@phdthesis{Hoelldorfer2020,
  author    = {H{\"o}lldorfer, Constanze Lotte-Marie},
  title     = {Einfluss der Src-kinase-Inhibitoren auf die TLR-4-induzierte IL-10 bzw. IL-12 Produktion in Tumor-assoziierten Makrophagen},
  doi       = {10.25972/OPUS-21889},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218890},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Tumormikroumgebung (TME) spielt eine wichtige Rolle in Bezug auf das Ansprechen von Therapien, Tumorwachstum und die Bildung von Metastasen. In den letzten Jahren konnte belegt werden, dass Tyrosinkinaseinhibitoren (TKIs) Einfluss auf Zellen des TME haben und vor allem die dort vorherrschenden Zellen, Tumor-assoziierte Makrophagen (TAM), durch die TKIs moduliert werden k{\"o}nnen. Sie entsprechen meist dem M2-Ph{\"a}notyp, sezernieren antiinflammatorische Zytokine und sind protumoral, indem sie u.a. die Metastasierung und das Tumorwachstum unterst{\"u}tzen. Zentrale Targets f{\"u}r die Reprogrammierung von Makrophagen stellen sowohl der NF-κB als auch die Inhibition des CSF1-Rezeptors dar. An diesen beiden Schl{\"u}sselstellen wirken u.a. TKIs. In den durchgef{\"u}hrten Versuchen wurden drei TKIs verwendet - Dasatinib, Src-Kinase-Inhibitor-I, Bosutinib - um die Ergebnisse von Vorarbeiten zu verifizieren und um zu untersuchen, ob ein Klasseneffekt in Bezug auf eine gesteigerte IL-12-Produktion vorliegen k{\"o}nnte. Ein wichtiger Ansatzpunkt in der Bek{\"a}mpfung von Tumoren ist die Aktivierung von Immunzellen gegen Tumorzellen, in unserem Fall eine Modulation von TAM in Richtung M1-Makrophagen. Eine signifikante {\"A}nderung des Ph{\"a}notyps konnte nicht festgestellt werden. Allerdings wurde eine gesteigerte IL-12-Produktion aller Makrophagensubtypen durch die Inkubation mit Dasatinib- bzw. Src-kinase-inhibitor-I oder Bosutinib gezeigt. IL-12 ist ein wichtiges proinflammatorisches Schl{\"u}sselzytokin des Immunsystems, indem es u.a. NK-Zellen und T-Zellen aktiviert. Die funktionellen Auswirkungen der verst{\"a}rkten IL-12-Produktion in Hinblick auf NK-Zellen haben wir untersucht. Eine deutlich verst{\"a}rkte Aktivierung anhand Aktvierungsmarker von NK-Zellen konnten wir nicht beweisen. Allerdings wurde eine erh{\"o}hte Zytotoxizit{\"a}t durch Ko-Kultivierung der NK-Zellen mit den unterschiedlichen Makrophagensubtypen und gleichzeitiger Inkubation mit Dasatinib demonstriert. Die erh{\"o}hte IL-12-Produktion von APCs sowie verringerte IL-10-Produktion und der Einfluss auf andere Immunzellen, hier am Beispiel der NK-Zellen, zeigen u.a. das therapeutische Potential der TKIs als antineoplastisch wirksame Substanz. Als alleinige Therapie ist deren Wirkungsbereich nach den hier vorliegenden Ergebnissen jedoch noch zu gering. In Kombination mit anderen Therapieoptionen stellen die TKIs allerdings ein m{\"o}gliches Therapieregime dar. Der genaue Wirkmechanismus und die dadurch entstehenden Ver{\"a}nderungen sind noch genauer zu untersuchen. Ein weiteres Ziel ist in vitro etablierte Ergebnisse auch in die klinische Anwendung einfließen zu lassen. Der zweite Teil der Arbeit befasste sich mit einem proinflammatorischen Zytokin IL-32γ und dessen Wirkung auf Makrophagen. Wie bereits auch bei den TKIs wurde der Einfluss des Interleukins auf das Tumormikromilieu und die entsprechenden Auswirkungen untersucht. IL-32γ wirkt nicht nur selbst als proinflammatorisches Zytokin, sondern reguliert eine Vielzahl an weiteren Zytokinen. Der Einfluss von IL-32 auf das Tumormikromilieu und dessen Zellen stellt einen der zentralen Interessenspunkte dar. In unseren Versuchen konnte unter IL-32γ eine effektivere Antigenpr{\"a}sentation der Makrophagen - gemessen an einer verst{\"a}rkten Expression von CD80 und CD86 - gezeigt werden. Auf der anderen Seite wurde das antiinflammatorische Zytokin, IL-10, von IL-32γ-stimulierten Makrophagen ebenfalls verst{\"a}rkt sezerniert. Eine Ko-Kultivierung von Makrophagen und NK-Zellen und gleichzeitige Inkubation mit IL-32γ f{\"u}hrte bei NK-Zellen zu einer verst{\"a}rkten Aktivierung sowie zu einer erh{\"o}hten Zytotoxizit{\"a}t. Die Auswirkungen auf NK-Zellen deuten eine antitumorale Wirkung von IL-32γ an. Das breite Wirkspektrum des Interleukins ist vielversprechend und k{\"o}nnte neue Therapiestrategien er{\"o}ffnen, wof{\"u}r allerdings weitere Versuche sowohl in vitro als auch in vivo notwendig sind, um das Interleukin und seine Wirkungen genauestens zu verstehen.},
  subject      = {Makrophagen},
  language  = {de}
}
@article{HagemannStrengKraemeretal.2017,
  author    = {Hagemann, Christine and Streng, Andrea and Kraemer, Alexander and Liese, Johannes G.},
  title     = {Heterogeneity in coverage for measles and varicella vaccination in toddlers - analysis of factors influencing parental acceptance},
  series = {BMC Public Health},
  volume    = {17},
  journal   = {BMC Public Health},
  number    = {724},
  doi       = {10.1186/s12889-017-4725-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157827},
  year      = {2017},
  abstract  = {Background: In 2004, routine varicella vaccination was introduced in Germany for children aged 11-14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still too low (<95\%) in some areas to eliminate measles. The present study assessed varicella and measles vaccination coverage and determinants of parental acceptance in two study regions, situated in Northern and Southern Bavaria (Germany). Methods: From 2009 to 2011, annual cross-sectional parent surveys were performed on random samples of 600 children aged 18-36 months in the Bavarian regions of both Munich and W{\"u}rzburg. Logistic regression models were used to identify factors associated with varicella and measles vaccination. Results: In 2009, 2010 and 2011, vaccination coverage was lower in Munich than in W{\"u}rzburg, for both varicella (Munich 53\%, 67\%, 69\% vs. W{\"u}rzburg 72\%, 81\%, 83\%) and for measles (Munich 88\%, 89\%, 91\% vs. W{\"u}rzburg 92\%, 93\%, 95\%). Recommendation by the physician was the main independent factor associated with varicella vaccination in both regions (adjusted odd ratios (OR) with 95\% confidence interval (CI): Munich OR 19.7, CI 13.6-28.6; W{\"u}rzburg OR 34.7, CI 22.6-53.2). Attendance at a childcare unit was positively associated with a higher acceptance of varicella vaccination in Munich (OR 1.5, CI 1.1-2.2). Regarding measles vaccination, attendance at a childcare unit was positively associated in both regions (Munich OR 2.0; CI 1.3-3.0; W{\"u}rzburg OR 1.8; CI 1.1-3.1), and a higher level of parental school education was negatively associated in W{\"u}rzburg (OR 0.5, CI 0.3-0.9). Conclusions: Vaccination rates differed between regions, with rates constantly higher in W{\"u}rzburg. Within each region, vaccination rates were lower for varicella than for measles. Measles vaccination status was mainly dependent upon socio-demographic factors (attendance at a childcare unit, parental school education), whereas for the more recently introduced varicella vaccination recommendation by the physician had the strongest impact. Hence, different strategies are needed to further improve vaccination rates for both diseases.},
  language  = {en}
}
@article{BonigKuciKucietal.2019,
  author    = {Bonig, Halvard and Ku{\c{c}}i, Zyrafete and Ku{\c{c}}i, Selim and Bakhtiar, Shahrzad and Basu, Oliver and Bug, Gesine and Dennis, Mike and Greil, Johann and Barta, Aniko and K{\´a}llay, Kriszti{\´a}n M. and Lang, Peter and Lucchini, Giovanna and Pol, Raj and Schulz, Ansgar and Sykora, Karl-Walter and Teichert von Luettichau, Irene and Herter-Sprie, Grit and Ashab Uddin, Mohammad and Jenkin, Phil and Alsultan, Abdulrahman and Buechner, Jochen and Stein, Jerry and Kelemen, Agnes and Jarisch, Andrea and Soerensen, Jan and Salzmann-Manrique, Emilia and Hutter, Martin and Sch{\"a}fer, Richard and Seifried, Erhard and Paneesha, Shankara and Novitzky-Basso, Igor and Gefen, Aharon and Nevo, Neta and Beutel, Gernot and Schlegel, Paul-Gerhardt and Klingebiel, Thomas and Bader, Peter},
  title     = {Children and adults with Refractory acute Graft-versus-Host Disease respond to treatment with the Mesenchymal Stromal cell preparation "MSC-FFM"—Outcome report of 92 patients},
  series = {Cells},
  volume    = {8},
  journal   = {Cells},
  number    = {12},
  issn      = {2073-4409},
  doi       = {10.3390/cells8121577},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193878},
  pages     = {1577},
  year      = {2019},
  abstract  = {(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15\% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82\% and 81\% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64\%, while the cumulative incidence of death from underlying disease was 3\%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.},
  language  = {en}
}
@article{KunzmannNgyuenStahletal.2019,
  author    = {Kunzmann, S. and Ngyuen, T. and Stahl, A. and Walz, J. M. and Nentwich, M. M. and Speer, C. P. and Ruf, K.},
  title     = {Necrotizing enterocolitis after intravitreal bevacizumab in an infant with Incontinentia Pigmenti - a case report},
  series = {BMC Pediatrics},
  volume    = {19},
  journal   = {BMC Pediatrics},
  doi       = {10.1186/s12887-019-1732-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201024},
  pages     = {353},
  year      = {2019},
  abstract  = {Background Incontinentia Pigmenti is a rare disease affecting multiple organs. Fifty of patients show affection of the eye with retinopathy and possible amaurosis being the worst outcome. Treatment has commonly been panretinal laser coagulation but intravitreal application of bevacizumab as VEGF-inhibitor has shown to effectively suppress retinal neovascularization. Case presentation A six-week-old female infant with Incontinentia Pigmenti developed a foudroyant necrotizing enterocolitis shortly after intravitreal injection of bevazicumab due to a retinopathy with impending tractional detachment of the left eye. Since the onset of abdominal symptoms occurred immediately after the intravitreal application, a link between the two events seemed likely. Sequential analyses of the VEGF serum concentrations showed a massive suppression of endogenous VEGF with only a very slow recovery over weeks. Such a severe systemic adverse event has not been reported after intravitreal treatment with bevacizumab in an infant. Conclusion This case report shows a relevant systemic uptake of bevacizumab after intravitreal application as suppressed VEGF levels show. There seems to be a connection between suppressed VEGF levels and the onset of necrotizing enterocolitis. Therefore, treatment with bevacizumab should be carefully considered and further research is needed to assess this drug's safety profile.},
  language  = {en}
}
@article{HanitschBaumannBoztugetal.2020,
  author    = {Hanitsch, Leif and Baumann, Ulrich and Boztug, Kaan and Burkhard-Meier, Ulrike and Fasshauer, Maria and Habermehl, Pirmin and Hauck, Fabian and Klock, Gerd and Liese, Johannes and Meyer, Oliver and M{\"u}ller, Rainer and Pachlopnik-Schmid, Jana and Pfeiffer-Kascha, Dorothea and Warnatz, Klaus and Wehr, Claudia and Wittke, Kirsten and Niehues, Tim and von Bernuth, Horst},
  title     = {Treatment and management of primary antibody deficiency: German interdisciplinary evidence-based consensus guideline},
  series = {European Journal of Immunology},
  volume    = {50},
  journal   = {European Journal of Immunology},
  number    = {10},
  doi       = {10.1002/eji.202048713},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225731},
  pages     = {1432 -- 1446},
  year      = {2020},
  abstract  = {This evidence-based clinical guideline provides consensus-recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non-infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG-replacement therapy. Summary and consensus-recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG-replacement therapy. Special aspects of concomitant impaired T-cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA-4-, and LRBA-deficiency).},
  language  = {en}
}
@article{RufDemerathHebestreitetal.2018,
  author    = {Ruf, Katharina and Demerath, Antonia and Hebestreit, Helge and Kunzmann, Steffen},
  title     = {Is sweat testing for cystic fibrosis feasible in patients with down syndrome?},
  series = {BMC Pulmonary Medicine},
  volume    = {18},
  journal   = {BMC Pulmonary Medicine},
  number    = {8},
  doi       = {10.1186/s12890-018-0580-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175519},
  year      = {2018},
  abstract  = {Background: Recurrent airway infections are common in patients with Down's syndrome (DS). Hence, ruling out Cystic Fibrosis (CF) in these patients is often required. In the past, the value of sweat testing the gold standard to diagnose CF -has been questioned in DS as false positive results have been reported. However, these reports are based on measurements of sweat osmolality or sodium concentrations, not chloride concentrations. This study analyses sweat secretion rate and chloride concentration in sweat samples of patients with DS in comparison to healthy controls. Methods: We assessed sweat samples in 16 patients with DS and 16 healthy controls regarding sweat secretion rate (SSR) and sweat chloride concentration. Results: All measured chloride concentrations were within the normal range. The chloride concentrations were slightly, but not significantly lower in patients with DS (15,54 mmol/l (±4,47)) compared to healthy controls (18,31 mmol/l (±10,12)). While no gender gap in chloride concentration could be found, chloride concentration increased with age in both groups. Insufficient sweat was collected in 2 females with DS (12.5\% of the study group) but not in an individual of the control group. A significant lower sweat secretion rate was found in the DS group (27,6 μl/30 min (± 12,18)) compared to the control group (42,7 μl/30 min (± 21,22)). In a sub-analysis, female patients produced significantly less sweat (20,8 ± 10,6 μl/30 min) than male patients with DS (36,4 ± 7,8 μl/30 min), which accounts for the difference between patients and controls. Furthermore, while the sweating secretion rate increased with age in the control group, it did not do so in the DS group. Once again this was due to female patients with DS, who did not show a significant increase of sweat secretion rate with age. Conclusions: Sweat chloride concentrations were within the normal range in patients with DS and therefore seem to be a reliable tool for testing for CF in these patients. Interestingly, we found a reduced sweat secretion rate in the DS group. Whether the last one has a functional and clinical counterpart, possibly due to a disturbed thermoregulation in DS patients, requires further investigation.},
  language  = {en}
}
@phdthesis{Hafner2021,
  author    = {Hafner, Julia Alexandra},
  title     = {Prospektives Biomarker Screening zur Diagnose der Invasiven Aspergillose bei p{\"a}diatrischen Hochrisikopatienten},
  doi       = {10.25972/OPUS-23722},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237226},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Invasive Aspergillose (IA) stellt eine Hauptursache der infektassoziierten Morbidit{\"a}t und Mortalit{\"a}t bei p{\"a}diatrischen Patienten mit h{\"a}mato-onkologischer Grunderkrankung und/oder allogener Stammzelltransplantation dar. Die sichere und fr{\"u}hzeitige Diagnose ist bei Kindern aufgrund sp{\"a}rlicher p{\"a}diatrischer Daten weiterhin eine klinische Herausforderung. Die Kombination der Biomarker Galactomannanantigen und Aspergillus DNA hat sich in Erwachsenenstudien als vorteilhaft in der Diagnose der IA erwiesen. Ziel der durchgef{\"u}hrten Studie war daher, die diagnostische G{\"u}te des kombinierten Biomarkerscreenings in einer p{\"a}diatrischen Hochrisikokohorte zu ermitteln. Hierf{\"u}r wurden 39 p{\"a}diatrische Patienten, die w{\"a}hrend eines Zeitraumes von drei Jahren aufgrund einer h{\"a}mato-onkologischen Grunderkrankung und Notwendigkeit einer Stammzelltransplantation in der W{\"u}rzburger Kinderklinik behandelt wurden, einem hochstandardisierten, zweimal w{\"o}chentlichen Screening auf Galactomannanantigen und fungaler DNA zugef{\"u}hrt. Zus{\"a}tzlich wurde f{\"u}r jeden Patienten ein breites Spektrum an klinischen Daten sowie mikrobiologischen und radiologischen Ergebnissen erfasst und die IA-Klassifikation nach den EORTC/MSG-Kriterien durchgef{\"u}hrt. Unsere Daten zeigten eine IA-Inzidenz (probable IA) von 10\%, was per definitionem einer Hochrisikokohorte entspricht. Das kombinierte Monitoring der Biomarker Galactomannanantigen und Aspergillus-DNA wies eine hohe diagnostische Genauigkeit mit einer Sensitivit{\"a}t/Spezifit{\"a}t/PPV/NPV von 1.00 und gute Eignung als Screeningtest auf. Die antifungale Prophylaxe zeigte keinen negativen Einfluss auf die diagnostischen G{\"u}tekriterien der beiden Biomarker, wie in anderen Studien postuliert. Der Galactomannanindex erwies sich als vielversprechender Surrogatmarker f{\"u}r das Outcome und das Therapieansprechen. Weiterf{\"u}hrende Studien sind notwendig, um festzulegen, ob die Biomarkerkombination eine Detektion asymptomatischer subklinischer Infektionen als eine Art „Fr{\"u}hwarnsystem" erm{\"o}glicht und somit eine Reduktion der Mortalit{\"a}t bedingen kann.},
  subject      = {Aspergillose},
  language  = {de}
}
@article{ManukjanWiegeringReindletal.2020,
  author    = {Manukjan, Georgi and Wiegering, Verena and Reindl, Tobias and Strauß, Gabriele and Klopocki, Eva and Schulze, Harald and Andres, Oliver},
  title     = {Novel variants in FERMT3 and RASGRP2 - Genetic linkage in Glanzmann-like bleeding disorders},
  series = {Pediatric Blood \& Cancer},
  volume    = {67},
  journal   = {Pediatric Blood \& Cancer},
  number    = {2},
  doi       = {10.1002/pbc.28078},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208129},
  pages     = {e28078},
  year      = {2020},
  abstract  = {Defects of platelet intracellular signaling can result in severe platelet dysfunction. Several mutations in each of the linked genes FERMT3 and RASGRP2 on chromosome 11 causing a Glanzmann-like bleeding phenotype have been identified so far. We report on novel variants in two unrelated pediatric patients with severe bleeding diathesis—one with leukocyte adhesion deficiency type III due to a homozygous frameshift in FERMT3 and the other with homozygous variants in both, FERMT3 and RASGRP2 . We focus on the challenging genetic and functional variant assessment and aim to accentuate the risk of obtaining misleading results due to the phenomenon of genetic linkage.},
  language  = {en}
}
@article{HankeRauschSosnowskietal.2022,
  author    = {Hanke, Kathrin and Rausch, Tanja K. and Sosnowski, Runa and Paul, Pia and Spiegler, Juliane and M{\"u}ller, Mirja and K{\"o}nig, Inke R. and G{\"o}pel, Wolfgang and Herting, Egbert and H{\"a}rtel, Christoph},
  title     = {Early skin-to-skin contact does not affect cerebral tissue oxygenation in preterm infants <32 weeks of gestation},
  series = {Children},
  volume    = {9},
  journal   = {Children},
  number    = {2},
  issn      = {2227-9067},
  doi       = {10.3390/children9020211},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262290},
  year      = {2022},
  abstract  = {Aim: It was the aim of our study to determine the regional cerebral tissue oxygenation saturation (rcSO\(_2\)) as an additional monitoring parameter during early skin-to-skin contact (SSC) in preterm infants with a gestational age of <32 gestational weeks. Methods: We conducted two observational convenience sample studies using additional monitoring with near-infrared spectroscopy (NIRS) in the first 120 h of life: (a) NIRS 1 (gestational age of 26 0/7 to 31 6/7 weeks) and (b) NIRS 2 (gestational age of 24 0/7 to 28 6/7 weeks). The rcSO\(_2\) values were compared between resting time in the incubator (period I), SSC (period II) and handling nursing care (period III). For the comparison, we separated the sequential effects by including a "wash-out phase" of 1 h between each period. Results: During the first 120 h of life 38/53 infants in NIRS 1 and 15/23 infants in NIRS 2 received SSC, respectively. We found no remarkable differences for rcSO\(_2\) values of NIRS 1 patients between SSC time and period I (95\% confidence interval (CI) for the difference in \%: SSC vs. period I [1; 3]). In NIRS 2, rcSO\(_2\) values during SSC were only 2\% lower compared with period I [median [1. quartile; 3. quartile] in \%; 78 [73; 82] vs. 80 [74; 85]] but were similar to period III [78 [72; 83]]. In a combined analysis, a small difference in rcSO\(_2\) values between SSC and resting times was found using a generalized linear mixed model that included gender and gestational age (OR 95\% CI; 1.178 [1.103; 1.253], p < 0.0001). Episodes below the cut-off for "hypoxia"; e.g., <55\%, were comparable during SSC and periods I and III (0.3-2.1\%). No FiO\(_2\) adjustment was required in the vast majority of SSC episodes. Conclusions: Our observational data indicate that rcSO\(_2\) values of infants during SSC were comparable to rcSO\(_2\) values during incubator care and resting time. This additional monitoring supports a safe implementation of early SSC in extremely preterm infants in NICUs.},
  language  = {en}
}
@phdthesis{Landmesser2024,
  author    = {Landmesser, Patricia Sophia},
  title     = {Seropr{\"a}valenz von SARS-CoV-2 Antik{\"o}rpern bei Medizinstudierenden im zweiten klinischen Semester von Juli 2020 bis Juni 2021},
  doi       = {10.25972/OPUS-35924},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359246},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Im sechsten Semester des Medizinstudiums an der Julius-Maximilians-Universit{\"a}t W{\"u}rzburg findet das verpflichtende Praktikum „Impfkurs" statt. Im Rahmen dieses Kurses wurde vom Sommersemester 2020 bis zum Sommersemester 2021 ein standardisierter online Fragebogen erhoben, der unter anderem demographische Daten sowie Expositionsm{\"o}glichkeiten gegen{\"u}ber SARS-CoV-2 im privaten, beruflichen und universit{\"a}ren Umfeld erfragte. Zus{\"a}tzlich wurde im gleichen Zeitraum der SARS-CoV-2 Serostatus der Medizinstudierenden erhoben und ausgewertet und dieser mit den Daten des Fragebogens zusammengef{\"u}hrt. Daf{\"u}r wurden Blutproben entnommen, welche im Labor des Instituts f{\"u}r Virologie der Universit{\"a}t W{\"u}rzburg mittels Western Blot auf IgG/IgM/IgA Antik{\"o}rper gegen SARS-CoV-2 untersucht wurden.},
  subject      = {SARS-CoV-2},
  language  = {de}
}
@article{ElHelouBiegnerBodeetal.2019,
  author    = {El-Helou, Sabine M. and Biegner, Anika-Kerstin and Bode, Sebastian and Ehl, Stephan R. and Heeg, Maximilian and Maccari, Maria E. and Ritterbusch, Henrike and Speckmann, Carsten and Rusch, Stephan and Scheible, Raphael and Warnatz, Klaus and Atschekzei, Faranaz and Beider, Renata and Ernst, Diana and Gerschmann, Stev and Jablonka, Alexandra and Mielke, Gudrun and Schmidt, Reinhold E. and Sch{\"u}rmann, Gesine and Sogkas, Georgios and Baumann, Ulrich H. and Klemann, Christian and Viemann, Dorothee and Bernuth, Horst von and Kr{\"u}ger, Renate and Hanitsch, Leif G. and Scheibenbogen, Carmen M. and Wittke, Kirsten and Albert, Michael H. and Eichinger, Anna and Hauck, Fabian and Klein, Christoph and Rack-Hoch, Anita and Sollinger, Franz M. and Avila, Anne and Borte, Michael and Borte, Stephan and Fasshauer, Maria and Hauenherm, Anja and Kellner, Nils and M{\"u}ller, Anna H. and {\"U}lzen, Anett and Bader, Peter and Bakhtiar, Shahrzad and Lee, Jae-Yun and Heß, Ursula and Schubert, Ralf and W{\"o}lke, Sandra and Zielen, Stefan and Ghosh, Sujal and Laws, Hans-Juergen and Neubert, Jennifer and Oommen, Prasad T. and H{\"o}nig, Manfred and Schulz, Ansgar and Steinmann, Sandra and Klaus, Schwarz and D{\"u}ckers, Gregor and Lamers, Beate and Langemeyer, Vanessa and Niehues, Tim and Shai, Sonu and Graf, Dagmar and M{\"u}glich, Carmen and Schmalzing, Marc T. and Schwaneck, Eva C. and Tony, Hans-Peter and Dirks, Johannes and Haase, Gabriele and Liese, Johannes G. and Morbach, Henner and Foell, Dirk and Hellige, Antje and Wittkowski, Helmut and Masjosthusmann, Katja and Mohr, Michael and Geberzahn, Linda and Hedrich, Christian M. and M{\"u}ller, Christiane and R{\"o}sen-Wolff, Angela and Roesler, Joachim and Zimmermann, Antje and Behrends, Uta and Rieber, Nikolaus and Schauer, Uwe and Handgretinger, Rupert and Holzer, Ursula and Henes, J{\"o}rg and Kanz, Lothar and Boesecke, Christoph and Rockstroh, J{\"u}rgen K. and Schwarze-Zander, Carolynne and Wasmuth, Jan-Christian and Dilloo, Dagmar and H{\"u}lsmann, Brigitte and Sch{\"o}nberger, Stefan and Schreiber, Stefan and Zeuner, Rainald and Ankermann, Tobias and Bismarck, Philipp von and Huppertz, Hans-Iko and Kaiser-Labusch, Petra and Greil, Johann and Jakoby, Donate and Kulozik, Andreas E. and Metzler, Markus and Naumann-Bartsch, Nora and Sobik, Bettina and Graf, Norbert and Heine, Sabine and Kobbe, Robin and Lehmberg, Kai and M{\"u}ller, Ingo and Herrmann, Friedrich and Horneff, Gerd and Klein, Ariane and Peitz, Joachim and Schmidt, Nadine and Bielack, Stefan and Groß-Wieltsch, Ute and Classen, Carl F. and Klasen, Jessica and Deutz, Peter and Kamitz, Dirk and Lassy, Lisa and Tenbrock, Klaus and Wagner, Norbert and Bernbeck, Benedikt and Brummel, Bastian and Lara-Villacanas, Eusebia and M{\"u}nstermann, Esther and Schneider, Dominik T. and Tietsch, Nadine and Westkemper, Marco and Weiß, Michael and Kramm, Christof and K{\"u}hnle, Ingrid and Kullmann, Silke and Girschick, Hermann and Specker, Christof and Vinnemeier-Laubenthal, Elisabeth and Haenicke, Henriette and Schulz, Claudia and Schweigerer, Lothar and M{\"u}ller, Thomas G. and Stiefel, Martina and Belohradsky, Bernd H. and Soetedjo, Veronika and Kindle, Gerhard and Grimbacher, Bodo},
  title     = {The German national registry of primary immunodeficiencies (2012-2017)},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2019.01272},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226629},
  year      = {2019},
  abstract  = {Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57\% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36\% of patients. Familial cases were observed in 21\% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74\%) and immune dysregulation (22\%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49\% of all patients received immunoglobulin G (IgG) substitution (70\%-subcutaneous; 29\%-intravenous; 1\%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.},
  language  = {en}
}
@article{JarickMokhtariSchelleretal.2018,
  author    = {Jarick, Katja J. and Mokhtari, Zeinab and Scheller, Lukas and Hartweg, Julia and Thusek, Sina and Le, Duc-Dung and Ranecky, Maria and Shaikh, Haroon and Qureischi, Musga and Heinze, Katrin G. and Beilhack, Andreas},
  title     = {Photoconversion of Alloreactive T Cells in Murine Peyer's Patches During Acute Graft-Versus-Host Disease: Tracking the Homing Route of Highly Proliferative Cells In Vivo},
  series = {Frontiers in Immunology},
  volume    = {9},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2018.01468},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323309},
  year      = {2018},
  abstract  = {The regulation of immune cell migration throughout the body is essential to warrant immunosurveillance and to maintain immune homeostasis. Marking and tracking of these cells has proven important to study mechanisms of immune cell trafficking and cell interaction in vivo. Photoconversion is a well-suited technique for intravital application because it enables contactless time- and location-specific marking of cells in the tissue without surgically manipulating the microenvironment of the cells in question. However, in dividing cells the converted fluorescent protein may decline quickly. Here, we provide a detailed description of the photoconversion technique and its applicability to tracking highly proliferating T cells from the priming site of T cell activation to peripheral target organs of effector function in a preclinical model. Dendra2+ T cells were photoconverted in the Peyer's patches during the initiation phase of acute graft-versus-host disease (GvHD) and tracked through the mesenteric lymph nodes and the peripheral blood to the small intestine with flow cytometry and intravital two-photon microscopy. Photoconverted alloreactive T cells preserved the full proliferative capacity, homing, and migration of alloreactive T cells in the intestinal lamina propria. We conclusively proved that photoconversion of highly proliferative alloreactive T cells in the Peyer's patches is an effective tool to study trafficking of alloreactive T cells under physiologic conditions and to GvHD target tissues. This technique can also be applied to the study of immune cell tracking under inflammatory and non-inflammatory conditions.},
  language  = {en}
}
@phdthesis{Fischer2024,
  author    = {Fischer, Jonas Maria},
  title     = {Ph{\"a}notyp und Funktion von Follikul{\"a}ren Helfer Zell-{\"a}hnlichen T-Zellen im entz{\"u}ndeten Gelenk von Patientinnen und Patienten mit Juveniler Idiopathischer Arthritis},
  doi       = {10.25972/OPUS-36302},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363022},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Innerhalb der Juvenilen Idiopathischen Arthritis (JIA) bilden Patienten mit Antinukle{\"a}ren Antik{\"o}rpern (ANA) Subgruppen-{\"u}bergreifend eine klinisch homogene Erkrankungsgruppe. Ob diesen klinischen Gemeinsamkeiten jedoch auch eine einheitliche Pathogenese zugrunde liegt, ist bisher unbekannt. Sogenannte periphere T-Helferzellen (TPH) spielen im Kontext zahlreicher Autoimmunerkrankungen eine entscheidende Rolle bei der Aktivierung autoreaktiver B-Zellen. Ziel dieser Arbeit war daher die ph{\"a}notypische und funktionelle Analyse von PD-1hiCXCR5-CD4+ TPH-Zellen, sowie deren Verteilung in der Synovialfl{\"u}ssigkeit von Patienten unterschiedlicher Subgruppen der JIA. Hierzu wurden Ph{\"a}notyp und Zytokinprofil von PD-1hiCD4+ T-Zellen durchflusszytometrisch analysiert. Der funktionelle Einfluss von PD-1hiCD4+ T-Zellen auf die B-Zell-Differenzierung wurde mittels in vitro Kokulturen FACS-sortierter TPH-Zellen der Synovialfl{\"u}ssigkeit untersucht. IL-21- und IL-17-produzierende T-Ged{\"a}chtniszellen der Synovialfl{\"u}ssigkeit zeigten eine negative Korrelation zueinander. Die IL-21-Produktion ging besonders von PD-1hiCXCR5-HLA-DR+CD4+ T-Zellen aus, welche besonders in den Gelenken ANA-positiver JIA-Patienten akkumulierten. Diese Population zeigte ph{\"a}notypische {\"A}hnlichkeit mit TPH-Zellen und leistete in vitro effiziente B-Zell-Hilfe zu Plasmazelldifferenzierung und Immunglobulinsekretion, induzierte jedoch zudem einen CD21lo/-CD11c+T-bet+ Ph{\"a}notyp in B-Zellen. Passend hierzu bestand auch ex vivo eine signifikante Korrelation zwischen TPH und CD21lo/-CD11c+T-bet+ doppelt-negativen B-Zellen (BDN). Es konnte also die Expansion einer spezifischen T-Zellpopulation mit ph{\"a}notypischen und funktionellen Charakteristika von TPH-Zellen beobachtet und deren funktioneller Zusammenhang mit CD21lo/-CD11c+T-bet+ BDN in der Synovialfl{\"u}ssigkeit von JIA-Patienten aufgezeigt werden. Dies k{\"o}nnte die Autoimmunantwort auf ubiquit{\"a}re Autoantigene innerhalb betroffener Gelenke ANA-positiver JIA-Patienten widerspiegeln.},
  subject      = {Rheumatologie},
  language  = {de}
}
@article{GoreLocatelliZugmaieretal.2018,
  author    = {Gore, Lia and Locatelli, Franco and Zugmaier, Gerhard and Handgretinger, Rupert and O'Brien, Maureen M. and Bader, Peter and Bhojwani, Deepa and Schlegel, Paul-Gerhardt and Tuglus, Catherine A. and Stackelberg, Arend von},
  title     = {Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia},
  series = {Blood Cancer Journal},
  volume    = {8},
  journal   = {Blood Cancer Journal},
  doi       = {10.1038/s41408-018-0117-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230726},
  year      = {2018},
  abstract  = {no abstract available},
  language  = {en}
}
@article{LieseSchoenvanderLindenetal.2019,
  author    = {Liese, J. G. and Schoen, C. and van der Linden, M. and Lehmann, L. and Goettler, D. and Keller, S. and Maier, A. and Segerer, F. and Rose, M. A. and Streng, A.},
  title     = {Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study},
  series = {Clinical Microbiology and Infection},
  volume    = {25},
  journal   = {Clinical Microbiology and Infection},
  doi       = {10.1016/j.cmi.2018.10.020},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236866},
  pages     = {857-864},
  year      = {2019},
  abstract  = {Objectives Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. Methods Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. Results The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34\%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87\%); these were most frequently Streptococcus pneumoniae (41\%), Streptococcus pyogenes (19\%) and Staphylococcus aureus (6\%). Serotype 3 accounted for 45\% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95\%CI 12-16) and 18 (95\%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95\%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95\%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95\%CI 1.5-3.2) by 2016/17 (p 0.205). Conclusions In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.},
  language  = {en}
}
@phdthesis{NoppergebAckermann2024,
  author    = {Nopper [geb. Ackermann], Nadja},
  title     = {Impf- und Immunstatus W{\"u}rzburger Medizinstudierender von 2004-2020},
  doi       = {10.25972/OPUS-36968},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369689},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In dieser Arbeit wurde der Impfstatus der W{\"u}rzburger Medizinstudierenden von 2004-2020 entsprechend der jeweils im sechsten Semester geltenden STIKO Empfehlungen ausgewertet (im folgenden Impfquote genannt) und mit den Ergebnissen von Studien an Universit{\"a}ten in Frankfurt, Bochum und Dresden, sowie der Allgemeinbev{\"o}lkerung und dem medizinischen Personal in Deutschland verglichen. Außerdem wurde ausgewertet, inwiefern das Angebot der Nachimpfungen im Impfkurs angenommen wurde und m{\"o}gliche Zusammenh{\"a}nge mit aufgedeckten Impfl{\"u}cken wurden diskutiert. Bei manchen impfpr{\"a}ventablen Infektionskrankheiten (IPIE) wie Pertussis war von 2004-2020 ein deutlicher Anstieg der Impfquote (von <2\% auf knapp 90\%) zu beobachten, bei anderen, wie Tetanus war bereits seit 2004 eine Impfquote von etwa 75-90\% zu sehen, der {\"u}ber die gesamte Beobachtungszeit auf etwa 85-90\% anstieg. Im Vergleich zu anderen Studien mit Medizinstudierenden anderer Universit{\"a}ten in Deutschland schnitten die W{\"u}rzburger Medizinstudierenden in Bezug auf Masern, Mumps, R{\"o}teln und Varizellen mit Impfquoten um die 80-90\% oder h{\"o}her im Vergleich zu 73-86\% in den anderen St{\"a}dten durchweg besser ab. Bei Hepatitis B war anfangs eine vergleichbare (65-90\%), sp{\"a}ter eine h{\"o}here Impfquote (um die 80\%) als in den Vergleichsstudien (um die 40\%) zu beobachten. In Bezug auf Tetanus (Impfquote im Schnitt 85,2\%), Diphtherie (Impfquote im Schnitt 82,9\%), Pertussis (Impfquote im Schnitt 49,3\%) und Influenza (Impfung in Vorsaison im Schnitt bei 29,3\%) waren die Daten aus W{\"u}rzburg gut mit den Daten aus Vorstudien in {\"a}hnlichen Zeitr{\"a}umen vergleichbar. Im Vergleich zu Daten zur Impfquote bei Meningokokken und HPV aus der Allgemeinbev{\"o}lkerung lagen die W{\"u}rzburger Medizinstudierenden von 2017-2020 {\"u}ber den dort verzeichneten Werten (48\% zu 29\% bzw. 63\% zu 53). Im Vergleich zu Daten der Impfsurveillance des RKI aus 2020 zeigte sich der Effekt der Impfempfehlung bei Kindern (Meningokokken: 90\% der 4-7 J{\"a}hrigen, HPV: 63,3\% der 14 J{\"a}hrigen). Bei der Pneumokokken Impfung gaben - obwohl die STIKO Empfehlung nicht auf medizinisches Personal zutrifft - 10,8\% der Studierenden an, mindestens einmal geimpft zu sein. Dies k{\"o}nnte ein erh{\"o}htes Gesundheitsbewusstsein der Medizinstudierenden widerspiegeln. Zusammenfassend kann gesagt werden, dass der Anteil der W{\"u}rzburger Medizinstudierenden, deren Impfstatus f{\"u}r die einzelnen IPIE den STIKO Empfehlungen f{\"u}r medizinisches Personal entsprach, {\"u}ber die Jahre 2004 bis 2020 angestiegen ist. Zum Großteil lag der Anteil der Studierenden mit Impfstatus entsprechend den STIKO Empfehlungen {\"u}ber dem aus den Studien der anderen Universit{\"a}ten. Trotzdem blieben noch deutliche L{\"u}cken im Impfstatus, bspw. bei Pertussis oder Masern, und Wissen der W{\"u}rzburger Medizinstudierenden bestehen. Diese L{\"u}cken werden sich auf Dauer in die {\"A}rzteschaft und schließlich auch in die Empfehlungen durch das {\"a}rztliche Personal fortsetzen. Deshalb sollte ein besonderer Fokus auf die Verbesserung des Impfstatus Medizinstudierender gelegt werden, beispielsweise durch regelm{\"a}ßige verpflichtende Kontrollen durch Betrieb{\"a}rzt*in, intensivierte Lehre sowie bessere Aufkl{\"a}rung bereits zu Beginn des Studiums. Das Format des Impfkurses, wie er in W{\"u}rzburg durchgef{\"u}hrt wird, scheint ein gut gew{\"a}hltes Format, um den Studierenden die M{\"o}glichkeit zu geben, ihren eigenen Impfstatus zu {\"u}berpr{\"u}fen und diesen weiter zu verbessern. Die Impfquote der Studierenden lag in den Jahren 2014 bis 2020 - den Jahren, in denen die Nachimpfungen im Kurs erfasst wurden - im Schnitt nach dem Kurs bei fast allen IPIE {\"u}ber 90\%. Nur bei Pertussis lag die Impfquote nach dem Kurs bei 83,4\% (vgl. vor dem Kurs 68,4\%). Durch nationale Vereinheitlichung der Lehre im NKLM zum Thema Impfen, fr{\"u}he Auseinandersetzung mit dem Thema und regelm{\"a}ßige {\"U}berpr{\"u}fung des eigenen Impfstatus sowie niederschwellige Impfangebote im Medizinstudium, kann einerseits eine Verbesserung des Impfstatus von Medizinstudierenden erreicht werden. Andererseits k{\"o}nnen so auch insgesamt bessere Impfquoten in der Bev{\"o}lkerung durch die verbesserte Ausbildung von {\"A}rztinnen bereits im Medizinstudium erzielt werden.},
  subject      = {Impfung},
  language  = {de}
}
@phdthesis{Woidich2024,
  author    = {Woidich, Robert},
  title     = {Einfluss von IL-17 auf die Stabilit{\"a}t und Funktion von regulatorischen T-Zellen},
  doi       = {10.25972/OPUS-37019},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370199},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In der Pathogenese der Psoriasis spielen IL 17 und die Plastizit{\"a}t von Tregs zu Th17 Zellen mit Produktion proinflammatorischer Zytokine sowie die m{\"o}glicherweise reduzierte suppressive Funktion von Tregs eine entscheidende Rolle. Wir versuchten daher in unserer Arbeit einen {\"U}berblick {\"u}ber die T Zellverteilung im peripherem Blut bei PSO und HC zu erhalten und die Reaktion der Zellen auf IL 17, anti IL 17 und Secukinumab sowie ein Th 17 induzierendes Milieu im Vergleich von PSO und HC zu evaluieren. In der Analyse der PBMCs von PSO und HC konnten bei PSO tendenziell weniger inflammatorische Marker, wahrscheinlich aufgrund der niedrigen Krankheitsaktivit{\"a}t und der bereits eingeleiteten medikament{\"o}sen Therapie festgestellt werden. Nach Isolierung der Tregs und Kultivierung konnten bei PSO im Vergleich zu HC erh{\"o}hte inflammatorische Marker nachgewiesen werden. Dies kann an der h{\"o}heren Plastizit{\"a}t von Tregs bei PSO ex vivo ohne den Einfluss einer medikament{\"o}sen Therapie hin zu inflammatorischen Zellen. In den Suppressionsversuchen zeigte sich sowohl bei PSO als auch bei HC unter Th17 Milieu eine verminderte Inhibition der PBMCs durch die autologen Tregs. Urs{\"a}chlich hierf{\"u}r k{\"o}nnte eine Dysregulation der Tregs durch das Th17 Milieu oder eine Auswirkung des Th17-induzierenden Cocktails auf die PBMCs im Sinne einer Effektorresistenz gegen{\"u}ber den Tregs sein. Eine Ver{\"a}nderung der Suppression ergab sich f{\"u}r IL 17 oder anti IL 17 nicht. Unter der gleichzeitigen Kultivierung mit Secukinumab und einem Th17 induzierendem Cocktail konnte keine verbesserte Inhibition festgestellt werden. Insgesamt best{\"a}tigt die Arbeit eine Instabilit{\"a}t der Tregs bei PSO mit der M{\"o}glichkeit der Plastizit{\"a}t zu Th17 Zellen unter proinflammatorischem Milieu, sowie einen Verlust der Suppressionsf{\"a}higkeit durch eine Treg Dysfunktion oder eine erh{\"o}hte Effektorresistenz. F{\"u}r IL 17 oder die Blockade von IL 17 durch monoklonale Antik{\"o}rper konnte in unserer Studie kein Einfluss festgestellt werden.},
  subject      = {Regulatorischer T-Lymphozyt},
  language  = {de}
}
@article{OmenacaVazquezGarciaCorbeiraetal.2018,
  author    = {Ome{\~n}aca, Felix and V{\´a}zquez, Liliana and Garcia-Corbeira, Pilar and Mesaros, Narcisa and Hanssens, Linda and Dolhain, Jan and Puente G{\´o}mez, Ivonne and Liese, Johannes and Knuf, Markus},
  title     = {Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity},
  series = {Vaccine},
  volume    = {36},
  journal   = {Vaccine},
  doi       = {10.1016/j.vaccine.2018.01.005},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234450},
  pages     = {986-996},
  year      = {2018},
  abstract  = {Background Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed. Methods Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials. Results At least 92.5\% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30\% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens. Conclusion GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.},
  language  = {en}
}
@article{StromeckiTatariCoudiereMorrisonetal.2018,
  author    = {Stromecki, Margaret and Tatari, Nazanin and Coudi{\`e}re Morrison, Ludivine and Kaur, Ravinder and Zagozewski, Jamie and Palidwor, Gareth and Ramaswamy, Vijay and Skowron, Patryk and W{\"o}lfl, Matthias and Milde, Till and Del Bigio, Marc R. and Taylor, Michael D. and Werbowetski-Ogilvie, Tamra E.},
  title     = {Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma},
  series = {Molecular Oncology},
  volume    = {12},
  journal   = {Molecular Oncology},
  doi       = {10.1002/1878-0261.12177},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240089},
  pages     = {495-513},
  year      = {2018},
  abstract  = {Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo. To determine how OTX2 contributes to these processes, we employed complementary bioinformatic approaches to characterize the OTX2 regulatory network and identified novel relationships between OTX2 and genes associated with neuronal differentiation and axon guidance signaling in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome specifically in Group 4 tumors. Functional proof-of-principle studies demonstrated that increased levels of select SEMA pathway genes are associated with decreased self-renewal and growth in vitro and in vivo and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides mechanistic insight into the networks controlled by OTX2 in MB stem/progenitor cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors in MB.},
  language  = {en}
}
@article{KunzmannKremplSeidenspinneretal.2018,
  author    = {Kunzmann, Steffen and Krempl, Christine and Seidenspinner, Silvia and Glaser, Kirsten and Speer, Christian P. and Fehrholz, Markus},
  title     = {Increase in CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells},
  series = {Influenza and Other Respiratory Viruses},
  volume    = {12},
  journal   = {Influenza and Other Respiratory Viruses},
  doi       = {10.1111/irv.12561},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230909},
  pages     = {662-666},
  year      = {2018},
  abstract  = {Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase in CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis.},
  language  = {en}
}