TY - JOUR A1 - Wünsch, Anna Chiara A1 - Ries, Elena A1 - Heinzelmann, Sina A1 - Frabschka, Andrea A1 - Wagner, Peter Christoph A1 - Rauch, Theresa A1 - Koderer, Corinna A1 - El-Mesery, Mohamed A1 - Volland, Julian Manuel A1 - Kübler, Alexander Christian A1 - Hartmann, Stefan A1 - Seher, Axel T1 - Metabolic silencing via methionine-based amino acid restriction in head and neck cancer JF - Current Issues in Molecular Biology N2 - In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines. KW - amino acid restriction KW - caloric restriction KW - methionine KW - HNSCC KW - SCCHN KW - cisplatin KW - amino acid transporter KW - SLC-family KW - cell vitality KW - low energy metabolism Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319257 SN - 1467-3045 VL - 45 IS - 6 SP - 4557 EP - 4573 ER - TY - JOUR A1 - Winter, Anna A1 - Schulz, Stefan M. A1 - Schmitter, Marc A1 - Brands, Roman C. A1 - Straub, Anton A1 - Kübler, Alexander A1 - Borgmann, Anna A1 - Hartmann, Stefan T1 - Oral-health-related quality of life in patients with medication-related osteonecrosis of the jaw: a prospective clinical study JF - International Journal of Environmental Research and Public Health N2 - 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. KW - oral-health-related quality of life KW - satisfaction with life KW - oral health KW - medication-related osteonecrosis of the jaw KW - treatment benefit KW - OHIP-49 KW - SWLS Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288141 SN - 1660-4601 VL - 19 IS - 18 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Vollmer, Michael A1 - Lang, Gernot A1 - Straub, Anton A1 - Shavlokhova, Veronika A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Brands, Roman A1 - Hartmann, Stefan A1 - Saravi, Babak T1 - Associations between periodontitis and COPD: An artificial intelligence-based analysis of NHANES III JF - Journal of Clinical Medicine N2 - 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. KW - COPD KW - periodontitis KW - bone loss KW - machine learning KW - prediction KW - artificial intelligence KW - model KW - gingivitis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312713 SN - 2077-0383 VL - 11 IS - 23 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Vollmer, Michael A1 - Lang, Gernot A1 - Straub, Anton A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Brands, Roman C. A1 - Hartmann, Stefan A1 - Saravi, Babak T1 - Performance analysis of supervised machine learning algorithms for automatized radiographical classification of maxillary third molar impaction JF - Applied Sciences N2 - 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. KW - oro-antral communication KW - oro-antral fistula KW - prediction KW - machine learning KW - teeth extraction KW - complications KW - classification KW - artificial intelligence Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281662 SN - 2076-3417 VL - 12 IS - 13 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Vollmer, Michael A1 - Lang, Gernot A1 - Straub, Anton A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Brands, Roman C. A1 - Hartmann, Stefan A1 - Saravi, Babak T1 - Automated assessment of radiographic bone loss in the posterior maxilla utilizing a multi-object detection artificial intelligence algorithm JF - Applied Sciences N2 - Periodontitis is one of the most prevalent diseases worldwide. The degree of radiographic bone loss can be used to assess the course of therapy or the severity of the disease. Since automated bone loss detection has many benefits, our goal was to develop a multi-object detection algorithm based on artificial intelligence that would be able to detect and quantify radiographic bone loss using standard two-dimensional radiographic images in the maxillary posterior region. This study was conducted by combining three recent online databases and validating the results using an external validation dataset from our organization. There were 1414 images for training and testing and 341 for external validation in the final dataset. We applied a Keypoint RCNN with a ResNet-50-FPN backbone network for both boundary box and keypoint detection. The intersection over union (IoU) and the object keypoint similarity (OKS) were used for model evaluation. The evaluation of the boundary box metrics showed a moderate overlapping with the ground truth, revealing an average precision of up to 0.758. The average precision and recall over all five folds were 0.694 and 0.611, respectively. Mean average precision and recall for the keypoint detection were 0.632 and 0.579, respectively. Despite only using a small and heterogeneous set of images for training, our results indicate that the algorithm is able to learn the objects of interest, although without sufficient accuracy due to the limited number of images and a large amount of information available in panoramic radiographs. Considering the widespread availability of panoramic radiographs as well as the increasing use of online databases, the presented model can be further improved in the future to facilitate its implementation in clinics. KW - radiographic bone loss KW - alveolar bone loss KW - maxillofacial surgery KW - deep learning KW - classification KW - artificial intelligence KW - object detection Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305050 SN - 2076-3417 VL - 13 IS - 3 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Saravi, Babak A1 - Vollmer, Michael A1 - Lang, Gernot Michael A1 - Straub, Anton A1 - Brands, Roman C. A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Hartmann, Stefan T1 - Artificial intelligence-based prediction of oroantral communication after tooth extraction utilizing preoperative panoramic radiography JF - Diagnostics N2 - 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. KW - artificial intelligence KW - deep learning KW - X-ray KW - tooth extraction KW - oroantral fistula KW - operative planning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278814 SN - 2075-4418 VL - 12 IS - 6 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Nagler, Simon A1 - Hörner, Marius A1 - Hartmann, Stefan A1 - Brands, Roman C. A1 - Breitenbücher, Niko A1 - Straub, Anton A1 - Kübler, Alexander A1 - Vollmer, Michael A1 - Gubik, Sebastian A1 - Lang, Gernot A1 - Wollborn, Jakob A1 - Saravi, Babak T1 - Performance of artificial intelligence-based algorithms to predict prolonged length of stay after head and neck cancer surgery JF - Heliyon N2 - Background Medical resource management can be improved by assessing the likelihood of prolonged length of stay (LOS) for head and neck cancer surgery patients. The objective of this study was to develop predictive models that could be used to determine whether a patient's LOS after cancer surgery falls within the normal range of the cohort. Methods We conducted a retrospective analysis of a dataset consisting of 300 consecutive patients who underwent head and neck cancer surgery between 2017 and 2022 at a single university medical center. Prolonged LOS was defined as LOS exceeding the 75th percentile of the cohort. Feature importance analysis was performed to evaluate the most important predictors for prolonged LOS. We then constructed 7 machine learning and deep learning algorithms for the prediction modeling of prolonged LOS. Results The algorithms reached accuracy values of 75.40 (radial basis function neural network) to 97.92 (Random Trees) for the training set and 64.90 (multilayer perceptron neural network) to 84.14 (Random Trees) for the testing set. The leading parameters predicting prolonged LOS were operation time, ischemia time, the graft used, the ASA score, the intensive care stay, and the pathological stages. The results revealed that patients who had a higher number of harvested lymph nodes (LN) had a lower probability of recurrence but also a greater LOS. However, patients with prolonged LOS were also at greater risk of recurrence, particularly when fewer (LN) were extracted. Further, LOS was more strongly correlated with the overall number of extracted lymph nodes than with the number of positive lymph nodes or the ratio of positive to overall extracted lymph nodes, indicating that particularly unnecessary lymph node extraction might be associated with prolonged LOS. Conclusions The results emphasize the need for a closer follow-up of patients who experience prolonged LOS. Prospective trials are warranted to validate the present results. KW - prediction KW - head and neck cancer KW - machine learning KW - deep learning KW - artificial intelligence KW - length of stay KW - cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350416 SN - 2405-8440 VL - 9 IS - 11 ER - TY - JOUR A1 - Volland, Julian Manuel A1 - Kaupp, Johannes A1 - Schmitz, Werner A1 - Wünsch, Anna Chiara A1 - Balint, Julia A1 - Möllmann, Marc A1 - El-Mesery, Mohamed A1 - Frackmann, Kyra A1 - Peter, Leslie A1 - Hartmann, Stefan A1 - Kübler, Alexander Christian A1 - Seher, Axel T1 - 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 JF - International Journal of Molecular Sciences N2 - 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. KW - amino acid restriction KW - glucose restriction KW - mass spectrometry KW - low carb KW - 2-deoxy-D-glucose KW - 2-DG KW - methionine KW - perfusion culture KW - energy restriction KW - caloric restriction Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286007 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Straub, Anton A1 - Vollmer, Andreas A1 - Lâm, Thiên-Trí A1 - Brands, Roman C. A1 - Stapf, Maximilian A1 - Scherf-Clavel, Oliver A1 - Bittrich, Max A1 - Fuchs, Andreas A1 - Kübler, Alexander C. A1 - Hartmann, Stefan T1 - Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam JF - Clinical Oral Investigations N2 - 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. KW - osteonecrosis of the jaw KW - osteoradionecrosis KW - antiresorptive drug-related osteonecrosis of the jaw KW - ARONJ KW - oral microbiome KW - agar diffusion test Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324515 VL - 26 IS - 12 ER - TY - JOUR A1 - Straub, Anton A1 - Stapf, Maximilian A1 - Fischer, Markus A1 - Vollmer, Andreas A1 - Linz, Christian A1 - Lâm, Thiên-Trí A1 - Kübler, Alexander A1 - Brands, Roman C. A1 - Scherf-Clavel, Oliver A1 - Hartmann, Stefan T1 - Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw JF - International Journal of Environmental Research and Public Health N2 - 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. KW - osteonecrosis of the jaw KW - ARONJ KW - MRONJ KW - ONJ KW - osteoradionecrosis KW - antibiotic bone concentration KW - jaw bone KW - beta-lactam KW - ampicillin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297413 SN - 1660-4601 VL - 19 IS - 22 ER -