@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{RauschenbergerSchmittAzeemetal.2019,
  author    = {Rauschenberger, Tabea and Schmitt, Viola and Azeem, Muhammad and Klein-Hessling, Stefan and Murti, Krisna and Gr{\"a}n, Franziska and Goebeler, Matthias and Kerstan, Andreas and Klein, Matthias and Bopp, Tobias and Serfling, Edgar and Muhammad, Khalid},
  title     = {T cells control chemokine secretion by keratinocytes},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {1917},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2019.01917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195695},
  year      = {2019},
  abstract  = {The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible "defense genes" in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.},
  language  = {en}
}
@article{RechHueberFinzeletal.2016,
  author    = {Rech, Juergen and Hueber, Axel J. and Finzel, Stephanie and Englbrecht, Matthias and Haschka, Judith and Manger, Bernhard and Kleyer, Arnd and Reiser, Michaela and Cobra, Jayme Fogagnolo and Figueiredo, Camille and Tony, Hans-Peter and Kleinert, Stefan and Wendler, Joerg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hanns-Martin and Nuesslein, Hubert and Alten, Rieke and Henes, Joerg and Krueger, Klaus and Schett, Georg},
  title     = {Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment},
  series = {Annals of the Rheumatic Diseases},
  volume    = {75},
  journal   = {Annals of the Rheumatic Diseases},
  number    = {9},
  doi       = {10.1136/annrheumdis-2015-207900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187519},
  pages     = {1637-1644},
  year      = {2016},
  abstract  = {Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33\% of patients with RA overall. Twice as many patients who relapsed (58\%) had moderate/high MBDA compared with patients who remained in remission (21\%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13\%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3\%) and MBDA-ACPA+ (31.8\%) and high in patients who were MBDA+/ACPA+ (76.4\%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80\% of the patients. Trial registration number EudraCT 2009-015740-42.},
  language  = {en}
}
@article{GabelPickemScheidereretal.2022,
  author    = {Gabel, Judith and Pickem, Matthias and Scheiderer, Philipp and Dudy, Lenart and Leikert, Berengar and Fuchs, Marius and St{\"u}binger, Martin and Schmitt, Matthias and K{\"u}spert, Julia and Sangiovanni, Giorgio and Tomczak, Jan M. and Held, Karsten and Lee, Tien-Lin and Claessen, Ralph and Sing, Michael},
  title     = {Toward Functionalized Ultrathin Oxide Films: The Impact of Surface Apical Oxygen},
  series = {Advanced Electronic Materials},
  volume    = {8},
  journal   = {Advanced Electronic Materials},
  number    = {4},
  issn      = {2199-160X},
  doi       = {10.1002/aelm.202101006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318914},
  year      = {2022},
  abstract  = {Thin films of transition metal oxides open up a gateway to nanoscale electronic devices beyond silicon characterized by novel electronic functionalities. While such films are commonly prepared in an oxygen atmosphere, they are typically considered to be ideally terminated with the stoichiometric composition. Using the prototypical correlated metal SrVO\(_{3}\) as an example, it is demonstrated that this idealized description overlooks an essential ingredient: oxygen adsorbing at the surface apical sites. The oxygen adatoms, which are present even if the films are kept in an ultrahigh vacuum environment and not explicitly exposed to air, are shown to severely affect the intrinsic electronic structure of a transition metal oxide film. Their presence leads to the formation of an electronically dead surface layer but also alters the band filling and the electron correlations in the thin films. These findings highlight that it is important to take into account surface apical oxygen or—mutatis mutandis—the specific oxygen configuration imposed by a capping layer to predict the behavior of ultrathin films of transition metal oxides near the single unit-cell limit.},
  language  = {en}
}
@article{SchilbachAlkhaledWelkeretal.2015,
  author    = {Schilbach, Karin and Alkhaled, Mohammed and Welker, Christian and Eckert, Franziska and Blank, Gregor and Ziegler, Hendrik and Sterk, Marco and M{\"u}ller, Friederike and Sonntag, Katja and Wieder, Thomas and Braum{\"u}ller, Heidi and Schmitt, Julia and Eyrich, Matthias and Schleicher, Sabine and Seitz, Christian and Erbacher, Annika and Pichler, Bernd J. and M{\"u}ller, Hartmut and Tighe, Robert and Lim, Annick and Gillies, Stephen D. and Strittmatter, Wolfgang and R{\"o}cken, Martin and Handgretinger, Rupert},
  title     = {Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation},
  series = {OncoImmunology},
  volume    = {4},
  journal   = {OncoImmunology},
  number    = {7},
  doi       = {10.1080/2162402X.2015.1014760},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154579},
  pages     = {e1014760},
  year      = {2015},
  abstract  = {Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.},
  language  = {en}
}
@article{EliasHeuschmannSchmittetal.2013,
  author    = {Elias, Johannes and Heuschmann, Peter U. and Schmitt, Corinna and Eckhardt, Frithjof and Boehm, Hartmut and Maier, Sebastian and Kolb-M{\"a}urer, Annette and Riedmiller, Hubertus and M{\"u}llges, Wolfgang and Weisser, Christoph and Wunder, Christian and Frosch, Matthias and Vogel, Ulrich},
  title     = {Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus},
  series = {BMC Infectious Diseases},
  journal   = {BMC Infectious Diseases},
  doi       = {10.1186/1471-2334-13-111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96091},
  year      = {2013},
  abstract  = {Background Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. Methods Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton \& Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. Results Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8\% and 54.0\% in derivation and internal validation corhorts with prevalences of 2.3\% and 1.7\%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66\%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with "A" or "J" were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test's expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. Conclusions Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test's expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.},
  language  = {en}
}
@phdthesis{Schmitt2022,
  author    = {Schmitt, Matthias},
  title     = {High Energy Spin- and Momentum-Resolved Photoelectron Spectroscopy of Complex Oxides},
  doi       = {10.25972/OPUS-26475},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264757},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Spin- and \(k\)-resolved hard X-ray photoelectron spectroscopy (HAXPES) is a powerful tool to probe bulk electronic properties of complex metal oxides. Due to the low efficiency of common spin detectors of about \(10^{-4}\), such experiments have been rarely performed within the hard X-ray regime since the notoriously low photoionization cross sections further lower the performance tremendously. This thesis is about a new type of spin detector, which employs an imaging spin-filter with multichannel electron recording. This increases the efficiency by a factor of \(10^4\) and makes spin- and \(k\)-resolved photoemission at high excitation energies possible. Two different technical approaches were pursued in this thesis: One using a hemispherical deflection analyzer (HDA) and a separate external spin detector chamber, the other one resorting to a momentum- or \(k\)-space microscope with time-of-flight (TOF) energy recording and an integrated spin-filter crystal. The latter exhibits significantly higher count rates and - since it was designed for this purpose from scratch - the integrated spin-filter option found out to be more viable than the subsequent upgrade of an existing setup with an HDA. This instrumental development is followed by the investigation of the complex metal oxides (CMOs) KTaO\(_3\) by angle-resolved HAXPES (HARPES) and Fe\(_3\)O\(_4\) by spin-resolved HAXPES (spin-HAXPES), respectively. KTaO\(_3\) (KTO) is a band insulator with a valence-electron configuration of Ta 5\(d^0\). By angle- and spin-integrated HAXPES it is shown that at the buried interface of LaAlO\(_3\)/KTO - by the generation of oxygen vacancies and hence effective electron doping - a conducting electron system forms in KTO. Further investigations using the momentum-resolution of the \(k\)-space TOF microscope show that these states are confined to the surface in KTO and intensity is only obtained from the center or the Gamma-point of each Brillouin zone (BZ). These BZs are furthermore square-like arranged reflecting the three-dimensional cubic crystal structure of KTO. However, from a comparison to calculations it is found that the band structure deviates from that of electron-doped bulk KTaO\(_3\) due to the confinement to the interface. There is broad consensus that Fe\(_3\)O\(_4\) is a promising material for spintronics applications due to its high degree of spin polarization at the Fermi level. However, previous attempts to measure the spin polarization by spin-resolved photoemission spectroscopy have been hampered by the use of low photon energies resulting in high surface sensitivity. The surfaces of magnetite, though, tend to reconstruct due to their polar nature, and thus their magnetic and electronic properties may strongly deviate from each other and from the bulk, dependent on their orientation and specific preparation. In this work, the intrinsic bulk spin polarization of magnetite at the Fermi level (\(E_F\)) by spin-resolved photoelectron spectroscopy, is determined by spin-HAXPES on (111)-oriented thin films, epitaxially grown on ZnO(0001) to be \(P(E_F) = -80^{+10}_{-20}\) \%.},
  subject      = {Elektronenkorrelation},
  language  = {en}
}
@article{WeiderWegenerSchmittetal.2015,
  author    = {Weider, Matthias and Wegener, Am{\´e}lie and Schmitt, Christian and K{\"u}spert, Melanie and Hillg{\"a}rtner, Simone and B{\"o}sl, Michael R. and Hermans-Borgmeyer, Irm and Nait-Oumesmar, Brahim and Wegner, Michael},
  title     = {Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells},
  series = {PLoS Genetics},
  volume    = {11},
  journal   = {PLoS Genetics},
  number    = {2},
  doi       = {10.1371/journal.pgen.1005008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144123},
  pages     = {e1005008},
  year      = {2015},
  abstract  = {Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.},
  language  = {en}
}
@article{CzyschMedina‐MontanoZhongetal.2022,
  author    = {Czysch, Christian and Medina-Montano, Carolina and Zhong, Zifu and Fuchs, Alexander and Stickdorn, Judith and Winterwerber, Pia and Schmitt, Sascha and Deswarte, Kim and Raabe, Marco and Scherger, Maximilian and Combes, Francis and De Vrieze, Jana and Kasmi, Sabah and Sandners, Niek N. and Lienenklaus, Stefan and Koynov, Kaloian and R{\"a}der, Hans-Joachim and Lambrecht, Bart N. and David, Sunil A. and Bros, Matthias and Schild, Hansj{\"o}rg and Grabbe, Stephan and De Geest, Bruno G. and Nuhn, Lutz},
  title     = {Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels},
  series = {Advanced Functional Materials},
  volume    = {32},
  journal   = {Advanced Functional Materials},
  number    = {35},
  doi       = {10.1002/adfm.202203490},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287255},
  year      = {2022},
  abstract  = {The development of controlled biodegradable materials is of fundamental importance in immunodrug delivery to spatiotemporally controlled immune stimulation but avoid systemic inflammatory side effects. Based on this, polycarbonate nanogels are developed as degradable micellar carriers for transient immunoactivation of lymph nodes. An imidazoquinoline-type TLR7/8 agonist is covalently conjugated via reactive ester chemistry to these nanocarriers. The nanogels not only provide access to complete disintegration by the hydrolysable polymer backbone, but also demonstrate a gradual disintegration within several days at physiological conditions (PBS, pH 6.4-7.4, 37 °C). These intrinsic properties limit the lifetime of the carriers but their payload can still be successfully leveraged for immunological studies in vitro on primary immune cells as well as in vivo. For the latter, a spatiotemporal control of immune cell activation in the draining lymph node is found after subcutaneous injection. Overall, these features render polycarbonate nanogels a promising delivery system for transient activation of the immune system in lymph nodes and may consequently become very attractive for further development toward vaccination or cancer immunotherapy. Due to the intrinsic biodegradability combined with the high chemical control during the manufacturing process, these polycarbonate-based nanogels may also be of great importance for clinical translation.},
  language  = {en}
}
@article{HellmannLotherWursteretal.2017,
  author    = {Hellmann, Anna-Maria and Lother, Jasmin and Wurster, Sebastian and Lutz, Manfred B. and Schmitt, Anna Lena and Morton, Charles Oliver and Eyrich, Matthias and Czakai, Kristin and Einsele, Hermann and Loeffler, Juergen},
  title     = {Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus},
  series = {Frontiers in Immunology},
  volume    = {8},
  journal   = {Frontiers in Immunology},
  number    = {1716},
  doi       = {10.3389/fimmu.2017.01716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169926},
  year      = {2017},
  abstract  = {Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host-pathogen interaction studies.},
  language  = {en}
}
@article{GrunzGietzenLuetkensetal.2020,
  author    = {Grunz, Jan-Peter and Gietzen, Carsten Herbert and Luetkens, Karsten and Wagner, Matthias and Kalb, Karlheinz and Bley, Thorsten Alexander and Lehmkul, Luka and van Schoonhoven, J{\"o}rg and Gassenmaier, Tobias and Schmitt, Rainer},
  title     = {The importance of radial multiplanar reconstructions for assessment of triangular fibrocartilage complex injury in CT arthrography of the wrist},
  series = {BMC Musculoskeletal Disorders},
  volume    = {21},
  journal   = {BMC Musculoskeletal Disorders},
  doi       = {10.1186/s12891-020-03321-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236075},
  year      = {2020},
  abstract  = {Background: Triangular fibrocartilage complex (TFCC) lesions commonly cause ulnar-sided wrist pain and instability of the distal radioulnar joint. Due to its triangular shape, discontinuity of the TFCC is oftentimes difficult to visualize in radiological standard planes. Radial multiplanar reconstructions (MPR) may have the potential to simplify diagnosis in CT wrist arthrography. The objective of this study was to assess diagnostic advantages provided by radial MPR over standard planes for TFCC lesions in CT arthrography. Methods: One hundred six patients (49 women, 57 men; mean age 44.2 ± 15.8 years) underwent CT imaging after wrist arthrography. Two radiologists (R1, R2) retrospectively analyzed three randomized datasets for each CT arthrography. One set contained axial, coronal and sagittal planes (MPR\(_{Standard}\)), while the other two included an additional radial reconstruction with the rotating center either atop the ulnar styloid (MPR\(_{Styloid}\)) or in the ulnar fovea (MPR\(_{Fovea}\)). Readers evaluated TFCC differentiability and condition. Suspected lesions were categorized using Palmer's and Atzei's classification and diagnostic confidence was stated on a fivepoint Likert scale. Results: Compared to standard planes, differentiability of the superficial and deep TFCC layer was superior in radial reconstructions (R1/R2; MPR\(_{Fovea}\): p < 0.001; MPRStyloid: p ≤ 0.007). Palmer and Atzei lesions were present in 86.8\% (92/106) and 52.8\% (56/106) of patients, respectively. Specificity, sensitivity and accuracy for central Palmer lesions did not differ in radial and standard MPR. For peripheral Atzei lesions, sensitivity (MPR\(_{Standard}\) 78.6\%/80.4\%, MPR\(_{Styloid}\) 94.6\%/94.6\%, MPR\(_{Fovea}\) 91.1\%/89.3\%) and accuracy (MPR\(_{Standard}\) 86.8\%/86.8\%, MPR\(_{Styloid}\) 96.2\%/96.2\%, MPR\(_{Fovea}\) 94.3\%/93.4\%) improved with additional styloid-centered (p = 0.004/0.008) and foveacentered (p = 0.039/0.125) reconstructions. No substantial difference was observed between both radial MPR (p = 0.688/0.250). Interrater agreement was almost perfect for each dataset (κ\(_{Standard}\) = 0.876, κ\(_{Styloid}\) = 0.894, κ\(_{Fovea}\) = 0.949). Diagnostic confidence increased with addition of either radial MPR (p < 0.001). Conclusions: Ancillary radial planes improve accuracy and diagnostic confidence for detection of peripheral TFCC lesions in CT arthrography of the wrist.},
  language  = {en}
}
@article{PeindlGoettlichCrouchetal.2022,
  author    = {Peindl, Matthias and G{\"o}ttlich, Claudia and Crouch, Samantha and Hoff, Niklas and L{\"u}ttgens, Tamara and Schmitt, Franziska and Pereira, Jes{\´u}s Guillermo Nieves and May, Celina and Schliermann, Anna and Kronenthaler, Corinna and Cheufou, Danjouma and Reu-Hofer, Simone and Rosenwald, Andreas and Weigl, Elena and Walles, Thorsten and Sch{\"u}ler, Julia and Dandekar, Thomas and Nietzer, Sarah and Dandekar, Gudrun},
  title     = {EMT, stemness, and drug resistance in biological context: a 3D tumor tissue/in silico platform for analysis of combinatorial treatment in NSCLC with aggressive KRAS-biomarker signatures},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14092176},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270744},
  year      = {2022},
  abstract  = {Epithelial-to-mesenchymal transition (EMT) is discussed to be centrally involved in invasion, stemness, and drug resistance. Experimental models to evaluate this process in its biological complexity are limited. To shed light on EMT impact and test drug response more reliably, we use a lung tumor test system based on a decellularized intestinal matrix showing more in vivo-like proliferation levels and enhanced expression of clinical markers and carcinogenesis-related genes. In our models, we found evidence for a correlation of EMT with drug resistance in primary and secondary resistant cells harboring KRAS\(^{G12C}\) or EGFR mutations, which was simulated in silico based on an optimized signaling network topology. Notably, drug resistance did not correlate with EMT status in KRAS-mutated patient-derived xenograft (PDX) cell lines, and drug efficacy was not affected by EMT induction via TGF-β. To investigate further determinants of drug response, we tested several drugs in combination with a KRAS\(^{G12C}\) inhibitor in KRAS\(^{G12C}\) mutant HCC44 models, which, besides EMT, display mutations in P53, LKB1, KEAP1, and high c-MYC expression. We identified an aurora-kinase A (AURKA) inhibitor as the most promising candidate. In our network, AURKA is a centrally linked hub to EMT, proliferation, apoptosis, LKB1, and c-MYC. This exemplifies our systemic analysis approach for clinical translation of biomarker signatures.},
  language  = {en}
}
@article{SchmittMeybohmNeefetal.2022,
  author    = {Schmitt, Elke and Meybohm, Patrick and Neef, Vanessa and Baumgarten, Peter and Bayer, Alexandra and Choorapoikayil, Suma and Friederich, Patrick and Friedrich, Jens and Geisen, Christof and G{\"u}resir, Erdem and Gr{\"u}newald, Matthias and Gutjahr, Martin and Helmer, Philipp and Herrmann, Eva and M{\"u}ller, Markus and Narita, Diana and Raadts, Ansgar and Schwendner, Klaus and Seifried, Erhard and Stark, Patrick and Steinbicker, Andrea U. and Thoma, Josef and Velten, Markus and Weigt, Henry and Wiesenack, Christoph and Wittmann, Maria and Zacharowski, Kai and Piekarski, Florian},
  title     = {Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage - a multicentre subanalysis of the German PBM Network Registry},
  series = {Acta Neurochirurgica},
  volume    = {164},
  journal   = {Acta Neurochirurgica},
  organization    = {German PBM Network Collaborators},
  doi       = {10.1007/s00701-022-05144-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346754},
  pages     = {985-999},
  year      = {2022},
  abstract  = {Purpose Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. Methods This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Results A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3\% in aSAH and 40.9\% in ICH. RBC transfusion rates were 29.9\% in aSAH and 29.3\% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. Conclusions Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH.},
  language  = {en}
}
@article{CurtazReifschlaegerStraehleetal.2022,
  author    = {Curtaz, Carolin J. and Reifschl{\"a}ger, Leonie and Str{\"a}hle, Linus and Feldheim, Jonas and Feldheim, Julia J. and Schmitt, Constanze and Kiesel, Matthias and Herbert, Saskia-Laureen and W{\"o}ckel, Achim and Meybohm, Patrick and Burek, Malgorzata},
  title     = {Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073683},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284476},
  year      = {2022},
  abstract  = {Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.},
  language  = {en}
}
@article{StephanTascilarYalcinMutluetal.2023,
  author    = {Stephan, Marlene and Tascilar, Koray and Yalcin-Mutlu, Melek and Hagen, Melanie and Haschka, Judith and Reiser, Michaela and Hartmann, Fabian and Kleyer, Arnd and Hueber, Axel J. and Manger, Bernhard and Figueiredo, Camille and Cobra, Jayme Fogagnolo and Tony, Hans-Peter and Finzel, Stephanie and Kleinert, Stefan and Wendler, J{\"o}rg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hannes Martin and N{\"u}sslein, Hubert and Alten, Rieke and Henes, Joerg and Kr{\"u}ger, Klaus and Schett, Georg and Rech, J{\"u}rgen},
  title     = {Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {11},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12113723},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319349},
  year      = {2023},
  abstract  = {Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50\% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.},
  language  = {en}
}