Leha, Andreas

[["dc.bibliographiccitation.firstpage","e0224453"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Unsöld, Bernhard"],["dc.contributor.author","Mushemi-Blake, Sitali"],["dc.contributor.author","Shah, Ajay M."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Seidler, Tim"],["dc.contributor.editor","Ehrman, Robert"],["dc.date.accessioned","2020-12-10T18:42:11Z"],["dc.date.available","2020-12-10T18:42:11Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1371/journal.pone.0224453"],["dc.identifier.eissn","1932-6203"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16598"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77837"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A machine learning approach for the prediction of pulmonary hypertension"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","JBMR Plus"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Wilde, Deborah"],["dc.contributor.author","Wilken, Lara"],["dc.contributor.author","Stamm, Bettina"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Heppner, Christina"],["dc.contributor.author","Chavanon, Mira‐Lynn"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Herrmann‐Lingen, Christoph"],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2021-06-01T10:50:47Z"],["dc.date.available","2021-06-01T10:50:47Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1002/jbm4.10245"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17136"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86788"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2473-4039"],["dc.relation.issn","2473-4039"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The HPQ—Development and First Administration of a Questionnaire for Hypoparathyroid Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Götz, Marcus R."],["dc.contributor.author","Collado, Juan A."],["dc.contributor.author","Fernández-Ruiz, Javier"],["dc.contributor.author","Fiebich, Bernd L."],["dc.contributor.author","García-Toscano, Laura"],["dc.contributor.author","Gómez-Cañas, María"],["dc.contributor.author","Koch, Oskar"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Muñoz, Eduardo"],["dc.contributor.author","Navarrete, Carmen"],["dc.contributor.author","Pazos, Maria R."],["dc.contributor.author","Holzgrabe, Ulrike"],["dc.date.accessioned","2020-12-10T18:44:36Z"],["dc.date.available","2020-12-10T18:44:36Z"],["dc.date.issued","2019"],["dc.description.abstract","Background: As a library of cannabinoid (CB) derivatives with (-)-trans-cannabidiol (CBD) or (-)-trans-cannabidivarin (CBDV) scaffold, we synthesized nine novel cannabinoids: 2-hydroxyethyl cannabidiolate (2-HEC), 2-hydroxypentyl cannabidiolate (2-HPC), 2,3-dihydroxypropyl cannabidiolate (GCBD), cyclohexyl cannabidiolate (CHC), n-hexyl-cannabidiolate (HC), 2-(methylsulfonamido)ethyl cannabidiolate (NMSC), 2-hydroxyethyl cannabidivarinolate (2-HECBDV), cyclohexyl cannabidivarinolate (CHCBDV), and n-hexyl cannabidivarinolate (HCBDV). Their binding and intrinsic effects at the CB1- and CB2-receptors and the effects on inflammatory signaling cascades were investigated in in vitro and ex vivo cell models. Materials and Methods: Binding affinity was studied in membranes isolated from CB-receptor-transfected HEK293EBNA cells, intrinsic functional activity in Chinese hamster ovary (CHO) cells, and activation of nuclear factor κB (NF-κB) and nuclear factor of activated T-cells (NFAT) in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)-treated Jurkat T-cells. Inhibition of interleukin (IL)-17-induced pro-inflammatory cytokines and chemokines [IL-6, IL-1β, CC-chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α] was studied in RAW264.7 macrophages at the RNA level. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) expression and prostaglandin E2 (PGE2) expression were investigated at the protein level in lipopolysaccharide (LPS)-treated primary human monocytes. Results: Derivatives with long aliphatic side chains at the ester position at R1 [HC (5)] as well as the ones with polar side chains [2-HECBDV (7), NMSC (6), and 2-HEC (1)] can be selective for CB2-receptors. The CBDV-derivatives HCBDV and CHCBDV demonstrated specific binding at CB1- and CB2-receptors at nanomolar concentrations. 2-HEC, 2-HPC, GCBD, and NMSC were agonists at CB2-receptor and antagonists at CB1-receptor. CHC bound both receptors at submicromolar ranges and was an agonist for these receptors. 2-HECBDV was an agonist at CB2-receptor and an antagonist at the CB1-receptor despite its modest affinity at this receptor (micromolar range). NMSC inhibited NF-κB and NFAT activity, and 2-HEC, 2-HPC, and GCBD dose-dependently inhibited PMA/IO-stimulated NFAT activation. CHC and HC dose-dependently reduced IL-1β and CCL2 messenger RNA (mRNA) expression. NMSC inhibited IL-1β, CCL2, and TNF-α at lower doses. At higher doses, it induced a pronounced increase in IL-6 mRNA. 2-HEC, 2-HPC, and GCBD dose-dependently inhibited LPS-induced IL-1β, TNF-α, and IL-6 synthesis. NMSC further increased LPS-stimulated IL-1β release but inhibited IL-8, TNF-α, and PGE2. Conclusion: The CBD- and CBDV-derivatives studied are suitable for targeting CB-receptors. Some may be used as selective CB2 agonists. The length of the aliphatic rest at R2 of CBD (pentyl) and CBDV (propyl) did not correlate with the binding affinity. Higher polarity at R1 appeared to favor the agonistic activity at CB2-receptors."],["dc.identifier.doi","10.3389/fphar.2019.01284"],["dc.identifier.eissn","1663-9812"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78525"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1663-9812"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Structure–Effect Relationships of Novel Semi-Synthetic Cannabinoid Derivatives"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3010"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Uhlig, Johannes"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Delonge, Laura M."],["dc.contributor.author","Haack, Anna-Maria"],["dc.contributor.author","Shuch, Brian"],["dc.contributor.author","Kim, Hyun S."],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Lotz, Joachim"],["dc.contributor.author","Uhlig, Annemarie"],["dc.date.accessioned","2021-04-14T08:31:08Z"],["dc.date.available","2021-04-14T08:31:08Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3390/cancers12103010"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83497"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Radiomic Features and Machine Learning for the Discrimination of Renal Tumor Histological Subtypes: A Pragmatic Study Using Clinical-Routine Computed Tomography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","593"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Histopathology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Filmar, Simon"],["dc.contributor.author","Gaisa, Nadine T"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Reis, Henning"],["dc.contributor.author","Nettersheim, Daniel"],["dc.contributor.author","Oing, Christoph"],["dc.contributor.author","Gayer, Fabian A"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Bremmer, Felix"],["dc.date.accessioned","2021-04-14T08:23:39Z"],["dc.date.available","2021-04-14T08:23:39Z"],["dc.date.issued","2020"],["dc.description.abstract","Aims Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so‐called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in‐situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time‐consuming, demanding, and not being a stand‐alone method. The aim of the present study was to establish a quantitative real‐time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin‐fixed paraffin‐embedded tissue. Methods and results A cut‐off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour‐free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p). Conclusion In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin."],["dc.description.sponsorship","Wilhelm Sander‐Stiftung http://dx.doi.org/10.13039/100008672"],["dc.identifier.doi","10.1111/his.14258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81003"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1365-2559"],["dc.relation.issn","0309-0167"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","The detection of isochromosome i(12p) in malignant germ cell tumours and tumours with somatic malignant transformation by the use of quantitative real‐time polymerase chain reaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","127"],["dc.bibliographiccitation.journal","BMC Bioinformatics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Jung, Klaus"],["dc.date.accessioned","2018-11-07T08:56:54Z"],["dc.date.available","2018-11-07T08:56:54Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Discovery of biomarkers that are correlated with therapy response and thus with survival is an important goal of medical research on severe diseases, e. g. cancer. Frequently, microarray studies are performed to identify genes of which the expression levels in pretherapeutic tissue samples are correlated to survival times of patients. Typically, such a study can take several years until the full planned sample size is available. Therefore, interim analyses are desirable, offering the possibility of stopping the study earlier, or of performing additional laboratory experiments to validate the role of the detected genes. While many methods correcting the multiple testing bias introduced by interim analyses have been proposed for studies of one single feature, there are still open questions about interim analyses of multiple features, particularly of high-dimensional microarray data, where the number of features clearly exceeds the number of samples. Therefore, we examine false discovery rates and power rates in microarray experiments performed during interim analyses of survival studies. In addition, the early stopping based on interim results of such studies is evaluated. As stop criterion we employ the achieved average power rate, i.e. the proportion of detected true positives, for which a new estimator is derived and compared to existing estimators. Results: In a simulation study, pre-specified levels of the false discovery rate are maintained in each interim analysis, where reduced levels as used in classical group sequential designs of one single feature are not necessary. Average power rates increase with each interim analysis, and many studies can be stopped prior to their planned end when a certain pre-specified power rate is achieved. The new estimator for the power rate slightly deviates from the true power rate but is comparable to other estimators. Conclusions: Interim analyses of microarray experiments can provide evidence for early stopping of long-term survival studies. The developed simulation framework, which we also offer as a new R package 'SurvGenesInterim' available at http://survgenesinter.R-Forge.R-Project.org, can be used for sample size planning of the evaluated study design."],["dc.identifier.doi","10.1186/1471-2105-12-127"],["dc.identifier.isi","000290784600001"],["dc.identifier.pmid","21527044"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6343"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23260"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2105"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Sequential interim analyses of survival data in DNA microarray experiments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","48"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Radiotherapy and Oncology"],["dc.bibliographiccitation.lastpage","54"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Hohenberger, Werner"],["dc.contributor.author","Merkel, Susanne"],["dc.contributor.author","Fietkau, Rainer"],["dc.contributor.author","Raab, Hans-Rudolf"],["dc.contributor.author","Tschmelitsch, Joerg"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Wittekind, Christian"],["dc.contributor.author","Sauer, Rolf"],["dc.contributor.author","Roedel, Claus"],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T09:22:42Z"],["dc.date.available","2018-11-07T09:22:42Z"],["dc.date.issued","2013"],["dc.description.abstract","Introduction: The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome. Patients and methods: According to actual treatment analyses, 654 of 799 patients had received pre-(n = 406) or postoperative CRT (n = 248); in 145 patients postoperative CRT was not applied. Gender, age and clinicopathological parameters were correlated with CRT-associated acute toxicity and survival. Results: The 10-year survival was higher in women than in men, with 72.4% versus 65.6% for time to recurrence (p = 0.088) and 62.7% versus 58.4% for overall-survival (OS) (p = 0.066), as expected. For patients receiving CRT, women showed higher hematologic (p < 0.001) and acute organ toxicity (p < 0.001) in the entire cohort as well as in subgroup analyses according to pre- (p = 0.016) and postoperative CRT (p < 0.001). Lowest OS was seen in patients without acute toxicity (p = 0.0271). Multivariate analyses for OS showed that acute organ toxicity (p = 0.034) was beneficial while age (p < 0.001) was associated with worse OS. Discussion: Female gender is significantly associated with CRT-induced acute toxicity in rectal cancer. Acute toxicity during CRT may be associated with improved long-term outcome. (C) 2013 Elsevier Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.radonc.2013.05.009"],["dc.identifier.isi","000324155900007"],["dc.identifier.pmid","23768685"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11335"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29411"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","0167-8140"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Gender affects acute organ toxicity during radiochemotherapy for rectal cancer: Long-term results of the German CAO/ARO/AIO-94 phase III trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","JBMR Plus"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Stamm, Bettina"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Wilken, Lara"],["dc.contributor.author","Wilde, Deborah"],["dc.contributor.author","Heppner, Christina"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Herrmann‐Lingen, Christoph"],["dc.contributor.author","Siggelkow, Heide"],["dc.date.accessioned","2022-04-01T10:01:30Z"],["dc.date.available","2022-04-01T10:01:30Z"],["dc.date.issued","2022"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1002/jbm4.10586"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105677"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","2473-4039"],["dc.relation.issn","2473-4039"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","The Influence of Conventional Treatment on Symptoms and Complaints in Patients With Chronic Postsurgical Hypoparathyroidism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3086"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Jarausch, Johannes; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Neuenroth, Lisa; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Andag, Reiner; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Leha, Andreas; 3Department of Medical Statistics, University Medical Center Goettingen, Humboldtallee 32, 37073 Goettingen, Germany"],["dc.contributor.affiliation","Fischer, Andreas; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Asif, Abdul R.; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Lenz, Christof; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Eidizadeh, Abass; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.author","Jarausch, Johannes"],["dc.contributor.author","Neuenroth, Lisa"],["dc.contributor.author","Andag, Reiner"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Fischer, Andreas"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.editor","Zhou, Changcheng"],["dc.contributor.editor","Chen, Hong"],["dc.date.accessioned","2022-11-01T10:17:24Z"],["dc.date.available","2022-11-01T10:17:24Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:12:33Z"],["dc.description.abstract","Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cells11193086"],["dc.identifier.pii","cells11193086"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116800"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","CC BY 4.0"],["dc.title","Influence of Shear Stress, Inflammation and BRD4 Inhibition on Human Endothelial Cells: A Holistic Proteomic Approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3148"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.author","Fraune, Laura"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Wachter, Rolf"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Binder, Lutz"],["dc.date.accessioned","2021-08-12T07:46:00Z"],["dc.date.available","2021-08-12T07:46:00Z"],["dc.date.issued","2021"],["dc.description.abstract","Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity."],["dc.description.abstract","Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/jcm10143148"],["dc.identifier.pii","jcm10143148"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88596"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","2077-0383"],["dc.relation.orgunit","Institut für Klinische Chemie"],["dc.rights","CC BY 4.0"],["dc.title","Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]