start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=22 article-no= start-page=5155 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, dental pulp has been attracting attention as a promising source of multipotent mesenchymal stem cells (MSCs) for various clinical applications of regeneration fields. To date, we have succeeded in establishing rat dental pulp-derived cells showing the characteristics of odontoblasts under in vitro conditions. We named them Tooth matrix-forming, GFP rat-derived Cells (TGC). However, though TGC form massive dentin-like hard tissues under in vivo conditions, this does not lead to the induction of polar odontoblasts. Focusing on the importance of the geometrical structure of an artificial biomaterial to induce cell differentiation and hard tissue formation, we previously have succeeded in developing a new biomaterial, honeycomb tricalcium phosphate (TCP) scaffold with through-holes of various diameters. In this study, to induce polar odontoblasts, TGC were induced to form odontoblasts using honeycomb TCP that had various hole diameters (75, 300, and 500 mu m) as a scaffold. The results showed that honeycomb TCP with 300-mu m hole diameters (300TCP) differentiated TGC into polar odontoblasts that were DSP positive. Therefore, our study indicates that 300TCP is an appropriate artificial biomaterial for dentin regeneration. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=QiushengShan en-aut-sei=Qiusheng en-aut-mei=Shan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FushimiShigeko en-aut-sei=Fushimi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=dental pulp kn-keyword=dental pulp en-keyword=honeycomb TCP kn-keyword=honeycomb TCP en-keyword=matrix formation kn-keyword=matrix formation en-keyword=dentin formation kn-keyword=dentin formation en-keyword=geometrical structure kn-keyword=geometrical structure en-keyword=scaffold kn-keyword=scaffold END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=1534 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Learning for Osteoporosis Classification Using Hip Radiographs and Patient Clinical Covariates en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study considers the use of deep learning to diagnose osteoporosis from hip radiographs, and whether adding clinical data improves diagnostic performance over the image mode alone. For objective labeling, we collected a dataset containing 1131 images from patients who underwent both skeletal bone mineral density measurement and hip radiography at a single general hospital between 2014 and 2019. Osteoporosis was assessed from the hip radiographs using five convolutional neural network (CNN) models. We also investigated ensemble models with clinical covariates added to each CNN. The accuracy, precision, recall, specificity, negative predictive value (npv), F1 score, and area under the curve (AUC) score were calculated for each network. In the evaluation of the five CNN models using only hip radiographs, GoogleNet and EfficientNet b3 exhibited the best accuracy, precision, and specificity. Among the five ensemble models, EfficientNet b3 exhibited the best accuracy, recall, npv, F1 score, and AUC score when patient variables were included. The CNN models diagnosed osteoporosis from hip radiographs with high accuracy, and their performance improved further with the addition of clinical covariates from patient records. en-copyright= kn-copyright= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitamuraAkira en-aut-sei=Kitamura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyosuke en-aut-sei=Goto en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaTomoyuki en-aut-sei=Noda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Search Space Inc. kn-affil= affil-num=4 en-affil=Search Space Inc. kn-affil= affil-num=5 en-affil=Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=deep learning kn-keyword=deep learning en-keyword=hip radiograph kn-keyword=hip radiograph en-keyword=ensemble model kn-keyword=ensemble model END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=21 article-no= start-page=4761 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Honeycomb -TCP Geometrical Structure on Bone Tissue Regeneration in Skull Defect en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of the geometric structure of artificial biomaterials on skull regeneration remains unclear. In a previous study, we succeeded in developing honeycomb beta-tricalcium phosphate (beta-TCP), which has through-and-through holes and is able to provide the optimum bone microenvironment for bone tissue regeneration. We demonstrated that beta-TCP with 300-mu m hole diameters induced vigorous bone formation. In the present study, we investigated how differences in hole directions of honeycomb beta-TCP (horizontal or vertical holes) influence bone tissue regeneration in skull defects. Honeycomb beta-TCP with vertical and horizontal holes was loaded with BMP-2 using Matrigel and Collagen gel as carriers, and transplanted into skull bone defect model rats. The results showed that in each four groups (Collagen alone group, Matrigel alone group, Collagen + BMP group and Matrigel + BMP-2), vigorous bone formation was observed on the vertical beta-TCP compared with horizontal beta-TCP. The osteogenic area was larger in the Matrigel groups (with and without BMP-2) than in the Collagen group (with and without BMP-2) in both vertical beta-TCP and horizontal beta-TCP. However, when BMP-2 was added, the bone formation area was not significantly different between the Collagen group and the Matrigel group in the vertical beta-TCP. Histological finding showed that, in vertical honeycomb beta-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes. Therefore, we can control efficient bone formation by creating a bone microenvironment provided by vertical honeycomb beta-TCP. Vertical honeycomb beta-TCP has the potential to be an excellent biomaterial for bone tissue regeneration in skull defects and is expected to have clinical applications. en-copyright= kn-copyright= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeSatoko en-aut-sei=Watanabe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagiriRyoko en-aut-sei=Nakagiri en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Life Science, Faculty of Science, Okayama University Science kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword= honeycomb -TCP kn-keyword= honeycomb -TCP en-keyword=bone tissue regeneration kn-keyword=bone tissue regeneration en-keyword=bone microenvironment kn-keyword=bone microenvironment en-keyword=Vertical and Horizontal holes kn-keyword=Vertical and Horizontal holes en-keyword=geometrical structure kn-keyword=geometrical structure END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=20 article-no= start-page=7714 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201018 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriHaruka en-aut-sei=Omori en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiushengShan en-aut-sei=Qiusheng en-aut-mei=Shan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=tumor stroma kn-keyword=tumor stroma en-keyword=tumor parenchyma kn-keyword=tumor parenchyma en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=biological characteristics kn-keyword=biological characteristics END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical study on primary screening of oral cancer and precancerous lesions by oral cytology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background This study was conducted to compare the histological diagnostic accuracy of conventional oral-based cytology and liquid-based cytology (LBC) methods. Methods Histological diagnoses of 251 cases were classified as negative (no malignancy lesion, inflammation, or mild/moderate dysplasia) and positive [severe dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC)]. Cytological diagnoses were classified as negative for intraepithelial lesion or malignancy (NILM), oral low-grade squamous intraepithelial lesion (OLSIL), oral high-grade squamous intraepithelial lesion (OHSIL), or SCC. Cytological diagnostic results were compared with histology results. Results Of NILM cytology cases, the most frequent case was negative [LBCn = 50 (90.9%), conventionaln = 22 (95.7%)]. Among OLSIL cytodiagnoses, the most common was negative (LBCn = 34; 75.6%, conventionaln = 14; 70.0%). Among OHSIL cytodiagnoses (LBCn = 51, conventionaln = 23), SCC was the most frequent (LBCn = 31; 60.8%, conventionaln = 7; 30.4%). Negative cases were common (LBCn = 13; 25.5%, conventionaln = 14; 60.9%). Among SCC cytodiagnoses SCC was the most common (LBCn = 16; 88.9%, conventionaln = 14; 87.5%). Regarding the diagnostic results of cytology, assuming OHSIL and SCC as cytologically positive, the LBC method/conventional method showed a sensitivity of 79.4%/76.7%, specificity of 85.1%/69.2%, false-positive rate of 14.9%/30.7%, and false-negative rate of 20.6%/23.3%. Conclusions LBC method was superior to conventional cytodiagnosis methods. It was especially superior for OLSIL and OHSIL. Because of the false-positive and false-negative cytodiagnoses, it is necessary to make a comprehensive diagnosis considering the clinical findings. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=Cytology kn-keyword=Cytology en-keyword=Pathology kn-keyword=Pathology en-keyword=Liquid-based cytology kn-keyword=Liquid-based cytology en-keyword=Screening kn-keyword=Screening en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=7 article-no= start-page=984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deep Neural Networks for Dental Implant System Classification en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic radiographs obtained from patients who underwent dental implant treatment at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2019. Five deep CNN models (specifically, a basic CNN with three convolutional layers, VGG16 and VGG19 transfer-learning models, and finely tuned VGG16 and VGG19) were evaluated for implant classification. Among the five models, the finely tuned VGG16 model exhibited the highest implant classification performance. The finely tuned VGG19 was second best, followed by the normal transfer-learning VGG16. We confirmed that the finely tuned VGG16 and VGG19 CNNs could accurately classify dental implant systems from 11 types of panoramic X-ray images. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiiKazumasa en-aut-sei=Yoshii en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraTakeshi en-aut-sei=Hara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaKatsusuke en-aut-sei=Yamashita en-aut-mei=Katsusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=3 en-affil=Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University kn-affil= affil-num=4 en-affil=Polytechnic Center Kagawa kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil= kn-affil= en-keyword=dental implant kn-keyword=dental implant en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=classification kn-keyword=classification en-keyword=deep learning kn-keyword=deep learning en-keyword=convolutional neural networks kn-keyword=convolutional neural networks END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=22 article-no= start-page=3681 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advantage of Alveolar Ridge Augmentation with Bioactive/Bioresorbable Screws Made of Composites of Unsintered Hydroxyapatite and Poly-L-lactide en-subtitle= kn-subtitle= en-abstract= kn-abstract=We studied human bone healing characteristics and the histological osteogenic environment by using devices made of a composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-L-lactide (PLLA). In eight cases of fixation, we used u-HA/PLLA screws for maxillary alveolar ridge augmentation, for which mandibular cortical bone block was used in preimplantation surgery. Five appropriate samples with screws were evaluated histologically and immunohistochemically for runt-related transcription factor 2 (RUNX2), transcription factor Sp7 (Osterix), and leptin receptor (LepR). In all cases, histological evaluation revealed that bone components had completely surrounded the u-HA/PLLA screws, and the bone was connected directly to the biomaterial. Inflammatory cells did not invade the space between the bone and the u-HA/PLLA screw. Immunohistochemical evaluation revealed that many cells were positive for RUNX2 or Osterix, which are markers for osteoblast and osteoprogenitor cells, in the tissues surrounding u-HA/PLLA. In addition, many bone marrow-derived mesenchymal stem cells were notably positive for both LepR and RUNX2. The u-HA/PLLA material showed excellent bioactive osteoconductivity and a highly biocompatibility with bone directly attached. In addition, our findings suggest that many bone marrow-derived mesenchymal stem cells and mature osteoblast are present in the osteogenic environment created with u-HA/PLLA screws and that this environment is suitable for osteogenesis. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KannoTakahiro en-aut-sei=Kanno en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=poly-L-lactide kn-keyword=poly-L-lactide en-keyword=uncalcined and unsintered hydroxyapatite kn-keyword=uncalcined and unsintered hydroxyapatite en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=osteoconductivity kn-keyword=osteoconductivity en-keyword=mesenchymal stem cell kn-keyword=mesenchymal stem cell END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=766 end-page=773 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Yes-associated protein (YAP) is a candidate oncogene in various human cancers, and recently, it has been reported that YAP expression and its activity was enhanced by Delta Np63. However, the role of YAP and Delta Np63 expression in carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has been unknown. Therefore, we investigated how YAP and Delta Np63 influence carcinogenesis and progression of OSCC.
Methods: We performed immunohistochemical analyses in whole tissue samples to investigate YAP and Delta Np63 expression in normal oral mucosa, epithelial hyperplasia, oral epithelial dysplasia (OED; low/high grade), carcinoma in situ (CIS), and OSCC. Furthermore, in OSCC, we analyzed clinical significance by using Kaplan-Meier survival analysis. Results: In normal oral mucosa and epithelial hyperplasia, YAP expression was primarily confined to the basal and parabasal layers, but YAP expression was elevated in OED, CIS, and OSCC. In OED, YAP and Delta Np63 expression levels were markedly higher in high grade than in low grade. In OSCC groups, YAP and Delta Np63 expression patterns tended to differ according to histopathological differentiation of OSCC. Furthermore, the YAP high expression group, which showed YAP staining in >50% positive cells with strong cytoplasmic staining or >10% positive cells with nuclear reactivity, showed a tendency to have a poor survival rate.
Conclusion: YAP and Delta Np63 expression levels correlated with grade of oral OED. Additionally, YAP expression was associated with OSCC survival rate. Our results suggested that YAP and Delta Np63 expression might serve as predictive markers to distinguish OSCC development and progression. en-copyright= kn-copyright= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=YAP kn-keyword=YAP en-keyword=Np63 kn-keyword=Np63 en-keyword=oral epithelial dysplasia kn-keyword=oral epithelial dysplasia en-keyword=carcinoma in situ kn-keyword=carcinoma in situ en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=1557 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biomechanical Loading Comparison between Titanium and Unsintered Hydroxyapatite/Poly-L-Lactide Plate System for Fixation of Mandibular Subcondylar Fractures en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosynthesis absorbable materials made of uncalcined and unsintered hydroxyapatite (u-HA) particles, poly-l-lactide (PLLA), and u-HA/PLLA are bioresorbable, and these plate systems have feasible bioactive osteoconductive capacities. However, their strength and stability for fixation in mandibular subcondylar fractures remain unclear. This in vitro study aimed to assess the biomechanical strength of u-HA/PLLA bioresorbable plate systems after internal fixation of mandibular subcondylar fractures. Tensile and shear strength were measured for each u-HA/PLLA and titanium plate system. To evaluate biomechanical behavior, 20 hemimandible replicas were divided into 10 groups, each comprising a titanium plate and a bioresorbable plate. A linear load was applied anteroposteriorly and lateromedially to each group to simulate the muscular forces in mandibular condylar fractures. All samples were analyzed for each displacement load and the displacement obtained by the maximum load. Tensile and shear strength of the u-HA/PLLA plate were each approximately 45% of those of the titanium plates. Mechanical resistance was worst in the u-HA/PLLA plate initially loaded anteroposteriorly. Titanium plates showed the best mechanical resistance during lateromedial loading. Notably, both plates showed similar resistance when a lateromedially load was applied. In the biomechanical evaluation of mandibular condylar fracture treatment, the u-HA/PLLA plates had sufficiently high resistance in the two-plate fixation method. en-copyright= kn-copyright= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KannoTakahiro en-aut-sei=Kanno en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= en-keyword=mandibular condylar fracture kn-keyword=mandibular condylar fracture en-keyword=unsintered hydroxyapatite kn-keyword=unsintered hydroxyapatite en-keyword=poly-l-lactide composite plate kn-keyword=poly-l-lactide composite plate en-keyword=bioactive resorbable plate kn-keyword=bioactive resorbable plate en-keyword=biomechanical loading evaluation kn-keyword=biomechanical loading evaluation en-keyword=fracture fixation kn-keyword=fracture fixation END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=8 article-no= start-page=1973 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics en-subtitle= kn-subtitle= en-abstract= kn-abstract= Histopathological findings of oral neoplasm cell differentiation and metaplasia suggest that tumor cells induce their own dedifferentiation and re-differentiation and may lead to the formation of tumor-specific histological features. Notch signaling is involved in the maintenance of tissue stem cell nature and regulation of differentiation and is responsible for the cytological regulation of cell fate, morphogenesis, and/or development. In our previous study, immunohistochemistry was used to examine Notch expression using cases of odontogenic tumors and pleomorphic adenoma as oral neoplasms. According to our results, Notch signaling was specifically associated with tumor cell differentiation and metaplastic cells of developmental tissues. Notch signaling was involved in the differentiation of the ductal epithelial cells of salivary gland tumors and ameloblast-like cells of odontogenic tumors. However, Notch signaling was also involved in squamous metaplasia, irrespective of the type of developmental tissue. In odontogenic tumors, Notch signaling was involved in epithelial-mesenchymal interactions and may be related to tumor development and tumorigenesis. This signaling may also be associated with the malignant transformation of ameloblastomas. Overall, Notch signaling appears to play a major role in the formation of the characteristic cellular composition and histological features of oral neoplasms, and this involvement has been reviewed here. en-copyright= kn-copyright= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaedaHatsuhiko en-aut-sei=Maeda en-aut-mei=Hatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawakamiToshiyuki en-aut-sei=Kawakami en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name=ːm kn-aut-sei= kn-aut-mei=m aut-affil-num=7 ORCID= affil-num=1 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= Department of Oral Pathology, School of Dentistry, Aichi Gakuin University, kn-affil= affil-num=6 en-affil= Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine kn-affil= affil-num=7 en-affil= Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cell differentiation kn-keyword=cell differentiation en-keyword=epithelial-mesenchymal interaction kn-keyword=epithelial-mesenchymal interaction en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=malignant transformation kn-keyword=malignant transformation en-keyword=notch signaling kn-keyword=notch signaling en-keyword=odontogenic tumor kn-keyword=odontogenic tumor en-keyword=pleomorphic adenoma kn-keyword=pleomorphic adenoma END