@article{KuhtzSchneiderElHajjetal.2014,
  author    = {Kuhtz, Juliane and Schneider, Eberhard and El Hajj, Nady and Zimmermann, Lena and Fust, Olga and Linek, Bartosz and Seufert, Rudolf and Hahn, Thomas and Schorsch, Martin and Haaf, Thomas},
  title     = {Epigenetic heterogeneity of developmentally important genes in human sperm: Implications for assisted reproduction outcome},
  series = {Epigenetics},
  volume    = {9},
  journal   = {Epigenetics},
  number    = {12},
  doi       = {10.4161/15592294.2014.988063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150261},
  pages     = {1648-1658},
  year      = {2014},
  abstract  = {The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1\%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1\% GTL2 epimutations, whereas one (7\%) of 14 normozoospermic and 7 (50\%) of 14 OAT samples without pregnancy displayed 1-14\% GTL2 epimutations.},
  language  = {en}
}
@article{LapaReiterKircheretal.2016,
  author    = {Lapa, Constantin and Reiter, Theresa and Kircher, Malte and Schirbel, Andreas and Werner, Rudolf A. and Pelzer, Theo and Pizarro, Carmen and Skowasch, Dirk and Thomas, Lena and Schlesinger-Irsch, Ulrike and Thomas, Daniel and Bundschuh, Ralph A. and Bauer, Wolfgang R. and Gartner, Florian C.},
  title     = {Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175423},
  pages     = {77807-77814},
  year      = {2016},
  abstract  = {Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25\% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1\% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.},
  language  = {en}
}
@article{ManchiaAdliAkulaetal.2013,
  author    = {Manchia, Mirko and Adli, Mazda and Akula, Nirmala and Arda, Raffaella and Aubry, Jean-Michel and Backlund, Lena and Banzato, Claudio E. M. and Baune, Bernhard T. and Bellivier, Frank and Bengesser, Susanne and Biernacka, Joanna M. and Brichant-Petitjean, Clara and Bui, Elise and Calkin, Cynthia V. and Cheng, Andrew Tai Ann and Chillotti, Caterina and Cichon, Sven and Clark, Scott and Czerski, Piotr M. and Dantas, Clarissa and Del Zompo, Maria and DePaulo, J. Raymond and Detera-Wadleigh, Sevilla D. and Etain, Bruno and Falkai, Peter and Fris{\´e}n, Louise and Frye, Mark A. and Fullerton, Jan and Gard, S{\´e}bastien and Garnham, Julie and Goes, Fernando S. and Grof, Paul and Gruber, Oliver and Hashimoto, Ryota and Hauser, Joanna and Heilbronner, Urs and Hoban, Rebecca and Hou, Liping and Jamain, St{\´e}phane and Kahn, Jean-Pierre and Kassem, Layla and Kato, Tadafumi and Kelsoe, John R. and Kittel-Schneider, Sarah and Kliwicki, Sebastian and Kuo, Po-Hsiu and Kusumi, Ichiro and Laje, Gonzalo and Lavebratt, Catharina and Leboyer, Marion and Leckband, Susan G. and L{\´o}pez Jaramillo, Carlos A. and Maj, Mario and Malafosse, Alain and Martinsson, Lina and Masui, Takuya and Mitchell, Philip B. and Mondimore, Frank and Monteleone, Palmiero and Nallet, Audrey and Neuner, Maria and Nov{\´a}k, Tom{\´a}s and O'Donovan, Claire and {\"O}sby, Urban and Ozaki, Norio and Perlis, Roy H. and Pfennig, Andrea and Potash, James B. and Reich-Erkelenz, Daniela and Reif, Andreas and Reininghaus, Eva and Richardson, Sara and Rouleau, Guy A. and Rybakowski, Janusz K. and Schalling, Martin and Schofield, Peter R. and Schubert, Oliver K. and Schweizer, Barbara and Seem{\"u}ller, Florian and Grigoroiu-Serbanescu, Maria and Severino, Giovanni and Seymour, Lisa R. and Slaney, Claire and Smoller, Jordan W. and Squassina, Alessio and Stamm, Thomas and Steele, Jo and Stopkova, Pavla and Tighe, Sarah K. and Tortorella, Alfonso and Turecki, Gustavo and Wray, Naomi R. and Wright, Adam and Zandi, Peter P. and Zilles, David and Bauer, Michael and Rietschel, Marcella and McMahon, Francis J. and Schulze, Thomas G. and Alda, Martin},
  title     = {Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0065636},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130938},
  pages     = {e65636},
  year      = {2013},
  abstract  = {Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.},
  language  = {en}
}
@article{KlineLoessleinKurianetal.2022,
  author    = {Kline, Rachel A. and L{\"o}ßlein, Lena and Kurian, Dominic and Aguilar Mart{\´i}, Judit and Eaton, Samantha L. and Court, Felipe A. and Gillingwater, Thomas H. and Wishart, Thomas M.},
  title     = {An optimized comparative proteomic approach as a tool in neurodegenerative disease research},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {17},
  issn      = {2073-4409},
  doi       = {10.3390/cells11172653},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285912},
  year      = {2022},
  abstract  = {Recent advances in proteomic technologies now allow unparalleled assessment of the molecular composition of a wide range of sample types. However, the application of such technologies and techniques should not be undertaken lightly. Here, we describe why the design of a proteomics experiment itself is only the first step in yielding high-quality, translatable results. Indeed, the effectiveness and/or impact of the majority of contemporary proteomics screens are hindered not by commonly considered technical limitations such as low proteome coverage but rather by insufficient analyses. Proteomic experimentation requires a careful methodological selection to account for variables from sample collection, through to database searches for peptide identification to standardised post-mass spectrometry options directed analysis workflow, which should be adjusted for each study, from determining when and how to filter proteomic data to choosing holistic versus trend-wise analyses for biologically relevant patterns. Finally, we highlight and discuss the difficulties inherent in the modelling and study of the majority of progressive neurodegenerative conditions. We provide evidence (in the context of neurodegenerative research) for the benefit of undertaking a comparative approach through the application of the above considerations in the alignment of publicly available pre-existing data sets to identify potential novel regulators of neuronal stability.},
  language  = {en}
}
@article{BenkertDietzHartmannetal.2012,
  author    = {Benkert, Thomas F. and Dietz, Lena and Hartmann, Elena M. and Leich, Ellen and Rosenwald, Andreas and Serfling, Edgar and Buttmann, Mathias and Berberich-Siebelt, Friederike},
  title     = {Natalizumab Exerts Direct Signaling Capacity and Supports a Pro-Inflammatory Phenotype in Some Patients with Multiple Sclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77905},
  year      = {2012},
  abstract  = {Natalizumab is a recombinant monoclonal antibody raised against integrin alpha-4 (CD49d). It is approved for the treatment of patients with multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the CNS. While having shown high therapeutic efficacy, treatment by natalizumab has been linked to progressive multifocal leukoencephalopathy (PML) as a serious adverse effect. Furthermore, drug cessation sometimes induces rebound disease activity of unknown etiology. Here we investigated whether binding of this adhesion-blocking antibody to T lymphocytes could modulate their phenotype by direct induction of intracellular signaling events. Primary CD4+ T lymphocytes either from healthy donors and treated with natalizumab in vitro or from MS patients receiving their very first dose of natalizumab were analyzed. Natalizumab induced a mild upregulation of IL-2, IFN-c and IL-17 expression in activated primary human CD4+ T cells propagated ex vivo from healthy donors, consistent with a pro-inflammatory costimulatory effect on lymphokine expression. Along with this, natalizumab binding triggered rapid MAPK/ERK phosphorylation. Furthermore, it decreased CD49d surface expression on effector cells within a few hours. Sustained CD49d downregulation could be attributed to integrin internalization and degradation. Importantly, also CD4+ T cells from some MS patients receiving their very first dose of natalizumab produced more IL-2, IFN-c and IL-17 already 24 h after infusion. Together these data indicate that in addition to its adhesion-blocking mode of action natalizumab possesses mild direct signaling capacities, which can support a pro-inflammatory phenotype of peripheral blood T lymphocytes. This might explain why a rebound of disease activity or IRIS is observed in some MS patients after natalizumab cessation.},
  subject      = {Medizin},
  language  = {en}
}
@article{SchleicherArbetEngelsBaacketal.2019,
  author    = {Schleicher, Bernd and Arbet-Engels, Axel and Baack, Dominik and Balbo, Matteo and Biland, Adrian and Blank, Michael and Bretz, Thomas and Bruegge, Kai and Bulinski, Michael and Buss, Jens and Doerr, Manuel and Dorner, Daniela and Elsaesser, Dominik and Grischagin, Sergej and Hildebrand, Dorothee and Linhoff, Lena and Mannheim, Karl and Mueller, Sebastian Achim and Neise, Dominik and Neronov, Andrii and Noethe, Maximilian and Paravac, Aleksander and Rhode, Wolfgang and Schulz, Florian and Sedlaczek, Kevin and Shukla, Amit and Sliusar, Vitalii and Willert, Elan and Walter, Roland},
  title     = {Fractional Variability—A Tool to Study Blazar Variability},
  series = {Galaxies},
  volume    = {7},
  journal   = {Galaxies},
  number    = {2},
  issn      = {2075-4434},
  doi       = {10.3390/galaxies7020062},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197348},
  year      = {2019},
  abstract  = {Active Galactic Nuclei emit radiation over the whole electromagnetic spectrum up to TeV energies. Blazars are one subtype with their jets pointing towards the observer. One of their typical features is extreme variability on timescales, from minutes to years. The fractional variability is an often used parameter for investigating the degree of variability of a light curve. Different detection methods and sensitivities of the instruments result in differently binned data and light curves with gaps. As they can influence the physics interpretation of the broadband variability, the effects of these differences on the fractional variability need to be studied. In this paper, we study the systematic effects of completeness in time coverage and the sampling rate. Using public data from instruments monitoring blazars in various energy ranges, we study the variability of the bright TeV blazars Mrk 421 and Mrk 501 over the electromagnetic spectrum, taking into account the systematic effects, and compare our findings with previous results. Especially in the TeV range, the fractional variability is higher than in previous studies, which can be explained by the much longer (seven years compared to few weeks) and more complete data sample.},
  language  = {en}
}
@article{TemmeAdamAhnenetal.2017,
  author    = {Temme, Fabian and Adam, Jan and Ahnen, Max L. and Baack, Dominik and Balbo, Matteo and Bergmann, Matthias and Biland, Adrian and Blank, Michael and Bretz, Thomas and Br{\"u}gge, Kai A. and Buss, Jens and Dmytriiev, Anton and Dorner, Daniela and Einecke, Sabrina and Hempfling, Christina and Hildebrand, Dorothee and Hughes, Gareth and Linhoff, Lena and Mannheim, Karl and M{\"u}ller, Sebastian and Neise, Dominik and Neronov, Andrii and N{\"o}the, Max and Paravac, Aleksander and Pauss, Felicitas and Rhode, Wolfgang and Shukla, Amit and Thaele, Julia and Walter, Roland},
  title     = {Long-Term monitoring of bright blazars in the multi-GeV to TeV range with FACT},
  series = {Galaxies},
  volume    = {5},
  journal   = {Galaxies},
  number    = {1},
  publisher = {MDPI},
  issn      = {2075-4434},
  doi       = {10.3390/galaxies5010018},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198088},
  pages     = {18},
  year      = {2017},
  abstract  = {Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed.},
  language  = {en}
}
@article{HahnBeudertGutmannetal.2021,
  author    = {Hahn, Lukas and Beudert, Matthias and Gutmann, Marcus and Keßler, Larissa and Stahlhut, Philipp and Fischer, Lena and Karakaya, Emine and Lorson, Thomas and Thievessen, Ingo and Detsch, Rainer and L{\"u}hmann, Tessa and Luxenhofer, Robert},
  title     = {From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking},
  series = {Macromolecular Bioscience},
  volume    = {21},
  journal   = {Macromolecular Bioscience},
  number    = {10},
  doi       = {10.1002/mabi.202100122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257542},
  year      = {2021},
  abstract  = {Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.},
  language  = {en}
}
@article{WildeLiebLeichtetal.2021,
  author    = {Wilde, Anne-Christin Beatrice and Lieb, Charlotte and Leicht, Elise and Greverath, Lena Maria and Steinhagen, Lara Marleen and Wald de Chamorro, Nina and Petersen, J{\"o}rg and Hofmann, Wolf Peter and Hinrichsen, Holger and Heyne, Renate and Berg, Thomas and Naumann, Uwe and Schwenzer, Jeannette and Vermehren, Johannes and Geier, Andreas and Tacke, Frank and M{\"u}ller, Tobias},
  title     = {Real-world clinical management of patients with primary biliary cholangitis — a retrospective multicenter study from Germany},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10051061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234003},
  year      = {2021},
  abstract  = {Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3\% of patients, respectively. In 83.8\% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2\%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60\%, p = 0.005), Barcelona (13 vs. 34\%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75\%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74\%, p = 0.004; Barcelona: 50 vs. 84\%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86\%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.},
  language  = {en}
}
@article{SadovnickTraboulseeBernalesetal.2016,
  author    = {Sadovnick, A. Dessa and Traboulsee, Anthony L. and Bernales, Cecily Q. and Ross, Jay P. and Forwell, Amanda L. and Yee, Irene M. and Guillot-Noel, Lena and Fontaine, Bertrand and Cournu-Rebeix, Isabelle and Alcina, Antonio and Fedetz, Maria and Izquierdo, Guillermo and Matesanz, Fuencisla and Hilven, Kelly and Dubois, B{\´e}n{\´e}dicte and Goris, An and Astobiza, Ianire and Alloza, Iraide and Antig{\"u}edad, Alfredo and Vandenbroeck, Koen and Akkad, Denis A. and Aktas, Orhan and Blaschke, Paul and Buttmann, Mathias and Chan, Andrew and Epplen, Joerg T. and Gerdes, Lisa-Ann and Kroner, Antje and Kubisch, Christian and K{\"u}mpfel, Tania and Lohse, Peter and Rieckmann, Peter and Zettl, Uwe K. and Zipp, Frauke and Bertram, Lars and Lill, Christina M. and Fernandez, Oscar and Urbaneja, Patricia and Leyva, Laura and Alvarez-Cerme{\~n}o, Jose Carlos and Arroyo, Rafael and Garagorri, Aroa M. and Garc{\´i}a-Mart{\´i}nez, Angel and Villar, Luisa M. and Urcelay, Elena and Malhotra, Sunny and Montalban, Xavier and Comabella, Manuel and Berger, Thomas and Fazekas, Franz and Reindl, Markus and Schmied, Mascha C. and Zimprich, Alexander and Vilari{\~n}o-G{\"u}ell, Carles},
  title     = {Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients},
  series = {G3: Genes Genomes Genetics},
  volume    = {6},
  journal   = {G3: Genes Genomes Genetics},
  number    = {7},
  doi       = {10.1534/g3.116.030841},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165405},
  pages     = {2073-2079},
  year      = {2016},
  abstract  = {Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95\% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.},
  language  = {en}
}
@article{HerrmannMuellerOrthetal.2020,
  author    = {Herrmann, Andreas B. and M{\"u}ller, Martha-Lena and Orth, Martin F. and M{\"u}ller, J{\"o}rg P. and Zernecke, Alma and Hochhaus, Andreas and Ernst, Thomas and Butt, Elke and Frietsch, Jochen J.},
  title     = {Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance},
  series = {Journal of Cellular and Molecular Medicine},
  volume    = {24},
  journal   = {Journal of Cellular and Molecular Medicine},
  number    = {5},
  doi       = {10.1111/jcmm.14910},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214122},
  pages     = {2942 -- 2955},
  year      = {2020},
  abstract  = {Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR-ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR-ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1-mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell-mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.},
  language  = {en}
}
@article{SchmidFalterWeberetal.2017,
  author    = {Schmid, Tobias and Falter, Lena and Weber, Sabine and M{\"u}ller, Nils and Molitor, Konstantin and Zeller, David and Weber-Steffens, Dorothea and Hehlgans, Thomas and Wajant, Harald and Mostb{\"o}ck, Sven and M{\"a}nnel, Daniela N.},
  title     = {Chronic inflammation increases the sensitivity of mouse Treg for TNFR2 costimulation},
  series = {Frontiers in Immunology},
  volume    = {8},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2017.01471},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173259},
  year      = {2017},
  abstract  = {TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. \(In\) \(vitro\), TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported \(in\) \(vitro\) expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function. \(In\) \(vivo\) application of TNCscTNF80-induced mild myelopoiesis in na{\"i}ve mice without affecting the immune cell composition. Already a single application expanded Treg cells and improved suppression of CD4 T cells in mice with chronic inflammation. By contrast, multiple applications of the TNFR2 agonist were required to expand Treg cells in na{\"i}ve mice. Improved suppression of T cell proliferation depended on expression of TNFR2 by T cells in mice repeatedly treated with TNCscTNF80, without a major contribution of TNFR2 on myeloid cells. Thus, TNFR2 activation on T cells in na{\"i}ve mice can lead to immune suppression \(in\) \(vivo\). These findings support the important role of TNFR2 for Treg cells in immune regulation.},
  language  = {en}
}
@article{KuehnemundtLeifeldSchergetal.2021,
  author    = {K{\"u}hnemundt, Johanna and Leifeld, Heidi and Scherg, Florian and Schmitt, Matthias and Nelke, Lena C. and Schmitt, Tina and Bauer, Florentin and G{\"o}ttlich, Claudia and Fuchs, Maximilian and Kunz, Meik and Peindl, Matthias and Br{\"a}hler, Caroline and Kronenthaler, Corinna and Wischhusen, J{\"o}rg and Prelog, Martina and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun and Nietzer, Sarah L.},
  title     = {Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing},
  series = {ALTEX},
  volume    = {38},
  journal   = {ALTEX},
  doi       = {10.14573/altex.2008141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231465},
  pages     = {289-306},
  year      = {2021},
  abstract  = {High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.},
  language  = {en}
}
@article{NaglerNaegeleGillietal.2018,
  author    = {Nagler, Matthias and N{\"a}gele, Thomas and Gilli, Christian and Fragner, Lena and Korte, Arthur and Platzer, Alexander and Farlow, Ashley and Nordborg, Magnus and Weckwerth, Wolfram},
  title     = {Eco-Metabolomics and Metabolic Modeling: Making the Leap From Model Systems in the Lab to Native Populations in the Field},
  series = {Frontiers in Plant Science},
  volume    = {9},
  journal   = {Frontiers in Plant Science},
  number    = {1556},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2018.01556},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189560},
  year      = {2018},
  abstract  = {Experimental high-throughput analysis of molecular networks is a central approach to characterize the adaptation of plant metabolism to the environment. However, recent studies have demonstrated that it is hardly possible to predict in situ metabolic phenotypes from experiments under controlled conditions, such as growth chambers or greenhouses. This is particularly due to the high molecular variance of in situ samples induced by environmental fluctuations. An approach of functional metabolome interpretation of field samples would be desirable in order to be able to identify and trace back the impact of environmental changes on plant metabolism. To test the applicability of metabolomics studies for a characterization of plant populations in the field, we have identified and analyzed in situ samples of nearby grown natural populations of Arabidopsis thaliana in Austria. A. thaliana is the primary molecular biological model system in plant biology with one of the best functionally annotated genomes representing a reference system for all other plant genome projects. The genomes of these novel natural populations were sequenced and phylogenetically compared to a comprehensive genome database of A. thaliana ecotypes. Experimental results on primary and secondary metabolite profiling and genotypic variation were functionally integrated by a data mining strategy, which combines statistical output of metabolomics data with genome-derived biochemical pathway reconstruction and metabolic modeling. Correlations of biochemical model predictions and population-specific genetic variation indicated varying strategies of metabolic regulation on a population level which enabled the direct comparison, differentiation, and prediction of metabolic adaptation of the same species to different habitats. These differences were most pronounced at organic and amino acid metabolism as well as at the interface of primary and secondary metabolism and allowed for the direct classification of population-specific metabolic phenotypes within geographically contiguous sampling sites.},
  language  = {en}
}
@article{KoehlerReeseKastneretal.2022,
  author    = {K{\"o}hler, Franziska and Reese, Lena and Kastner, Carolin and Hendricks, Anne and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis},
  series = {Frontiers in Surgery},
  volume    = {9},
  journal   = {Frontiers in Surgery},
  issn      = {2296-875X},
  doi       = {10.3389/fsurg.2022.919744},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276943},
  year      = {2022},
  abstract  = {Introduction Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only.},
  language  = {en}
}
@article{LeverkusGustafssonLindenmayeretal.2020,
  author    = {Leverkus, Alexandro B and Gustafsson, Lena and Lindenmayer, David B and Castro, Jorge and Rey Benayas, Jos{\´e} Mar{\´i}a and Ranius, Thomas and Thorn, Simon},
  title     = {Salvage logging effects on regulating ecosystem services and fuel loads},
  series = {Frontiers in Ecology and the Environment},
  volume    = {18},
  journal   = {Frontiers in Ecology and the Environment},
  number    = {7},
  doi       = {10.1002/fee.2219},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216111},
  pages     = {391 -- 400},
  year      = {2020},
  abstract  = {Salvage logging, or logging after natural disturbances such as wildfires, insect outbreaks, and windstorms, is carried out to recover some of a forest's natural and/or economic capital. However, trade-offs between management objectives and a lack of consensus on the ecological consequences of salvage logging impair science-based decision making on the management of forests after natural disturbances. We conducted a global meta-analysis of the impacts of salvage logging on regulating ecosystem services and on fuel loads, as a frequent post-disturbance objective is preventing subsequent wildfires that could be fueled by the accumulation of dead trunks and branches. Salvage logging affected ecosystem services in a moderately negative way, regardless of disturbance type and severity, time elapsed since salvage logging, intensity of salvage logging, and the group of regulating ecosystem services being considered. However, prolonging the time between natural disturbance and salvage logging mitigated negative effects on regulating ecosystem services. Salvage logging had no overall effect on surface fuels; rather, different fuel types responded differently depending on the time elapsed since salvage logging. Delaying salvage logging by ~2-4 years may reduce negative ecological impacts without affecting surface fuel loads.},
  language  = {en}
}
@article{BeierleSchobelVogeletal.2021,
  author    = {Beierle, Felix and Schobel, Johannes and Vogel, Carsten and Allgaier, Johannes and Mulansky, Lena and Haug, Fabian and Haug, Julian and Schlee, Winfried and Holfelder, Marc and Stach, Michael and Schickler, Marc and Baumeister, Harald and Cohrdes, Caroline and Deckert, J{\"u}rgen and Deserno, Lorenz and Edler, Johanna-Sophie and Eichner, Felizitas A. and Greger, Helmut and Hein, Grit and Heuschmann, Peter and John, Dennis and Kestler, Hans A. and Krefting, Dagmar and Langguth, Berthold and Meybohm, Patrick and Probst, Thomas and Reichert, Manfred and Romanos, Marcel and St{\"o}rk, Stefan and Terhorst, Yannik and Weiß, Martin and Pryss, R{\"u}diger},
  title     = {Corona Health — A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {18},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {14},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph18147395},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242658},
  year      = {2021},
  abstract  = {Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.},
  language  = {en}
}
@article{KoehlerReeseHendricksetal.2022,
  author    = {K{\"o}hler, Franziska and Reese, Lena and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI)},
  series = {Langenbeck's Archives of Surgery},
  volume    = {407},
  journal   = {Langenbeck's Archives of Surgery},
  number    = {8},
  doi       = {10.1007/s00423-022-02639-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323919},
  pages     = {3615-3622},
  year      = {2022},
  abstract  = {Introduction Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1\% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. Methods Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum f{\"u}r Krebsregisterdaten—ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. Results A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07\% were female and 36.93\% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86\% of cases (n = 152). A total of 49.34\% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52\%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77\% vs. 73.27\%). Discussion In this study, we observed an incidence of LAMN in 0.13\% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.},
  language  = {en}
}