@article{EberhardtHaasGirschicketal.2015,
  author    = {Eberhardt, Christiane S. and Haas, Johannes-Peter and Girschick, Hermann and Schwarz, Tobias and Morbach, Henner and R{\"o}sen-Wolff, Angela and Foell, Dirk and Dannecker, Guenther and Schepp, Carsten and Ganser, Gerd and Honke, Nora and Eggermann, Thomas and M{\"u}ller-Berghaus, Jan and Wagner, Norbert and Ohl, Kim and Tenbrock, Klaus},
  title     = {No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis},
  series = {Pediatric Rheumatology},
  volume    = {13},
  journal   = {Pediatric Rheumatology},
  number    = {61},
  doi       = {10.1186/s12969-015-0059-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136281},
  year      = {2015},
  abstract  = {Background: IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population. Methods: In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR. Results: There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4 \%) and in rheumatoid factor negative polyarthritis (30.5 \%) and a lower pro1.1 genotype in persistent oligoarthritis (20.7 \%) and in enthesitis-related arthritis (17 \%). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95 \% 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95 \% 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 \% 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant. Conclusion: A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.},
  language  = {en}
}
@article{SedaghatHamedaniRebsElBattrawyetal.2021,
  author    = {Sedaghat-Hamedani, Farbod and Rebs, Sabine and El-Battrawy, Ibrahim and Chasan, Safak and Krause, Tobias and Haas, Jan and Zhong, Rujia and Liao, Zhenxing and Xu, Qiang and Zhou, Xiaobo and Akin, Ibrahim and Zitron, Edgar and Frey, Norbert and Streckfuss-B{\"o}meke, Katrin and Kayvanpour, Elham},
  title     = {Identification of SCN5a p.C335R variant in a large family with dilated cardiomyopathy and conduction disease},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {23},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222312990},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284442},
  year      = {2021},
  abstract  = {Introduction: Familial dilated cardiomyopathy (DCM) is clinically variable and has been associated with mutations in more than 50 genes. Rapid improvements in DNA sequencing have led to the identification of diverse rare variants with unknown significance (VUS), which underlines the importance of functional analyses. In this study, by investigating human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we evaluated the pathogenicity of the p.C335R sodium voltage-gated channel alpha subunit 5 (SCN5a) variant in a large family with familial DCM and conduction disease. Methods: A four-generation family with autosomal dominant familial DCM was investigated. Next-generation sequencing (NGS) was performed in all 16 family members. Clinical deep phenotyping, including endomyocardial biopsy, was performed. Skin biopsies from two patients and one healthy family member were used to generate human-induced pluripotent stem cells (iPSCs), which were then differentiated into cardiomyocytes. Patch-clamp analysis with Xenopus oocytes and iPSC-CMs were performed. Results: A SCN5a variant (c.1003T>C; p.C335R) could be detected in all family members with DCM or conduction disease. A novel truncating TTN variant (p.Ser24998LysfsTer28) could also be identified in two family members with DCM. Family members with the SCN5a variant (p.C335R) showed significantly longer PQ and QRS intervals and lower left ventricular ejection fractions (LV-EF). All four patients who received CRT-D were non-responders. Electrophysiological analysis with Xenopus oocytes showed a loss of function in SCN5a p.C335R. Na\(^+\) channel currents were also reduced in iPSC-CMs from DCM patients. Furthermore, iPSC-CM with compound heterozygosity (SCN5a p.C335R and TTNtv) showed significant dysregulation of sarcomere structures, which may be contributed to the severity of the disease and earlier onset of DCM. Conclusion: The SCN5a p.C335R variant is causing a loss of function of peak INa in patients with DCM and cardiac conduction disease. The co-existence of genetic variants in channels and structural genes (e.g., SCN5a p.C335R and TTNtv) increases the severity of the DCM phenotype.},
  language  = {en}
}
@phdthesis{Haas2022,
  author    = {Haas, Tobias Eberhard},
  title     = {Analyse der RNA-Landschaft und Chromatinorganisation in lytischer HSV-1 Infektion und Stress},
  doi       = {10.25972/OPUS-28302},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283028},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Zellstress in Form von lytischer Herpes-simplex-Virustyp-1-Infektion, Hitze und Salzstress f{\"u}hrt dazu, dass die RNA-Polymerase II {\"u}ber das 3'-Ende von manchen Genen hinaus transkribiert. Dies geht bei Herpes-simplex-Virustyp-1-Infektion teilweise mit offenem Chromatin nach dem 3'-Ende einher. In dieser Arbeit wurden verschiedene Methoden getestet, um diese Effekte genomweit zu eruieren. Dabei wurden die Peak-Caller ATAC-seq-Pipeline, F-Seq, Hotspots und MACS2 getestet sowie mit der Hilfsgr{\"o}ße „downstream Open Chromatin Regions" gearbeitet. Weiterhin wurde das R-Skript „Pipeline for ATAC-seq and 4sU-seq plotting" entwickelt, mit dem sich die Dynamik der oben beschriebenen Effekte zeigen l{\"a}sst: Die Offenheit des Chromatins ist bei Herpesinfektion zus{\"a}tzlich zur Erh{\"o}hung nach dem 3'-Ende generell erh{\"o}ht. Die Transkription der RNA-Polymerase II {\"u}ber das 3'-Ende hingegen nimmt nach 75k Basenpaaren rapide ab. Die Ergebnisse des R-Skripts im Bezug auf Salz und Hitzestress decken sich mit vorbeschriebener Literatur, in der gezeigt wurde, dass eine Erh{\"o}hung der Offenheit des Chromatins nach dem 3'-Ende nicht stattfindet.},
  subject      = {Herpes-simplex-Virus},
  language  = {de}
}
@article{TuetuencueOlmaKunzeetal.2022,
  author    = {T{\"u}t{\"u}nc{\"u}, Serdar and Olma, Manuel and Kunze, Claudia and Dietzel, Joanna and Schurig, Johannes and Fiessler, Cornelia and Malsch, Carolin and Haas, Tobias Eberhard and Dimitrijeski, Boris and Doehner, Wolfram and Hagemann, Georg and Hamilton, Frank and Honermann, Martin and Jungehulsing, Gerhard Jan and Kauert, Andreas and Koennecke, Hans-Christian and Mackert, Bruno-Marcel and Nabavi, Darius and Nolte, Christian H. and Reis, Joschua Mirko and Schmehl, Ingo and Sparenberg, Paul and Stingele, Robert and V{\"o}lzke, Enrico and Waldschmidt, Carolin and Zeise-Wehry, Daniel and Heuschmann, Peter U. and Endress, Matthias and Haeusler, Karl Georg},
  title     = {Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry},
  series = {Journal of Neurology},
  volume    = {269},
  journal   = {Journal of Neurology},
  number    = {1},
  issn      = {1432-1459},
  doi       = {10.1007/s00415-021-10866-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266969},
  pages     = {470-480},
  year      = {2022},
  abstract  = {Aims We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. Methods The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. Results At stroke onset, an off-label daily dose was prescribed in 61 (25.5\%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8\%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95\% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95\% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2\%) of 61 patients. Overall, 79 (13.7\%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6\%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95\% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95\% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95\% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95\% CI 1.28-2.84, P < 0.01]. Conclusion At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.},
  language  = {en}
}
@article{KippnichSkazelKlingshirnetal.2022,
  author    = {Kippnich, Maximilian and Skazel, Tobias and Klingshirn, Hanna and Gerken, Laura and Heuschmann, Peter and Haas, Kirsten and Schutzmeier, Martha and Brandstetter, Lilly and Weismann, Dirk and Reuschenbach, Bernd and Meybohm, Patrick and Wurmb, Thomas},
  title     = {Analyse des Weaningprozesses bei Intensivpatienten im Hinblick auf Dokumentation und Verlegung in weiterbehandelnde Einheiten},
  series = {Medizinische Klinik, Intensivmedizin und Notfallmedizin},
  volume    = {118},
  journal   = {Medizinische Klinik, Intensivmedizin und Notfallmedizin},
  doi       = {10.1007/s00063-022-00941-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346742},
  pages     = {269-276},
  year      = {2022},
  abstract  = {Hintergrund und Fragestellung Die Entw{\"o}hnung von Beatmungsger{\"a}ten wird nicht immer auf der prim{\"a}r behandelnden Intensivstation abgeschlossen. Die Weiterverlegung in andere Behandlungseinrichtungen stellt einen sensiblen Abschnitt in der Behandlung und Rehabilitation des Weaningpatienten dar. Ziel der vorliegenden Studie war die Untersuchung des {\"U}berleitungsmanagements und des Interhospitaltransfers von Weaningpatienten unter besonderer Ber{\"u}cksichtigung der Dokumentationsqualit{\"a}t. Methodik Es erfolge eine retrospektive Datenanalyse eines Jahrs (2018) auf 2 Intensivstationen eines Universit{\"a}tsklinikums. Eingeschlossen wurden alle beatmeten Patienten mit folgenden Tracerdiagnosen: COPD, Asthma, Polytrauma, Pneumonie, Sepsis, ARDS und Reanimation (Beatmung > 24 h). Ergebnisse Insgesamt konnten 750 Patienten in die Untersuchung eingeschlossen werden (Alter 64 [52, 8-76; Median, IQR]; 32 \% weiblich). Davon waren 48 (6,4 \%) Patienten zum Zeitpunkt der Verlegung nicht entw{\"o}hnt (v. a. Sepsis und ARDS). Die Routinedokumentation war bei den Abschnitten „Spontaneous Breathing Trial", „Bewertung der Entw{\"o}hungsbereitschaft" und „vermutete Entw{\"o}hnbarkeit" ausreichend, um die Erf{\"u}llung der Parameter der S2k-Leitlinie „Prolongiertes Weaning" ad{\"a}quat zu beurteilen. Vorwiegend wurden diese Patienten mit Tracheostoma (76 \%) in Rehabilitationskliniken (44 \%) mittels spezialisierten Rettungsmitteln des arztbegleiteten Patiententransports verlegt (75 \%). Diskussion Die Verlegung nicht entw{\"o}hnter Patienten nach initialem Intensivaufenthalt ist ein relevantes Thema f{\"u}r den Interhospitaltransfer. Die Routinedokumentation eines strukturierten Weaningprozesses ist in Kernelementen ausreichend, um den Weaningprozess l{\"u}ckenlos zu beschreiben. Dies ist f{\"u}r die Kontinuit{\"a}t in der Weiterbehandlung dieser Patienten von großer Bedeutung.},
  language  = {de}
}
@article{DjakovicHennigReinischetal.2023,
  author    = {Djakovic, Lara and Hennig, Thomas and Reinisch, Katharina and Milić, Andrea and Whisnant, Adam W. and Wolf, Katharina and Weiß, Elena and Haas, Tobias and Grothey, Arnhild and J{\"u}rges, Christopher S. and Kluge, Michael and Wolf, Elmar and Erhard, Florian and Friedel, Caroline C. and D{\"o}lken, Lars},
  title     = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-40217-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358161},
  year      = {2023},
  abstract  = {Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.},
  language  = {en}
}
@article{GiansantiTheinertBoeingetal.2023,
  author    = {Giansanti, Manuela and Theinert, Tobias and Boeing, Sarah Katharina and Haas, Dorothee and Schlegel, Paul-Gerhardt and Vacca, Paola and Nazio, Francesca and Caruana, Ignazio},
  title     = {Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies},
  series = {Molecular Cancer},
  volume    = {22},
  journal   = {Molecular Cancer},
  doi       = {10.1186/s12943-023-01893-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357515},
  year      = {2023},
  abstract  = {Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.},
  language  = {en}
}