TY  - THES
A1  - Haas, Tobias Eberhard
T1  - Analyse der RNA-Landschaft und Chromatinorganisation in lytischer HSV-1 Infektion und Stress
T1  - Analysis of RNA landscape and chromatin organization in lytic HSV-1 infection and stress
N2  - Zellstress in Form von lytischer Herpes-simplex-Virustyp-1-Infektion, Hitze und Salzstress führt dazu, dass die RNA-Polymerase II über 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 Hilfsgröße „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 lässt: Die Offenheit des Chromatins ist bei Herpesinfektion zusätzlich zur Erhöhung nach dem 3'-Ende generell erhöht. Die Transkription der RNA-Polymerase II über 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 Erhöhung der Offenheit des Chromatins nach dem 3'-Ende nicht stattfindet.
N2  - Cell stress in the form of lytic herpes simplex virus type 1 infection, heat, and salt stress causes RNA polymerase II to transcribe beyond the 3' end of some genes. This is sometimes associated with open chromatin beyond the 3' end in herpes simplex virus type 1 infection. In this work, several methods were tested to elicit these effects genome-wide. The peak caller ATAC-seq-Pipeline, F-Seq, hotspots, and MACS2 were tested, and the auxiliary variable "downstream open chromatin regions" was used. Furthermore, the R script "Pipeline for ATAC-seq and 4sU-seq plotting" was developed to show the dynamics of the effects described above: Chromatin openness is generally increased in herpes infection in addition to being increased after the 3' end. In contrast, RNA polymerase II transcription across the 3' end decreases rapidly after 75k base pairs. The results of the R-script in relation to salt and heat stress are consistent with pre-described literature showing that an increase in chromatin openness after the 3' end does not occur.
KW  - Herpes-simplex-Virus
KW  - Salzstress
KW  - Hitzestress
KW  - Chromatin
KW  - Peak Caller
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283028
ER  - 
TY  - JOUR
A1  - Tütüncü, Serdar
A1  - Olma, Manuel
A1  - Kunze, Claudia
A1  - Dietzel, Joanna
A1  - Schurig, Johannes
A1  - Fiessler, Cornelia
A1  - Malsch, Carolin
A1  - Haas, Tobias Eberhard
A1  - Dimitrijeski, Boris
A1  - Doehner, Wolfram
A1  - Hagemann, Georg
A1  - Hamilton, Frank
A1  - Honermann, Martin
A1  - Jungehulsing, Gerhard Jan
A1  - Kauert, Andreas
A1  - Koennecke, Hans-Christian
A1  - Mackert, Bruno-Marcel
A1  - Nabavi, Darius
A1  - Nolte, Christian H.
A1  - Reis, Joschua Mirko
A1  - Schmehl, Ingo
A1  - Sparenberg, Paul
A1  - Stingele, Robert
A1  - Völzke, Enrico
A1  - Waldschmidt, Carolin
A1  - Zeise-Wehry, Daniel
A1  - Heuschmann, Peter U.
A1  - Endress, Matthias
A1  - Haeusler, Karl Georg
T1  - 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
JF  - Journal of Neurology
N2  - 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.
KW  - NOAC
KW  - ischemic stroke
KW  - atrial fibrillation
KW  - under-dosing
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266969
SN  - 1432-1459
VL  - 269
IS  - 1
ER  -