TY - JOUR A1 - Goebeler, M. A1 - Bata-Csörgő, Z. A1 - Simone, C. de A1 - Didona, B. A1 - Remenyik, E. A1 - Reznichenko, N. A1 - Stoevesandt, J. A1 - Ward, E. S. A1 - Parys, W. A1 - Haard, H. de A1 - Dupuy, P. A1 - Verheesen, P. A1 - Schmidt, E. A1 - Joly, P. T1 - Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial JF - British Journal of Dermatology N2 - Background Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. Objectives To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. Methods Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg\(^{-1}\) intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). Results Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg\(^{-1}\) and 13 of 15 (87%) patients receiving 25 mg kg−1, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg \(^{-1}\) per day (range 0·06–0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2–41 weeks. Conclusions Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus. KW - pemphigus vulgaris KW - efgartigimod KW - pemphigus foliaceus Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258328 VL - 186 IS - 3 ER - TY - JOUR A1 - Uhler, Johannes A1 - Redlich, Sarah A1 - Zhang, Jie A1 - Hothorn, Torsten A1 - Tobisch, Cynthia A1 - Ewald, Jörg A1 - Thorn, Simon A1 - Seibold, Sebastian A1 - Mitesser, Oliver A1 - Morinère, Jérôme A1 - Bozicevic, Vedran A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Fricke, Ute A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Riebl, Rebekka A1 - Rojas-Botero, Sandra A1 - Rummler, Thomas A1 - Uphus, Lars A1 - Schmidt, Stefan A1 - Steffan-Dewenter, Ingolf A1 - Müller, Jörg T1 - Relationships of insect biomass and richness with land use along a climate gradient JF - Nature Communications N2 - Recently reported insect declines have raised both political and social concern. Although the declines have been attributed to land use and climate change, supporting evidence suffers from low taxonomic resolution, short time series, a focus on local scales, and the collinearity of the identified drivers. In this study, we conducted a systematic assessment of insect populations in southern Germany, which showed that differences in insect biomass and richness are highly context dependent. We found the largest difference in biomass between semi-natural and urban environments (-42%), whereas differences in total richness (-29%) and the richness of threatened species (-56%) were largest from semi-natural to agricultural environments. These results point to urbanization and agriculture as major drivers of decline. We also found that richness and biomass increase monotonously with increasing temperature, independent of habitat. The contrasting patterns of insect biomass and richness question the use of these indicators as mutual surrogates. Our study provides support for the implementation of more comprehensive measures aimed at habitat restoration in order to halt insect declines. KW - biodiversity KW - ecology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265058 VL - 12 IS - 1 ER - TY - JOUR A1 - Tanoey, Justine A1 - Baechle, Christina A1 - Brenner, Hermann A1 - Deckert, Andreas A1 - Fricke, Julia A1 - Günther, Kathrin A1 - Karch, André A1 - Keil, Thomas A1 - Kluttig, Alexander A1 - Leitzmann, Michael A1 - Mikolajczyk, Rafael A1 - Obi, Nadia A1 - Pischon, Tobias A1 - Schikowski, Tamara A1 - Schipf, Sabine M. A1 - Schulze, Matthias B. A1 - Sedlmeier, Anja A1 - Moreno Velásquez, Ilais A1 - Weber, Katharina S. A1 - Völzke, Henry A1 - Ahrens, Wolfgang A1 - Gastell, Sylvia A1 - Holleczek, Bernd A1 - Jöckel, Karl-Heinz A1 - Katzke, Verena A1 - Lieb, Wolfgang A1 - Michels, Karin B. A1 - Schmidt, Börge A1 - Teismann, Henning A1 - Becher, Heiko T1 - Birth order, Caesarean section, or daycare attendance in relation to child- and adult-onset type 1 diabetes: results from the German National Cohort JF - International Journal of Environmental Research and Public Health N2 - (1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection. KW - perinatal KW - adult-onset KW - late-onset KW - autoimmune KW - delivery mode KW - sex KW - offspring KW - NAKO Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286216 SN - 1660-4601 VL - 19 IS - 17 ER - TY - JOUR A1 - Ziegler, C. A1 - Richter, J. A1 - Mahr, M. A1 - Gajewska, A. A1 - Schiele, M.A. A1 - Gehrmann, A. A1 - Schmidt, B. A1 - Lesch, K.-P. A1 - Lang, T. A1 - Helbig-Lang, S. A1 - Pauli, P. A1 - Kircher, T. A1 - Reif, A. A1 - Rief, W. A1 - Vossbeck-Elsebusch, A.N. A1 - Arolt, V. A1 - Wittchen, H.-U. A1 - Hamm, A.O. A1 - Deckert, J. A1 - Domschke, K. T1 - MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy JF - Translational Psychiatry N2 - Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects. KW - Adult KW - Case-Control Studies KW - Cognitive Therapy KW - DNA Methylation KW - Epigenesis KW - Genetic KW - Female KW - Humans KW - Monoamine Oxidase/genetics KW - Panic Disorder/genetics KW - Panic Disorder/therapy KW - Sequence Analysis KW - DNA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164422 IS - 6 ER - TY - JOUR A1 - Schmidt, Enno A1 - Sticherling, Michael A1 - Sárdy, Miklós A1 - Eming, Rüdiger A1 - Goebeler, Matthias A1 - Hertl, Michael A1 - Hofmann, Silke C. A1 - Hunzelmann, Nicolas A1 - Kern, Johannes S. A1 - Kramer, Harald A1 - Nast, Alexander A1 - Orzechowski, Hans‐Dieter A1 - Pfeiffer, Christiane A1 - Schuster, Volker A1 - Sitaru, Cassian A1 - Zidane, Miriam A1 - Zillikens, Detlef A1 - Worm, Margitta T1 - S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update JF - JDDG: Journal der Deutschen Dermatologischen Gesellschaft KW - pemphigus vulgaris KW - pemphigus foliaceus KW - S2k guidelines Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217806 VL - 18 IS - 5 SP - 516 EP - 526 ER - TY - JOUR A1 - Milanese, Alessio A1 - Mende, Daniel R A1 - Paoli, Lucas A1 - Salazar, Guillem A1 - Ruscheweyh, Hans-Joachim A1 - Cuenca, Miguelangel A1 - Hingamp, Pascal A1 - Alves, Renato A1 - Costea, Paul I A1 - Coelho, Luis Pedro A1 - Schmidt, Thomas S. B. A1 - Almeida, Alexandre A1 - Mitchell, Alex L A1 - Finn, Robert D. A1 - Huerta-Cepas, Jaime A1 - Bork, Peer A1 - Zeller, Georg A1 - Sunagawa, Shinichi T1 - Microbial abundance, activity and population genomic profiling with mOTUs2 JF - Nature Communications N2 - Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites). KW - microbiome KW - software Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224089 VL - 10 ER - TY - JOUR A1 - Kroeber, Jana A1 - Wenger, Barbara A1 - Schwegler, Manuela A1 - Daniel, Christoph A1 - Schmidt, Manfred A1 - Djuzenova, Cholpon S A1 - Polat, Bülent A1 - Flentje, Michael A1 - Fietkau, Rainer A1 - Distel, Luitpold V. T1 - Distinct increased outliers among 136 rectal cancer patients assessed by \(\gamma\)H2AX JF - Radiation Oncology N2 - Background: In recent years attention has focused on \(\gamma\)H2AX as a very sensitive double strand break indicator. It has been suggested that \(\gamma\)H2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by \(\gamma\)H2AX in a large cohort. Methods: In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-\(\gamma\)H2AX antibodies and microscopic images with an extended depth of field were acquired. \(\gamma\)H2AX foci counting was performed using a semi-automatic image analysis software. Results: Distinct increased values of preexisting and remaining \(\gamma\)H2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR. Conclusions: The \(\gamma\)H2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae. KW - histone H2AX KW - blood lymphocytes KW - in vivo KW - foci KW - individual radiosensitivity KW - rectal cancer KW - radiotherapy KW - DNA double strand breaks KW - phosphorylation KW - neck cancer KW - oral mucositis KW - DNA damage KW - radiosensitivity KW - repair KW - \(\gamma\)h2ax Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144085 VL - 10 IS - 36 ER -