@article{AbdelhameedEltamanyHaletal.2020,
  author    = {Abdelhameed, Reda F. A. and Eltamany, Enas E. and Hal, Dina M. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Al-Warhi, Tarfah and Youssif, Khayrya A. and Abd El-kader, Adel M. and Hassanean, Hashim A. and Fayez, Shaimaa and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {8},
  issn      = {1660-3397},
  doi       = {10.3390/md18080405},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211089},
  year      = {2020},
  abstract  = {Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.},
  language  = {en}
}
@article{AbdelhameedHabibEltahawyetal.2020,
  author    = {Abdelhameed, Reda F. A. and Habib, Eman S. and Eltahawy, Nermeen A. and Hassanean, Hashim A. and Ibrahim, Amany K. and Mohammed, Anber F. and Fayez, Shaimaa and Hayallah, Alaa M. and Yamada, Koji and Behery, Fathy A. and Al-Sanea, Mohammad M. and Alzarea, Sami I. and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {New cytotoxic natural products from the Red Sea sponge Stylissa carteri},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {5},
  issn      = {1660-3397},
  doi       = {10.3390/md18050241},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205795},
  year      = {2020},
  abstract  = {Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.},
  language  = {en}
}
@article{AbdelhameedHabibGodaetal.2020,
  author    = {Abdelhameed, Reda F. A. and Habib, Eman S. and Goda, Marwa S. and Fahim, John Refaat and Hassanean, Hashem A. and Eltamany, Enas E. and Ibrahim, Amany K. and AboulMagd, Asmaa M. and Fayez, Shaimaa and Abd El-kader, Adel M. and Al-Warhi, Tarfah and Bringmann, Gerhard and Ahmed, Safwat A. and Abdelmohsen, Usama Ramadan},
  title     = {Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {7},
  doi       = {10.3390/md18070354},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236085},
  year      = {2020},
  abstract  = {Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.},
  language  = {en}
}
@phdthesis{Abt2020,
  author    = {Abt, Alexander},
  title     = {Einfluss von HGF und Foretinib auf den Glukosestoffwechsel bei Zelllinien des oralen Plattenepithelkarzinoms},
  doi       = {10.25972/OPUS-20728},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207286},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Aktivierung des HGF/c-Met-Signalweges wird unter anderem seit l{\"a}ngerer Zeit als verantwortlicher Mechanismus f{\"u}r die Entwicklung von Resistenzen gegen den EGF-Rezeptor gerichteter Medikamente diskutiert. In verschiedenen Studien konnte die klinische Bedeutung des HGF/c-Met-Signalwegs belegt werden. In der j{\"u}ngeren Vergangenheit konzentriert sich die Forschung immer mehr auf das Tumormikromilieu und dessen Einfluss auf die Tumorprogression. So konnte gezeigt werden, dass erh{\"o}hte Laktatwerte, resultierend aus einer gesteigerten Glykolyse, zytotoxische T-Zellen inhibieren. Es wurden vier etablierte Zelllinien des oralen Plattenepithelkarzinoms sowie eine Zelllinie eines Mukoepidermoidkarzinom verwendet, um den Einfluss von HGF und des Tyrosinkinaseinhibitors Foretinib auf den Glukosemetabolismus zu pr{\"u}fen. Bei allen Zelllinien konnte der c-Met-Rezeptor nachgewiesen werden. Ebenso konnte in einem ELISA belegt werden, dass die Zelllinien selbst kein HFG produzieren. Es wurden proliferationsf{\"o}rdernde Effekte f{\"u}r HGF sowie zytotoxische Effekte durch Foretinib aufgezeigt. Ferner konnte der proliferationsf{\"o}rdernde Effekt durch HGF durch die Behandlung mit Foretinib aufgehoben werden. Im RT-PCR-Verfahren wurden die Auswirkungen auf die Transkription verschiedener Gene, die f{\"u}r wichtige Enzyme des Glukosemetabolismus kodieren, nach der Stimulation mit HGF sowie der Inhibition mit Foretinib untersucht. Es konnten substanzielle Ver{\"a}nderungen in der Expression einzelner Gene nachgewiesen werden. Zelllinien{\"u}bergreifend konnte allerdings keine verst{\"a}rkte bzw. verminderte Transkription durch die Behandlung mit HGF bzw. Foretinib nachgewiesen werden. Die Ergebnisse lassen auf die Komplexit{\"a}t der Regulierung des Glukosemetabolismus schließen. In der Durchflusszytometrie konnte gezeigt werden, dass eine Behandlung mit HGF nicht zu einer Zunahme des GLUT1 in der Zellmembran f{\"u}hrt, wohingegen eine Behandlung mit Foretinib mit einer gesteigerten Menge von GLUT1 einhergeht. Die Ergebnisse der vorliegenden Arbeit belegen einen Einfluss des HGF/c-Met-Signalwegs auf den Glukosemetabolismus bei Zelllinien des oralen Plattenepithelkarzinoms.},
  subject      = {Hepatozyten-Wachstumsfaktor},
  language  = {de}
}
@phdthesis{Ackermann2020,
  author    = {Ackermann, Sabine},
  title     = {Auswirkungen der multimodalen Therapie und der Einf{\"u}hrung der Vorsorgekoloskopie auf die {\"U}berlebensraten beim Kolonkarzinom},
  doi       = {10.25972/OPUS-20611},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206118},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Ziel dieser Arbeit war es, die Auswirkungen der {\"A}nderungen der Therapiestandards in der Behandlung des Kolonkarzinoms und die Auswirkungen der Einf{\"u}hrung der Vorsorgekoloskopie auf die {\"U}berlebensraten der Patienten mit Kolonkarzinom zu untersuchen. Die umfassende Analyse der therapieabh{\"a}ngigen {\"U}berlebensraten von 1016 Patienten mit Kolonkarzinom aus 20 Jahren zeigt eine Verbesserung der {\"U}berlebenswahrscheinlichkeit durch den Einsatz adjuvanter Therapie und multimodaler Therapieregime. Durch Neuerungen in der Therapie konnten die 5-Jahres-{\"U}berlebensraten seit Anfang der 90er Jahre nahezu verdoppelt werden. Als wichtigste Pr{\"a}diktoren f{\"u}r das Langzeit{\"u}berleben stellten sich das Alter der Patienten bei Erstdiagnose, das UICC Stadium und die Art der adjuvanten Therapie heraus. Der {\"U}berlebenszeit verl{\"a}ngernde Effekt war f{\"u}r den Einsatz der heutigen Standardtherapie mit 5-Flourouracil (5-FU) schon signifikant und zeigt sich f{\"u}r die Kombination mit neueren Medikamenten, insbesondere Oxaliplatin, noch deutlicher. Neue Operationstechniken, Fortschritte in der Metastasenchirurgie, ein optimiertes supportives Management und weitere Erkenntnisse onkologischer Prinzipien beeinflussten die erzielten Erfolge synergistisch. Das Gesamt{\"u}berleben der Patienten, die per Vorsorgekoloskopie detektiert werden ist besser als das der Patienten, die aufgrund klinischer Symptome diagnostiziert werden. Neben dem signifikanten {\"U}berlebensvorteil der Fr{\"u}herkennungs-Patienten, der sich durch die niedrigeren UICC Stadien in dieser Gruppe ergibt, finden sich auch Trends bez{\"u}glich eines besseren Outcomes dieser Patienten innerhalb der selben UICC Stadien. Die Patienten, deren Tumor im Rahmen des Screenings detektiert wurde, waren signifikant j{\"u}nger, wiesen signifikant weniger Begleiterkrakungen auf und zeigten signifikant niedrigere Tumorstadien. Eine adjuvante Therapie wurde in der Screening-Gruppe signifikant h{\"a}ufiger durchgef{\"u}hrt. Mehr als einer von f{\"u}nf tumorbedingten Todesf{\"a}llen der Patienten, die augrund von Symptomen diagnostiziert wurden, h{\"a}tte in dieser Studienpopulation verhindert werden k{\"o}nnen, wenn eine routinem{\"a}ßige Vorsorgekoloskopie durchgef{\"u}hrt worden w{\"a}re. Das Fazit lautet: die Vorsorgekoloskopie ist effektiv. Die Tumorgenese kann durch Entfernung von Vor{\"a}uferl{\"a}sionen durchbrochen werden, Tumoren k{\"o}nnen in fr{\"u}hen asymptomatischen Stadien detektiert werden. Screeningprogramme sollten erweitert werden, um die Inzidenz und die Mortalit{\"a}t von Darmkrebs weiter zu senken.},
  subject      = {Kolonkarzinom},
  language  = {de}
}
@article{AdakuChilakaMally2020,
  author    = {Adaku Chilaka, Cynthia and Mally, Angela},
  title     = {Mycotoxin Occurrence, Exposure and Health Implications in Infants and Young Children in Sub-Saharan Africa: A Review},
  series = {Foods},
  volume    = {9},
  journal   = {Foods},
  number    = {11},
  issn      = {2304-8158},
  doi       = {10.3390/foods9111585},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219250},
  year      = {2020},
  abstract  = {Infants and young children (IYC) remain the most vulnerable population group to environmental hazards worldwide, especially in economically developing regions such as sub-Saharan Africa (SSA). As a result, several governmental and non-governmental institutions including health, environmental and food safety networks and researchers have been proactive toward protecting this group. Mycotoxins, toxic secondary fungal metabolites, contribute largely to the health risks of this young population. In SSA, the scenario is worsened by socioeconomic status, poor agricultural and storage practices, and low level of awareness, as well as the non-establishment and lack of enforcement of regulatory limits in the region. Studies have revealed mycotoxin occurrence in breast milk and other weaning foods. Of concern is the early exposure of infants to mycotoxins through transplacental transfer and breast milk as a consequence of maternal exposure, which may result in adverse health effects. The current paper presents an overview of mycotoxin occurrence in foods intended for IYC in SSA. It discusses the imperative evidence of mycotoxin exposure of this population group in SSA, taking into account consumption data and the occurrence of mycotoxins in food, as well as biomonitoring approaches. Additionally, it discusses the health implications associated with IYC exposure to mycotoxins in SSA.},
  language  = {en}
}
@article{AdolfBraunFussetal.2020,
  author    = {Adolf, Christian and Braun, Leah T. and Fuss, Carmina T. and Hahner, Stefanie and K{\"u}nzel, Heike and Handgriff, Laura and Sturm, Lisa and Heinrich, Daniel A. and Schneider, Holger and Bidlingmaier, Martin and Reincke, Martin},
  title     = {Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism},
  series = {Endocrine},
  volume    = {69},
  journal   = {Endocrine},
  number    = {3},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-020-02348-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315966},
  pages     = {625-633},
  year      = {2020},
  abstract  = {Context Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. Patients and methods We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. Conclusion This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.},
  language  = {en}
}
@phdthesis{Ahrens2020,
  author    = {Ahrens, Lea Marlen},
  title     = {The Role of Attentional Control and Fear Acquisition and Generalization in Social Anxiety Disorder},
  doi       = {10.25972/OPUS-17162},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171622},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Although Social Anxiety Disorder (SAD) is one of the most prevalent mental disorders, still little is known about its development and maintenance. Cognitive models assume that deviations in attentional as well as associative learning processes play a role in the etiology of SAD. Amongst others, deficits in inhibitory attentional control as well as aberrations during fear generalization, which have already been observed in other anxiety disorders, are two candidate mechanisms that might contribute to the onset and retention of SAD. However, a review of the literature shows that there is a lack of research relating to these topics. Thus, the aim of the present thesis was to examine in which way individuals with SAD differ from healthy controls regarding attentional control and generalization of acquired fear during the processing of social stimuli. Study 1 tested whether impairment in the inhibitory control of attention is a feature of SAD, and how it might be influenced by emotional expression and gaze direction of an interactional partner. For this purpose, individuals with SAD and healthy controls (HC) participated in an antisaccade task with faces displaying different emotional expressions (angry, neutral and happy) and gaze directions (direct and averted) serving as target stimuli. While the participants performed either pro- or antisaccades in response to the peripherally presented faces, their gaze behavior was recorded via eye-tracking, and ratings of valence and arousal were obtained. Results revealed that both groups showed prolonged latencies and increased error rates in trials with correct anti- compared to prosaccades. However, there were no differences between groups with regard to response latency or error rates, indicating that SAD patients did not exhibit impairment on inhibitory attentional control in comparison to HC during eye-tracking. Possible explanations for this finding could be that reduced inhibitory attentional control in SAD only occurs under certain circumstances, for example, when these individuals currently run the risk of being negatively evaluated by others and not in the mere presence of phobic stimuli, or when the cognitive load of a task is so high that it cannot be unwound by compensatory strategies, such as putting more effort into a task. As not only deviations in attentional, but also associative learning processes might be pathogenic markers of SAD, these mechanisms were further addressed in the following experiments. Study 2 is the first that attempted to investigate the generalization of conditioned fear in patients with SAD. To this end, patients with SAD and HC were conditioned to two neutral female faces serving as conditioned stimuli (CS+: reinforced; CS-: non-reinforced) and a fearful face paired with a loud scream serving as unconditioned stimulus (US). Fear generalization was tested by presenting morphs of the two faces (GS: generalization stimuli), which varied in their similarity to the original faces. During the whole experiment, self-report ratings, heart rate (HR) and skin conductance responses (SCR) were recorded. Results demonstrated that SAD patients rated all stimuli as less pleasant and more arousing, and overestimated the occurrence of the US compared to HC, indicating a general hyperarousal in individuals with SAD. In addition, ratings and SCR indicated that both groups generalized their acquired fear from the CS+ to intermediate GSs as a function of their similarity to the CS+. However, except for the HR data, which indicated that only SAD patients but not HC displayed a generalization response in this measure, most of the results did not support the hypothesis that SAD is characterized by overgeneralization. A plausible reason for this finding could be that overgeneralization is just a key characteristic of some anxiety disorders and SAD is not one of them. Still, other factors, such as comorbidities in the individuals with SAD, could also have had an influence on the results, which is why overgeneralization was further examined in study 3. The aim of study 3 was to investigate fear generalization on a neuronal level. Hence, high (HSA) and low socially anxious participants (LSA) underwent a conditioning paradigm, which was an adaption of the experimental design used study 2 for EEG. During the experiment, steady-state visually evoked potentials (ssVEPs) and ratings of valence and arousal were recorded. Analyses revealed significant generalization gradients in all ratings with highest fear responses to the CS+ and a progressive decline of these reactions with increasing similarity to the CS-. In contrast, the generalization gradient on a neuronal level showed highest amplitudes for the CS+ and a reduction in amplitude to the most proximal, but not distal GSs in the ssVEP signal, which might be interpreted as lateral inhibition in the visual cortex. The observed dissociation among explicit and implicit measures points to different functions of behavioral and sensory cortical processes during fear generalization: While the ratings might reflect an individual's consciously increased readiness to react to threat, the lateral inhibition pattern in the occipital cortex might serve to maximize the contrast among stimuli with and without affective value and thereby improve adaptive behavior. As no group differences could be observed, the finding of study 2 that overgeneralization does not seem to be a marker of SAD is further consolidated. In sum, the conducted experiments suggest that individuals with SAD are characterized by a general hyperarousal during the exposition to disorder-relevant stimuli as indicated by enhanced arousal and reduced valence ratings of the stimuli compared to HC. However, the hypotheses that reduced inhibitory attentional control and overgeneralization of conditioned fear are markers of SAD were mostly not confirmed. Further research is required to elucidate whether they only occur under certain circumstances, such as high cognitive load (e.g. handling two tasks simultaneously) or social stress (e.g. before giving a speech), or whether they are not characteristics of SAD at all. With the help of these findings, new interventions for the treatment of SAD can be developed, such as attentional bias modification or discrimination learning.},
  subject      = {Sozialangst},
  language  = {en}
}
@phdthesis{Aicha2020,
  author    = {Aicha, Diaa},
  title     = {Hypertrophe obstruktive Kardiomyopathie: Vorhersagewert des ESC-Risikoscore f{\"u}r den pl{\"o}tzlichen Herztod bei Patienten nach Alkoholseptumablation},
  doi       = {10.25972/OPUS-19364},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193649},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Abstrakt Hypertrophe Kardiomyopathie (HCM) ist eine genetisch bedingte Herzmuskelerkrankung mit einer Pr{\"a}valenz von 0,2 bis 0,6\% und einem SCD-Risiko von 0,5 bis 1\% pro Jahr. HCM ist die h{\"a}ufigste Ursache f{\"u}r pl{\"o}tzlichen Herztod in jungem Alter. Seit Jahrzehnten wird bei HCM der optimale Vorhersagescore f{\"u}r SCD untersucht. Der erste validierte SCD-Sore bei HCM wurde im Jahr 2014 in die ESC-Leitlinien integriert. Ziel der Studie: Vergleich des berechneten SCD-Scores bei HCM aus dem Jahr 2014 vor und nach Alkohol- Septum-Ablation (PTSMA) mit dem erreichten Endpunkt (SCD). Methoden: 56 Patienten mit hypertropher obstruktiver Kardiomyopathie (HOCM) und Erst-PTSMA im Jahr 2009 wurden eingeschlossen: Alter 53,9 ± 11,5 Jahre, 7\% positive Familienanamnese f{\"u}r SCD, 9\% ungekl{\"a}rte Synkope im letzten Jahr, 43\% NSVT, maximale LV-Wanddicke 20,2 ± 4,3 mm, maximaler LVOT-Gradient 118 ± 42 mmHg, LA-Durchmesser 45,3 ± 6,4 mm. Ergebnisse: Vor dem ersten PTSMA hatten die HOCM-Patienten einen errechneten SCD-Wert von 4,2 ± 3,2\%, nach PTSMA von 3,2 ± 2,2\%. Wir beobachteten 2 (3,6\%) SCD-F{\"a}lle in 5 Jahren. Die PTSMA f{\"u}hrte zu einer signifikanten Reduktion des errechneten SCD-Scores von 1,0 ± 2,8\%, p <0,05. Diese Reduktion war haupts{\"a}chlich durch die signifikante Reduktion des LVOT-Gradienten (durchschnittlich 54 ± 42 mmHg, p <0,05) zur{\"u}ckzuf{\"u}hren. Fazit: PTSMA ist eine etablierte Behandlung zur Verbesserung der Symptome bei HOCM-Patienten ohne Hinweis auf eine h{\"o}here Mortalit{\"a}t nach induziertem Infarkt. Der ESC-SCD-Score ist nur ein Hilfsalgorithmus f{\"u}r die individuelle Entscheidung bez{\"u}glich einer prim{\"a}rprophylaktischen AICD-Implantation.},
  subject      = {HCM},
  language  = {de}
}
@phdthesis{Aichholzer2020,
  author    = {Aichholzer, Mareike},
  title     = {Ver{\"a}nderungen im intestinalen Mikrobiom bei Patienten mit akuter Leuk{\"a}mie im longitudinalen Verlauf},
  doi       = {10.25972/OPUS-19921},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199213},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In der vorliegenden Studie wurden Ver{\"a}nderungen des Darmmikrobioms anhand von Stuhlproben von Patienten mit akuter Leuk{\"a}mie longitudinal untersucht. Die Patienten wurden mit intensiver Chemotherapie behandelt. Die Therapie als auch die Erkrankung selbst f{\"u}hrte zu einer erheblichen Immunsuppression der Patienten. Prophylaktisch und therapeutisch wurden intensive Antibiotikatherapien bei allen Patienten durchgef{\"u}hrt. Das Mikrobiom wurde quantitativ und qualitativ analysiert. Die Bakterienmenge der Stuhlproben wurde mittels quantitativer Polymerase-Kettenreaktion und die Diversit{\"a}t des Mikrobioms mittels 16s rDNA Sequenzierung aufgezeigt. Zus{\"a}tzlich dazu fand eine mikrobiologische Kultivierung von Bakterien in Rektalabstrichen statt, um multiresistente Keime nachzuweisen. Ebenso wurde der klinische Verlauf der Patienten dokumentiert. Insgesamt wurde das Mikrobiom von drei verschiedenen Studiengruppen untersucht: Patienten mit akuter Leuk{\"a}mie, Patienten, die mit multiresistenten Keimen besiedelt waren und sich in der Nachsorge der W{\"u}rzburger interdisziplin{\"a}ren onkologischen Tagesklinik befanden sowie gesunde Probanden. Im Mikrobiom der Patienten mit akuter Leuk{\"a}mie war eine deutlich geringere Diversit{\"a}t sowie eine deutlich geringere Bakterienmenge im Vergleich zu beiden anderen Studiengruppen festzustellen. Das Mikrobiom {\"a}nderte sich w{\"a}hrend des Therapieverlaufs erheblich und am Beispiel von einigen Patienten konnte gezeigt werden, dass einzelne Bakterien das Mikrobiom dominierten. Des Weiteren waren im Mikrobiom der Patienten mit akuter Leuk{\"a}mie mehr potenziell pathogene sowie weniger potenziell protektive Bakterien im Vergleich zur Kontrollgruppe vorhanden. Zusammenfassend l{\"a}sst sich sagen, dass sich das Mikrobiom der Patienten mit akuter Leuk{\"a}mie deutlich von dem der anderen Studiengruppen unterscheidet. Um die Daten zu validieren und einen eventuellen Einfluss des Mikrobioms auf das {\"U}berleben der Patienten zu identifizieren, sollten die Untersuchungen an einer deutlich gr{\"o}ßeren Studienpopulation wiederholt werden.},
  subject      = {Akute Leuk{\"a}mie},
  language  = {de}
}
@phdthesis{Akhrif2020,
  author    = {Akhrif, Atae},
  title     = {The BOLD Signal is more than a Brain Activation Index},
  doi       = {10.25972/OPUS-20729},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207299},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In the recent years, translational studies comparing imaging data of animals and humans have gained increasing scientific interests with crucial findings stemming from both, human and animal work. In order to harmonize statistical analyses of data from different species and to optimize the transfer of knowledge between them, shared data acquisition protocols and combined statistical approaches have to be identified. Following this idea, methods of data analysis, which have until now mainly been used to model neural responses of electrophysiological recordings from rodent data, were applied on human hemodynamic responses (i.e. Blood-Oxygen-Level-Dependent BOLD signal) as measured via functional magnetic resonance imaging (fMRI). At the example of two attention and impulsivity networks, timing dynamics and amplitude of the fMRI signal were determined (study 1). Study 2 described the same parameters frequency-specifically, and in study 3, the complexity of neural processing was quantified in terms of fractality. Determined parameters were compared with regard to the subjects' task performance / impulsivity to validate findings with regard to reports of the current scientific debate. In a general discussion, overlapping as well as additional information of methodological approaches were discussed with regard to its potential for biomarkers in the context of neuropsychiatric disorders.},
  subject      = {funktionelle Kernspintomographie},
  language  = {en}
}
@article{AkhundzadahSoltaniAich2020,
  author    = {Akhundzadah, Noor Ahmad and Soltani, Salim and Aich, Valentin},
  title     = {Impacts of climate change on the water resources of the Kunduz River Basin, Afghanistan},
  series = {Climate},
  volume    = {8},
  journal   = {Climate},
  number    = {10},
  issn      = {2225-1154},
  doi       = {10.3390/cli8100102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213199},
  year      = {2020},
  abstract  = {The Kunduz River is one of the main tributaries of the Amu Darya Basin in North Afghanistan. Many communities live in the Kunduz River Basin (KRB), and its water resources have been the basis of their livelihoods for many generations. This study investigates climate change impacts on the KRB catchment. Rare station data are, for the first time, used to analyze systematic trends in temperature, precipitation, and river discharge over the past few decades, while using Mann-Kendall and Theil-Sen trend statistics. The trends show that the hydrology of the basin changed significantly over the last decades. A comparison of landcover data of the river basin from 1992 and 2019 shows significant changes that have additional impact on the basin hydrology, which are used to interpret the trend analysis. There is considerable uncertainty due to the data scarcity and gaps in the data, but all results indicate a strong tendency towards drier conditions. An extreme warming trend, partly above 2 °C since the 1960s in combination with a dramatic precipitation decrease by more than -30\% lead to a strong decrease in river discharge. The increasing glacier melt compensates the decreases and leads to an increase in runoff only in the highland parts of the upper catchment. The reduction of water availability and the additional stress on the land leads to a strong increase of barren land and a reduction of vegetation cover. The detected trends and changes in the basin hydrology demand an active management of the already scarce water resources in order to sustain water supply for agriculture and ecosystems in the KRB.},
  language  = {en}
}
@phdthesis{AlYousef2020,
  author    = {Al Yousef, Yousef},
  title     = {Retrospektiver Vergleich eines trabekul{\"a}ren Bypass Stents der zweiten Generation (iStent inject) zur ab-interno Trabekulektomie (Trabectome) mittels Exact Matching},
  publisher = {Graefs Archiv for clinical and experimental ophthalmology},
  doi       = {10.25972/OPUS-21662},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216623},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Abstract Purpose To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. Methods Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. Results A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. Conclusion T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.},
  language  = {de}
}
@phdthesis{AlNasser2020,
  author    = {Al-Nasser, Mohammed Mohammed Ali},
  title     = {Vergleich der peroralen endoskopischen Myotomie (POEM) und der laparoskopischen Heller Myotomie (LHM) in der Therapie der prim{\"a}r idiopathischen Achalasie und anderer {\"O}sophagusmotilit{\"a}tsst{\"o}rungen},
  doi       = {10.25972/OPUS-20431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204319},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Hier wird {\"u}ber den objektiven Vergleich der Kurz- und Langzeitergebnisse, die mit der laparoskopischen Heller-Myotomie plus Dor-Fundoplikatio (LHM + Dor) und der per-oralen endoskopischen Myotomie (POEM) an einer einzigen Institution erzielt wurden und {\"u}ber die Entwicklung eines "maßgeschneiderten Ansatzes" berichtet. Die laparosko-pischen Heller Myotomie (LHM) gilt aktuell als das Standardverfahren zur Therapie der Achalasie. Die perorale endoskopische Myotomie (POEM) bietet eine neue Alternative zur Durchf{\"u}hrung der Heller-Myotomie auf endoskopischem und natural orifice translu-minal endoscopic surgery (NOTES) Wege. Wir berichten {\"u}ber unsere unselektierte konsekutive Patientenserien (n = 238), die zwi-schen 2009 und 2017 entweder einer LHM + Dor Prozedur (n = 100) oder einer POEM Operation (n = 138) unterzogen wurden. Es gab keine Unterschiede hinsichtlich des Behandlungserfolgs (Eckardt-Score ≤ 3) nach 3 - 6 Monaten (LHM: 90,1\% vs. POEM: 90,5\%; p = 0,735), 12 Monate (LHM 84,4\% vs. POEM 84,0\%; p = 0,766 und> 2 Jahre (LHM 81,1\% vs. POEM 79,2\%; p = 0,432). Die Verbesserung der Lebensqualit{\"a}t (GIQLI-Score) und die Patientenzufriedenheit waren in beiden Gruppen ebenfalls ver-gleichbar gut (~ 90\%) und zu jedem Zeitpunkt der Nachbeobachtung. Refluxraten sind ebenfalls {\"a}hnlich (Sodbrennen LHM: 32,9\% vs. POEM: 30,1\%; {\"O}sophagitis LHM: 16,3\% vs. POEM: 14,6\%; PPI-Aufnahme 21,2\% vs. 32,5\%, pathologischer pH-Wert -Meter-LHM: 8,8\% vs. POEM: 23,3\%) ohne Signifikanz der Unterschiede. Die „maßgeschneiderte Verfahrenswahl POEM vs. LHM" k{\"o}nnte geeignet sein und sollte in weiteren Studien weiter untersucht werden.},
  subject      = {Achalasie},
  language  = {de}
}
@phdthesis{Alkhargi2020,
  author    = {Alkhargi, Manuel},
  title     = {Cancer And Living Meaningfully: eine qualitative Studie zur Treatment Integrity der CALM-Therapie im Vergleich zu einer Kontrollbedingung},
  doi       = {10.25972/OPUS-19939},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199390},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Hintergrund: Circa ein Drittel der Patientinnen und Patienten mit fortgeschrittenen Krebserkrankungen ist von psychischen Komorbidit{\"a}ten betroffen und circa die H{\"a}lfte weist eine psychische Belastung im klinisch signifikanten Bereich auf. Zur psychotherapeutischen Behandlung dieser Patientengruppe stehen unterschiedliche psychotherapeutische Interventionen zur Verf{\"u}gung. Die CALM-Therapie, eine manualisierte Kurzintervention im Einzelsetting, ist eine dieser Interventionen. Hier bilden vier Module, welche auf den wichtigsten Anliegen und Belastungsfaktoren von Patientinnen und Patienten mit fortgeschrittenen Krebserkrankungen basieren, den inhaltlichen Rahmen. Ziel: Die Treatment Integrity beschreibt das Maß, inwieweit eine psychotherapeutische Intervention wie vorgesehen umgesetzt wurde. F{\"u}r eine fundierte Interpretation psychotherapeutischer Interventionseffekte sind Kenntnisse {\"u}ber die Treatment Integrity entscheidend. Die vorliegende Arbeit untersuchte Teilaspekte der Treatment Integrity durchgef{\"u}hrter CALM-Therapien im Vergleich zu durchgef{\"u}hrten konventionellen psychoonkologischen Therapien, um einen Beitrag zu einer fundierten Interpretation von Interventionseffekten der CALM-Therapie zu leisten. Methoden: Transkriptionen von zwei CALM-Therapien und zwei Therapien einer konventionellen psychoonkologischen Intervention wurden anhand einer qualitativen Inhaltsanalyse nach P. Mayring untersucht. Im Zentrum stand hierbei ein selbst entwickeltes Kategoriensystem zur Analyse des gesamten Textmaterials. Zus{\"a}tzlich wurden Auff{\"a}lligkeiten bez{\"u}glich Ansprachen von Themenbereichen der CALM-Module unsystematisch beobachtet. Ergebnisse: Die Inhalte der untersuchten CALM-Therapien bezogen sich durchschnittlich zu 99,54\% und die der konventionellen psychoonkologischen Therapien durchschnittlich zu 98,71\% auf die Themenbereiche der CALM-Module. Die ermittelten Werte f{\"u}r einzelne Therapiesitzungen lagen f{\"u}r CALM-Sitzungen zwischen 98,12\% und 100\% und f{\"u}r Sitzungen der konventionellen psychoonkologischen Therapie zwischen 96,20\% und 100\%. Unsystematisch beobachtete Auff{\"a}lligkeiten zeigten, dass die Themenbereiche der CALM-Module zum Teil sehr spezifisch durch die CALM-Therapeutinnen und -Therapeuten angesprochen und vernetzt wurden. Schlussfolgerung: Unter Ber{\"u}cksichtigung von methodischen Grenzen zeigte sich bez{\"u}glich des Anteils von Themenbereichen der CALM-Module innerhalb der beiden untersuchten Therapiegruppen kein maßgeblicher Unterschied. Zus{\"a}tzlich liefert die vorliegende Arbeit Hinweise f{\"u}r einen spezifischen therapeutischen Umgang mit den Themenbereichen der CALM-Module innerhalb der untersuchten CALM-Therapien. Um ermittelte Interventionseffekte der CALM-Therapie fundiert interpretieren zu k{\"o}nnen, sollten zuk{\"u}nftige Untersuchungen unterschiedliche Umgangsweisen von Therapeutinnen und Therapeuten der beiden Therapiegruppen mit den Themenbereichen der CALM-Module genauer in den Blick nehmen.},
  subject      = {Psychoonkologie},
  language  = {de}
}
@phdthesis{AlonsoCanizal2020,
  author    = {Alonso Ca{\~n}izal, Maria Consuelo},
  title     = {Detection of ligand dependent Frizzled conformational changes},
  doi       = {10.25972/OPUS-17833},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178335},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Frizzled (FZD) are highly conserved receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. They are involved in a great variety of processes during embryonic development, organogenesis, and adult tissue homeostasis. In particular, FZD5 is an important therapeutic target due to its involvement in several pathologies, such as tumorigenesis. Nevertheless, little is known regarding the activation of FZD receptors and the signal initiation, and their GPCR nature has been debated. In order to investigate the activation mechanism of these receptors, FRET (F{\"o}rster Resonance Energy Transfer)-based biosensors for FZD5 have been developed and characterized. A cyan fluorescent protein (CFP) was fused to the C-terminus of the receptor and the specific FlAsH-binding sequence (CCPGCC) was inserted within the 2nd or the 3rd intracellular loop. Single-cell FRET experiments performed using one of these sensors, V5-mFZD5-FlAsH436-CFP, reported structural rearrangements in FZD5 upon stimulation with the endogenous ligand WNT-5A. These movements are similar to those observed in other GPCRs using the same technique, which suggests an activation mechanism for FZD reminiscent of GPCRs. Furthermore, stimulation of the FZD5 FRET-based sensor with various recombinant WNT proteins in a microplate FRET reader allowed to obtain concentration-response curves for several ligands, being possible to distinguish between full and partial agonists. This technology allowed to address the selectivity between WNTs and FZD5 using a full-length receptor in living cells. In addition, G protein FRET-based sensors revealed that WNT-5A specifically induced Gαq activation mediated by FZD5, but not Gαi activation. Other WNT proteins were also able to induce Gαq activation, but with lower efficacy than WNT-5A. In addition, a dual DAG/calcium sensor further showed that WNT-5A stimulation led to the activation of the Gαq-dependent signaling pathway mediated by FZD5, which outcome was the activation of Protein Kinase C (PKC) and the release of intracellular calcium. Altogether, these data provide evidence that the activation process of FZD5 resembles the general characteristics of class A and B GPCR activation, and this receptor also mediates the activation of the heterotrimeric Gαq protein and its downstream signaling pathway. In addition, the FZD5 receptor FRET-based sensor provides a valuable tool to characterize the pharmacological properties of WNTs and other potential ligands for this receptor.},
  subject      = {Fluoreszenz-Resonanz-Energie-Transfer},
  language  = {en}
}
@article{AltieriDiDatoModicaetal.2020,
  author    = {Altieri, Barbara and Di Dato, Carla and Modica, Roberta and Bottiglieri, Filomena and Di Sarno, Antonella and Pittaway, James F.H. and Martini, Chiara and Faggiano, Antongiulio and Colao, Annamaria},
  title     = {Bone metabolism and vitamin D implication in gastroenteropancreatic neuroendocrine tumors},
  series = {Nutrients},
  volume    = {12},
  journal   = {Nutrients},
  number    = {4},
  issn      = {2072-6643},
  doi       = {10.3390/nu12041021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203823},
  year      = {2020},
  abstract  = {Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.},
  language  = {en}
}
@article{AltieriSbieraHerterichetal.2020,
  author    = {Altieri, Barbara and Sbiera, Silviu and Herterich, Sabine and De Francia, Silvia and Della Casa, Silvia and Calabrese, Anna and Pontecorvi, Alfredo and Quinkler, Marcus and Kienitz, Tina and Mannelli, Massimo and Canu, Letizia and Angelousi, Anna and Chortis, Vasileios and Kroiss, Matthias and Terzolo, Massimo and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12020359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200565},
  pages     = {359},
  year      = {2020},
  abstract  = {Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2\% vs 51.7\%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55\% of patients with CYP2B6*6 vs. 28.2\% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6\%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.},
  language  = {en}
}
@article{AlzheimerSvenssonKoenigetal.2020,
  author    = {Alzheimer, Mona and Svensson, Sarah L. and K{\"o}nig, Fabian and Schweinlin, Matthias and Metzger, Marco and Walles, Heike and Sharma, Cynthia M.},
  title     = {A three-dimensional intestinal tissue model reveals factors and small regulatory RNAs important for colonization with Campylobacter jejuni},
  series = {PLoS Pathogens},
  volume    = {16},
  journal   = {PLoS Pathogens},
  number    = {2},
  doi       = {10.1371/journal.ppat.1008304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229454},
  year      = {2020},
  abstract  = {The Gram-negative Epsilonproteobacterium Campylobacter jejuni is currently the most prevalent bacterial foodborne pathogen. Like for many other human pathogens, infection studies with C. jejuni mainly employ artificial animal or cell culture models that can be limited in their ability to reflect the in-vivo environment within the human host. Here, we report the development and application of a human three-dimensional (3D) infection model based on tissue engineering to study host-pathogen interactions. Our intestinal 3D tissue model is built on a decellularized extracellular matrix scaffold, which is reseeded with human Caco-2 cells. Dynamic culture conditions enable the formation of a polarized mucosal epithelial barrier reminiscent of the 3D microarchitecture of the human small intestine. Infection with C. jejuni demonstrates that the 3D tissue model can reveal isolate-dependent colonization and barrier disruption phenotypes accompanied by perturbed localization of cell-cell junctions. Pathogenesis-related phenotypes of C. jejuni mutant strains in the 3D model deviated from those obtained with 2D-monolayers, but recapitulated phenotypes previously observed in animal models. Moreover, we demonstrate the involvement of a small regulatory RNA pair, CJnc180/190, during infections and observe different phenotypes of CJnc180/190 mutant strains in 2D vs. 3D infection models. Hereby, the CJnc190 sRNA exerts its pathogenic influence, at least in part, via repression of PtmG, which is involved in flagellin modification. Our results suggest that the Caco-2 cell-based 3D tissue model is a valuable and biologically relevant tool between in-vitro and in-vivo infection models to study virulence of C. jejuni and other gastrointestinal pathogens.},
  language  = {en}
}
@article{AmeriSchiattarellaCrottietal.2020,
  author    = {Ameri, Pietro and Schiattarella, Gabriele Giacomo and Crotti, Lia and Torchio, Margherita and Bertero, Edoardo and Rodolico, Daniele and Forte, Maurizio and Di Mauro, Vittoria and Paolillo, Roberta and Chimenti, Cristina and Torella, Daniele and Catalucci, Daniele and Sciarretta, Sebastiano and Basso, Cristina and Indolfi, Ciro and Perrino, Cinzia},
  title     = {Novel basic science insights to improve the management of heart failure: Review of the working group on cellular and molecular biology of the heart of the Italian Society of Cardiology},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21041192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285085},
  year      = {2020},
  abstract  = {Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.},
  language  = {en}
}