@article{OdorferHomolaReichetal.2019, author = {Odorfer, Thorsten M. and Homola, Gy{\"o}rgy A. and Reich, Martin M. and Volkmann, Jens and Zeller, Daniel}, title = {Increased finger-tapping related cerebellar activation in cervical dystonia, enhanced by transcranial stimulation: an indicator of compensation?}, series = {Frontiers in Neurology}, volume = {10}, journal = {Frontiers in Neurology}, number = {231}, issn = {1664-2295}, doi = {10.3389/fneur.2019.00231}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196249}, year = {2019}, abstract = {Background: Cervical dystonia is a movement disorder causing abnormal postures and movements of the head. While the exact pathophysiology of cervical dystonia has not yet been fully elucidated, a growing body of evidence points to the cerebellum as an important node. Methods: Here, we examined the impact of cerebellar interference by transcranial magnetic stimulation on finger-tapping related brain activation and neurophysiological measures of cortical excitability and inhibition in cervical dystonia and controls. Bilateral continuous theta-burst stimulation was used to modulate cerebellar cortical excitability in 16 patients and matched healthy controls. In a functional magnetic resonance imaging arm, data were acquired during simple finger tapping before and after cerebellar stimulation. In a neurophysiological arm, assessment comprised motor-evoked potentials amplitude and cortical silent period duration. Theta-burst stimulation over the dorsal premotor cortex and sham stimulation (neurophysiological arm only) served as control conditions. Results: At baseline, finger tapping was associated with increased activation in the ipsilateral cerebellum in patients compared to controls. Following cerebellar theta-burst stimulation, this pattern was even more pronounced, along with an additional movement-related activation in the contralateral somatosensory region and angular gyrus. Baseline motor-evoked potential amplitudes were higher and cortical silent period duration shorter in patients compared to controls. After cerebellar theta-burst stimulation, cortical silent period duration increased significantly in dystonia patients. Conclusion: We conclude that in cervical dystonia, finger movements—though clinically non-dystonic—are associated with increased activation of the lateral cerebellum, possibly pointing to general motor disorganization, which remains subclinical in most body regions. Enhancement of this activation together with an increase of silent period duration by cerebellar continuous theta-burst stimulation may indicate predominant disinhibitory effects on Purkinje cells, eventually resulting in an inhibition of cerebello-thalamocortical circuits.}, language = {en} } @article{RauchEndresFriedrichetal.2020, author = {Rauch, Florian and Endres, Peter and Friedrich, Alexandra and Sieh, Daniel and H{\"a}hnel, Martin and Krummenacher, Ivo and Braunschweig, Holger and Finze, Maik and Ji, Lei and Marder, Todd B.}, title = {An Iterative Divergent Approach to Conjugated Starburst Borane Dendrimers}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {57}, doi = {10.1002/chem.202001985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218345}, pages = {12951 -- 12963}, year = {2020}, abstract = {Using a new divergent approach, conjugated triarylborane dendrimers were synthesized up to the 2nd generation. The synthetic strategy consists of three steps: 1) functionalization, via iridium catalyzed C-H borylation; 2) activation, via fluorination of the generated boronate ester with K[HF\(_{2}\)] or [N(nBu\(_{4}\))][HF\(_{2}\)]; and 3) expansion, via reaction of the trifluoroborate salts with aryl Grignard reagents. The concept was also shown to be viable for a convergent approach. All but one of the conjugated borane dendrimers exhibit multiple, distinct and reversible reduction potentials, making them potentially interesting materials for applications in molecular accumulators. Based on their photophysical properties, the 1st generation dendrimers exhibit good conjugation over the whole system. However, the conjugation does not increase further upon expansion to the 2nd generation, but the molar extinction coefficients increase linearly with the number of triarylborane subunits, suggesting a potential application as photonic antennas.}, language = {en} } @article{SchieleZieglerKollertetal.2018, author = {Schiele, Miriam A. and Ziegler, Christiane and Kollert, Leonie and Katzorke, Andrea and Schartner, Christoph and Busch, Yasmin and Gromer, Daniel and Reif, Andreas and Pauli, Paul and Deckert, J{\"u}rgen and Herrmann, Martin J. and Domschke, Katharina}, title = {Plasticity of Functional MAOA Gene Methylation in Acrophobia}, series = {International Journal of Neuropsychopharmacology}, volume = {21}, journal = {International Journal of Neuropsychopharmacology}, number = {9}, doi = {10.1093/ijnp/pyy050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228571}, pages = {822-827}, year = {2018}, abstract = {Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.}, language = {en} } @article{DoghmanBouguerraFinettiDurandetal.2020, author = {Doghman-Bouguerra, Mabrouka and Finetti, Pascal and Durand, Nelly and Parise, Ivy Zort{\´e}a S. and Sbiera, Silviu and Cantini, Giulia and Canu, Letizia and Hescot, S{\´e}gol{\`e}ne and Figueiredo, Mirna M. O. and Komechen, Heloisa and Sbiera, Iuliu and Nesi, Gabriella and Paci, Angelo and Al Ghuzlan, Abir and Birnbaum, Daniel and Baudin, Eric and Luconi, Michaela and Fassnacht, Martin and Figueiredo, Bonald C. and Bertucci, Fran{\c{c}}ois and Lalli, Enzo}, title = {Cancer-testis antigen FATE1 expression in adrenocortical tumors is associated with a pervasive autoimmune response and is a marker of malignancy in adult, but not children, ACC}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {3}, issn = {2072-6694}, doi = {10.3390/cancers12030689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203211}, year = {2020}, abstract = {The SF-1 transcription factor target gene FATE1 encodes a cancer-testis antigen that has an important role in regulating apoptosis and response to chemotherapy in adrenocortical carcinoma (ACC) cells. Autoantibodies directed against FATE1 were previously detected in patients with hepatocellular carcinoma. In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.}, language = {en} } @article{SchischlevskijCordtsGuentheretal.2021, author = {Schischlevskij, Pavel and Cordts, Isabell and G{\"u}nther, Ren{\´e} and Stolte, Benjamin and Zeller, Daniel and Schr{\"o}ter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and Stendel, Claudia and M{\"u}schen, Lars H. and Osmanovic, Alma and Binz, Camilla and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia}, title = {Informal caregiving in amyotrophic lateral sclerosis (ALS): a high caregiver burden and drastic consequences on caregivers' lives}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {6}, issn = {2076-3425}, doi = {10.3390/brainsci11060748}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240981}, year = {2021}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients' informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients' functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King's Stages for ALS. The caregivers' burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers' burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients' functional status (r\(_p\) = -0.555, p < 0.001, n = 242). It was influenced by the CGs' own mental health issues due to caregiving (+11.36, 95\% CI [6.84; 15.87], p < 0.001), patients' wheelchair dependency (+9.30, 95\% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs' depression (r\(_p\) = 0.627, p < 0.001, n = 234), anxiety (r\(_p\) = 0.550, p < 0.001, n = 234), and poorer physical condition (r\(_p\) = -0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients' impairment in daily routine (r\(_s\) = -0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs' lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs' work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.}, language = {en} } @article{TucaBernardellideMattosFunketal.2022, author = {Tuca, Alexandru-Cristian and Bernardelli de Mattos, Ives and Funk, Martin and Winter, Raimund and Palackic, Alen and Groeber-Becker, Florian and Kruse, Daniel and Kukla, Fabian and Lemarchand, Thomas and Kamolz, Lars-Peter}, title = {Orchestrating the dermal/epidermal tissue ratio during wound healing by controlling the moisture content}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {6}, issn = {2227-9059}, doi = {10.3390/biomedicines10061286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275115}, year = {2022}, abstract = {A balanced and moist wound environment and surface increases the effect of various growth factors, cytokines, and chemokines, stimulating cell growth and wound healing. Considering this fact, we tested in vitro and in vivo water evaporation rates from the cellulose dressing epicite\(^{hydro}\) when combined with different secondary dressings as well as the resulting wound healing efficacy in a porcine donor site model. The aim of this study was to evaluate how the different rates of water evaporation affected wound healing efficacy. To this end, epicite\(^{hydro}\) primary dressing, in combination with different secondary dressing materials (cotton gauze, JELONET\(^◊\), AQUACEL\(^®\) Extra\(^™\), and OPSITE\(^◊\) Flexifix), was placed on 3 × 3 cm-sized dermatome wounds with a depth of 1.2 mm on the flanks of domestic pigs. The healing process was analyzed histologically and quantified by morphometry. High water evaporation rates by using the correct secondary dressing, such as cotton gauze, favored a better re-epithelialization in comparison with the low water evaporation resulting from an occlusive secondary dressing, which favored the formation of a new and intact dermal tissue that nearly fully replaced all the dermis that was removed during wounding. This newly available evidence may be of great benefit to clinical wound management.}, language = {en} } @article{VogelMarkertRueckertetal.2019, author = {Vogel, Patrick and Markert, Jonathan and R{\"u}ckert, Martin A. and Herz, Stefan and Keßler, Benedikt and Dremel, Kilian and Althoff, Daniel and Weber, Matthias and Buzug, Thorsten M. and Bley, Thorsten A. and Kullmann, Walter H. and Hanke, Randolf and Zabler, Simon and Behr, Volker C.}, title = {Magnetic Particle Imaging meets computed tomography: first simultaneous imaging}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-48960-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202501}, pages = {12627}, year = {2019}, abstract = {Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented.}, language = {en} } @article{KaiserAggensteinerHoltmannetal.2021, author = {Kaiser, Anna and Aggensteiner, Pascal-M. and Holtmann, Martin and Fallgatter, Andreas and Romanos, Marcel and Abenova, Karina and Alm, Barbara and Becker, Katja and D{\"o}pfner, Manfred and Ethofer, Thomas and Freitag, Christine M. and Geissler, Julia and Hebebrand, Johannes and Huss, Michael and Jans, Thomas and Jendreizik, Lea Teresa and Ketter, Johanna and Legenbauer, Tanja and Philipsen, Alexandra and Poustka, Luise and Renner, Tobias and Retz, Wolfgang and R{\"o}sler, Michael and Thome, Johannes and Uebel-von Sandersleben, Henrik and von Wirth, Elena and Zinnow, Toivo and Hohmann, Sarah and Millenet, Sabina and Holz, Nathalie E. and Banaschewski, Tobias and Brandeis, Daniel}, title = {EEG data quality: determinants and impact in a multicenter study of children, adolescents, and adults with attention-deficit/hyperactivity disorder (ADHD)}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {2}, issn = {2076-3425}, doi = {10.3390/brainsci11020214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228788}, year = {2021}, abstract = {Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (n\(_{total}\) = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.}, language = {en} } @article{GeisslerJansBanaschewskietal.2018, author = {Geissler, Julia and Jans, Thomas and Banaschewski, Tobias and Becker, Katja and Renner, Tobias and Brandeis, Daniel and D{\"o}pfner, Manfred and Dose, Christina and Hautmann, Christopher and Holtmann, Martin and Jenkner, Carolin and Millenet, Sabina and Romanos, Marcel}, title = {Individualised short-term therapy for adolescents impaired by attention-deficit/hyperactivity disorder despite previous routine care treatment (ESCAadol)-Study protocol of a randomised controlled trial within the consortium ESCAlife}, series = {Trials}, volume = {19}, journal = {Trials}, number = {254}, doi = {10.1186/s13063-018-2635-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176061}, year = {2018}, abstract = {Background: Despite the high persistence rate of attention-deficit/hyperactivity disorder (ADHD) throughout the lifespan, there is a considerable gap in knowledge regarding effective treatment strategies for adolescents with ADHD. This group in particular often shows substantial psychosocial impairment, low compliance and insufficient response to psychopharmacological interventions. Effective and feasible treatments should further consider the developmental shift in ADHD symptoms, comorbidity and psychosocial adversity as well as family dysfunction. Thus, individualised interventions for adolescent ADHD should comprise a multimodal treatment strategy. The randomised controlled ESCAadol study addresses the needs of this patient group and compares the outcome of short-term cognitive behavioural therapy with parent-based telephone-assisted self-help. Methods/design: In step 1, 160 adolescents aged 12 to 17 years with a diagnosis of ADHD will undergo a treatment as usual (TAU) observation phase of 1 month. In step 2, those still severely affected are randomised to the intervention group with an Individualised Modular Treatment Programme (IMTP) or a telephone-assisted self-help programme for parents (TASH) as an active control condition. The IMTP was specifically designed for the needs of adolescent ADHD. It comprises 10 sessions of individual cognitive behavioural therapy with the adolescents and/or the parents, for which participants choose three out of 10 available focus modules (e.g. organisational skills and planning, emotion regulation, problem solving and stress management, dysfunctional family communication). TASH combines a bibliotherapeutic component with 10 counselling sessions for the parents via telephone. Primary outcome is the change in ADHD symptoms in a clinician-rated diagnostic interview. Outcomes are assessed at inclusion into the study, after the TAU phase, after the intervention phase and after a further 12-week follow-up period. The primary statistical analysis will be by intention-to-treat, using linear regression models. Additionally, we will analyse psychometric and biological predictors and moderators of treatment response. Discussion: ESCAadol compares two short-term non-pharmacological interventions as cost-efficient and feasible treatment options for adolescent ADHD, addressing the specific needs and obstacles to treatment success in this group. We aim to contribute to personalised medicine for adolescent ADHD intended to be implemented in routine clinical care.}, language = {en} } @article{PeseschkianCordtsGuentheretal.2021, author = {Peseschkian, Tara and Cordts, Isabell and G{\"u}nther, Ren{\´e} and Stolte, Benjamin and Zeller, Daniel and Schr{\"o}ter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and B{\"u}chner, Boriana and Weiland, Ulrike and Sch{\"o}nfelder, Erik and Heinrich, Felix and Osmanovic, Alma and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia}, title = {A nation-wide, multi-center study on the quality of life of ALS patients in Germany}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {3}, issn = {2076-3425}, doi = {10.3390/brainsci11030372}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234147}, year = {2021}, abstract = {Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = -1.96 per increase of one point in the ALSFRS-R score, p < 0.001). "Limb-onset" ALS (lALS) was associated with a better QoL than "bulbar-onset" ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = -7.60, p = 0.001), being tracheostomized (β = -14.80, p = 0.004) and using non-invasive ventilation (β = -5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care.}, language = {en} } @article{VedderLensMartinetal.2022, author = {Vedder, Daniel and Lens, Luc and Martin, Claudia A. and Pellikka, Petri and Adhikari, Hari and Heiskanen, Janne and Engler, Jan O. and Sarmento Cabral, Juliano}, title = {Hybridization may aid evolutionary rescue of an endangered East African passerine}, series = {Evolutionary Applications}, volume = {15}, journal = {Evolutionary Applications}, number = {7}, doi = {10.1111/eva.13440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287264}, pages = {1177-1188}, year = {2022}, abstract = {Abstract Introgressive hybridization is a process that enables gene flow across species barriers through the backcrossing of hybrids into a parent population. This may make genetic material, potentially including relevant environmental adaptations, rapidly available in a gene pool. Consequently, it has been postulated to be an important mechanism for enabling evolutionary rescue, that is the recovery of threatened populations through rapid evolutionary adaptation to novel environments. However, predicting the likelihood of such evolutionary rescue for individual species remains challenging. Here, we use the example of Zosterops silvanus, an endangered East African highland bird species suffering from severe habitat loss and fragmentation, to investigate whether hybridization with its congener Zosterops flavilateralis might enable evolutionary rescue of its Taita Hills population. To do so, we employ an empirically parameterized individual-based model to simulate the species' behaviour, physiology and genetics. We test the population's response to different assumptions of mating behaviour and multiple scenarios of habitat change. We show that as long as hybridization does take place, evolutionary rescue of Z. silvanus is likely. Intermediate hybridization rates enable the greatest long-term population growth, due to trade-offs between adaptive and maladaptive introgressed alleles. Habitat change did not have a strong effect on population growth rates, as Z. silvanus is a strong disperser and landscape configuration is therefore not the limiting factor for hybridization. Our results show that targeted gene flow may be a promising avenue to help accelerate the adaptation of endangered species to novel environments, and demonstrate how to combine empirical research and mechanistic modelling to deliver species-specific predictions for conservation planning.}, language = {en} } @article{LopezKleinheinzAukemaetal.2019, author = {L{\´o}pez, Cristina and Kleinheinz, Kortine and Aukema, Sietse M. and Rohde, Marius and Bernhart, Stephan H. and H{\"u}bschmann, Daniel and Wagener, Rabea and Toprak, Umut H. and Raimondi, Francesco and Kreuz, Markus and Waszak, Sebastian M. and Huang, Zhiqin and Sieverling, Lina and Paramasivam, Nagarajan and Seufert, Julian and Sungalee, Stephanie and Russell, Robert B. and Bausinger, Julia and Kretzmer, Helene and Ammerpohl, Ole and Bergmann, Anke K. and Binder, Hans and Borkhardt, Arndt and Brors, Benedikt and Claviez, Alexander and Doose, Gero and Feuerbach, Lars and Haake, Andrea and Hansmann, Martin-Leo and Hoell, Jessica and Hummel, Michael and Korbel, Jan O. and Lawerenz, Chris and Lenze, Dido and Radlwimmer, Bernhard and Richter, Julia and Rosenstiel, Philip and Rosenwald, Andreas and Schilhabel, Markus B. and Stein, Harald and Stilgenbauer, Stephan and Stadler, Peter F. and Szczepanowski, Monika and Weniger, Marc A. and Zapatka, Marc and Eils, Roland and Lichter, Peter and Loeffler, Markus and M{\"o}ller, Peter and Tr{\"u}mper, Lorenz and Klapper, Wolfram and Hoffmann, Steve and K{\"u}ppers, Ralf and Burkhardt, Birgit and Schlesner, Matthias and Siebert, Reiner}, title = {Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, organization = {ICGC MMML-Seq Consortium}, doi = {10.1038/s41467-019-08578-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237281}, year = {2019}, abstract = {Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.}, language = {en} } @article{GodelPhamKeleetal.2019, author = {Godel, Tim and Pham, Mirko and Kele, Henrich and Kronlage, Moritz and Schwarz, Daniel and Brun{\´e}e, Merle and Heiland, Sabine and Bendszus, Martin and B{\"a}umer, Philipp}, title = {Diffusion tensor imaging in anterior interosseous nerve syndrome - functional MR Neurography on a fascicular level}, series = {NeuroImage: Clinical}, volume = {21}, journal = {NeuroImage: Clinical}, doi = {10.1016/j.nicl.2019.101659}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233061}, year = {2019}, abstract = {Purpose By applying diffusor tensor imaging (DTI) in patients with anterior interosseous nerve syndrome (AINS), this proof of principle study aims to quantify the extent of structural damage of a peripheral nerve at the anatomical level of individual fascicles. Methods In this institutional review board approved prospective study 13 patients with spontaneous AINS were examined at 3 Tesla including a transversal T2-weighted turbo-spin-echo and a spin-echo echo-planar-imaging pulse sequence of the upper arm level. Calculations of quantitative DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for median nerve lesion and non-lesion fascicles as well as ulnar and radial nerve were obtained. DTI values were compared to each other and to a previously published dataset of 58 healthy controls using one-way Analysis of Variance with Bonferroni correction and p-values <.05 were considered significant. Receiver operating characteristic (ROC) curves were performed to assess diagnostic accuracy. Results FA of median nerve lesion fascicles was decreased compared to median nerve non-lesion fascicles, ulnar nerve and radial nerve while MD, RD, and AD was increased (p < .001 for all parameters). Compared to median nerve values of healthy controls, lesion fascicles showed a significant decrease in FA while MD, RD, and AD was increased (p < .001 for all parameters). FA of median nerve non-lesion fascicles showed a weak significant decrease compared to healthy controls (p < .01) while there was no difference in MD, RD, and AD. ROC analyses revealed an excellent diagnostic accuracy of FA, MD and RD in the discrimination of median nerve lesion and non-lesion fascicles in AINS patients as well as in the discrimination of lesion fascicles and normative median nerve values of healthy controls. Conclusion By applying this functional MR Neurography technique in patients with AINS, this proof of principle study demonstrates that diffusion tensor imaging is feasible to quantify structural nerve injury at the anatomical level of individual fascicles.}, language = {en} } @article{LevitisGouldvan PraagGauetal.2021, author = {Levitis, Elizabeth and Gould van Praag, Cassandra D and Gau, R{\´e}mi and Heunis, Stephan and DuPre, Elizabeth and Kiar, Gregory and Bottenhorn, Katherine L and Glatard, Tristan and Nikolaidis, Aki and Whitaker, Kirstie Jane and Mancini, Matteo and Niso, Guiomar and Afyouni, Soroosh and Alonso-Ortiz, Eva and Appelhoff, Stefan and Arnatkeviciute, Aurina and Atay, Selim Melvin and Auer, Tibor and Baracchini, Giulia and Bayer, Johanna M M and Beauvais, Michael J S and Bijsterbosch, Janine D and Bilgin, Isil P and Bollmann, Saskia and Bollmann, Steffen and Botvinik-Nezer, Rotem and Bright, Molly G and Calhoun, Vince D and Chen, Xiao and Chopra, Sidhant and Chuan-Peng, Hu and Close, Thomas G and Cookson, Savannah L and Craddock, R Cameron and De La Vega, Alejandro and De Leener, Benjamin and Demeter, Damion V and Di Maio, Paola and Dickie, Erin W and Eickhoff, Simon B and Esteban, Oscar and Finc, Karolina and Frigo, Matteo and Ganesan, Saampras and Ganz, Melanie and Garner, Kelly G and Garza-Villarreal, Eduardo A and Gonzalez-Escamilla, Gabriel and Goswami, Rohit and Griffiths, John D and Grootswagers, Tijl and Guay, Samuel and Guest, Olivia and Handwerker, Daniel A and Herholz, Peer and Heuer, Katja and Huijser, Dorien C and Iacovella, Vittorio and Joseph, Michael J E and Karakuzu, Agah and Keator, David B and Kobeleva, Xenia and Kumar, Manoj and Laird, Angela R and Larson-Prior, Linda J and Lautarescu, Alexandra and Lazari, Alberto and Legarreta, Jon Haitz and Li, Xue-Ying and Lv, Jinglei and Mansour L., Sina and Meunier, David and Moraczewski, Dustin and Nandi, Tulika and Nastase, Samuel A and Nau, Matthias and Noble, Stephanie and Norgaard, Martin and Obungoloch, Johnes and Oostenveld, Robert and Orchard, Edwina R and Pinho, Ana Lu{\´i}sa and Poldrack, Russell A and Qiu, Anqi and Raamana, Pradeep Reddy and Rokem, Ariel and Rutherford, Saige and Sharan, Malvika and Shaw, Thomas B and Syeda, Warda T and Testerman, Meghan M and Toro, Roberto and Valk, Sofie L and Van Den Bossche, Sofie and Varoquaux, Ga{\"e}l and V{\´a}ša, František and Veldsman, Michele and Vohryzek, Jakub and Wagner, Adina S and Walsh, Reubs J and White, Tonya and Wong, Fu-Te and Xie, Xihe and Yan, Chao-Gan and Yang, Yu-Fang and Yee, Yohan and Zanitti, Gaston E and Van Gulick, Ana E and Duff, Eugene and Maumet, Camille}, title = {Centering inclusivity in the design of online conferences—An OHBM-Open Science perspective}, series = {GigaScience}, volume = {10}, journal = {GigaScience}, doi = {10.1093/gigascience/giab051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371574}, pages = {1-14}, year = {2021}, abstract = {As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.}, language = {en} } @article{LiangCostanzaPrutschetal.2021, author = {Liang, Huan-Chang and Costanza, Mariantonia and Prutsch, Nicole and Zimmerman, Mark W. and Gurnhofer, Elisabeth and Montes-Mojarro, Ivonne A. and Abraham, Brian J. and Prokoph, Nina and Stoiber, Stefan and Tangermann, Simone and Lobello, Cosimo and Oppelt, Jan and Anagnostopoulos, Ioannis and Hielscher, Thomas and Pervez, Shahid and Klapper, Wolfram and Zammarchi, Francesca and Silva, Daniel-Adriano and Garcia, K. Christopher and Baker, David and Janz, Martin and Schleussner, Nikolai and Fend, Falko and Posp{\´i}šilov{\´a}, Š{\´a}rka and Janikov{\´a}, Andrea and Wallwitz, Jacqueline and Stoiber, Dagmar and Simonitsch-Klupp, Ingrid and Cerroni, Lorenzo and Pileri, Stefano and de Leval, Laurence and Sibon, David and Fataccioli, Virginie and Gaulard, Philippe and Assaf, Chalid and Kn{\"o}rr, Fabian and Damm-Welk, Christine and Woessmann, Wilhelm and Turner, Suzanne D. and Look, A. Thomas and Mathas, Stephan and Kenner, Lukas and Merkel, Olaf}, title = {Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-25379-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371581}, year = {2021}, abstract = {Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and BATF3 is recruited to IL2R regulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patients is linked to more aggressive clinical presentation. Finally, an IL-2Rα-targeting antibody-drug conjugate efficiently kills ALCL cells in vitro and in vivo. Our results highlight the importance of the BATF3/IL-2R-module for ALCL biology and identify IL-2Rα-targeting as a promising treatment strategy for ALCL.}, language = {en} } @article{LeProvostThieleWestphaletal.2021, author = {Le Provost, Ga{\"e}tane and Thiele, Jan and Westphal, Catrin and Penone, Caterina and Allan, Eric and Neyret, Margot and van der Plas, Fons and Ayasse, Manfred and Bardgett, Richard D. and Birkhofer, Klaus and Boch, Steffen and Bonkowski, Michael and Buscot, Francois and Feldhaar, Heike and Gaulton, Rachel and Goldmann, Kezia and Gossner, Martin M. and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Renner, Swen and Scherreiks, Pascal and Sikorski, Johannes and Baulechner, Dennis and Bl{\"u}thgen, Nico and Bolliger, Ralph and B{\"o}rschig, Carmen and Busch, Verena and Chist{\´e}, Melanie and Fiore-Donno, Anna Maria and Fischer, Markus and Arndt, Hartmut and Hoelzel, Norbert and John, Katharina and Jung, Kirsten and Lange, Markus and Marzini, Carlo and Overmann, J{\"o}rg and Paŝalić, Esther and Perović, David J. and Prati, Daniel and Sch{\"a}fer, Deborah and Sch{\"o}ning, Ingo and Schrumpf, Marion and Sonnemann, Ilja and Steffan-Dewenter, Ingolf and Tschapka, Marco and T{\"u}rke, Manfred and Vogt, Juliane and Wehner, Katja and Weiner, Christiane and Weisser, Wolfgang and Wells, Konstans and Werner, Michael and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Zaitsev, Andrey S. and Manning, Peter}, title = {Contrasting responses of above- and belowground diversity to multiple components of land-use intensity}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23931-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371552}, year = {2021}, abstract = {Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.}, language = {en} } @article{MarcuBichmannKuchenbeckeretal.2021, author = {Marcu, Ana and Bichmann, Leon and Kuchenbecker, Leon and Kowalewski, Daniel Johannes and Freudenmann, Lena Katharina and Backert, Linus and M{\"u}hlenbruch, Lena and Szolek, Andr{\´a}s and L{\"u}bke, Maren and Wagner, Philipp and Engler, Tobias and Matovina, Sabine and Wang, Jian and Hauri-Hohl, Mathias and Martin, Roland and Kapolou, Konstantina and Walz, Juliane Sarah and Velz, Julia and Moch, Holger and Regli, Luca and Silginer, Manuela and Weller, Michael and L{\"o}ffler, Markus W. and Erhard, Florian and Schlosser, Andreas and Kohlbacher, Oliver and Stevanović, Stefan and Rammensee, Hans-Georg and Neidert, Marian Christoph}, title = {HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy}, series = {Journal for ImmunoTherapy of Cancer}, volume = {9}, journal = {Journal for ImmunoTherapy of Cancer}, doi = {10.1136/jitc-2020-002071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370160}, year = {2021}, abstract = {Background The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. Methods Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. Results The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. Conclusion Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org .}, language = {en} }