@article{JockelSchneiderHarksHaubitzetal.2014, author = {Jockel-Schneider, Yvonne and Harks, Inga and Haubitz, Imme and Fickl, Stefan and Eigenthaler, Martin and Schlagenhauf, Ulrich and Baulmann, Johannes}, title = {Arterial Stiffness and Pulse Wave Reflection Are Increased in Patients Suffering from Severe Periodontitis}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {8}, issn = {1932-6203}, doi = {10.1371/journalone.0103449}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119459}, pages = {e103449}, year = {2014}, abstract = {Aim: This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA). Material and Methods: In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph). Results: Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls. Conclusions: The results of this study confirm the association between periodontal inflammation and increased cardiovascular risk shown by impaired vascular health in case of severe periodontitis. As impaired vascular health is a common finding in patients suffering from severe periodontal disease a concomitant routine cardiovascular evaluation may be advised.}, 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{MaternKochPetersmannetal.2020, author = {Matern, Johannes and Koch, Raphael and Petersmann, Astrid and Kocher, Thomas and Eickholz, Peter and Lorenz, Katrin and Kim, Ti-Sun and Meyle, J{\"o}rg and Kaner, Doğan and Schlagenhauf, Ulrich and Gravemeier, Martina and Harks, Inga and Ehmke, Benjamin}, title = {Effect of periodontal therapy on adipokine biomarkers in overweight}, series = {Journal of Clinical Periodontology}, volume = {47}, journal = {Journal of Clinical Periodontology}, number = {7}, doi = {10.1111/jcpe.13288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215546}, pages = {842 -- 850}, year = {2020}, abstract = {Aim The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy. Materials and methods This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m\(^{2}\)) or moderate (21-24 kg/m\(^{2}\)) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4. Results At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable. Conclusion Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients.}, language = {en} } @article{JockelSchneiderStoelzelHessetal.2022, author = {Jockel-Schneider, Yvonne and Stoelzel, Peggy and Hess, Jeanine and Haubitz, Imme and Fickl, Stefan and Schlagenhauf, Ulrich}, title = {Impact of a specific collagen peptide food supplement on periodontal inflammation in aftercare patients — a randomised controlled trial}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {21}, issn = {2072-6643}, doi = {10.3390/nu14214473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290471}, year = {2022}, abstract = {Background: This controlled clinical trial evaluated the impact of a specific collagen peptide food supplement on parameters of periodontal inflammation in aftercare patients. Methods: A total of 39 study patients were enrolled. At baseline, bleeding on probing (BoP; primary outcome), gingival index (GI), plaque control record (PCR), recession (REC) and probing pocket depth (PPD) for the calculation of the periodontal inflamed surface area (PISA) were documented. After subsequent professional mechanical plaque removal (PMPR), participants were randomly provided with a supply of sachets containing either a specific collagen peptide preparation (test group; n = 20) or a placebo (placebo group; n = 19) to be consumed dissolved in liquid once daily until reevaluation at day 90. Results: PMPR supplemented with the consumption of the specific collagen peptides resulted in a significantly lower mean percentage of persisting BoP-positive sites than PMPR plus placebo (test: 10.4\% baseline vs. 3.0\% reevaluation; placebo: 14.2\% baseline vs. 9.4\% reevaluation; effect size: 0.86). Mean PISA and GI values were also reduced compared to baseline, with a significant difference in favor of the test group (PISA test: 170.6 mm\(^2\) baseline vs. 53.7 mm\(^2\) reevaluation; PISA placebo: 229.4 mm\(^2\) baseline vs. 184.3 mm\(^2\) reevaluation; GI test: 0.5 baseline vs. 0.1 reevaluation; GI placebo: 0.4 baseline vs. 0.3 reevaluation). PCR was also significantly decreased in both experimental groups at revaluation, but the difference between the groups did not reach the level of significance. Conclusions: The supplementary intake of specific collagen peptides may further enhance the anti-inflammatory effect of PMPR in periodontal recall patients.}, language = {en} } @article{KorkmazPuladiGalleretal.2021, author = {Korkmaz, Y{\"u}ksel and Puladi, Behrus and Galler, Kerstin and K{\"a}mmerer, Peer W. and Schr{\"o}der, Agnes and G{\"o}lz, Lina and Sparwasser, Tim and Bloch, Wilhelm and Friebe, Andreas and Deschner, James}, title = {Inflammation in the human periodontium induces downregulation of the α\(_1\)- and β\(_1\)-subunits of the sGC in cementoclasts}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {2}, issn = {1422-0067}, doi = {10.3390/ijms22020539}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285783}, year = {2021}, abstract = {Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α\(_1\)- and β\(_1\)-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α\(_1\)- and β\(_1\)-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α\(_1\)- and β\(_1\)-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.}, language = {en} } @phdthesis{Hutter2008, author = {Hutter, Gerhard J.}, title = {Kulturunabh{\"a}ngige 16S rRNA Analyse des subgingivalen bakteriellen Biofilms bei der aggressiven Parodontitis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28944}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Kulturunabh{\"a}ngige 16S rRNA Analyse des subgingivalen bakteriellen Biofilms bei der aggressiven Parodontitis und Vergleich mit bekannten Bakterien bzw. Phylotypen, die im Zusammenhang mit der parodontalen Flora nachgewiesen wurde. Putative Pathogene wurden bestimmt.}, subject = {Bakterien}, language = {de} } @article{Schlagenhauf2022, author = {Schlagenhauf, Ulrich}, title = {On the role of dietary nitrate in the maintenance of systemic and oral health}, series = {Dentistry Journal}, volume = {10}, journal = {Dentistry Journal}, number = {5}, issn = {2304-6767}, doi = {10.3390/dj10050084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275168}, year = {2022}, abstract = {The assessment of the significance of nitrates ingested with food has undergone a fundamental change in recent years after many controversial discussions. While for a long time, a diet as low in nitrates as possible was advocated on the basis of epidemiological data suggesting a cancer-promoting effect of nitrate-rich diets, more recent findings show that dietary nitrate, after its conversion to nitrite by nitrate-reducing bacteria of the oral microbiota, is an indispensable alternative source for the formation of nitric oxide (NO), which comprises a key element in the physiology of a variety of central body functions such as blood pressure control, defense against invading bacteria and maintenance of a eubiotic microbiota in the gut and oral cavity. This compact narrative review aims to present the evidence supported by clinical and in vitro studies on the ambivalent nature of dietary nitrates for general and oral health and to explain how the targeted adjuvant use of nitrate-rich diets could open new opportunities for a more cause-related control of caries and periodontal disease.}, language = {en} } @phdthesis{Herrmann2011, author = {Herrmann, Claudia}, title = {Parodontaler Status bei Typ-1-Diabetikern und insulinpflichtigen Typ-2-Diabetikern}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71271}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Hintergrund: Ein bidirektionaler Zusammenhang zwischen Diabetes mellitus und Parodontitis wird durch zahlreiche wissenschaftliche Arbeiten best{\"a}tigt. Bislang weitgehend unerforscht bleibt jedoch die Frage, ob die beiden pathophysiologisch verschiedenen Krankheitsbilder des Typ-1- und des Typ-2-Diabetes bez{\"u}glich H{\"a}ufigkeit und Ausmaß parodontaler Erkrankungen Divergenzen aufzeigen. Zielstellung: Ziel der vorliegenden Untersuchung war es die parodontale Gesundheit eines Patientenkollektivs alterskorrelierter Diabetiker mit inad{\"a}quat eingestelltem Blutzucker in Abh{\"a}ngigkeit vom vorliegenden Diabetestyp (Typ-1 bzw. Typ-2) zu evaluieren. Material und Methoden: 101 insulinpflichtige Diabetiker (Typ-1: n=47, Typ-2: n=54.), welche in der Klinik Saale im Rahmen einer station{\"a}ren Reha-Maßnahme behandelt wurden, nahmen an der Studie teil. Dabei mussten sie folgende Einschlusskriterien erf{\"u}llen: Alter 35-60J., HbA1c≥7\%, Insulintherapie, Nichtraucher, ≥10 nat{\"u}rliche Z{\"a}hne, keine parodontale Therapie oder syste¬mische Antibiose in den letzten 6 Monaten. Erfasst wurden die Zahl der nat{\"u}rlichen Z{\"a}hne sowie an den Z{\"a}hnen 16,21,24,36,41,44 (Ramfjord-Z{\"a}hne) die Parameter Taschentiefe, Attachmentniveau, Gingiva-Index (GI) nach L{\"o}e\&Silness und Plaque-Index (PI) nach Quigley\&Hein. Basierend auf Attachmentniveau und Sondie-rungstiefen wurden die Patienten zudem gem{\"a}ß den Kriterien der CDC/AAP-Arbeitsgruppe zur Klassifizierung parodontaler Erkrankungen einer von drei parodontalen Erkrankungskategorien (gesund-mild/moderat/schwer) zugeordnet. Des Weiteren wurden den {\"a}rztlichen Entlassungsbriefen der Klinik Saale zahlreiche charakteristische Daten entnommen, wie Patientenalter, Krankheitsdauer, HbA1c, Ausmaß von Folge- und Begleiterkrankungen sowie insbesondere auch BMI und CRP. Ergebnisse: Trotz erheblich k{\"u}rzerer Krankheitsdauer (11,7 vs. 20,3 Jahre) und bei vergleichbarer Altersstruktur (51,3 vs. 48,3 Jahre) zeigten Typ-2-Diabetiker gegen{\"u}ber Typ-1-Diabetikern eine signifikant geringere Zahnzahl (24,5 vs. 26,2 Z{\"a}hne; p<0,05), einen signifikant erh{\"o}hten GI-Score (4,8 vs. 2,9; p<0,001), einen signifikant erh{\"o}hten PI-Score (8,8 vs. 6,4), einen signifikant h{\"o}heren Anteil schwerer Parodontalerkankungen gem{\"a}ß CDC/AAP-Kriterien (40,7\% vs. 23,4\%; p<0,05), signifikant h{\"o}here CRP-Werte (0,66 vs.0,31 mg/dl; p<0,001) und einen signifikant h{\"o}heren BMI (37,08 vs. 27,05 kg/m²; p<0,001). Die HbA1c-Werte beider Gruppen waren nicht statistisch signifikant unterschiedlich (8,88 vs. 8,39\%). Schlussfolgerung: Im Vergleich von Typ-1- und insulinpflichtigen Typ-2-Diabetikern mit ann{\"a}hernd vergleichbarer Altersstruktur und Diabeteseinstellung zeigen Typ-2-Diabetiker, trotz deutlich k{\"u}rzerer Diabetesdauer, signifikant h{\"a}ufiger Symptome einer schweren Parodontitis. Dies deutet darauf hin, dass neben Hyperglyk{\"a}mien weitere f{\"u}r Typ-2-Diabetes typische {\"a}tiologische Faktoren, insbesondere subklinische Inflammationen im Rahmen des Metabolischen Syndroms, f{\"u}r die erh{\"o}hte Pr{\"a}valenz parodontaler Erkrankungen unter Diabetikern von Bedeutung sind. F{\"u}r detaillierte Aussagen sind weitere gezielte klinische Studien notwendig.}, subject = {Parodontitis}, language = {de} } @phdthesis{Suhl2009, author = {Suhl, Anja}, title = {Phylogenetische Analyse und Antibiotikaresistenzbestimmung von subgingivalen bakteriellen Isolaten aus Parodontitispatienten}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40076}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Parodontitis ist eine Erkrankung des Zahnhalteapparates, die durch einen komplexen bakteriellen Biofilm unterhalten wird. Neben Mikroorganismen wie A. actinomycetemcomitans, P. gingivalis, T. denticola und T. forsythensis werden Keime unbekannter Spezies in parodontalen Taschen ausfindig gemacht. Durch die Entschl{\"u}sselung von 16S rRNA-Gensequenzen konnte die orale Flora nahezu vollst{\"a}ndig katalogisiert werden. Allerdings fehlen bei vielen Phylotypen die entsprechenden Typst{\"a}mme f{\"u}r weitergehende ph{\"a}notypische Analysen. Grundlage dieser Arbeit bildeten 59 Patientenisolate der Parodontitis-Stammsammlung des Instituts f{\"u}r Hygiene und Mikrobiologie bei denen partielle 16S rRNA Sequenzen keine Spezieszuordnung erm{\"o}glichten. Nahezu vollst{\"a}ndige 16S rRNA-Sequenzen wurden erstellt und mit Datenbankeintr{\"a}gen verglichen. Bei mehr als der H{\"a}lfte der St{\"a}mme konnte keine taxonomische Zuordnung auf Sequenzierebene getroffen werden. 43 Isolate wuchsen unter aerober Atmosph{\"a}re, 16 ben{\"o}tigten eine anaerobe Umgebung. Alle Kulturmorphologien und nach Gram gef{\"a}rbten mikroskopischen Pr{\"a}parate wurden fotografisch dokumentiert und katalogisiert. Die hier untersuchten St{\"a}mme, die zuf{\"a}llig auf der Basis taxonomischer Fragestellungen ausgew{\"a}hlt wurden, waren zum {\"u}berwiegenden Teil auf Amoxicillin und Metronidazol empfindlich. Diese Antibiotika finden alle ihre Verwendung bei der Parodontitistherapie. Ciprofloxacin, das wegen seiner intrazellul{\"a}ren Wirkung ein interessantes Agens ist, wies v.a. bei Actinomyceten und Streptokokken Wirkungsl{\"u}cken auf. Es bleibt zu diskutieren, ob dieser Umstand nachteilig ist, da auf der einen Seite diese Genera ein orales Reservoir f{\"u}r Gyrasehemmer-Resistenzen ausbilden k{\"o}nnen, auf der anderen Seite diese grampositiven Keime m{\"o}glicherweise parodontalprotektiv wirken k{\"o}nnten. In dieser Studie konnte eine Stammsammlung charakterisiert werden, die zuk{\"u}nftig insbesondere angesichts der zu erwartenden Entschl{\"u}sselung des oralen Metagenoms f{\"u}r weitere funktionelle Untersuchungen von Interesse sein d{\"u}rfte.}, subject = {Parodontitis}, language = {de} } @article{DannewitzSommererStoelzeletal.2020, author = {Dannewitz, Bettina and Sommerer, Claudia and St{\"o}lzel, Peggy and Baid-Agrawal, Seema and Nadal, Jennifer and B{\"a}rthlein, Barbara and Wanner, Christoph and Eckardt, Kai-Uwe and Zeier, Martin and Schlagenhauf, Ulrich and Krane, Vera and Jockel-Schneider, Yvonne}, title = {Status of periodontal health in German patients suffering from chronic kidney disease—Data from the GCKD study}, series = {Journal of Clinical Periodontology}, volume = {47}, journal = {Journal of Clinical Periodontology}, number = {1}, doi = {10.1111/jcpe.13208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217821}, pages = {19 -- 29}, year = {2020}, abstract = {Aim To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. Material and methods The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. Results 24.4\% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6\% displayed moderate and 27\% severe periodontitis. Questionnaire data revealed that 62.3\% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4\% denied having received any systematic periodontal therapy so far, although 50\% of them indicated to visit their dentist regularly for professional tooth cleanings. Conclusion While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.}, language = {en} } @article{WaltherGonzalesGroegeretal.2022, author = {Walther, Kay-Arne and Gonzales, Jos{\´e} Roberto and Gr{\"o}ger, Sabine and Ehmke, Benjamin and Kaner, Dogan and Lorenz, Katrin and Eickholz, Peter and Kocher, Thomas and Kim, Ti-Sun and Schlagenhauf, Ulrich and Koch, Raphael and Meyle, J{\"o}rg}, title = {The role of polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 genes in non-surgical periodontal therapy}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {13}, issn = {1422-0067}, doi = {10.3390/ijms23137266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284386}, year = {2022}, abstract = {Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.}, language = {en} }