Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis.

BACKGROUND: Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. METHODS: Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes. RESULTS: We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1-4) were one woman and three men with a mean age of 53.75 years (range: 15-74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1-3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. CONCLUSIONS: We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated.

Risk factors for post-extraction infection of mandibular third molar: A retrospective clinical study.

Post-extraction infection is one of the most concerning complications of mandibular third molar extraction, which is the most common procedure in oral and maxillofacial surgery. We investigated risk factors for post-extraction infection by retrospectively analyzing 2,513 teeth/cases of mandibular third molar extraction (1,040 males, 1,473 females) performed at a single medical facility in Kobe, Japan from January 2014 to May 2022. The predictive variables were categorized as patient attributes, health status, and anatomic, pathological, and operative variables that may be associated with post-extraction infection. The outcome variable was the post-extraction infection rate. The post-extraction infection rate was 5.73 % (144 of the 2,513 teeth), and the mean age of the patients with a post-extraction infection was 41.76 ± 16.8 years. Our analyses also revealed that the postoperative infection rate was significantly increased in patients aged ≥36 years. A multivariate logistic regression analysis showed that the following variables were significantly associated with post-extraction infection: preoperative antibiotic administration (odds ratio [OR] 4.68, p < 0.001), postoperative paresthesia of the inferior alveolar nerve (OR 4.34, p < 0.001), intraoperative hemostatic procedure (OR 1. 74, p = 0.008), position of Pell and Gregory classifications (OR 1. 70, p < 0.001), Winter's classification (OR 1.28, p < 0.03), and age (OR 1.03, p < 0.001). Oral and maxillofacial surgeons should be aware of these risk factors.

Risk factors for postoperative infection after bilateral sagittal split ramus osteotomy: A retrospective analysis.

BACKGROUND: This retrospective clinical study investigated risk factors for infection following bilateral sagittal split ramus osteotomy (BSSO) as orthognathic surgery, including the patients' general condition, local factors, and surgical factors. PATIENTS AND METHODS: The cases of 160 mandibular sites of 80 Japanese patients (26 males, 54 females; mean ± SD age: 25.3 ± 7.7 years, range 16-55 yrs) with a jaw deformity who underwent BSSO orthognathic surgery at our Department of Oral and Maxillofacial Surgery between Jan. 2017 and Dec. 2022 were analyzed. Potential risk factors were classified as clinical predictive variables. Descriptive and univariate statistics were computed. A multivariate analysis was performed with logistic regression. RESULTS: Fifteen mandibular sites (9.4 %) were complicated with postoperative infection. The multivariate analysis revealed significant differences in facial asymmetry (OR 24.0, p = 0.0002) and the amount of mandibular movement (OR 0.664, p = 0.011) between the sites with and without infection. CONCLUSIONS: Among clinical variables, facial asymmetry was the strongest risk factor for post-BSSO infection, followed by the amount of mandibular movement.

Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists.

The study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis.

Endoscopic-assisted Surgical Removal of Infected Interosseous Wires 40 Years After Mandibular Surgery.

We demonstrate a highly reliable minimally invasive treatment for removal of residual wire from the mandible. The patient was a 55-year-old Japanese man who was referred to our department for a fistula in his submental area. The patient had undergone open reduction and fixation with wires for mandibular fractures (left parasymphysis, right angle fracture) more than 40 years prior and mandibular tooth extraction and drainage 6 months prior. Minimally invasive endoscopy-assisted wire removal surgery was performed under general anesthesia with good visualization in a narrow surgical field. Bone resection was minimized using an ultrasonic cutting instrument with a wide choice of tip shapes. The use of endoscopy with ultrasonic cutting tools makes it possible to effectively utilize narrow surgical fields with a small skin incision and minimal bone cutting. The advantages and disadvantages of the newer endoscopic systems in oral and maxillofacial surgical units are discussed.

Enzyme-Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem Cells.

Mesenchymal stem cell (MSC) therapy is a promising approach to curing bone diseases and disorders. In treating genetic bone disorders, MSC therapy is local or systemic transplantation of isolated and in vitro proliferated MSC rather than bone marrow transplantation. Recent evidence showed that bone marrow MSC engraftment to bone regeneration has been controversial in animal and human studies. Here, our modified bone marrow transplantation (BMT) method solved this problem. Like routine BMT, our modified method involves three steps: (i) isolation of bone marrow cells from the donor, (ii) whole-body lethal irradiation to the recipient, and (iii) injection of isolated bone marrow cells into irradiated recipient mice via the tail vein. The significant modification is imported at the bone marrow isolation step. While the bone marrow cells are flushed out from the bone marrow with the medium in routine BMT, we applied the enzymes' (collagenase type 4 and dispase) integrated medium to wash out the bone marrow cells. Then, cells were incubated in enzyme integrated solution at 37°C for 10 minutes. This modification designated BMT as collagenase-integrated BMT (c-BMT). Notably, successful engraftment of bone marrow MSC to the new bone formation, such as osteoblasts and chondrocytes, occurs in c-BMT mice, whereas routine BMT mice do not recruit bone marrow MSC. Indeed, flow cytometry data showed that c-BMT includes a higher proportion of LepR+, CD51+, or RUNX2+ non-hematopoietic cells than BMT. These findings suggested that c-BMT is a time-efficient and more reliable technique that ensures the disaggregation and collection of bone marrow stem cells and engraftment of bone marrow MSC to the recipient. Hence, we proposed that c-BMT might be a promising approach to curing genetic bone disorders. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Risk Factors for Delayed-Onset Infection after Mandibular Wisdom Tooth Extractions.

Wisdom tooth extraction is one of the most commonly performed procedures by oral maxillofacial surgeons. Delayed-onset infection (DOI) is a rare complication of wisdom tooth extraction, and it occurs ~1-4 weeks after the extraction. In the present study, risk factors for DOI were investigated by retrospectively analyzing the cases of 1400 mandibular wisdom tooth extractions performed at Kagawa University Hospital from April 2015 to June 2022. Inclusion criteria were patients aged >15 years with a wisdom tooth extraction per our procedure. The exclusion criteria were patients with insufficient medical records, a >30-mm lesion around the wisdom tooth shown via X-ray, colonectomy, radiotherapy treatment of the mandible, the lack of panoramic images, and lesions other than a follicular cyst. The DOI incidence was 1.1% (16 cases), and univariate analyses revealed that the development of DOI was significantly associated with the Winter classification (p = 0.003), position (p = 0.003), hypertension (p = 0.011), and hemostatic agent use (p = 0.004). A multivariate logistic regression analysis demonstrated that position (OR = B for A, 7.75; p = 0.0163), hypertension (OR = 7.60, p = 0.013), and hemostatic agent use (OR = 6.87, p = 0.0022) were significantly associated with DOI development. Hypertension, hemostatic use, and position were found to be key factors for DOI; long-term observation may thus be necessary for patients with these risk factors.

Cumulated ambulation score as predictor of postoperative mobility in patients with proximal femur fractures.

INTRODUCTION: The cumulated ambulation score (CAS) has been developed as an index for evaluating mobility in the early postoperative period. This study aimed to estimate the association between CAS and independent ambulation after surgery for proximal femur fractures. MATERIALS AND METHODS: This retrospective cohort study included 223 elderly patients who underwent surgery for proximal femur fractures and had independent ambulation before the injury. Multivariable logistic regression analyses with cognitive impairment, pre-injury Barthel index, and CAS as the test variables were used to predict independent ambulation at 2 weeks (model 1) and 3 months (model 2) postoperatively. We established scoring systems based on the modeling results. RESULTS: The number of patients with independent ambulation at 2 weeks and 3 months postoperatively was 115 and 169, respectively. Univariate analysis showed that the CAS was significantly associated with independent ambulation at 2 weeks and 3 months postoperatively. Multivariable analysis showed that models 1 and 2 had good predictive accuracies, with areas under the receiver-operating characteristic curve of 0.855 and 0.868, respectively. Among the explanatory variables, only the CAS in model 2 was not significantly associated with the postoperative ambulatory ability. Scoring systems for both models 1 and 2 also had good predictive accuracies, with cut-off scores of 3.5 for model 1 and 9.5 for model 2. CONCLUSIONS: The CAS predicted independent ambulation at 2 weeks postoperatively; however, this relationship was limited at 3 months postoperatively. Therefore, the CAS may help estimate independent ambulation at discharge from an acute-care hospital.

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

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.

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

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.

Multiple orthokeratinized odontogenic cysts: clinical, pathological, and genetic characteristics.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC) is a rare developmental odontogenic cyst of the jaw. It was originally believed to be a variant of odontogenic keratocyst (OKC) but is now considered to be a distinct entity. OOC usually presents as a single lesion and recurs infrequently. On the other hand, OKC often presents with multiple lesions and displays locally aggressive behavior and a high recurrence rate associated with the protein patched homolog 1 (PTCH1) gene mutation. Multiple OOC cases are extremely rare and seem to be aggressive, but their pathogenesis is not fully understood. This study aimed to determine the clinical, pathological, and genetic characteristics of multiple OCC. METHODS: Three cases of multiple OOC were evaluated for clinical and histological findings, and immunohistochemical expression of Ki-67 and Bcl-2. Furthermore, PTCH1 mutations were analyzed by next-generation sequencing using a custom panel to cover the entire exon of PTCH1. RESULTS: The three cases of multiple OOC included two men and one woman with a mean age of 25.3 years old (range, 18-38 years old). Each case had two or three OOCs (total of seven OOCs), all of which were simultaneously detected. Of the seven OOCs that manifested as multiple jaw cysts, seven (100%) occurred in the posterior regions, four (57.1%) occurred in the mandible, and four (57.1%) were associated with an impacted tooth. Histological examination revealed cysts lined by orthokeratinized stratified squamous epithelium. Immunohistochemistry showed a low Ki-67 labeling index and no Bcl-2 expression in the seven OOCs. No pathogenic PTCH1 mutations were detected in any of the seven OOCs. None of the patients had any other symptoms or signs of recurrence at the last follow-up (6-60 months). CONCLUSION: Multiple OOCs appeared to occur more often in younger patients than solitary OOC. Both multiple and solitary OOCs may be related diseases within the entity of odontogenic cysts. Multiple OOCs are clinicopathologically and genetically distinct from OKC.

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

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.

Effective deep learning for oral exfoliative cytology classification.

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.

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

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.

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

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.

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

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.

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

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.

Impact of System and Diagnostic Errors on Medical Litigation Outcomes: Machine Learning-Based Prediction Models.

No prediction models using use conventional logistic models and machine learning exist for medical litigation outcomes involving medical doctors. Using a logistic model and three machine learning models, such as decision tree, random forest, and light-gradient boosting machine (LightGBM), we evaluated the prediction ability for litigation outcomes among medical litigation in Japan. The prediction model with LightGBM had a good predictive ability, with an area under the curve of 0.894 (95% CI; 0.893-0.895) in all patients' data. When evaluating the feature importance using the SHApley Additive exPlanation (SHAP) value, the system error was the most significant predictive factor in all clinical settings for medical doctors' loss in lawsuits. The other predictive factors were diagnostic error in outpatient settings, facility size in inpatients, and procedures or surgery settings. Our prediction model is useful for estimating medical litigation outcomes.

Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor­associated macrophages into the tumor microenvironment of oral squamous cell carcinoma.

Tumor­associated 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 SCC­associated stromal cells (VSCC­SCs), SCC­associated stromal cells (SCC­SCs) 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 VSCC­SCs and SCC­SCs promoted the differentiation of macrophages into M2 type TAMs, as well as the proliferation and migration of macrophages following crosstalk with HSC­3 cells in vitro. Moreover, the SCC­SCs exerted a more prominent effect on TAMs than the VSCC­SCs. Immunohistochemical staining was used to examine the expression of CD34, CD45, CD11b and CD163 to assay the effects of VSCC­SCs, SCC­SCs and HDFs on microvessel density (MVD) and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type macrophages. The results suggested that both VSCC­SCs and SCC­SCs promoted MVD and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type TAMs into the TME of OSCC following crosstalk with HSC­3 cells in vivo. The SCC­SCs exerted a more prominent promoting effect than the VSCC­SCs. Finally, the potential genes underlying the differential effects of VSCC­SCs and SCC­SCs on the infiltration of TAMs were investigated using microarray analysis. The results revealed that interleukin 1ß, bone morphogenetic protein 4, interleukin 6 and C­X­C motif chemokine ligand 12 had great potential to mediate the differential effects of VSCC­SCs and SCC­SCs on TAM infiltration. On the whole, the findings presented herein, demonstrate that both VSCC­SCs and SCC­SCs promote the infiltration of TAMs into the TME of OSCC following crosstalk with HSC­3 cells; the SCC­SCs 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.

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

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.