Faculty Profiles - NAGATSUKA Hitoshi

Papers - NAGATSUKA Hitoshi

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Polymeric Materials, Advances and Applications in Tissue Engineering: A Review. Reviewed International journal

María Cecilia Socci, Gabriela Rodríguez, Emilia Oliva, Shigeko Fushimi, Kiyofumi Takabatake, Hitoshi Nagatsuka, Carmelo José Felice, Andrea Paola Rodríguez

Bioengineering (Basel, Switzerland) 10 ( 2 ) 2023.2

Language：English Publishing type：Research paper (scientific journal)

Tissue Engineering (TE) is an interdisciplinary field that encompasses materials science in combination with biological and engineering sciences. In recent years, an increase in the demand for therapeutic strategies for improving quality of life has necessitated innovative approaches to designing intelligent biomaterials aimed at the regeneration of tissues and organs. Polymeric porous scaffolds play a critical role in TE strategies for providing a favorable environment for tissue restoration and establishing the interaction of the biomaterial with cells and inducing substances. This article reviewed the various polymeric scaffold materials and their production techniques, as well as the basic elements and principles of TE. Several interesting strategies in eight main TE application areas of epithelial, bone, uterine, vascular, nerve, cartilaginous, cardiac, and urinary tissue were included with the aim of learning about current approaches in TE. Different polymer-based medical devices approved for use in clinical trials and a wide variety of polymeric biomaterials are currently available as commercial products. However, there still are obstacles that limit the clinical translation of TE implants for use wide in humans, and much research work is still needed in the field of regenerative medicine.

DOI： 10.3390/bioengineering10020218

Management of odontogenic foci of infection (dental caries, periodontal disease and odontogenic infections) in the oral functional management of patients receiving cancer treatments: Guidelines based on a systematic review Reviewed

Hiroshi Kurita, Masahiro Umeda, Takaaki Ueno, Narikazu Uzawa, Yasuyuki Shibuya, Norifumi Nakamura, Hitoshi Nagatsuka, Takafumi Hayashi, Itaru Mizoguch, Kei Tomihara, Yumiko Ikegami, Kazuma Noguchi, Yuichi Takiguchi, Nobuyuki Yamamoto, Hironori Sakai

Oral Science International 2023

In cancer treatment, perioperative oral functional management is used as a part of supportive care. Its main objectives are as follows: (1) preventing and reducing adverse events, (2) maintaining or improving nutritional status, (3) improving cancer treatment outcomes, (4) maintaining or improving quality of life, (5) providing high quality medical care through comprehensive oral care, (6) controlling odontogenic foci of infection, and (7) maintaining or improving oral function. A literature search was conducted using the electronic databases of Medical Journal and PubMed. Electronic database searches were performed using various combinations of the following key words: cancer, surgery, treatment, chemotherapy, radiotherapy and dental disease, oral care, oral management, dental intervention, oral health, dental care, and dental management. The selection of literature for inclusion in the review was restricted to dental management of patients receiving cancer treatment. In the course of the literature review, hand searches were also added as needed. The guideline was developed by summarizing the results of the review. Based on a review of the literature on the management of dental foci of infection in the oral functional management of patients undergoing cancer treatment, a guideline was developed by summarizing the results of the review. This report is a secondary publication of our previous review report “J. Stomatol. Soc. 70(4): 279–289. Dec 2021.”.

DOI： 10.1002/osi2.1209

分化度の異なる口腔扁平上皮癌におけるシスプラチンとCXCR4阻害剤併用の効果

吉田沙織, 河合穂高, 竹下洋平, 岡田俊輔, 藤倉満美子, 久富美紀, 河津俊幸, 長塚仁, 浅海淳一, 柳文修

日本口腔内科学会雑誌 28 ( 2 ) 106 - 106 2022.12

Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line-derived xenograft model. Reviewed International journal

Qiusheng Shan, Kiyofumi Takabatake, Haruka Omori, Hotaka Kawai, May Wathone Oo, Shintaro Sukegawa, Masae Fujii, Yasunori Inada, Sho Sano, Keisuke Nakano, Hitoshi Nagatsuka

Oncology letters 24 ( 5 ) 382 - 382 2022.11

Language：English Publishing type：Research paper (scientific journal)

The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue-derived stromal cells (G-SCs and P-SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate-resistant acid phosphatase staining in a cell line-derived xenograft model. The results demonstrated that G-SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC-3 cell line, whereas P-SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC-3 cells. Furthermore, the effects of G-SCs, P-SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)-9, membrane type 1 MMP (MT1-MMP), Snail, parathyroid hormone-related peptide (PTHrP) and receptor activator of NF-κB ligand (RANKL) in HSC-3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G-SCs had a more prominent effect on the expression of MMP-9, MT1-MMP, Snail, PTHrP, and RANKL, whereas P-SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP-9, MT1-MMP and Snail expression. The potential genes underlying the differential effects of G-SCs and P-SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin-dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G-SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P-SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.

DOI： 10.3892/ol.2022.13502

SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma. Reviewed International journal

May Wathone Oo, Hotaka Kawai, Htoo Shwe Eain, Yamin Soe, Kiyofumi Takabatake, Sho Sanou, Qiusheng Shan, Yasunori Inada, Masae Fujii, Yoko Fukuhara, Ziyi Wang, Shintaro Sukegawa, Mitsuaki Ono, Keisuke Nakano, Hitoshi Nagatsuka

Biomedicines 10 ( 11 ) 2022.10

Language：English Publishing type：Research paper (scientific journal)

Tumor angiogenesis is one of the hallmarks of solid tumor development. The progressive tumor cells produce the angiogenic factors and promote tumor angiogenesis. However, how the tumor stromal cells influence tumor vascularization is still unclear. In the present study, we evaluated the effects of oral squamous cell carcinoma (OSCC) stromal cells on tumor vascularization. The tumor stromal cells were isolated from two OSCC patients with different subtypes: low invasive verrucous squamous carcinoma (VSCC) and highly invasive squamous cell carcinoma (SCC) and co-xenografted with the human OSCC cell line (HSC-2) on nude mice. In comparison, the CD34+ vessels in HSC-2+VSCC were larger than in HSC-2+SCC. Interestingly, the vessels in the HSC-2+VSCC expressed vascular endothelial cadherin (VE-cadherin), indicating well-formed vascularization. Our microarray data revealed that the expression of extracellular superoxide dismutase, SOD3 mRNA is higher in VSCC stromal cells than in SCC stromal cells. Moreover, we observed that SOD3 colocalized with VE-cadherin on endothelial cells of low invasive stroma xenograft. These data suggested that SOD3 expression in stromal cells may potentially regulate tumor vascularization in OSCC. Thus, our study suggests the potential interest in SOD3-related vascular integrity for a better OSCC therapeutic strategy.

DOI： 10.3390/biomedicines10112729

Deep learning model for analyzing the relationship between mandibular third molar and inferior alveolar nerve in panoramic radiography. Reviewed International journal

Shintaro Sukegawa, Futa Tanaka, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Scientific reports 12 ( 1 ) 16925 - 16925 2022.10

Language：English Publishing type：Research paper (scientific journal)

In this study, the accuracy of the positional relationship of the contact between the inferior alveolar canal and mandibular third molar was evaluated using deep learning. In contact analysis, we investigated the diagnostic performance of the presence or absence of contact between the mandibular third molar and inferior alveolar canal. We also evaluated the diagnostic performance of bone continuity diagnosed based on computed tomography as a continuity analysis. A dataset of 1279 images of mandibular third molars from digital radiographs taken at the Department of Oral and Maxillofacial Surgery at a general hospital (2014-2021) was used for the validation. The deep learning models were ResNet50 and ResNet50v2, with stochastic gradient descent and sharpness-aware minimization (SAM) as optimizers. The performance metrics were accuracy, precision, recall, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). The results indicated that ResNet50v2 using SAM performed excellently in the contact and continuity analyses. The accuracy and AUC were 0.860 and 0.890 for the contact analyses and 0.766 and 0.843 for the continuity analyses. In the contact analysis, SAM and the deep learning model performed effectively. However, in the continuity analysis, none of the deep learning models demonstrated significant classification performance.

DOI： 10.1038/s41598-022-21408-9

Lip pleomorphic adenomas: case series and literature review Reviewed

Koki Umemori, Kisho Ono, Hideka Kanemoto, Kyoichi Obata, Hotaka Kawai, Tomoya Nakamura, Keisuke Nakano, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

Gland Surgery 11 ( 10 ) 1730 - 1740 2022.10

Elucidation of ameloblastoma fenestration mechanism via HIF-1α(和訳中) Reviewed

Inada Yasunori, Takabatake Kiyofumi, Fujii Masae, Tianyan Piao, Angi Chang, Kawai Hotaka, Nakano Keisuke, Nagatsuka Hitoshi

Journal of Hard Tissue Biology 31 ( 4 ) 272 - 272 2022.10

Effective deep learning for oral exfoliative cytology classification. Reviewed International journal

Shintaro Sukegawa, Futa Tanaka, Keisuke Nakano, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Sawako Ono, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Scientific reports 12 ( 1 ) 13281 - 13281 2022.8

Language：English Publishing type：Research paper (scientific journal)

The use of sharpness aware minimization (SAM) as an optimizer that achieves high performance for convolutional neural networks (CNNs) is attracting attention in various fields of deep learning. We used deep learning to perform classification diagnosis in oral exfoliative cytology and to analyze performance, using SAM as an optimization algorithm to improve classification accuracy. The whole image of the oral exfoliation cytology slide was cut into tiles and labeled by an oral pathologist. CNN was VGG16, and stochastic gradient descent (SGD) and SAM were used as optimizers. Each was analyzed with and without a learning rate scheduler in 300 epochs. The performance metrics used were accuracy, precision, recall, specificity, F1 score, AUC, and statistical and effect size. All optimizers performed better with the rate scheduler. In particular, the SAM effect size had high accuracy (11.2) and AUC (11.0). SAM had the best performance of all models with a learning rate scheduler. (AUC = 0.9328) SAM tended to suppress overfitting compared to SGD. In oral exfoliation cytology classification, CNNs using SAM rate scheduler showed the highest classification performance. These results suggest that SAM can play an important role in primary screening of the oral cytological diagnostic environment.

DOI： 10.1038/s41598-022-17602-4

The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery. Reviewed International journal

Shintaro Sukegawa, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Tomoya Nakamura, Ai Fujimura, Ayaka Fujisawa, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Yumika Mukainaka, Hitoshi Nagatsuka, Yoshihiko Furuki

Healthcare (Basel, Switzerland) 10 ( 7 ) 2022.7

Language：English Publishing type：Research paper (scientific journal)

We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8, $905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV.

DOI： 10.3390/healthcare10071348

Incidence and Risk of Anti-Resorptive Agent-Related Osteonecrosis of the Jaw after Tooth Extraction: A Retrospective Study. Reviewed International journal

Rieko Shimizu, Shintaro Sukegawa, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Tomoya Nakamura, Ai Fujimura, Ayaka Fujisawa, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Healthcare (Basel, Switzerland) 10 ( 7 ) 2022.7

Language：English Publishing type：Research paper (scientific journal)

Bone-modifying agents (BMA) such as bisphosphonates and denosumab are frequently used for the treatment of bone metastases, osteoporosis, and multiple myeloma. BMA may lead to anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). This study aimed to clarify the risk factors for and probabilities of developing ARONJ after tooth extraction in patients undergoing BMA therapy. In this study, the records of 505 target sites of 302 patients undergoing BMA who presented with mandibular fractures at the Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, from March 2014 to January 2022, were retrospectively analyzed for the onset of ARONJ after tooth extraction. The following variables were investigated as attributes: anatomy, health status, and dental treatment. The correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and the factors related to the onset of ARONJ were identified. The incidence rate of ARONJ was found to be 3.2%. Hypoparathyroidism was an important factor associated with ARONJ development. Thus, systemic factors are more strongly related to the onset of ARONJ after tooth extraction than local factors.

DOI： 10.3390/healthcare10071332

Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor‑associated macrophages into the tumor microenvironment of oral squamous cell carcinoma. Reviewed International journal

Qiusheng Shan, Kiyofumi Takabatake, Hotaka Kawai, May Wathone Oo, Shintaro Sukegawa, Masae Fujii, Keisuke Nakano, Hitoshi Nagatsuka

International journal of oncology 60 ( 6 ) 2022.6

Language：English Publishing type：Research paper (scientific journal)

Tumor‑associated macrophages (TAMs) are linked to the progression of numerous types of cancer. However, the effects of the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC), particularly the cancer stroma on TAMs, remains to be elucidated. In the present study, the effects of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the differentiation, proliferation and migration of macrophages in vitro was assayed using Giemsa staining, and immunofluorescence, MTS and Transwell (migration) assays, respectively. The combined results suggested that both VSCC‑SCs and SCC‑SCs promoted the differentiation of macrophages into M2 type TAMs, as well as the proliferation and migration of macrophages following crosstalk with HSC‑3 cells in vitro. Moreover, the SCC‑SCs exerted a more prominent effect on TAMs than the VSCC‑SCs. Immunohistochemical staining was used to examine the expression of CD34, CD45, CD11b and CD163 to assay the effects of VSCC‑SCs, SCC‑SCs and HDFs on microvessel density (MVD) and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type macrophages. The results suggested that both VSCC‑SCs and SCC‑SCs promoted MVD and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type TAMs into the TME of OSCC following crosstalk with HSC‑3 cells in vivo. The SCC‑SCs exerted a more prominent promoting effect than the VSCC‑SCs. Finally, the potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on the infiltration of TAMs were investigated using microarray analysis. The results revealed that interleukin 1β, bone morphogenetic protein 4, interleukin 6 and C‑X‑C motif chemokine ligand 12 had great potential to mediate the differential effects of VSCC‑SCs and SCC‑SCs on TAM infiltration. On the whole, the findings presented herein, demonstrate that both VSCC‑SCs and SCC‑SCs promote the infiltration of TAMs into the TME of OSCC following crosstalk with HSC‑3 cells; the SCC‑SCs were found to exert a more prominent promoting effect. This may represent a potential regulatory mechanism for the infiltration of TAMs into the TME of OSCC.

DOI： 10.3892/ijo.2022.5368

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study. Reviewed International journal

Shintaro Sukegawa, Rieko Shimizu, Yuka Sukegawa, Kazuaki Hasegawa, Sawako Ono, Ai Fujimura, Izumi Yamamoto, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Materials (Basel, Switzerland) 15 ( 9 ) 2022.5

Language：English Publishing type：Research paper (scientific journal)

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries.

DOI： 10.3390/ma15093353

Identification of osteoporosis using ensemble deep learning model with panoramic radiographs and clinical covariates. Reviewed International journal

Shintaro Sukegawa, Ai Fujimura, Akira Taguchi, Norio Yamamoto, Akira Kitamura, Ryosuke Goto, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Scientific reports 12 ( 1 ) 6088 - 6088 2022.4

Language：English Publishing type：Research paper (scientific journal)

Osteoporosis is becoming a global health issue due to increased life expectancy. However, it is difficult to detect in its early stages owing to a lack of discernible symptoms. Hence, screening for osteoporosis with widely used dental panoramic radiographs would be very cost-effective and useful. In this study, we investigate the use of deep learning to classify osteoporosis from dental panoramic radiographs. In addition, the effect of adding clinical covariate data to the radiographic images on the identification performance was assessed. For objective labeling, a dataset containing 778 images was collected from patients who underwent both skeletal-bone-mineral density measurement and dental panoramic radiography at a single general hospital between 2014 and 2020. Osteoporosis was assessed from the dental panoramic radiographs using convolutional neural network (CNN) models, including EfficientNet-b0, -b3, and -b7 and ResNet-18, -50, and -152. An ensemble model was also constructed with clinical covariates added to each CNN. The ensemble model exhibited improved performance on all metrics for all CNNs, especially accuracy and AUC. The results show that deep learning using CNN can accurately classify osteoporosis from dental panoramic radiographs. Furthermore, it was shown that the accuracy can be improved using an ensemble model with patient covariates.

DOI： 10.1038/s41598-022-10150-x

Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes. Reviewed International journal

Qiusheng Shan, Kiyofumi Takabatake, Hotaka Kawai, May Wathone Oo, Yasunori Inada, Shintaro Sukegawa, Shigeko Fushimi, Keisuke Nakano, Hitoshi Nagatsuka

Oncology reports 47 ( 4 ) 2022.4

Language：English Publishing type：Research paper (scientific journal)

Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts on bone resorption and the activation of HSC‑3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan‑cytokeratin) and tartrate‑resistant acid phosphatase staining. In addition, the expression levels of matrix metalloproteinase (MMP)9, membrane‑type 1 MMP (MT1‑MMP), Snail, receptor activator of NF‑κB ligand (RANKL) and parathyroid hormone‑related peptide (PTHrP) in the bone invasion regions of HSC‑3 cells were examined by immunohistochemistry. The results suggested that both SCC‑SCs and VSCC‑SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1‑MMP, Snail, RANKL and PTHrP. However, SCC‑SCs had a more prominent effect compared with VSCC‑SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC‑SCs and SCC‑SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC‑SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC.

DOI： 10.3892/or.2022.8292

がん治療患者の口腔機能管理における歯性感染病巣(歯の齲蝕、歯周病、歯性感染症)管理:システマティックレビューに基づいた指針(完全再掲載版) Reviewed

栗田浩, 梅田正博, 植野高章, 鵜澤成一, 渋谷恭之, 中村典史, 長塚仁, 林孝文, 溝口到, 冨原圭, 池上由美子, 野口一馬, 滝口裕一, 山本信之, 日本口腔科学会学術研究委員会, 日本口腔ケア学会学術委員会がん口腔ケアガイドライン作成委員会

日本口腔ケア学会雑誌 16 ( 2 ) 9 - 19 2022.3

Evaluation of multi-task learning in deep learning-based positioning classification of mandibular third molars. Reviewed International journal

Shintaro Sukegawa, Tamamo Matsuyama, Futa Tanaka, Takeshi Hara, Kazumasa Yoshii, Katsusuke Yamashita, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

Scientific reports 12 ( 1 ) 684 - 684 2022.1

Language：English Publishing type：Research paper (scientific journal)

Pell and Gregory, and Winter's classifications are frequently implemented to classify the mandibular third molars and are crucial for safe tooth extraction. This study aimed to evaluate the classification accuracy of convolutional neural network (CNN) deep learning models using cropped panoramic radiographs based on these classifications. We compared the diagnostic accuracy of single-task and multi-task learning after labeling 1330 images of mandibular third molars from digital radiographs taken at the Department of Oral and Maxillofacial Surgery at a general hospital (2014-2021). The mandibular third molar classifications were analyzed using a VGG 16 model of a CNN. We statistically evaluated performance metrics [accuracy, precision, recall, F1 score, and area under the curve (AUC)] for each prediction. We found that single-task learning was superior to multi-task learning (all p < 0.05) for all metrics, with large effect sizes and low p-values. Recall and F1 scores for position classification showed medium effect sizes in single and multi-task learning. To our knowledge, this is the first deep learning study to examine single-task and multi-task learning for the classification of mandibular third molars. Our results demonstrated the efficacy of implementing Pell and Gregory, and Winter's classifications for specific respective tasks.

DOI： 10.1038/s41598-021-04603-y

Is attention branch network effective in classifying dental implants from panoramic radiograph images by deep learning? Reviewed International journal

Shintaro Sukegawa, Kazumasa Yoshii, Takeshi Hara, Futa Tanaka, Katsusuke Yamashita, Tutaro Kagaya, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Yoshihiko Furuki

PloS one 17 ( 7 ) e0269016 2022

Language：English Publishing type：Research paper (scientific journal)

Attention mechanism, which is a means of determining which part of the forced data is emphasized, has attracted attention in various fields of deep learning in recent years. The purpose of this study was to evaluate the performance of the attention branch network (ABN) for implant classification using convolutional neural networks (CNNs). The data consisted of 10191 dental implant images from 13 implant brands that cropped the site, including dental implants as pretreatment, from digital panoramic radiographs of patients who underwent surgery at Kagawa Prefectural Central Hospital between 2005 and 2021. ResNet 18, 50, and 152 were evaluated as CNN models that were compared with and without the ABN. We used accuracy, precision, recall, specificity, F1 score, and area under the receiver operating characteristics curve as performance metrics. We also performed statistical and effect size evaluations of the 30-time performance metrics of the simple CNNs and the ABN model. ResNet18 with ABN significantly improved the dental implant classification performance for all the performance metrics. Effect sizes were equivalent to "Huge" for all performance metrics. In contrast, the classification performance of ResNet50 and 152 deteriorated by adding the attention mechanism. ResNet18 showed considerably high compatibility with the ABN model in dental implant classification (AUC = 0.9993) despite the small number of parameters. The limitation of this study is that only ResNet was verified as a CNN; further studies are required for other CNN models.

DOI： 10.1371/journal.pone.0269016

Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer. Reviewed International journal

Kisho Ono, Kohei Sato, Tomoya Nakamura, Yume Yoshida, Shogo Murata, Kunihiro Yoshida, Hideka Kanemoto, Koki Umemori, Hotaka Kawai, Kyoichi Obata, Shoji Ryumon, Kazuaki Hasegawa, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki

International journal of medical sciences 19 ( 8 ) 1320 - 1333 2022

Language：English Publishing type：Research paper (scientific journal)

Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality. Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared. Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods.

DOI： 10.7150/ijms.74109

A Case of Odontogenic Myxoma of the Mandible with Expansion to the Alveolar Crest - Comparison of Imaging Findings and Pathological Findings: A Case Report Reviewed

Saori Yoshida, Yohei Takeshita, Toshiyuki Kawazu, Tatsushi Matsumura, Junichi Asaumi, Hitoshi Nagatsuka, Yoshinobu Yanagi

OPEN DENTISTRY JOURNAL 16 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：BENTHAM SCIENCE PUBL LTD

Background:An odontogenic myxoma is an intraosseous tumor characterized by stellate and spindle-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. We herein describe an odontogenic myxoma that expanded not only to the bone marrow but also to the outside of the alveolar bone. Diagnosis of an odontogenic myxoma in a tooth-deficient region by imaging findings alone was difficult because the positional relationship between the tumor and the tooth is unknown. Furthermore, some of these odontogenic myxomas reportedly show rapid growth.Case Report:Here, we present the case of a patient, a 44-year-old man, who had a hard, bone-like swelling on his right mandible molar region and mild paresthesia on his right cheek. An odontogenic myxoma and ameloblastoma were suspected based on the imaging findings; however, pathological examination of the biopsy led to a diagnosis of odontogenic myxoma. Right segmental mandibulectomy was performed, and there was no recurrence observed after surgery.Conclusion:To improve the accuracy of imaging diagnosis, it is important to compare the imaging findings with the pathological findings of the surgical specimen. This comparison in the present case revealed differences in the magnetic resonance imaging signal intensity in regions with different types of cell components.

DOI： 10.2174/18742106-v16-2202140

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