Heßmann, Elisabeth

[["dc.bibliographiccitation.firstpage","688"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancer Discovery"],["dc.bibliographiccitation.lastpage","701"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Baumgart, Sandra"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Wolf, Elmar"],["dc.contributor.author","Bartkuhn, Marek"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Reinecke, Johanna"],["dc.contributor.author","Nikorowitsch, Julius"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Fernandez-Zapico, Martin E."],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Eilers, Martin"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Gress, Thomas M."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Tuveson, David A."],["dc.contributor.author","Urrutia, Raul"],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T09:39:31Z"],["dc.date.available","2018-11-07T09:39:31Z"],["dc.date.issued","2014"],["dc.description.abstract","Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote Kras(G12D) -driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in Kras(G12D) mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials. SIGNIFICANCE: Our study points to the existence of an oncogenic NFATc1-STAT3 cooperativity that mechanistically links inflammation with pancreatic cancer initiation and progression. Because NFATc1STAT3 nucleoprotein complexes control the expression of gene networks at the intersection of inflammation and cancer, our study has significant relevance for potentially managing pancreatic cancer and other inflammatory-driven malignancies. (C) 2014 AACR."],["dc.identifier.doi","10.1158/2159-8290.CD-13-0593"],["dc.identifier.isi","000337185500025"],["dc.identifier.pmid","24694735"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33304"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","2159-8290"],["dc.relation.issn","2159-8274"],["dc.title","Inflammation-Induced NFATc1-STAT3 Transcription Complex Promotes Pancreatic Cancer Initiation by Kras(G12D)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1024"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U502"],["dc.bibliographiccitation.volume","148"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Liou, Geou-Yarh"],["dc.contributor.author","Storz, Peter"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Regul, Lisanne"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Kuehnemuth, Benjamin"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.date.accessioned","2018-11-07T09:57:58Z"],["dc.date.available","2018-11-07T09:57:58Z"],["dc.date.issued","2015"],["dc.description.abstract","BACKGROUND & AIMS: Oncogenic mutations in KRAS contribute to the development of pancreatic ductal adenocarcinoma, but are not sufficient to initiate carcinogenesis. Secondary events, such as inflammation-induced signaling via the epidermal growth factor receptor (EGFR) and expression of the SOX9 gene, are required for tumor formation. Herein we sought to identify the mechanisms that link EGFR signaling with activation of SOX9 during acinar-ductal metaplasia, a transdifferentiation process that precedes pancreatic carcinogenesis. METHODS: We analyzed pancreatic tissues from KrasG12D; pdx1-Cre and KrasG12D; NFATc1D/D; pdx1-Cre mice after intraperitoneal administration of caerulein, vs cyclosporin A or dimethyl sulfoxide (controls). Induction of EGFR signaling and its effects on the expression of Nuclear factor of activated T cells c1 (NFATc1) or SOX9 were investigated by quantitative reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemical analyses of mouse and human tissues and acinar cell explants. Interactions between NFATc1 and partner proteins and effects on DNA binding or chromatin modifications were studied using co-immunoprecipitation and chromatin immunoprecipitation assays in acinar cell explants and mouse tissue. RESULTS: EGFR activation induced expression of NFATc1 in metaplastic areas from patients with chronic pancreatitis and in pancreatic tissue from KrasG12D mice. EGFR signaling also promoted formation of a complex between NFATc1 and C-JUN in dedifferentiating mouse acinar cells, leading to activation of Sox9 transcription and induction of acinar-ductal metaplasia. Pharmacologic inhibition of NFATc1 or disruption of the Nfatc1 gene inhibited EGFR-mediated induction of Sox9 transcription and blocked acinar-ductal transdifferentiation and pancreatic cancer initiation in mice. CONCLUSIONS: EGFR signaling induces expression of NFATc1 and Sox9, leading to acinar cell transdifferentiation and initiation of pancreatic cancer. Strategies designed to disrupt this pathway might be developed to prevent pancreatic cancer initiation in high-risk patients with chronic pancreatitis."],["dc.identifier.doi","10.1053/j.gastro.2015.01.033"],["dc.identifier.isi","000353335700033"],["dc.identifier.pmid","25623042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37276"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1528-0012"],["dc.relation.issn","0016-5085"],["dc.title","NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1609"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","1618"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Schneider, G."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Siveke, Jens T."],["dc.date.accessioned","2018-11-07T10:16:40Z"],["dc.date.available","2018-11-07T10:16:40Z"],["dc.date.issued","2016"],["dc.description.abstract","Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches."],["dc.identifier.doi","10.1038/onc.2015.216"],["dc.identifier.isi","000373064200001"],["dc.identifier.pmid","26119937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41079"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1507"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","152"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Neeße, Albrecht"],["dc.contributor.author","Dyck, Moritz Lino"],["dc.contributor.author","Steuber, Benjamin"],["dc.contributor.author","König, Alexander Otto"],["dc.contributor.author","Lubeseder-Martellato, Clara"],["dc.contributor.author","Winter, Thore"],["dc.contributor.author","Forster, Teresa"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Reuter-Jessen, Kirsten"],["dc.contributor.author","Griesmann, Heidi"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Tsai, Wan-Chi"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.date.accessioned","2018-11-07T10:24:16Z"],["dc.date.available","2018-11-07T10:24:16Z"],["dc.date.issued","2017"],["dc.description.abstract","BACKGROUND & AIMS: The ability of exocrine pancreatic cells to change the cellular phenotype is required for tissue regeneration upon injury, but also contributes to their malignant transformation and tumor progression. We investigated context-dependent signaling and transcription mechanisms that determine pancreatic cell fate decisions toward regeneration and malignancy. In particular, we studied the function and regulation of the inflammatory transcription factor nuclear factor of activated T cells 1 (NFATC1) in pancreatic cell plasticity and tissue adaptation. METHODS: We analyzed cell plasticity during pancreatic regeneration and transformation in mice with pancreas-specific expression of a constitutively active form of NFATC1, or depletion of enhancer of zeste 2 homologue 2 (EZH2), in the context of wild-type or constitutively activate Kras, respectively. Acute and chronic pancreatitis were induced by intraperitoneal injection of caerulein. EZH2-dependent regulation of NFATC1 expression was studied in mouse in human pancreatic tissue and cells by immunohistochemistry, immunoblotting, and quantitative reverse transcription polymerase chain reaction. We used genetic and pharmacologic approaches of EZH2 and NFATC1 inhibition to study the consequences of pathway disruption on pancreatic morphology and function. Epigenetic modifications on the NFATC1 gene were investigated by chromatin immunoprecipitation assays. RESULTS: NFATC1 was rapidly and transiently induced in early adaptation to acinar cell injury in human samples and in mice, where it promoted acinar cell trans-differentiation and blocked proliferation of metaplastic pancreatic cells. However, in late stages of regeneration, Nfatc1 was epigenetically silenced by EZH2-dependent histone methylation, to enable acinar cell redifferentiation and prevent organ atrophy and exocrine insufficiency. In contrast, oncogenic activation of KRAS signaling in pancreatic ductal adenocarcinoma cells reversed the EZH2-dependent effects on the NFATC1 gene and was required for EZH2-mediated transcriptional activation of NFATC1. CONCLUSIONS: In studies of human and mouse pancreatic cells and tissue, we identified context-specific epigenetic regulation of NFATc1 activity as an important mechanism of pancreatic cell plasticity. Inhibitors of EZH2 might therefore interfere with oncogenic activity of NFATC1 and be used in treatment of pancreatic ductal adenocarcinoma."],["dc.identifier.doi","10.1053/j.gastro.2017.01.043"],["dc.identifier.isi","000401811300041"],["dc.identifier.pmid","28188746"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42625"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1528-0012"],["dc.relation.issn","0016-5085"],["dc.title","Context-Dependent Epigenetic Regulation of Nuclear Factor of Activated T Cells 1 in Pancreatic Plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","168"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gut"],["dc.bibliographiccitation.lastpage","179"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T10:29:21Z"],["dc.date.available","2018-11-07T10:29:21Z"],["dc.date.issued","2017"],["dc.description.abstract","Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight. Nevertheless, recent translational research activities propose that either modulation of the immune response or pharmacological targeting of epigenetic modifications alone, or in combination with chemotherapy, might open highly powerful therapeutic avenues in GI cancer entities, including pancreatic cancer. Deregulation of key epigenetic factors and chromatin-modifying proteins, particularly those responsible for the addition, removal or recognition of post-translational histone modifications, are frequently found in human pancreatic cancer and hence constitute particularly exciting treatment opportunities. This review summarises both current clinical trial activities and discovery programmes initiated throughout the biopharma landscape, and critically discusses the chances, hurdles and limitations of epigenetic-based therapy in future PDAC treatment."],["dc.identifier.doi","10.1136/gutjnl-2016-312539"],["dc.identifier.isi","000392282900020"],["dc.identifier.pmid","27811314"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43628"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","1468-3288"],["dc.relation.issn","0017-5749"],["dc.title","Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1163"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Mazur, Pawel K."],["dc.contributor.author","Herner, Alexander"],["dc.contributor.author","Mello, Stephano S."],["dc.contributor.author","Wirth, Matthias"],["dc.contributor.author","Hausmann, Simone"],["dc.contributor.author","Sanchez-Rivera, Francisco J."],["dc.contributor.author","Lofgren, Shane M."],["dc.contributor.author","Kuschma, Timo"],["dc.contributor.author","Hahn, Stephan A."],["dc.contributor.author","Vangala, Deepak"],["dc.contributor.author","Trajkovic-Arsic, Marija"],["dc.contributor.author","Gupta, Aayush"],["dc.contributor.author","Heid, Iris M."],["dc.contributor.author","Noel, Peter B."],["dc.contributor.author","Braren, Rickmer"],["dc.contributor.author","Erkan, Mert"],["dc.contributor.author","Kleeff, Joerg"],["dc.contributor.author","Sipos, Bence"],["dc.contributor.author","Sayles, Leanne C."],["dc.contributor.author","Heikenwalder, Mathias"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Jacks, Tyler"],["dc.contributor.author","Bradner, James E."],["dc.contributor.author","Khatri, Purvesh"],["dc.contributor.author","Sweet-Cordero, E. Alejandro"],["dc.contributor.author","Attardi, Laura D."],["dc.contributor.author","Schmid, Roland M."],["dc.contributor.author","Schneider, Guenter"],["dc.contributor.author","Sage, Julien"],["dc.contributor.author","Siveke, Jens T."],["dc.date.accessioned","2018-11-07T09:51:04Z"],["dc.date.available","2018-11-07T09:51:04Z"],["dc.date.issued","2015"],["dc.description.abstract","Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9-based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy-induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors."],["dc.identifier.doi","10.1038/nm.3952"],["dc.identifier.isi","000362355400018"],["dc.identifier.pmid","26390243"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35837"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1546-170X"],["dc.relation.issn","1078-8956"],["dc.title","Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","517"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","530"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Lahmann, Marlen"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Voelker, Nadine"],["dc.contributor.author","Vogt, Sophia"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Schmidt, Ansgar"],["dc.contributor.author","Brendel, Cornelia"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Mernberger, Marco"],["dc.contributor.author","Crawford, Howard C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Li, Xiao-Kun"],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Neeße, Albrecht"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T10:00:56Z"],["dc.date.available","2018-11-07T10:00:56Z"],["dc.date.issued","2015"],["dc.description.abstract","In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities."],["dc.identifier.doi","10.15252/embj.201489574"],["dc.identifier.isi","000349695100009"],["dc.identifier.pmid","25586376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37913"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley"],["dc.relation.issn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]