@phdthesis{Zwick2022,
  author    = {Zwick, Leonie},
  title     = {Die Wirksamkeit von Cisplatin und 5-Fluoruracil im Oralen Plattenepithelkarzinom in Abh{\"a}ngigkeit von MAGE-Tumorantigen-Expression mit besonderem Fokus auf MAGE-A11},
  doi       = {10.25972/OPUS-25495},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254956},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In der vorliegenden experimentellen Arbeit wurde in in-vitro-Modellen der Zusammenhang zwischen Expression der Tumorantigene MAGE-A (melanoma-associated antigenes) und der Wirksamkeit von Chemotherapeutika untersucht. Die MAGE-Antigene MAGE-A1 bis MAGE-A12 (ohne A7) kommen in diversen malignen Tumoren vor; neben Melanomen auch in Tumoren der Lunge, Brust, Prostata, Ovarien, Harnblase, des Gastrointestinal-Trakts und des Kopf-Hals-Bereichs. Bereits vielfach wurden Zusammenh{\"a}nge zwischen MAGE-A-Tumorantigen-Expression und einer erh{\"o}hten Tumorinvasivit{\"a}t, Zellproliferation, Metastasierungsrate und k{\"u}rzerem {\"U}berleben hergestellt. In dieser Arbeit gelang nun der erstmalige Nachweis, dass MAGE-A-Tumorantigene die chemotherapeutische Wirksamkeit beeinflussen. Zun{\"a}chst gelang der Nachweis, dass die Expression von MAGE-A11 mit geringer Cisplatin-Wirksamkeit korreliert. Eine im Anschluss generierte MAGE-A11 {\"u}berexprimierende Zelllinie zeigte ein durchschnittlich um 9 \% schlechteres Ansprechen auf Cisplatin als die Kontrollzelllinie.},
  subject      = {Cisplatin},
  language  = {de}
}
@phdthesis{Kreiser2022,
  author    = {Kreiser, Laura},
  title     = {Hartgewebe-chirurgische Therapie der obstruktiven Schlafapnoe des Erwachsenen - eine Literaturanalyse mit Evidenztabellen},
  doi       = {10.25972/OPUS-25208},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252084},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Ein nicht erholsamer Schlaf kann vielf{\"a}ltige Konsequenzen sowohl gesundheitlicher als auch {\"o}konomischer Art aufweisen. Das durch den demografischen Wandel in seiner Bedeutung zunehmende obstruktive Schlafapnoesyndrom kann mit seinen gesundheitlichen Risiken weitreichende Auswir- kungen auf das Individuum besitzen sowie signifikante gesellschaftliche Risiken und Kosten bergen. Wichtig erscheint demnach, sich der Bedeutung dieser Erkrankung bewusst zu werden und die Notwendigkeit der Therapie zu erkennen. Ziel dieser Arbeit bestand darin, die knochenchirurgischen Therapiemethoden als kausalen Therapieansatz der OSA aus der Prim{\"a}rliteratur darzustellen, deren Wirksamkeit insbesondere im Vergleich zur CPAP-Therapie zu eruieren und darauf aufbauend gegebenenfalls notwendige Diagnostik und pr{\"a}disponierende Faktoren f{\"u}r einen chirurgischen Erfolg herauszuarbeiten. Dies geschah im Rahmen der Leitlinienerstellung der aktuellen S3-Leitlinie Nicht erholsamer Schlaf/Schlafst{\"o}rungen, Kapitel „Schlafbezogene Atmungsst{\"o}rungen bei Erwachsenen". Hierbei konnten nach definierten Ein- und Ausschlusskriterien in der Datenbank PubMed und den Literaturverzeichnissen relevanter Studien 50 Studien mit insgesamt 1461 Patienten und zumeist niedrigem Evidenzgrad identifiziert werden, die eine Behandlung der OSA mittels Maxillomandibul{\"a}rem Advancement MMA, Genioglossus Advancement GA oder der Distraktionsosteogenese DO analysierten. Nach neustem Kenntnisstand erscheinen der Apopnoe-Hypopnoe-Index AHI sowie Respiratory-Disturbance-Index RDI als alleiniges Erfolgskriterium obsolet, eine ganzheitliche Betrachtung des Patienten ist unabdingbar. Notwendig ist eine umfassende Diagnostik, welche {\"u}ber eine Polysomnografie hinausgeht. Das MMA zeigt sich im Rahmen dieser Literaturanalyse als erfolgreichste knochenchirurgische Therapiemethode. Auch wenn ein niedriger BMI sowie AHI und eine gering ausgepr{\"a}gte Tagessymptomatik positive pr{\"a}diktive Faktoren f{\"u}r einen Therapieerfolg darstellen, erscheint die MMA auch bei sorgf{\"a}ltig ausgew{\"a}hlten Patienten mit hohem BMI und schwerwiegender OSA erfolgsversprechend, deren Wirksamkeit mit der den Goldstandard setzenden CPAP Therapie in vielf{\"a}ltigen Aspekten ohne signifikanten Unterschied verglichen werden kann. Hierzu z{\"a}hlen unter anderem polysomnografische Werte sowie die Schlafarchitektur und subjektive Ver{\"a}nderungen wie beispielsweise die Tagesm{\"u}digkeit, quantifiziert anhand der Epworth Sleepiness Scale und die subjektive Zufriedenheit. Daneben erfolgte eine detaillierte Auswertung kephalometrischer Daten, der postoperativen Zufriedenheit, des Schnarchens sowie Komplikationen der Behandlungen. Schwierig erscheint allerdings auf der Basis des heutigen Wissenstandes pr{\"a}zise Grenzwerte festzulegen, anhand derer der Einsatz einer chirurgischen Therapie empfohlen werden kann. Die Tatsache der fehlenden Notwendigkeit einer kontinuierlichen Therapie ist ein wichtiger Vorteil dieser kausalen Therapiemethoden. Dennoch ben{\"o}tigt die Schlafmedizin als Querschnittsfach eine Bewertung der therapeutischen Methoden aus unterschiedlichen Sichtweisen. Die knochenchirurgischen Verfahren jedoch lediglich als Zweitlinientherapie anzusehen erscheint nach aktuellem Kenntnisstand obsolet. Die geringe Anzahl an qualitativ hochwertigen Studien erschweren eine differenzierte Aussage. Weitere Studien hoher Evidenz werden zuk{\"u}nftig notwendig sein, um die knochenchirurgischen Therapiemethoden als festen Bestandteil einer f{\"a}cher{\"u}bergreifenden Therapie der OSA zu etablieren.},
  subject      = {Schlafapnoe},
  language  = {de}
}
@phdthesis{Koehler2022,
  author    = {K{\"o}hler, Olga},
  title     = {Analysen von B{\"u}rstenbiopsien oraler L{\"a}sionen im Hinblick auf die Expression von GLUT1 und SHH und deren Bedeutung f{\"u}r die Diagnose maligner Transformationen},
  doi       = {10.25972/OPUS-27036},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270368},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Prinzipiell ist es m{\"o}glich, dass sich Plattenepithelkarzinome aus klinisch gesund erscheinender Mundschleimhaut bilden. Allerdings konnte nachgewiesen werden, dass ein hoher Anteil aus bereits langfristig bestehenden Vorl{\"a}uferl{\"a}sionen, wie z.B. Leukoplakien und L{\"a}sionen, die dem Lichen planus zugeschrieben werden, hervorgeht. Der Expressionsnachweis verschiedener Tumormarker konnte bereits genutzt werden, um den Prozess der Karzinogenese besser zu verstehen und vielversprechende Methoden der Fr{\"u}herkennung zu entwickeln. Die vorliegende Arbeit besch{\"a}ftigt sich mit der Analyse von immunzytochemisch gef{\"a}rbten B{\"u}rstenbiopsien oraler L{\"a}sionen im Hinblick auf die Expression von GLUT1 und SHH und deren Bedeutung f{\"u}r den Prozess der malignen Transformation. Die untersuchte diagnostische Methode erreichte in der vorliegenden Arbeit eine Sensitivit{\"a}t von 80 \% und eine Spezifit{\"a}t von 68 \% f{\"u}r die Verwendung eines GLUT1-Antik{\"o}rpers. F{\"u}r SHH konnte eine Sensitivit{\"a}t von 60 \% und eine Spezifit{\"a}t von 96 \% ermittelt werden.},
  subject      = {B{\"u}rstenbiopsie},
  language  = {de}
}
@phdthesis{Koderer2022,
  author    = {Koderer, Corinna},
  title     = {In Vitro Analyse der Methionin-Restriktion im murinen Modellsystem L929 sowie im Platteneptihelkarzinom - HNSCC},
  doi       = {10.25972/OPUS-27189},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271897},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Die Krebstherapie und Behandlung von Tumoren stellt f{\"u}r die moderne Medizin auch in Zukunft eine enorme Herausforderung dar. Trotz intensiver Forschung konnten in den letzten Jahrzehnten zwar zunehmend Fortschritte erzielt werden, allerdings muss das Spektrum an neuen Therapieformen und M{\"o}glichkeiten kontinuierlich erweitert werden. In den letzten Jahren haben die Kalorienrestriktion sowie die Aminos{\"a}uren- und Proteinrestriktion zunehmend an Bedeutung gewonnen, da sie einen erheblichen positiven Einfluss auf die Entstehung von altersassoziierten Erkrankungen wie z.B. Krebs haben. Allen Formen gemeinsam ist die Induktion eines Low-Energy-Metabolismus, der die Zellen in einen antiproliferativen und selbst-regenerierenden Zustand versetzt. In dieser Arbeit sollte untersucht werden, ob die Methionin-Restriktion als eine Form der Aminos{\"a}urerestriktion sich grunds{\"a}tzlich als Therapieform im Plattenepithelkarzinom (HNSCC) eignet. Zus{\"a}tzlich sollte ein einfaches zellul{\"a}res Modellsystem etabliert werden, das auf metaboler Ebene die Charakterisierung und Analyse des Low-Energy-Metabolismus erm{\"o}glicht. Es konnte aufgezeigt werden, dass die Methionin-Restriktion eine effektive Methode ist, um die Proliferation ausgesuchter Zelllinien des HNSCC zu inhibieren. Des Weiteren konnte aufgezeigt werden, dass der Einsatz von Aminos{\"a}ure-Analoga eine weitere M{\"o}glichkeit darstellt, auf die Proliferation von Tumorzellen Einfluss zu nehmen. Die massenspektrometrische Analyse der murinen Zelllinie L929 mittels LC/MS lieferte {\"u}ber einen Zeitraum von 5 Tagen ein detailliertes Bild des Stoffwechsels von mehr als 150 Metaboliten unter Methionin-Restriktion. Durch die Definition eines charakteristischen Fingerabdrucks nach 48 h und eines nur wenige Metabolite umfassenden Fußabdrucks konnte ein murines Modellsystem etabliert werden, dass die Analyse von potentiellen Wirkstoffen, u.a. sogenannten caloric restriction mimetics, erm{\"o}glicht.},
  language  = {de}
}
@phdthesis{Scheurer2022,
  author    = {Scheurer, Mario Joachim Johannes},
  title     = {Inhibitoren des NF-kappaB pathways zur in vitro Blockade der Inflammation und proapoptotischen Sensitivierung des oralen Plattenepithelkarzinoms f{\"u}r den prospektiven Einsatz in der Tumortherapie},
  doi       = {10.25972/OPUS-27152},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271521},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Entz{\"u}ndliche Prozesse stellen einen zentralen Aspekt der Karzinogenese dar und k{\"o}nnen sowohl zur Induktion als auch zum Progress von Tumoren beitragen. Der NF-kB-Signalweg ist einer der wichtigsten Signaltransduktionswege der In- flammation und Tumorpromotion, was ihn zur plausiblen Zielstruktur f{\"u}r die pros- pektive klinische Tumortherapie machen k{\"o}nnte. In der vorliegenden Arbeit wur- den die Eigenschaften von vier unterschiedlich targetierenden NF-kB-pathway- Inhibitoren - Cortisol, MLN4924, QNZ und TPCA1 - auf die Inflammation, Zell- proliferation und proapoptotische Sensitivierung am in vitro Modell des HNSCC untersucht. Es konnte gezeigt werden, dass die spezifische Auswahl des Inhi- bitors bzw. seines targets entscheidend f{\"u}r den wirkungsvollen Einsatz dieser Wirkstoffgruppe in der antiproliferativen Therapie des HNSCC zu sein scheint. Beispielsweise vermittelte MLN4924 die Freisetzung von IL-8. Cortisol bewirkte die Resistenz der FasL-induzierten Apoptose von HNSCC-Zellen. QNZ wirkte in einigen Zelllinien antiproliferativ und sensitivierend f{\"u}r den FasL-induzierten Zell- tod, beeinflusste jedoch in diesem Zusammenhang kontraproduktiv die IL-8-Sek- retion. Dies disqualifizierte diese Wirkstoffe f{\"u}r die Anwendung in der Therapie von Kopf-Hals-Tumoren. Dahingegen qualifizierte sich TPCA-1 aufgrund folgen- der Eigenschaften als geeigneter Wirkstoff f{\"u}r den prospektiven klinischen Ein- satz: 1) TPCA-1 wirkte antiproliferativ, 2) hemmte die TNF-a-induzierte Inflammation, 3) regulierte die IL-8-Expression herab, 4) wirkte sensitivierend f{\"u}r den TNF-a-induzierten Zelltod, 5) interferierte kaum mit der FasL-vermittelten Apoptose und 6) induzierte Apoptose.},
  subject      = {Plattenepithelcarcinom},
  language  = {de}
}
@article{LinzFaberSchmidetal.2022,
  author    = {Linz, Christian and Faber, Julian and Schmid, Reiner and Kunz, Felix and B{\"o}hm, Hartmut and Hartmann, Stefan and Schweitzer, Tilmann},
  title     = {Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-022-24555-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300427},
  year      = {2022},
  abstract  = {Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.},
  language  = {en}
}
@article{StraubBrandsBorgmannetal.2022,
  author    = {Straub, Anton and Brands, Roman and Borgmann, Anna and Vollmer, Andreas and Hohm, Julian and Linz, Christian and M{\"u}ller-Richter, Urs and K{\"u}bler, Alexander C. and Hartmann, Stefan},
  title     = {Free skin grafting to reconstruct donor sites after radial forearm flap harvesting: a prospective study with platelet-rich fibrin (PRF)},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {12},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11123506},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278854},
  year      = {2022},
  abstract  = {Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44\% versus 86.96\% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts.},
  language  = {en}
}
@article{KodererSchmitzWuenschetal.2022,
  author    = {Koderer, Corinna and Schmitz, Werner and W{\"u}nsch, Anna Chiara and Balint, Julia and El-Mesery, Mohamed and Volland, Julian Manuel and Hartmann, Stefan and Linz, Christian and K{\"u}bler, Alexander Christian and Seher, Axel},
  title     = {Low energy status under methionine restriction is essentially independent of proliferation or cell contact inhibition},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {3},
  issn      = {2073-4409},
  doi       = {10.3390/cells11030551},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262329},
  year      = {2022},
  abstract  = {Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.},
  language  = {en}
}
@phdthesis{Fischer2022,
  author    = {Fischer, Markus},
  title     = {Konzentrationsbestimmung von Ampicillin/Sulbactam in humanem Kieferknochengewebe nach intraven{\"o}ser Applikation bei Patienten mit Kieferosteonekrose},
  doi       = {10.25972/OPUS-28691},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286915},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Kieferosteonekrosen stellen ein relevantes und therapiebed{\"u}rftiges Krankheitsbild mit steigender Inzidenz dar. {\"A}tiologisch unterscheidet man dabei Osteoradionekrose, Medikamenten-induzierte Osteonekrose und Osteomyelitis. Die jeweiligen pathophysiologischen Entstehungsmechanismen sind noch weitgehend ungekl{\"a}rt. Sowohl im klinischen Erscheinungsbild, histologisch als auch therapeutisch bestehend starke Gemeinsamkeiten. Eine antibiotische Behandlung spielt bei allen Formen der Kieferosteonekrosen sowohl prophylaktisch, als auch therapeutisch eine entscheidende Rolle. Es ist bisher nicht bekannt, ob bei Patienten/-innen mit Kieferostenekrose nach intraven{\"o}ser Applikation von Ampicillin/Sulbactam relevante Antibiotikakonzentrationen im Kieferknochen erreicht werden k{\"o}nnen. Im Zeitraum Dezember 2020 bis November 2021 wurden f{\"u}r diese Studie insgesamt 31 Patienten/-innen an der Klinik und Poliklinik f{\"u}r Mund-, Kiefer- und Plastische Gesichtschirurgie des Universit{\"a}tsklinikums W{\"u}rzburg rekrutiert. Es wurden dabei die Gewebekonzentrationen von Ampicillin und Sulbactam jeweils in manifest nekrotischen Knochen und angrenzenden klinisch vitalen Bereichen bestimmt. Die Ergebnisse zeigen keine signifikanten Unterschiede in den Konzentrationen zwischen manifest nekrotischem und klinisch vitalem Kieferknochengewebe. Insgesamt k{\"o}nnen nach intraven{\"o}ser Applikation von Ampicillin und Sulbactam sowohl in klinisch vitalen, als auch manifest nekrotischen Kieferknochenarealen relevante Wirkstoffkonzentrationen erreicht werden. Im Rahmen einer explorativen Datenanalyse zeigte sich eine inverse Korrelation zwischen Zeitpunkt der letzten Antibiose und den erreichten Konzentrationen Ampicillin/Sulbactam im vitalen Knochengewebe. Auch wenn sich bei Kieferosteonekrosen der Einsatz von Antibiotika in Studien und der klinischen Praxis bew{\"a}hrt hat, bestehen noch große Wissensl{\"u}cken. Ein besseres Verst{\"a}ndnis der pathophysiologischen Mechanismen und der spezifischen Rolle daran beteiligter Mikroorganismen k{\"o}nnte dabei helfen zuk{\"u}nftig den Einsatz von Antibiotika deutlich zielgerichteter und effizienter gestalten.},
  subject      = {Knochennekrose},
  language  = {de}
}
@article{VollmerVollmerLangetal.2022,
  author    = {Vollmer, Andreas and Vollmer, Michael and Lang, Gernot and Straub, Anton and K{\"u}bler, Alexander and Gubik, Sebastian and Brands, Roman C. and Hartmann, Stefan and Saravi, Babak},
  title     = {Performance analysis of supervised machine learning algorithms for automatized radiographical classification of maxillary third molar impaction},
  series = {Applied Sciences},
  volume    = {12},
  journal   = {Applied Sciences},
  number    = {13},
  issn      = {2076-3417},
  doi       = {10.3390/app12136740},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281662},
  year      = {2022},
  abstract  = {Background: Oro-antral communication (OAC) is a common complication following the extraction of upper molar teeth. The Archer and the Root Sinus (RS) systems can be used to classify impacted teeth in panoramic radiographs. The Archer classes B-D and the Root Sinus classes III, IV have been associated with an increased risk of OAC following tooth extraction in the upper molar region. In our previous study, we found that panoramic radiographs are not reliable for predicting OAC. This study aimed to (1) determine the feasibility of automating the classification (Archer/RS classes) of impacted teeth from panoramic radiographs, (2) determine the distribution of OAC stratified by classification system classes for the purposes of decision tree construction, and (3) determine the feasibility of automating the prediction of OAC utilizing the mentioned classification systems. Methods: We utilized multiple supervised pre-trained machine learning models (VGG16, ResNet50, Inceptionv3, EfficientNet, MobileNetV2), one custom-made convolutional neural network (CNN) model, and a Bag of Visual Words (BoVW) technique to evaluate the performance to predict the clinical classification systems RS and Archer from panoramic radiographs (Aim 1). We then used Chi-square Automatic Interaction Detectors (CHAID) to determine the distribution of OAC stratified by the Archer/RS classes to introduce a decision tree for simple use in clinics (Aim 2). Lastly, we tested the ability of a multilayer perceptron artificial neural network (MLP) and a radial basis function neural network (RBNN) to predict OAC based on the high-risk classes RS III, IV, and Archer B-D (Aim 3). Results: We achieved accuracies of up to 0.771 for EfficientNet and MobileNetV2 when examining the Archer classification. For the AUC, we obtained values of up to 0.902 for our custom-made CNN. In comparison, the detection of the RS classification achieved accuracies of up to 0.792 for the BoVW and an AUC of up to 0.716 for our custom-made CNN. Overall, the Archer classification was detected more reliably than the RS classification when considering all algorithms. CHAID predicted 77.4\% correctness for the Archer classification and 81.4\% for the RS classification. MLP (AUC: 0.590) and RBNN (AUC: 0.590) for the Archer classification as well as MLP 0.638) and RBNN (0.630) for the RS classification did not show sufficient predictive capability for OAC. Conclusions: The results reveal that impacted teeth can be classified using panoramic radiographs (best AUC: 0.902), and the classification systems can be stratified according to their relationship to OAC (81.4\% correct for RS classification). However, the Archer and RS classes did not achieve satisfactory AUCs for predicting OAC (best AUC: 0.638). Additional research is needed to validate the results externally and to develop a reliable risk stratification tool based on the present findings.},
  language  = {en}
}
@article{FuchsKreczyBrueckneretal.2022,
  author    = {Fuchs, Andreas and Kreczy, Dorothea and Br{\"u}ckner, Theresa and Gbureck, Uwe and Stahlhut, Philipp and Bengel, Melanie and Hoess, Andreas and Nies, Berthold and Bator, Julia and Klammert, Uwe and Linz, Christian and Ewald, Andrea},
  title     = {Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules},
  series = {Clinical Oral Investigations},
  volume    = {26},
  journal   = {Clinical Oral Investigations},
  number    = {3},
  issn      = {1436-3771},
  doi       = {10.1007/s00784-021-04231-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268872},
  pages     = {2619-2633},
  year      = {2022},
  abstract  = {Objectives Magnesium phosphate-based cements begin to catch more attention as bone substitute materials and especially as alternatives for the more commonly used calcium phosphates. In bone substitutes for augmentation purposes, atraumatic materials with good biocompatibility and resorbability are favorable. In the current study, we describe the in vivo testing of novel bone augmentation materials in form of spherical granules based on a calcium-doped magnesium phosphate (CaMgP) cement. Materials and Methods Granules with diameters between 500 and 710 μm were fabricated via the emulsification of CaMgP cement pastes in a lipophilic liquid. As basic material, two different CaMgP formulations were used. The obtained granules were implanted into drill hole defects at the distal femoral condyle of 27 New Zealand white rabbits for 6 and 12 weeks. After explantation, the femora were examined via X-ray diffraction analysis, histological staining, radiological examination, and EDX measurement. Results Both granule types display excellent biocompatibility without any signs of inflammation and allow for proper bone healing without the interposition of connective tissue. CaMgP granules show a fast and continuous degradation and enable fully adequate bone regeneration. Conclusions Due to their biocompatibility, their degradation behavior, and their completely spherical morphology, these CaMgP granules present a promising bone substitute material for bone augmentation procedures, especially in sensitive areas. Clinical Relevance The mostly insufficient local bone supply after tooth extractions complicates prosthetic dental restoration or makes it even impossible. Therefore, bone augmentation procedures are oftentimes inevitable. Spherical CaMgP granules may represent a valuable bone replacement material in many situations.},
  language  = {en}
}
@article{BoschertTeuschMuellerRichteretal.2022,
  author    = {Boschert, Verena and Teusch, Jonas and M{\"u}ller-Richter, Urs D. A. and Brands, Roman C. and Hartmann, Stefan},
  title     = {PKM2 modulation in head and neck squamous cell carcinoma},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23020775},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284458},
  year      = {2022},
  abstract  = {The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.},
  language  = {en}
}
@article{VollmerSaraviVollmeretal.2022,
  author    = {Vollmer, Andreas and Saravi, Babak and Vollmer, Michael and Lang, Gernot Michael and Straub, Anton and Brands, Roman C. and K{\"u}bler, Alexander and Gubik, Sebastian and Hartmann, Stefan},
  title     = {Artificial intelligence-based prediction of oroantral communication after tooth extraction utilizing preoperative panoramic radiography},
  series = {Diagnostics},
  volume    = {12},
  journal   = {Diagnostics},
  number    = {6},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics12061406},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278814},
  year      = {2022},
  abstract  = {Oroantral communication (OAC) is a common complication after tooth extraction of upper molars. Profound preoperative panoramic radiography analysis might potentially help predict OAC following tooth extraction. In this exploratory study, we evaluated n = 300 consecutive cases (100 OAC and 200 controls) and trained five machine learning algorithms (VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50) to predict OAC versus non-OAC (binary classification task) from the input images. Further, four oral and maxillofacial experts evaluated the respective panoramic radiography and determined performance metrics (accuracy, area under the curve (AUC), precision, recall, F1-score, and receiver operating characteristics curve) of all diagnostic approaches. Cohen's kappa was used to evaluate the agreement between expert evaluations. The deep learning algorithms reached high specificity (highest specificity 100\% for InceptionV3) but low sensitivity (highest sensitivity 42.86\% for MobileNetV2). The AUCs from VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50 were 0.53, 0.60, 0.67, 0.51, and 0.56, respectively. Expert 1-4 reached an AUC of 0.550, 0.629, 0.500, and 0.579, respectively. The specificity of the expert evaluations ranged from 51.74\% to 95.02\%, whereas sensitivity ranged from 14.14\% to 59.60\%. Cohen's kappa revealed a poor agreement for the oral and maxillofacial expert evaluations (Cohen's kappa: 0.1285). Overall, present data indicate that OAC cannot be sufficiently predicted from preoperative panoramic radiography. The false-negative rate, i.e., the rate of positive cases (OAC) missed by the deep learning algorithms, ranged from 57.14\% to 95.24\%. Surgeons should not solely rely on panoramic radiography when evaluating the probability of OAC occurrence. Clinical testing of OAC is warranted after each upper-molar tooth extraction.},
  language  = {en}
}
@article{VollmerVollmerLangetal.2022,
  author    = {Vollmer, Andreas and Vollmer, Michael and Lang, Gernot and Straub, Anton and Shavlokhova, Veronika and K{\"u}bler, Alexander and Gubik, Sebastian and Brands, Roman and Hartmann, Stefan and Saravi, Babak},
  title     = {Associations between periodontitis and COPD: An artificial intelligence-based analysis of NHANES III},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {23},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11237210},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312713},
  year      = {2022},
  abstract  = {A number of cross-sectional epidemiological studies suggest that poor oral health is associated with respiratory diseases. However, the number of cases within the studies was limited, and the studies had different measurement conditions. By analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), this study aimed to investigate possible associations between chronic obstructive pulmonary disease (COPD) and periodontitis in the general population. COPD was diagnosed in cases where FEV (1)/FVC ratio was below 70\% (non-COPD versus COPD; binary classification task). We used unsupervised learning utilizing k-means clustering to identify clusters in the data. COPD classes were predicted with logistic regression, a random forest classifier, a stochastic gradient descent (SGD) classifier, k-nearest neighbors, a decision tree classifier, Gaussian naive Bayes (GaussianNB), support vector machines (SVM), a custom-made convolutional neural network (CNN), a multilayer perceptron artificial neural network (MLP), and a radial basis function neural network (RBNN) in Python. We calculated the accuracy of the prediction and the area under the curve (AUC). The most important predictors were determined using feature importance analysis. Results: Overall, 15,868 participants and 19 feature variables were included. Based on k-means clustering, the data were separated into two clusters that identified two risk characteristic groups of patients. The algorithms reached AUCs between 0.608 (DTC) and 0.953\% (CNN) for the classification of COPD classes. Feature importance analysis of deep learning algorithms indicated that age and mean attachment loss were the most important features in predicting COPD. Conclusions: Data analysis of a large population showed that machine learning and deep learning algorithms could predict COPD cases based on demographics and oral health feature variables. This study indicates that periodontitis might be an important predictor of COPD. Further prospective studies examining the association between periodontitis and COPD are warranted to validate the present results.},
  language  = {en}
}
@article{VollandKauppSchmitzetal.2022,
  author    = {Volland, Julian Manuel and Kaupp, Johannes and Schmitz, Werner and W{\"u}nsch, Anna Chiara and Balint, Julia and M{\"o}llmann, Marc and El-Mesery, Mohamed and Frackmann, Kyra and Peter, Leslie and Hartmann, Stefan and K{\"u}bler, Alexander Christian and Seher, Axel},
  title     = {Mass spectrometric metabolic fingerprinting of 2-Deoxy-D-Glucose (2-DG)-induced inhibition of glycolysis and comparative analysis of methionine restriction versus glucose restriction under perfusion culture in the murine L929 model system},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {16},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23169220},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286007},
  year      = {2022},
  abstract  = {All forms of restriction, from caloric to amino acid to glucose restriction, have been established in recent years as therapeutic options for various diseases, including cancer. However, usually there is no direct comparison between the different restriction forms. Additionally, many cell culture experiments take place under static conditions. In this work, we used a closed perfusion culture in murine L929 cells over a period of 7 days to compare methionine restriction (MetR) and glucose restriction (LowCarb) in the same system and analysed the metabolome by liquid chromatography mass spectrometry (LC-MS). In addition, we analysed the inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) over a period of 72 h. 2-DG induced very fast a low-energy situation by a reduced glycolysis metabolite flow rate resulting in pyruvate, lactate, and ATP depletion. Under perfusion culture, both MetR and LowCarb were established on the metabolic level. Interestingly, over the period of 7 days, the metabolome of MetR and LowCarb showed more similarities than differences. This leads to the conclusion that the conditioned medium, in addition to the different restriction forms, substantially reprogramm the cells on the metabolic level.},
  language  = {en}
}
@article{WinterSchulzSchmitteretal.2022,
  author    = {Winter, Anna and Schulz, Stefan M. and Schmitter, Marc and Brands, Roman C. and Straub, Anton and K{\"u}bler, Alexander and Borgmann, Anna and Hartmann, Stefan},
  title     = {Oral-health-related quality of life in patients with medication-related osteonecrosis of the jaw: a prospective clinical study},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {19},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {18},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph191811709},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288141},
  year      = {2022},
  abstract  = {Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients' OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov-Smirnov test, two-way mixed ANOVAs, and follow-up Mann-Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients' perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.},
  language  = {en}
}
@article{StraubStapfFischeretal.2022,
  author    = {Straub, Anton and Stapf, Maximilian and Fischer, Markus and Vollmer, Andreas and Linz, Christian and L{\^a}m, Thi{\^e}n-Tr{\´i} and K{\"u}bler, Alexander and Brands, Roman C. and Scherf-Clavel, Oliver and Hartmann, Stefan},
  title     = {Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {19},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {22},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph192214917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297413},
  year      = {2022},
  abstract  = {Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.},
  language  = {en}
}
@article{StraubVollmerLametal.2022,
  author    = {Straub, Anton and Vollmer, Andreas and L{\^a}m, Thi{\^e}n-Tr{\´i} and Brands, Roman C. and Stapf, Maximilian and Scherf-Clavel, Oliver and Bittrich, Max and Fuchs, Andreas and K{\"u}bler, Alexander C. and Hartmann, Stefan},
  title     = {Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam},
  series = {Clinical Oral Investigations},
  volume    = {26},
  journal   = {Clinical Oral Investigations},
  number    = {12},
  doi       = {10.1007/s00784-022-04663-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324515},
  pages     = {7033-7044},
  year      = {2022},
  abstract  = {Objectives Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. Materials and methods We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. Results Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. Conclusions The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. Clinical relevance We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.},
  language  = {en}
}