@article{SchwarzmeierLeehrBoehnleinetal.2020, author = {Schwarzmeier, Hanna and Leehr, Elisabeth Johanna and B{\"o}hnlein, Joscha and Seeger, Fabian Reinhard and Roesmann, Kati and Gathmann, Bettina and Herrmann, Martin J. and Siminski, Niklas and Jungh{\"o}fer, Markus and Straube, Thomas and Grotegerd, Dominik and Dannlowski, Udo}, title = {Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross-validation machine learning approach}, series = {International Journal of Methods in Psychiatric Research}, volume = {29}, journal = {International Journal of Methods in Psychiatric Research}, number = {2}, doi = {10.1002/mpr.1812}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213430}, year = {2020}, abstract = {Objectives Embedded in the Collaborative Research Center "Fear, Anxiety, Anxiety Disorders" (CRC-TRR58), this bicentric clinical study aims at identifying biobehavioral markers of treatment (non-)response by applying machine learning methodology with an external cross-validation protocol. We hypothesize that a priori prediction of treatment (non-)response is possible in a second, independent sample based on multimodal markers. Methods One-session virtual reality exposure treatment (VRET) with patients with spider phobia was conducted on two sites. Clinical, neuroimaging, and genetic data were assessed at baseline, post-treatment and after 6 months. The primary and secondary outcomes defining treatment response are as follows: 30\% reduction regarding the individual score in the Spider Phobia Questionnaire and 50\% reduction regarding the individual distance in the behavioral avoidance test. Results N = 204 patients have been included (n = 100 in W{\"u}rzburg, n = 104 in M{\"u}nster). Sample characteristics for both sites are comparable. Discussion This study will offer cross-validated theranostic markers for predicting the individual success of exposure-based therapy. Findings will support clinical decision-making on personalized therapy, bridge the gap between basic and clinical research, and bring stratified therapy into reach. The study is registered at ClinicalTrials.gov (ID: NCT03208400).}, language = {en} } @article{Gottschlich2020, author = {Gottschlich, G{\"u}nter}, title = {Synopse der f{\"u}r Deutschland nachgewiesenen Arten und Unterarten der Gattung Hieracium s. l. (Hieracium s. str. und Pilosella), aufgeschl{\"u}sselt nach Vorkommen in den einzelnen Bundesl{\"a}ndern}, series = {Forum geobotanicum}, volume = {9}, journal = {Forum geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2020.0114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198175}, pages = {1-59}, year = {2020}, abstract = {Eine Liste der 205 Arten und 1561 Unterarten der Gattung Hieracium s. l. , die in Deutschland, aufgeschl{\"u}sselt nach Bundesl{\"a}ndern vorkommen, wird vorgestellt. Da die meisten infraspezifischen Namen unter Hieracium publiziert wurden und um die Zahl der invaliden Namen unter Pilosella in der Liste zu minimieren, wird auf eine Aufteilung in Hieracium und Pilosella verzichtet. Durch Farbmarkierungen wird gekennzeichnet, welche Unterart urspr{\"u}nglich aus einem Bundesland beschrieben wurde bzw. ob ein Syntypus aus einem Bundesland stammt.}, subject = {Habichtskraut}, language = {de} } @article{Dunkel2020, author = {Dunkel, Franz G.}, title = {Ranunculus sarntheinianus Dunkel, spec. nova, eine neue Art aus dem Ranunculus-auricomus-Komplex - seit 135 Jahren im Oberen Inntal bei Innsbruck}, series = {Forum geobotanicum}, volume = {9}, journal = {Forum geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2020.0115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198183}, pages = {60-65}, year = {2020}, abstract = {F{\"u}r das Vorkommen einer Ranunculus auricomus-Sippe im Oberen Inntal bei Innnsbuck, Nordtirol, {\"O}sterreich, existieren belegte Nachweise seit 135 Jahren. Diese Sippe sammelte L. Sarnthein am 08.06.1884, J. Murr 1887 bei Flaurling. Von beiden Aufsammlungen befinden sich Belege im Tiroler Landesmuseum (Herbarium Ferdinandeum Innsbruck; IBF). Trotz Trockenlegung der Sumpfwiesen und Eutrophierung des Biotops kommt die Art noch aktuell in einem kleinen Nasswiesenrest vor. Sie wird hier als R. sarntheinianus Dunkel beschrieben, abgebildet und ihre Taxonomie wird diskutiert. Der mutmaßlich letzte Wuchsort ist vom Aussterben bedroht. Eine graphische Darstellung soll bei Artbestimmung und Auffinden neuer Wuchsorte behilflich sein.}, subject = {Hahnenfuß}, language = {de} } @article{DrenckhahnWeber2020, author = {Drenckhahn, Detlev and Weber, Heinrich E.}, title = {Die Nordfriesische Brombeere, Rubus boreofrisicus Drenckhahn \& H. E. Weber, eine endemische Rubus-Art der Westk{\"u}ste von Schleswig-Holstein, Deutschland}, series = {Forum geobotanicum}, volume = {9}, journal = {Forum geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2020.0116}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198194}, pages = {66-69}, year = {2020}, abstract = {Rubus boreofrisicus Drenckhahn \& H. E.Weber ist eine bisher unbeschriebene Rubus-Art der Untergattung Rubus, Serie Discolores. Die Endbl{\"a}ttchen der 5-z{\"a}hligen, handf{\"o}rmigen Sch{\"o}sslingsbl{\"a}tter sind breit eif{\"o}rmig bis ann{\"a}hernd rund, unterseits grau-weißlich, oberseits dunkelgr{\"u}n und schwach behaart. Die Sch{\"o}sslinge sind braunrot, kantig bis schwach gefurcht, etwas behaart mit geraden bis schwach gekr{\"u}mmten, 5-8 mm langen, braunroten Stacheln mit heller Spitzenh{\"a}lfte. Die Bl{\"u}tenstiele besitzen Stieldr{\"u}sen. Rubus boreofrisicus kommt h{\"a}ufig im Waldg{\"u}rtel und in der angrenzenden D{\"u}nenheide der nordfriesischen Insel Amrum vor und ist auch 50 km s{\"u}dlich von Amrum in St. Peter-Ording im Westen der Halbinsel Eiderstedt vertreten.}, subject = {Rubus}, language = {de} } @article{Gallo2020, author = {Gallo, Lorenzo}, title = {Nomenclatural adjustments and typifications in the genus Phedimus (Crassulaceae)}, series = {Forum Geobotanicum}, volume = {9}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2020.0616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206347}, pages = {70-73}, year = {2020}, abstract = {This paper deals with the taxonomical position and the nomenclature of two taxa belonging to the genus Sedum (Crassulaceae), today treated as Phedimus, namely Sedum middendorffianum Maxim var. diffusum Praeger and Sedum oppositifolium Sims. The correct taxonomical application of names is based on the nomenclatural types designated here.}, subject = {Sedum oppositifolium}, language = {en} } @article{OroujiPeitschOroujietal.2020, author = {Orouji, Elias and Peitsch, Wiebke K. and Orouji, Azadeh and Houben, Roland and Utikal, Jochen}, title = {Unique role of histone methyltransferase PRDM8 in the tumorigenesis of virus-negative Merkel cell carcinoma}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers12041057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203815}, year = {2020}, abstract = {Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80\% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.}, language = {en} } @article{EbnerOstheimerSautermeister2020, author = {Ebner, Katharina and Ostheimer, Jochen and Sautermeister, Jochen}, title = {The role of religious beliefs for the acceptance of xenotransplantation. Exploring dimensions of xenotransplantation in the field of hospital chaplaincy}, series = {Xenotransplantation}, volume = {27}, journal = {Xenotransplantation}, number = {4}, doi = {10.1111/xen.12579}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214114}, year = {2020}, abstract = {Background The Changsha Communiqu{\´e} (2008) calls for a greater account to be taken of the ethical aspects of xenotransplantation as well as of public perception. This also applies to the field of hospital chaplaincy. So far, there has been no empirical exploration of the assessment and acceptance of xenotransplantation by pastoral workers in German-speaking countries. In view of the prospect of clinical trials, in-depth research is both sensible and necessary, since both xeno- and allotransplantation can have far-reaching consequences for patients, their relatives, and the social environment. In addition to the tasks of health monitoring, questions of the individual handling with and integration of a xenotransplant must also be considered. They can affect one's own identity and self-image and thus also affect religious dimensions. Hence, they make a comprehensive range of accompaniment necessary. Methods This paper presents the first explorative results of a Dialogue Board with Christian, Jewish, and Muslim hospital chaplains. It explores pastoral challenges of xenotransplantation for the German-speaking countries, in particular (a) self-image and tasks of hospital pastoral care, (b) religious aspects of transplantation, and (c) religious aspects of xenotransplantation as anticipated by the hospital pastors. Results Depending on their religious background, hospital chaplains see different pastoral challenges when xenotransplantation reaches clinical stage. In particular, the effects on the identity and religious self-image of those affected must be taken into account. Three desiderata or recommendations for action emerged from the Dialogue Board: (a) initial, advanced and further training for hospital pastoral workers, (b) contact points for patients, and (c) interreligious cooperation and a joint statement. All participants of the Dialogue Board emphasized the chances of xenotransplantation and expressed their hope that xenogenic transplants could save patients or improve the quality of their life substantially. Conclusions Xenotransplantation can affect the identity work of patients and relatives also in religious terms. In order to provide better pastoral and psychosocial support for these persons within the framework of the hospital, it is important to reflect on such challenges at an early stage and to develop concepts for pastoral further training and pastoral care in xenotransplantation.}, language = {en} } @article{RonaldHoebartner2020, author = {Ronald, Micura and H{\"o}bartner, Claudia}, title = {Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes}, series = {Chemical Society Reviews}, journal = {Chemical Society Reviews}, edition = {Advance Article}, doi = {10.1039/D0CS00617C}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212133}, year = {2020}, abstract = {This review aims at juxtaposing common versus distinct structural and functional strategies that are applied by aptamers, riboswitches, and ribozymes/DNAzymes. Focusing on recently discovered systems, we begin our analysis with small-molecule binding aptamers, with emphasis on in vitro-selected fluorogenic RNA aptamers and their different modes of ligand binding and fluorescence activation. Fundamental insights are much needed to advance RNA imaging probes for detection of exo- and endogenous RNA and for RNA process tracking. Secondly, we discuss the latest gene expression-regulating mRNA riboswitches that respond to the alarmone ppGpp, to PRPP, to NAD+, to adenosine and cytidine diphosphates, and to precursors of thiamine biosynthesis (HMP-PP), and we outline new subclasses of SAM and tetrahydrofolate-binding RNA regulators. Many riboswitches bind protein enzyme cofactors that, in principle, can catalyse a chemical reaction. For RNA, however, only one system (glmS ribozyme) has been identified in Nature thus far that utilizes a small molecule - glucosamine-6-phosphate - to participate directly in reaction catalysis (phosphodiester cleavage). We wonder why that is the case and what is to be done to reveal such likely existing cellular activities that could be more diverse than currently imagined. Thirdly, this brings us to the four latest small nucleolytic ribozymes termed twister, twister-sister, pistol, and hatchet as well as to in vitro selected DNA and RNA enzymes that promote new chemistry, mainly by exploiting their ability for RNA labelling and nucleoside modification recognition. Enormous progress in understanding the strategies of nucleic acids catalysts has been made by providing thorough structural fundaments (e.g. first structure of a DNAzyme, structures of ribozyme transition state mimics) in combination with functional assays and atomic mutagenesis.}, language = {en} } @article{KrebsSolimandoKalogirouetal.2020, author = {Krebs, Markus and Solimando, Antonio Giovanni and Kalogirou, Charis and Marquardt, Andr{\´e} and Frank, Torsten and Sokolakis, Ioannis and Hatzichristodoulou, Georgios and Kneitz, Susanne and Bargou, Ralf and K{\"u}bler, Hubert and Schilling, Bastian and Spahn, Martin and Kneitz, Burkhard}, title = {miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {3}, issn = {2077-0383}, doi = {10.3390/jcm9030670}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203168}, year = {2020}, abstract = {Downregulation of miR-221-3p expression in prostate cancer (PCa) predicted overall and cancer-specific survival of high-risk PCa patients. Apart from PCa, miR-221-3p expression levels predicted a response to tyrosine kinase inhibitors (TKI) in clear cell renal cell carcinoma (ccRCC) patients. Since this role of miR-221-3p was explained with a specific targeting of VEGFR2, we examined whether miR-221-3p regulated VEGFR2 in PCa. First, we confirmed VEGFR2/KDR as a target gene of miR-221-3p in PCa cells by applying Luciferase reporter assays and Western blotting experiments. Although VEGFR2 was mainly downregulated in the PCa cohort of the TCGA (The Cancer Genome Atlas) database, VEGFR2 was upregulated in our high-risk PCa cohort (n = 142) and predicted clinical progression. In vitro miR-221-3p acted as an escape mechanism from TKI in PC3 cells, as displayed by proliferation and apoptosis assays. Moreover, we confirmed that Sunitinib induced an interferon-related gene signature in PC3 cells by analyzing external microarray data and by demonstrating a significant upregulation of miR-221-3p/miR-222-3p after Sunitinib exposure. Our findings bear a clinical perspective for high-risk PCa patients with low miR-221-3p levels since this could predict a favorable TKI response. Apart from this therapeutic niche, we identified a partially oncogenic function of miR-221-3p as an escape mechanism from VEGFR2 inhibition.}, language = {en} } @article{MezaChinchaLindnerSchindleretal.2020, author = {Meza-Chincha, Ana-Lucia and Lindner, Joachim O. and Schindler, Dorothee and Schmidt, David and Krause, Ana-Maria and R{\"o}hr, Merle I. S. and Mitrić, Roland and W{\"u}rthner, Frank}, title = {Impact of substituents on molecular properties and catalytic activities of trinuclear Ru macrocycles in water oxidation}, issn = {2041-6539}, doi = {10.1039/d0sc01097a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204653}, year = {2020}, abstract = {Herein we report a broad series of new trinuclear supramolecular Ru(bda) macrocycles bearing different substituents at the axial or equatorial ligands which enabled investigation of substituent effects on the catalytic activities in chemical and photocatalytic water oxidation. Our detailed investigations revealed that the activities of these functionalized macrocycles in water oxidation are significantly affected by the position at which the substituents were introduced. Interestingly, this effect could not be explained based on the redox properties of the catalysts since these are not markedly influenced by the functionalization of the ligands. Instead, detailed investigations by X-ray crystal structure analysis and theoretical simulations showed that conformational changes imparted by the substituents are responsible for the variation of catalytic activities of the Ru macrocycles. For the first time, macrocyclic structure of this class of water oxidation catalysts is unequivocally confirmed and experimental indication for a hydrogen-bonded water network present in the cavity of the macrocycles is provided by crystal structure analysis. We ascribe the high catalytic efficiency of our Ru(bda) macrocycles to cooperative proton abstractions facilitated by such a network of preorganized water molecules in their cavity, which is reminiscent of catalytic activities of enzymes at active sites.}, language = {en} } @article{UlbrichtNickelWeidenbachetal.2020, author = {Ulbricht, Andrea and Nickel, Lisa and Weidenbach, Katrin and Vargas Gebauer, Herman and Kießling, Claudia and F{\"o}rstner, Konrad U. and Schmitz, Ruth A.}, title = {The CARF protein MM_0565 affects transcription of the casposon-encoded cas1-solo gene in Methanosarcina mazei G{\"o}1}, series = {Biomolecules}, volume = {10}, journal = {Biomolecules}, number = {8}, issn = {2218-273X}, doi = {10.3390/biom10081161}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211097}, year = {2020}, abstract = {Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci are found in bacterial and archaeal genomes where they provide the molecular machinery for acquisition of immunity against foreign DNA. In addition to the cas genes fundamentally required for CRISPR activity, a second class of genes is associated with the CRISPR loci, of which many have no reported function in CRISPR-mediated immunity. Here, we characterize MM_0565 associated to the type I-B CRISPR-locus of Methanosarcina mazei G{\"o}1. We show that purified MM_0565 composed of a CRISPR-Cas Associated Rossmann Fold (CARF) and a winged helix-turn-helix domain forms a dimer in solution; in vivo, the dimeric MM_0565 is strongly stabilized under high salt stress. While direct effects on CRISPR-Cas transcription were not detected by genetic approaches, specific binding of MM_0565 to the leader region of both CRISPR-Cas systems was observed by microscale thermophoresis and electromobility shift assays. Moreover, overexpression of MM_0565 strongly induced transcription of the cas1-solo gene located in the recently reported casposon, the gene product of which shows high similarity to classical Cas1 proteins. Based on our findings, and taking the absence of the expressed CRISPR locus-encoded Cas1 protein into account, we hypothesize that MM_0565 might modulate the activity of the CRISPR systems on different levels.}, language = {en} } @article{Schwemer2020, author = {Schwemer, Daniel}, title = {Any Evil, a Stalking Ghost, and the Bull-Headed Demon}, series = {Zeitschrift f{\"u}r Assyriologie und vorderasiatische Arch{\"a}ologie}, volume = {110}, journal = {Zeitschrift f{\"u}r Assyriologie und vorderasiatische Arch{\"a}ologie}, number = {2}, issn = {0084-5299}, doi = {10.1515/za-2020-0015}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217763}, pages = {141 -- 160}, year = {2020}, abstract = {Based on first-millennium cuneiform manuscripts from Aššur, Babylon, and Uruk, this article offers an edition of a ritual against an illness conceptualized as the demon 'Any Evil'. The text sheds light on how the catch-all figure Any Evil corresponds to the idea of a universal cure for any physical ailment, and how the rhetoric of the incantation articulates this relationship and facilitates the active participation of the patient. The ritual instructions of this and a closely related text show that Any Evil is envisaged as a bull-headed, male demon. This points to an adaptation of motifs that are typically associated with ghosts in ancient Mesopotamian thought and raises questions concerning the pictorial representation of Any Evil and its conceptual foundations.}, language = {en} } @article{Ziegler2020, author = {Ziegler, Robert Hugo}, title = {Die R{\"u}ckkehr des Realen}, series = {Deutsche Zeitschrift f{\"u}r Philosophie}, volume = {68}, journal = {Deutsche Zeitschrift f{\"u}r Philosophie}, number = {4}, issn = {2192-1482}, doi = {10.1515/dzph-2020-0040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217771}, pages = {611 -- 626}, year = {2020}, abstract = {We are witnessing a return of the real which philosophy seems illequipped to handle. I argue (1) that this return of the real must be read as a rejection of those philosophical tendencies which were prevalent in the past decades and which I call philosophies of mediation: They supplanted all references to something real by the sole reference to those processes in which reality was supposed to be given or shaped (in interpretations, linguistic structures, historical or social conditions, media…). The current urgency of the question of the real indicates that those philosophies have lost credibility. On the other hand (2), the contemporary attempts to resuscitate philosophical realism cannot be considered satisfactory either. It is curiously the real itself they fail to fully appreciate. All in all (3), the return of the real has to be interpreted as the effect of an event that has little to do with philosophy, namely the return of politics.}, language = {de} } @article{SeefriedDahirPetryketal.2020, author = {Seefried, Lothar and Dahir, Kathryn and Petryk, Anna and H{\"o}gler, Wolfgang and Linglart, Agn{\`e}s and Martos-Moreno, Gabriel {\´A}ngel and Ozono, Keiichi and Fang, Shona and Rockman-Greenberg, Cheryl and Kishnani, Priya S}, title = {Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry}, series = {Journal of Bone and Mineral Research}, volume = {35}, journal = {Journal of Bone and Mineral Research}, number = {11}, doi = {10.1002/jbmr.4130}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217787}, pages = {2171 -- 2178}, year = {2020}, abstract = {Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non-specific alkaline phosphatase activity. This study aims to assess patient-reported pain, disability and health-related quality of life (HRQoL) in a real-world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient-reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI-SF], Health Assessment Questionnaire Disability Index [HAQ-DI], and 36-Item Short-Form Health Survey version 2 [SF-36v2], respectively) were stratified by pediatric- and adult-onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74\% women), 45\% had adult-onset HPP and 33\% had pediatric-onset HPP (unknown age of onset, 22\%). Of those with data, 38\% had experienced ≥5 HPP manifestations and 62\% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI-SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ-DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF-36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI-SF, HAQ-DI, and SF-36v2 (all p < 0.05). No significant differences between adults with pediatric- and adult-onset HPP were observed for patient-reported outcomes, except for disability and the BPI-SF question "pain at its worst," which were significantly higher among adults with pediatric- versus adult-onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient-reported HRQoL, regardless of age of disease onset.}, language = {en} } @article{ZhouRascheKortuemetal.2020, author = {Zhou, Xiang and Rasche, Leo and Kort{\"u}m, K. Martin and Danhof, Sophia and Hudecek, Michael and Einsele, Hermann}, title = {Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.620312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219911}, year = {2020}, abstract = {In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.}, language = {en} } @article{BrumbergBecklDierksetal.2020, author = {Brumberg, Joachim and Beckl, Melanie and Dierks, Alexander and Schirbel, Andreas and Krebs, Markus and Buck, Andreas and K{\"u}bler, Hubert and Lapa, Constantin and Seitz, Anna Katharina}, title = {Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy}, series = {Biomedicines}, volume = {8}, journal = {Biomedicines}, number = {11}, issn = {2227-9059}, doi = {10.3390/biomedicines8110511}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219301}, year = {2020}, abstract = {Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7\% vs. 72.6\%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.}, language = {en} } @article{WagenbrennerHeinzHorasetal.2020, author = {Wagenbrenner, Mike and Heinz, Tizian and Horas, Konstantin and Jakuscheit, Axel and Arnholdt, Joerg and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris M. and Weißenberger, Manuel}, title = {Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm9123880}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219410}, year = {2020}, abstract = {The topical application of tranexamic acid (TXA) helps to prevent post-operative blood loss in total joint replacements. Despite these findings, the effects on articular and periarticular tissues remain unclear. Therefore, this in vitro study examined the effects of varying exposure times and concentrations of TXA on proliferation rates, gene expression and differentiation capacity of chondrocytes and human mesenchymal stromal cells (hMSCs), which underwent osteogenic differentiation. Chondrocytes and hMSCs were isolated and multiplied in monolayer cell cultures. Osteogenic differentiation of hMSCs was induced for 21 days using a differentiation medium containing specific growth factors. Cell proliferation was analyzed using ATP assays. Effects of TXA on cell morphology were examined via light microscopy and histological staining, while expression levels of tissue-specific genes were measured using semiquantitative RT-PCR. After treatment with 50 mg/mL of TXA, a decrease in cell proliferation rates was observed. Furthermore, treatment with concentrations of 20 mg/mL of TXA for at least 48 h led to a visible detachment of chondrocytes. TXA treatment with 50 mg/mL for at least 24 h led to a decrease in the expression of specific marker genes in chondrocytes and osteogenically differentiated hMSCs. No significant effects were observed for concentrations beyond 20 mg/mL of TXA combined with exposure times of less than 24 h. This might therefore represent a safe limit for topical application in vivo. Further research regarding in vivo conditions and effects on hMSC functionality are necessary to fully determine the effects of TXA on articular and periarticular tissues.}, language = {en} } @article{SteinCoulibalyBalimaetal.2020, author = {Stein, Katharina and Coulibaly, Drissa and Balima, Larba Hubert and Goetze, Dethardt and Linsenmair, Karl Eduard and Porembski, Stefan and Stenchly, Kathrin and Theodorou, Panagiotis}, title = {Plant-pollinator networks in savannas of Burkina Faso, West Africa}, series = {Diversity}, volume = {13}, journal = {Diversity}, number = {1}, issn = {1424-2818}, doi = {10.3390/d13010001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220157}, year = {2020}, abstract = {West African savannas are severely threatened with intensified land use and increasing degradation. Bees are important for terrestrial biodiversity as they provide native plant species with pollination services. However, little information is available regarding their mutualistic interactions with woody plant species. In the first network study from sub-Saharan West Africa, we investigated the effects of land-use intensity and climatic seasonality on plant-bee communities and their interaction networks. In total, we recorded 5686 interactions between 53 flowering woody plant species and 100 bee species. Bee-species richness and the number of interactions were higher in the low compared to medium and high land-use intensity sites. Bee- and plant-species richness and the number of interactions were higher in the dry compared to the rainy season. Plant-bee visitation networks were not strongly affected by land-use intensity; however, climatic seasonality had a strong effect on network architecture. Null-model corrected connectance and nestedness were higher in the dry compared to the rainy season. In addition, network specialization and null-model corrected modularity were lower in the dry compared to the rainy season. Our results suggest that in our study region, seasonal effects on mutualistic network architecture are more pronounced compared to land-use change effects. Nonetheless, the decrease in bee-species richness and the number of plant-bee interactions with an increase in land-use intensity highlights the importance of savanna conservation for maintaining bee diversity and the concomitant provision of ecosystem services.}, language = {en} } @article{SchaeferZernecke2020, author = {Sch{\"a}fer, Sarah and Zernecke, Alma}, title = {CD8\(^+\) T cells in atherosclerosis}, series = {Cells}, volume = {10}, journal = {Cells}, number = {1}, issn = {2073-4409}, doi = {10.3390/cells10010037}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220170}, year = {2020}, abstract = {Atherosclerotic lesions are populated by cells of the innate and adaptive immune system, including CD8\(^+\) T cells. The CD8\(^+\) T cell infiltrate has recently been characterized in mouse and human atherosclerosis and revealed activated, cytotoxic, and possibly dysfunctional and exhausted cell phenotypes. In mouse models of atherosclerosis, antibody-mediated depletion of CD8\(^+\) T cells ameliorates atherosclerosis. CD8\(^+\) T cells control monopoiesis and macrophage accumulation in early atherosclerosis. In addition, CD8\(^+\) T cells exert cytotoxic functions in atherosclerotic plaques and contribute to macrophage cell death and necrotic core formation. CD8\(^+\) T cell activation may be antigen-specific, and epitopes of atherosclerosis-relevant antigens may be targets of CD8\(^+\) T cells and their cytotoxic activity. CD8\(^+\) T cell functions are tightly controlled by costimulatory and coinhibitory immune checkpoints. Subsets of regulatory CD25\(^+\)CD8\(^+\) T cells with immunosuppressive functions can inhibit atherosclerosis. Importantly, local cytotoxic CD8\(^+\) T cell responses may trigger endothelial damage and plaque erosion in acute coronary syndromes. Understanding the complex role of CD8\(^+\) T cells in atherosclerosis may pave the way for defining novel treatment approaches in atherosclerosis. In this review article, we discuss these aspects, highlighting the emerging and critical role of CD8\(^+\) T cells in atherosclerosis.}, language = {en} } @article{CavalettoFaccoliMarinietal.2020, author = {Cavaletto, Giacomo and Faccoli, Massimo and Marini, Lorenzo and Spaethe, Johannes and Magnani, Gianluca and Rassati, Davide}, title = {Effect of trap color on captures of bark- and wood-boring beetles (Coleoptera; Buprestidae and Scolytinae) and associated predators}, series = {Insects}, volume = {11}, journal = {Insects}, number = {11}, issn = {2075-4450}, doi = {10.3390/insects11110749}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216325}, year = {2020}, abstract = {Traps baited with attractive lures are increasingly used at entry-points and surrounding natural areas to intercept exotic wood-boring beetles accidentally introduced via international trade. Several trapping variables can affect the efficacy of this activity, including trap color. In this study, we tested whether species richness and abundance of jewel beetles (Buprestidae), bark and ambrosia beetles (Scolytinae), and their common predators (i.e., checkered beetles, Cleridae) can be modified using trap colors different to those currently used for surveillance of jewel beetles and bark and ambrosia beetles (i.e., green or black). We show that green and black traps are generally efficient, but also that many flower-visiting or dark-metallic colored jewel beetles and certain bark beetles are more attracted by other colors. In addition, we show that checkered beetles have color preferences similar to those of their Scolytinae preys, which limits using trap color to minimize their inadvertent removal. Overall, this study confirmed that understanding the color perception mechanisms in wood-boring beetles can lead to important improvements in trapping techniques and thereby increase the efficacy of surveillance programs.}, language = {en} }