role of arm orientation in bent pointing interpretation},
  series = {Acta Psychologica},
  volume    = {241},
  journal   = {Acta Psychologica},
  doi       = {10.1016/j.actpsy.2023.104062},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349839},
  year      = {2023},
  abstract  = {Pointing gestures can take on different shapes. For example, people often point with a bent wrist at a referent that is occluded by another object. We hypothesized that while the extrapolation of the index finger is the most important visual cue in such bent pointing gestures, arm orientation is affecting interpretations as well. We tested two competing hypotheses. First, the arm could be processed as a less reliable but additional direction cue also indicating the referent. Consequently, the index finger extrapolation would be biased towards the arm direction (assimilation effect). Second, the arm could be perceived as visual context of the index finger, leading to an interpretation that is repulsed from the arm direction (contrast effect). To differentiate between both, we conducted two experiments in which arm and finger orientation of a virtual pointer were independently manipulated. Participants were asked to determine the pointed-at location. As expected, participants based their interpretations on the extrapolation of the index finger. In line with the second hypothesis, the more the arm was oriented upwards, the lower the point was interpreted and vice versa. Thus, interpretation pattern indicated a contrast effect. Unexpectedly, gestures with aligned arm and index finger deviated from the general contrast effect and were interpreted linearly compared to bent gestures. In sum, the experiments show that interpretations of bent pointing gestures are not only based on the direction of the index finger but also depend on the arm orientation and its relationship to the index finger orientation.},
  language  = {en}
}
@article{WehrheimFaskowitzSpornsetal.2023,
  author    = {Wehrheim, Maren H. and Faskowitz, Joshua and Sporns, Olaf and Fiebach, Christian J. and Kaschube, Matthias and Hilger, Kirsten},
  title     = {Few temporally distributed brain connectivity states predict human cognitive abilities},
  series = {NeuroImage},
  volume    = {277},
  journal   = {NeuroImage},
  doi       = {10.1016/j.neuroimage.2023.120246},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349874},
  year      = {2023},
  abstract  = {Highlights • Brain connectivity states identified by cofluctuation strength. • CMEP as new method to robustly predict human traits from brain imaging data. • Network-identifying connectivity 'events' are not predictive of cognitive ability. • Sixteen temporally independent fMRI time frames allow for significant prediction. • Neuroimaging-based assessment of cognitive ability requires sufficient scan lengths. Abstract Human functional brain connectivity can be temporally decomposed into states of high and low cofluctuation, defined as coactivation of brain regions over time. Rare states of particularly high cofluctuation have been shown to reflect fundamentals of intrinsic functional network architecture and to be highly subject-specific. However, it is unclear whether such network-defining states also contribute to individual variations in cognitive abilities - which strongly rely on the interactions among distributed brain regions. By introducing CMEP, a new eigenvector-based prediction framework, we show that as few as 16 temporally separated time frames (< 1.5\% of 10 min resting-state fMRI) can significantly predict individual differences in intelligence (N = 263, p < .001). Against previous expectations, individual's network-defining time frames of particularly high cofluctuation do not predict intelligence. Multiple functional brain networks contribute to the prediction, and all results replicate in an independent sample (N = 831). Our results suggest that although fundamentals of person-specific functional connectomes can be derived from few time frames of highest connectivity, temporally distributed information is necessary to extract information about cognitive abilities. This information is not restricted to specific connectivity states, like network-defining high-cofluctuation states, but rather reflected across the entire length of the brain connectivity time series.},
  language  = {en}
}
@article{ZilligPauliWieseretal.2023,
  author    = {Zillig, Anna-Lena and Pauli, Paul and Wieser, Matthias and Reicherts, Philipp},
  title     = {Better safe than sorry? - On the influence of learned safety on pain perception},
  series = {PloS One},
  volume    = {18},
  journal   = {PloS One},
  number    = {11},
  doi       = {10.1371/journal.pone.0289047},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349905},
  year      = {2023},
  abstract  = {The experience of threat was found to result—mostly—in increased pain, however it is still unclear whether the exact opposite, namely the feeling of safety may lead to a reduction of pain. To test this hypothesis, we conducted two between-subject experiments (N = 94; N = 87), investigating whether learned safety relative to a neutral control condition can reduce pain, while threat should lead to increased pain compared to a neutral condition. Therefore, participants first underwent either threat or safety conditioning, before entering an identical test phase, where the previously conditioned threat or safety cue and a newly introduced visual cue were presented simultaneously with heat pain stimuli. Methodological changes were performed in experiment 2 to prevent safety extinction and to facilitate conditioning in the first place: We included additional verbal instructions, increased the maximum length of the ISI and raised CS-US contingency in the threat group from 50\% to 75\%. In addition to pain ratings and ratings of the visual cues (threat, safety, arousal, valence, and contingency), in both experiments, we collected heart rate and skin conductance. Analysis of the cue ratings during acquisition indicate successful threat and safety induction, however results of the test phase, when also heat pain was administered, demonstrate rapid safety extinction in both experiments. Results suggest rather small modulation of subjective and physiological pain responses following threat or safety cues relative to the neutral condition. However, exploratory analysis revealed reduced pain ratings in later trials of the experiment in the safety group compared to the threat group in both studies, suggesting different temporal dynamics for threat and safety learning and extinction, respectively. Perspective: The present results demonstrate the challenge to maintain safety in the presence of acute pain and suggest more research on the interaction of affective learning mechanism and pain processing.},
  language  = {en}
}
@article{GutzeitWellerMuthetal.2024,
  author    = {Gutzeit, Julian and Weller, Lisa and Muth, Felicitas and K{\"u}rten, Jens and Huestegge, Lynn},
  title     = {Eye did this! Sense of agency in eye movements},
  series = {Acta Psychologica},
  volume    = {243},
  journal   = {Acta Psychologica},
  doi       = {10.1016/j.actpsy.2023.104121},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349819},
  year      = {2024},
  abstract  = {This study investigates the sense of agency (SoA) for saccades with implicit and explicit agency measures. In two eye tracking experiments, participants moved their eyes towards on-screen stimuli that subsequently changed color. Participants then either reproduced the temporal interval between saccade and color-change (Experiment 1) or reported the time points of these events with an auditory Libet clock (Experiment 2) to measure temporal binding effects as implicit indices of SoA. Participants were either made to believe to exert control over the color change or not (agency manipulation). Explicit ratings indicated that the manipulation of causal beliefs and hence agency was successful. However, temporal binding was only evident for caused effects, and only when a sufficiently sensitive procedure was used (auditory Libet clock). This suggests a feebler connection between temporal binding and SoA than previously proposed. The results also provide evidence for a relatively fast acquisition of sense of agency for previously never experienced types of action-effect associations. This indicates that the underlying processes of action control may be rooted in more intricate and adaptable cognitive models than previously thought. Oculomotor SoA as addressed in the present study presumably represents an important cognitive foundation of gaze-based social interaction (social sense of agency) or gaze-based human-machine interaction scenarios. Public significance statement: In this study, sense of agency for eye movements in the non-social domain is investigated in detail, using both explicit and implicit measures. Therefore, it offers novel and specific insights into comprehending sense of agency concerning effects induced by eye movements, as well as broader insights into agency pertaining to entirely newly acquired types of action-effect associations. Oculomotor sense of agency presumably represents an important cognitive foundation of gaze-based social interaction (social agency) or gaze-based human-machine interaction scenarios. Due to peculiarities of the oculomotor domain such as the varying degree of volitional control, eye movements could provide new information regarding more general theories of sense of agency in future research.},
  language  = {en}
}
@article{StrobachKuertenHuestegge2023,
  author    = {Strobach, Tilo and K{\"u}rten, Jens and Huestegge, Lynn},
  title     = {Benefits of repeated alternations - task-specific vs. task-general sequential adjustments of dual-task order control},
  series = {Acta Psychologica},
  volume    = {236},
  journal   = {Acta Psychologica},
  doi       = {10.1016/j.actpsy.2023.103921},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349868},
  year      = {2023},
  abstract  = {An important cognitive requirement in multitasking is the decision of how multiple tasks should be temporally scheduled (task order control). Specifically, task order switches (vs. repetitions) yield performance costs (i.e., task-order switch costs), suggesting that task order scheduling is a vital part of configuring a task set. Recently, it has been shown that this process takes specific task-related characteristics into account: task order switches were easier when switching to a preferred (vs. non-preferred) task order. Here, we ask whether another determinant of task order control, namely the phenomenon that a task order switch in a previous trial facilitates a task order switch in a current trial (i.e., a sequential modulation of task order switch effect) also takes task-specific characteristics into account. Based on three experiments involving task order switches between a preferred (dominant oculomotor task prior to non-dominant manual/pedal task) and a non-preferred (vice versa) order, we replicated the finding that task order switching (in Trial N) is facilitated after a previous switch (vs. repetition in Trial N - 1) in task order. There was no substantial evidence in favor of a significant difference when switching to the preferred vs. non-preferred order and in the analyses of the dominant oculomotor task and the non-dominant manual task. This indicates different mechanisms underlying the control of immediate task order configuration (indexed by task order switch costs) and the sequential modulation of these costs based on the task order transition type in the previous trial.},
  language  = {en}
}
@article{HoppeKhanMeybohmetal.2023,
  author    = {Hoppe, K. and Khan, E. and Meybohm, P. and Riese, T.},
  title     = {Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?},
  series = {Critical Care},
  volume    = {27},
  journal   = {Critical Care},
  doi       = {10.1186/s13054-023-04375-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357181},
  year      = {2023},
  abstract  = {The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat < 30 cm H\(_2\)O), positive end expiratory pressure (PEEP > 5 cm H2O) and tidal volume (Vt of 6 ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.},
  language  = {en}
}
@article{MittermeierSeidelScheineretal.2024,
  author    = {Mittermeier, Sabrina and Seidel, Alexandra and Scheiner, Christin and Kleindienst, Nikolaus and Romanos, Marcel and Buerger, Arne},
  title     = {Emotional dysregulation and its pathways to suicidality in a community-based sample of adolescents},
  series = {Child and Adolescent Psychiatry and Mental Health},
  volume    = {18},
  journal   = {Child and Adolescent Psychiatry and Mental Health},
  issn      = {1753-2000},
  doi       = {10.1186/s13034-023-00699-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357501},
  year      = {2024},
  abstract  = {Objective Effective suicide prevention for adolescents is urgently needed but difficult, as suicide models lack a focus on age-specific influencing factors such as emotional dysregulation. Moreover, examined predictors often do not specifically consider the contribution to the severity of suicidality. To determine which adolescents are at high risk of more severe suicidality, we examined the association between emotional dysregulation and severity of suicidality directly as well as indirectly via depressiveness and nonsuicidal self-injury. Method Adolescents from 18 high schools in Bavaria were included in this cross-sectional and questionnaire-based study as part of a larger prevention study. Data were collected between November 2021 and March 2022 and were analyzed from January 2023 to April 2023. Students in the 6th or 7th grade of high school (11-14 years) were eligible to participate. A total of 2350 adolescents were surveyed and data from 2117 students were used for the analyses after excluding incomplete data sets. Our main outcome variable was severity of suicidality (Paykel Suicide Scale, PSS). Additionally, we assessed emotional dysregulation (Difficulties in Emotion Regulation Scale, DERS-SF), depressiveness (Patient Health Questionnaire, PHQ-9) and nonsuicidal self-injury (Deliberate Self-Harm Inventory, DSHI). Results In total, 2117 adolescents (51.6\% female; mean age, 12.31 years [standard deviation: 0.67]) were included in the structural equation model (SEM). Due to a clear gender-specific influence, the model was calculated separately for male and female adolescents. For male adolescents, there was a significant indirect association between emotional dysregulation and severity of suicidality, mediated by depressiveness (β = 0.15, SE = .03, p = .008). For female adolescents, there was a significant direct path from emotional dysregulation to severity of suicidality and also indirect paths via depressiveness (β = 0.12, SE = .05, p = 0.02) and NSSI (β = 0.18, SE = .04, p < .001). Conclusions Our results suggest that gender-related risk markers in 11-14-year-olds need to be included in future suicide models to increase their predictive power. According to our findings, early detection and prevention interventions based on emotion regulation skills might be enhanced by including gender-specific adjustments for the co-occurrence of emotional dysregulation, depressiveness, and nonsuicidal self-injury in girls and the co-occurrence of emotional dysregulation and depressiveness in boys.},
  language  = {en}
}
@article{HartmannsbergerScribaGuidolinetal.2024,
  author    = {Hartmannsberger, Beate and Scriba, Sabrina and Guidolin, Carolina and Becker, Juliane and Mehling, Katharina and Doppler, Kathrin and Sommer, Claudia and Rittner, Heike L.},
  title     = {Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome},
  series = {Journal of Neuroinflammation},
  volume    = {21},
  journal   = {Journal of Neuroinflammation},
  doi       = {10.1186/s12974-023-02969-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357164},
  year      = {2024},
  abstract  = {Background Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. Methods We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. Results Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. Conclusions Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.},
  language  = {en}
}
@article{GiansantiTheinertBoeingetal.2023,
  author    = {Giansanti, Manuela and Theinert, Tobias and Boeing, Sarah Katharina and Haas, Dorothee and Schlegel, Paul-Gerhardt and Vacca, Paola and Nazio, Francesca and Caruana, Ignazio},
  title     = {Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies},
  series = {Molecular Cancer},
  volume    = {22},
  journal   = {Molecular Cancer},
  doi       = {10.1186/s12943-023-01893-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357515},
  year      = {2023},
  abstract  = {Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.},
  language  = {en}
}
@article{BachfischerBarbosaRojasetal.,
  author    = {Bachfischer, Andreas and Barbosa, Martha Cecilia and Rojas, Angel Alberto Riveras and Bechler, Reinaldo and Schwienhorst-Stich, Eva-Maria and Kasang, Christa and Simmenroth, Anne and Parisi, Sandra},
  title     = {Implementing community based inclusive development for people with disability in Latin America: a mixed methods perspective on prioritized needs and lessons learned},
  series = {International Journal for Equity in Health},
  volume    = {22},
  journal   = {International Journal for Equity in Health},
  doi       = {10.1186/s12939-023-01966-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357261},
  abstract  = {Background Research on the needs of people with disability is scarce, which promotes inadequate programs. Community Based Inclusive Development interventions aim to promote rights but demand a high level of community participation. This study aimed to identify prioritized needs as well as lessons learned for successful project implementation in different Latin American communities. Methods This study was based on a Community Based Inclusive Development project conducted from 2018 to 2021 led by a Columbian team in Columbia, Brazil and Bolivia. Within a sequential mixed methods design, we first retrospectively analyzed the project baseline data and then conducted Focus Group Discussions, together with ratings of community participation levels. Quantitative descriptive and between group analysis of the baseline survey were used to identify and compare sociodemographic characteristics and prioritized needs of participating communities. We conducted qualitative thematic analysis on Focus Group Discussions, using deductive main categories for triangulation: 1) prioritized needs and 2) lessons learned, with subcategories project impact, facilitators, barriers and community participation. Community participation was assessed via spidergrams. Key findings were compared with triangulation protocols. Results A total of 348 people with disability from 6 urban settings participated in the baseline survey, with a mean age of 37.6 years (SD 23.8). Out of these, 18 participated within the four Focus Group Discussions. Less than half of the survey participants were able to read and calculate (42.0\%) and reported knowledge on health care routes (46.0\%). Unemployment (87.9\%) and inadequate housing (57.8\%) were other prioritized needs across countries. Focus Group Discussions revealed needs within health, education, livelihood, social and empowerment domains. Participants highlighted positive project impact in work inclusion, self-esteem and ability for self-advocacy. Facilitators included individual leadership, community networks and previous reputation of participating organizations. Barriers against successful project implementation were inadequate contextualization, lack of resources and on-site support, mostly due to the COVID-19 pandemic. The overall level of community participation was high (mean score 4.0/5) with lower levels in Brazil (3.8/5) and Bolivia (3.2/5). Conclusion People with disability still face significant needs. Community Based Inclusive Development can initiate positive changes, but adequate contextualization and on-site support should be assured.},
  language  = {en}
}
@article{AueEnglertHarreretal.2023,
  author    = {Aue, Annemarie and Englert, Nils and Harrer, Leon and Schwiering, Fabian and Gaab, Annika and K{\"o}nig, Peter and Adams, Ralf and Schmidtko, Achim and Friebe, Andreas and Groneberg, Dieter},
  title     = {NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis},
  series = {Respiratory Research},
  volume    = {24},
  journal   = {Respiratory Research},
  doi       = {10.1186/s12931-023-02479-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357805},
  year      = {2023},
  abstract  = {Background The origin of αSMA-positive myofibroblasts, key players within organ fibrosis, is still not fully elucidated. Pericytes have been discussed as myofibroblast progenitors in several organs including the lung. Methods Using tamoxifen-inducible PDGFRβ-tdTomato mice (PDGFRβ-CreERT2; R26tdTomato) lineage of lung pericytes was traced. To induce lung fibrosis, a single orotracheal dose of bleomycin was given. Lung tissue was investigated by immunofluorescence analyses, hydroxyproline collagen assay and RT-qPCR. Results Lineage tracing combined with immunofluorescence for nitric oxide-sensitive guanylyl cyclase (NO-GC) as marker for PDGFRβ-positive pericytes allows differentiating two types of αSMA-expressing myofibroblasts in murine pulmonary fibrosis: (1) interstitial myofibroblasts that localize in the alveolar wall, derive from PDGFRβ+ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRβ de novo after injury), are negative for NO-GC, have a large multipolar shape and appear to spread over several alveoli within the injured areas. Moreover, NO-GC expression is reduced during fibrosis, i.e., after pericyte-to-myofibroblast transition. Conclusion In summary, αSMA/PDGFRβ-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.},
  language  = {en}
}
@article{ZeinerSchroederMetzneretal.2023,
  author    = {Zeiner, Carsten and Schr{\"o}der, Malte and Metzner, Selina and Herrmann, Johannes and Notz, Quirin and Hottenrott, Sebastian and R{\"o}der, Daniel and Meybohm, Patrick and Lepper, Philipp M. and Lotz, Christopher},
  title     = {High-dose methylprednisolone pulse therapy during refractory COVID-19 acute respiratory distress syndrome: a retrospective observational study},
  series = {BMC Pulmonary Medicine},
  volume    = {23},
  journal   = {BMC Pulmonary Medicine},
  doi       = {10.1186/s12890-023-02664-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357231},
  year      = {2023},
  abstract  = {Background Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). Methods This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. Results Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54\%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65\%) survived to ICU discharge, including 13 out of 20 (65\%) needing ECMO support. Conclusions Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65\%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS.},
  language  = {en}
}
@article{BellingerWehrmannRohdeetal.2023,
  author    = {Bellinger, Daniel and Wehrmann, Kristin and Rohde, Anna and Schuppert, Maria and St{\"o}rk, Stefan and Flohr-Jost, Michael and Gall, Dominik and Pauli, Paul and Deckert, J{\"u}rgen and Herrmann, Martin J. and Erhardt-Lehmann, Angelika},
  title     = {The application of virtual reality exposure versus relaxation training in music performance anxiety: a randomized controlled study},
  series = {BMC Psychiatry},
  volume    = {23},
  journal   = {BMC Psychiatry},
  doi       = {10.1186/s12888-023-05040-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357833},
  year      = {2023},
  abstract  = {Background Performance anxiety is the most frequently reported anxiety disorder among professional musicians. Typical symptoms are - on a physical level - the consequences of an increase in sympathetic tone with cardiac stress, such as acceleration of heartbeat, increase in blood pressure, increased respiratory rate and tremor up to nausea or flush reactions. These symptoms can cause emotional distress, a reduced musical and artistical performance up to an impaired functioning. While anxiety disorders are preferably treated using cognitive-behavioral therapy with exposure, this approach is rather difficult for treating music performance anxiety since the presence of a public or professional jury is required and not easily available. The use of virtual reality (VR) could therefore display an alternative. So far, no therapy studies on music performance anxiety applying virtual reality exposure therapy have investigated the therapy outcome including cardiovascular changes as outcome parameters. Methods This mono-center, prospective, randomized and controlled clinical trial has a pre-post design with a follow-up period of 6 months. 46 professional and semi-professional musicians will be recruited and allocated randomly to an VR exposure group or a control group receiving progressive muscle relaxation training. Both groups will be treated over 4 single sessions. Music performance anxiety will be diagnosed based on a clinical interview using ICD-10 and DSM-5 criteria for specific phobia or social anxiety. A behavioral assessment test is conducted three times (pre, post, follow-up) in VR through an audition in a concert hall. Primary outcomes are the changes in music performance anxiety measured by the German B{\"u}hnenangstfragebogen and the cardiovascular reactivity reflected by heart rate variability (HRV). Secondary outcomes are changes in blood pressure, stress parameters such as cortisol in the blood and saliva, neuropeptides, and DNA-methylation. Discussion The trial investigates the effect of VR exposure in musicians with performance anxiety compared to a relaxation technique on anxiety symptoms and corresponding cardiovascular parameters. We expect a reduction of anxiety but also a consecutive improvement of HRV with cardiovascular protective effects. Trial registration This study was registered on clinicaltrials.gov. (ClinicalTrials.gov Number: NCT05735860)},
  language  = {en}
}
@article{McNeillRadtkeNieberleretal.2023,
  author    = {McNeill, Rhiannon V. and Radtke, Franziska and Nieberler, Matthias and Koreny, Carolin and Chiocchetti, Andreas G. and Kittel-Schneider, Sarah},
  title     = {Generation of four human induced pluripotent stem cells derived from ADHD patients carrying different genotypes for the risk SNP rs1397547 in the ADHD-associated gene ADGRL3},
  series = {Stem Cell Research},
  volume    = {67},
  journal   = {Stem Cell Research},
  doi       = {10.1016/j.scr.2023.103016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350099},
  year      = {2023},
  abstract  = {Single nucleotide polymorphisms (SNPs) in the ADGRL3 gene have been significantly associated with the development of ADHD, the aetiology of which remains poorly understood. The rs1397547 SNP has additionally been associated with significantly altered ADGRL3 transcription. We therefore generated iPSCs from two wild type ADHD patients, and two ADHD patients heterozygous for the risk SNP. With this resource we aim to facilitate further investigation into the complex and heterogenous pathology of ADHD. Furthermore, we demonstrate the feasibility of using magnetic activated cell sorting to allow the unbiased selection of fully reprogrammed iPSCs.},
  language  = {en}
}
@article{LisowskiHartrampfHasenaueretal.2023,
  author    = {Lisowski, Dominik and Hartrampf, Philipp E. and Hasenauer, Natalie and Nickl, Vera and Monoranu, Camelia-Maria and Tamihardja, J{\"o}rg},
  title     = {Complete loss of E-cadherin expression in a rare case of metastatic malignant meningioma: a case report},
  series = {BMC Neurology},
  volume    = {23},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-023-03450-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357996},
  year      = {2023},
  abstract  = {Background Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis. Case presentation We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment. Conclusions E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.},
  language  = {en}
}