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Five million non-melanoma skin cancers occur globally each year, and it is one of the most common malignant cancers. The dysregulation of the endocannabinoid system, particularly cannabinoid receptor 2 (CB2), is implicated in skin cancer development, progression, and metastasis. Comparing wildtype (WT) to systemic CB2 knockout (CB2-/-) mice, we performed a spontaneous cancer study in one-year old mice, and subsequently used the multi-stage chemical carcinogenesis model, wherein cancer is initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that aging CB2-/- mice have an increased incidence of spontaneous cancerous and precancerous skin lesions compared to their WT counterparts. In the DMBA/TPA model, CB2-/- developed more and larger papillomas, had decreased spontaneous regression of papillomas, and displayed an altered systemic immune profile, including upregulated CD4+ T cells and dendritic cells, compared to WT mice. Immune cell infiltration in the tumor microenvironment was generally low for both genotypes, although a trend of higher myeloid-derived suppressor cells was observed in the CB2-/- mice. CB2 expression in carcinogen-exposed skin was significantly higher compared to naïve skin in WT mice, suggesting a role of CB2 on keratinocytes. Taken together, our data show that endogenous CB2 activation plays an anti-tumorigenic role in non-melanoma skin carcinogenesis, potentially via an immune-mediated response involving the alteration of T cells and myeloid cells coupled with the modulation of keratinocyte activity.

The 5(th) edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (2022) comes out only five years after the previous edition, however it presents important updates that run in parallel with the rapid progression involving the increasingly sophisticated molecular investigation and its interpretation, some of which already have therapy-related impact. This manuscript provides an overview of the leading changes introduced in the classification of Odontogenic and Maxillofacial Bone Tumours that encompasses cysts of the jaws, odontogenic tumours, giant cell lesions and bone cysts, and bone and cartilage tumours. This is the first edition that Essential and Desirable Diagnostic Features were added for each entity, so that the most important clinical, microscopic and/or radiologic features were encapsulated and briefly highlighted. Surgical ciliated cyst was added to the group of odontogenic cysts, adenoid ameloblastoma was a newly recognized benign epithelial odontogenic tumour, and segmental odontomaxillary dysplasia was introduced in the group of fibro-osseous tumours and dysplasia. In addition, rhabdomyosarcoma with TFCP2 rearrangement, was introduced into the group of malignant jawbone tumours. The unique genetic aberrations distinguish it from other types of rhabdomyosarcomas. On the other hand, melanotic neuroectodermal tumour of infancy and osteoid osteoma were deleted from the benign bone and cartilageneous tumours, as was the hematolymphoid tumour of solitary plasmacytoma of bone. We systematically reviewed each entity in this chapter and provided important updated findings for selected topics that can further aid in the diagnostic process for challenging cases, broaden insights on the logic of the present classification, and finally, emphasize the potential that some of the molecular results may have in the near future to set new treatment approaches.

The objectives were to characterize clinico-pathologically a large series of peri-implant peripheral giant cell granuloma (PGCG), and investigate the role of foreign material as a possible etiological factor.The study was retrospective, conducted on peri-implant specimens submitted for histology between 2005 and 2021.Three hundred and thirty-five peri-implant biopsies were retrieved, of which 52 (15.5%) were PGCG. The study population included 28 females and 24 males, age 35-92 years, mean 61. 51.2% reported bone involvement. The lesion involved the margins of the specimen in 65.3%, recurrence was reported in 46.1%. In 58.8% the implant was removed at the same time the specimen was submitted for histopathological analysis. Small foci of black granular foreign material were observed in 53.8% of cases of which 67.8% were birefringent under polarized light. The foreign material granules were not ingested inside multinucleated giant cells, but were scattered in the stromal compartment.Peri-implant PGCG is locally aggressive, with frequent bone involvement and high recurrence rate, resulting in implant loss in the majority of cases. The high recurrence rate may be related to conservative or inadequate surgery. Foreign material although common does not seem to have a role in its development.

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The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2−/−) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (ApcMin/+). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2−/− mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2−/− and ApcMin/+CB2−/− mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans. Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients.

Background and objectives Ameloblastoma is a neoplasm arising in the craniofacial skeleton. Proliferating odontogenic epithelial cells comprise this benign, yet locally invasive tumor, often causing severe disfiguration. High recurrence rate entails ablative surgical resection, which is the current standard of care, resulting in subsequent critical size osteocutaneous defects. The high incidence of BRAF mutations in ameloblastoma, most notably the BRAFV600E mutation, enabled the use of BRAF inhibiting agent in a neoadjuvant setting. Methods In this investigator-initiated, open-label study, three consecutive pediatric patients, with confirmed BRAFV600E ameloblastoma deemed marginally resectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. Results The use of upfront BRAF inhibitor treatment resulted in substantial tumor regression, allowing for non-mutilating complete surgical removal, ad integrum bone regeneration and organ preservation. All patients showed a marked radiologic and clinical response to medical treatment, enabling successful conservative surgery. Microscopically, all patients showed evidence of minimal residual tumor with extensive tumor necrosis, fibrosis and generation of new bone. At a median follow up of 31 months, all patients remained free of disease. Conclusions Face preservation therapy was achieved in pediatric patients presenting with BRAFV600E mutated ameloblastoma. Our study demonstrates the translational potential of targeted therapy as a neoadjuvant agent. Patient-specific organ preservation therapy should be considered as the new standard of care in ameloblastoma, mainly for children and adolescents. This article is protected by copyright. All rights reserved.

Compare recognized microscopic parameters, including variations in width, plaque-like thickenings, intra-epithelial microcysts, clefts, mucous, hob-nail, ciliated and clear cells, between glandular odontogenic cyst (GOC) and GOC-like cysts, investigate the extent of cyst circumference exhibiting these features, and inflammation.Archival records of cysts with histological features of GOC evaluated between 2000 and2020 were retrieved. Slides were revised, and the expression of features throughout the cyst wall was analyzed. Cysts with at least 5 features were classified as GOC, cysts with 3-4 features as GOC-like.The study included 74 cysts, 47 males M, 25 females (2 unknown gender), aged 19-81 years, 62 (83.8%) GOC, 12 (16.2%) GOC-like. Mandible was involved in 44 (59.5%), maxilla in 30 (40.5%), 18 (25%) were associated with unerupted teeth. Cyst classified as GOC had significantly higher rates of all parameters investigated, (except ciliated and clear cells), than GOC-like cysts (p ≤ 0.05). 26 (40.6%) cases showed GOC features in50% of cyst circumference, 21 (32.8%) involved 25-50%, 17 (26.6%)25%. More than 50% circumference involvement was highly and independently predictive for a diagnosis of GOC,25% was highly and independently predictive for GOC-like (p = 0.003). Hobnail cells (p = 0.008) and plaque-like thickenings (p = 0.038) were significantly more frequent in inflamed cysts.Besides the number and type of histological features, GOC can be characterized by their distribution within the cyst circumference (focal Vs diffuse), and it may serve as a new diagnostic aid. It is suggested that GOC and GOC-like may represent a single spectrum.

Objective: To apply the technique of transfer deep learning on a small data set for automatic classification of X-ray modalities in dentistry. Study design: For solving the problem of classification, the convolution neural networks based on VGG16, NASNetLarge and Xception architectures were used, which received pre-training on ImageNet subset. In this research, we used an in-house dataset created within the School of Dental Medicine, Tel Aviv University. The training dataset contained anonymized 496 digital Panoramic and Cephalometric X-ray images for orthodontic examinations from CS 8100 Digital Panoramic System (Carestream Dental LLC, Atlanta, USA). The models were trained using NVIDIA GeForce GTX 1080 Ti GPU. The study was approved by the ethical committee of Tel Aviv University. Results: The test dataset contained 124 X-ray images from 2 different devices: CS 8100 Digital Panoramic System and Planmeca ProMax 2D (Planmeca, Helsinki, Finland). X-ray images in the test database were not pre-processed. The accuracy of all neural network architectures was 100%. Following a result of almost absolute accuracy, the other statistical metrics were not relevant. Conclusions: In this study, good results have been obtained for the automatic classification of different modalities of X-ray images used in dentistry. The most promising direction for the development of this kind of application is the transfer deep learning. Further studies on automatic classification of modalities, as well as sub-modalities, can maximally reduce occasional difficulties arising in this field in the daily practice of the dentist and, eventually, improve the quality of diagnosis and treatment.

We aimed to collect and analyze available cases of intraoral acantholytic squamous cell carcinoma (aSCC), that consisted of the authors’ cases and cases derived from the existing literature, with an emphasis on the pathological staging and patient outcome. Our research question was whether aSCC is more aggressive than conventional SCC. The literature was searched for documented cases of aSCC involving the intra-oral mucosa, excluding those from the lips and tonsils, and seven new cases were added from our files. The authors compared the obtained aSCC data to existing data for conventional SCC. Fisher Exact or Pearson’s χ(2) tests were used for categorical variables. Fifty-five cases of intraoral aSCC were reviewed, of which 48 were retrieved from the literature. Analysis of the published cases was reinforced by contacting the authors of all the papers with incomplete data for further clarifications. The most common sites of aSCC were the tongue (24/55) and the maxilla/maxillary gingiva and/or palate (11/55). The overall survival rate was 36/53 (67.9%) with a mean follow-up period of 22 months against 62.5% for conventional SCC (p = 0.6). No statistically significant difference between the two variants of the tumor with respect to the oral cavity was detected. The differences in age, sex, survival rate, staging, and locations were not statistically significant. Based on the available data from 55 cases, there is no evidence to suggest that aSCC is more aggressive than conventional SCC in intraoral cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01368-8.

Background Recent evidence suggests that bone marrow-derived stem cells may have an important role in the natural process of wound healing. The aim of the present study was to examine the effect of orabase paste application on primary wound healing in a palatal rat model. Materials and methods A total of 48 six-month-old male Wistar rats weighting 427 to 650 g were included. A mid-crestal incision was made on the maxillary alveolar ridge. A full-thickness flap was raised on either side of the incision and was then repositioned and sutured. Three experimental groups were used: O-study group-orabase, N-negative control group, and I-intact control group. Half of the animals were killed on 7 days and the remaining on 14 days postoperatively. Outcome parameters included epithelial gap; inflammatory infiltration; expression of stem cell markers within the oral epithelium and stromal cells; and physical properties of stromal collagen fibers and myofibroblasts. Investigations were performed at 2 time points (7 and 14 d) during the wound healing process. Results The epithelial gap closed completely after 7 days in the O group versus 14 days or more in the N group. The inflammatory reaction was relatively low and not significantly different between groups O and N. Orabase upregulated the expression of CK14, CK15, and epithelial SOX2. Connective tissue SOX2, CD34, and α-smooth muscle actin and physical properties of stromal collagen fibers were not influenced by the application of orabase. Conclusions Orabase promotes epithelial gap closure in a primary wound healing model in rats. The effect is exerted through promotion of epithelial differentiation from stem cells.

The aim of the present study was to compare the clinical, radiological and histomorphometrical outcome of simultaneous implant placement following augmentation of atrophic maxillary sinuses using allograft (block or particles). Consecutive patients with maxillary residual alveolar ridge height ≤3 mm, scheduled for sinus floor augmentation with simultaneous implant placement, were randomly included. Allograft bone-block or bone-particles served as grafting material. Simultaneously, dental implants were inserted. Biopsies were taken at second stage surgery (after 9 months) for histomorphometric evaluation. Initially 38 sinus augmentations (29 individuals) were allocated for the study. In 4 out of 21(19%) sinuses using particles it was impossible to stabilize the implants and a second stage insertion was preferred, leaving 34 sinuses for histomorphometric evaluation. The difference in the ability to perform simultaneous implant placement was statistically significant (p

The aim of the present study was to assess macroscopically the time-related dimensional pattern of excisional palatal mucoperiosteal wound closure in rats, concomitantly with microscopic analysis of the density of inflammatory infiltrate and myofibroblasts. Excisional palatal wounds, 4.2 mm in diameter, were made in twenty-one 2-month-old male Wistar rats. The total area and anteroposterior/laterolateral dimensions of the wounds were measured macroscopically at 1, 2, and 3 weeks post-operatively. In addition, histomorphometry was used for assessment of the intensity of inflammation and density of myofibroblasts in the wound area. A significant decrease was found in the total area and anteroposterior but not the laterolateral dimension of the wounds during the 2nd week. These changes were less prominent in the 3rd week. Three weeks post-operatively, the density of inflammatory infiltrate remained high in the central part of the wound concomitant with a significant increase in the number of myofibroblasts. We concluded that the second week was the most significant in wound closure, with wound contraction first occurring in an anteroposterior plane followed by the laterolateral plane. The increased inflammatory reaction and changes in the density of myofibroblasts may explain the macroscopic decrease in wound dimensions in a time-related manner. These findings emphasize the importance of the amount of soft tissue left at surgery, and suggest that the most appropriate time for the use of healing promoters would be the second post-operative week.

This study aims to examine the composition of lining and masticatory mucosa at the pre- and post-soft tissue augmentation procedures with a volume-stable cross-linking collagen matrix (VCMX) in humans. In 12 patients, single implant sites were augmented with a VCMX. Biopsies were obtained including masticatory (MM) and lining (LM) mucosa before augmentation and at 12 weeks post-augmentation procedures. Rete pegs density (RPD), length (RPL), and blood vessel density (BVD) were histomorphometrically analyzed at both time points. Picrosirius red staining under polarized light microscopy was used to evaluate collagen fiber organization. The effects of time and tissue type were evaluated by ANOVA with repeated measures. Both MM and LM areas demonstrated an increase in mean RPL following augmentation, 382.6 µm ± 95.1 vs. 290.5 µm ± 79.3 and 335.6 µm ± 94.2 vs. 292.9 µm ± 77.0, respectively (p

Irradiation of facial bones is associated with a lifelong risk of osteonecrosis. In a rat model, maxillae were exposed to a single 5 Gy dose of external beam radiation and orthodontic force was applied for 2 weeks on the first maxillary molar, control rats were treated identically without radiation. Tooth movement in irradiated jaws was 30% less than in controls, representing radiation-related damage. Micro-CT, histological, and molecular outcomes of orthodontic tooth movement were studied. Microstructurally, bone parameters (trabecular thickness, bone volume fraction, bone mineral density) were significantly affected by orthodontic force but not by radiation. Histological parameters were influenced only by orthodontic force, especially by an increase in osteoclasts. A molecular study revealed a differential distribution of cells expressing pre-osteoclast markers (RANK+—majority, CD11b+, CD14+—minority), with changes being influenced by orthodontic force (increased CD11b+ and CD14+ cells) and also by radiation (decreased RANK+ cells). The activation status of osteoclasts (TRAP staining) showed an orthodontic-force-related increase, which probably could not fully compensate for the radiation-associated impairment. The overall balance showed that orthodontic force had elicited a substantial microstructural, histological, and functional normalization process in irradiated maxillae but a radiation-induced impact was still conspicuous. Additional studies are needed to validate these findings.

Exophytic lesions of the tongue encompass a diverse spectrum of entities. These are most commonly reactive, arising in response to local trauma but can also be neoplastic of epithelial, mesenchymal or miscellaneous origin. In most cases, the microscopic examination is likely to provide a straightforward diagnosis. However, some cases can still raise microscopic diagnostic dilemmas, such as conditions that mimic malignancies, benign tumors with overlapping features and anecdotal lesions. A series of "lumps and bumps" of the tongue are presented together with suggested clues that can assist in reaching a correct diagnosis, emphasizing the importance of the clinico-pathological correlations.

To determine the Fourier-transform infrared (FTIR) spectra of salivary exosomes from oral cancer (OC) patients and healthy individuals (HI) and to assess its diagnostic potential using computational-aided models. Whole saliva samples were collected from 21 OC patients and 13 HI. Exosomes were pelleted using differential centrifugation (12,000g, 120,000g). The mid-infrared (IR) absorbance spectra (900–5000 cm− 1 range) were measured using MIR8025 Oriel Fourier-transform IR equipped with a PIKE MIRacle ZnSe attenuated total reflectance attachment. Machine learning techniques, utilized to build discrimination models for the absorbance data of OC and HI, included the principal component analysis–linear discriminant analysis (PCA–LDA) and support vector machine (SVM) classification. Sensitivity, specificity and the area under the receiver operating characteristic curve were calculated. IR spectra of OC were consistently different from HI at 1072 cm− 1 (nucleic acids), 2924 cm− 1 and 2854 cm− 1 (membranous lipids), and 1543 cm− 1 (transmembrane proteins). The PCA–LDA discrimination model correctly classified the samples with a sensitivity of 100%, specificity of 89% and accuracy of 95%, and the SVM showed a training accuracy of 100% and a cross-validation accuracy of 89%. We showed the specific IR spectral signature for OC salivary exosomes, which was accurately differentiated from HI exosomes based on detecting subtle changes in the conformations of proteins, lipids and nucleic acids using optimized artificial neural networks with small data sets. This non-invasive method should be further investigated for diagnosis of oral cancer at its very early stages or in oral lesions with potential for malignant transformation.

Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs).Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score >1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs.Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases.Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients.

Ameloblastic fibro-odontoma (AFO) is a controversial, rare benign mixed odontogenic tumour that was re-defined as "developing odontoma" in the 2017 WHO classification arguing that once dental hard tissues form, it is programmed to transform into odontoma. However, AFO still remains unclear in terms of its nature. We aimed to analyze a large series of AFOs and compare it to a large series of odontomas (ODs) in an attempt to set cut-off diagnostic parameters between these entities and discuss latest updates on AFO histopathologic, clinical and molecular features. A total of 23 well-documented AFOs were analyzed versus 310 ODs focusing on the age of the patients and size of the lesions. For AFO, mean age was 9.4 ± 3.9 years (range 3–16 years) and mean size (greatest diameter) was 2.9 ± 1.5 cm (range 0.8–5.5 cm). For OD—mean age was 26.5 ± 15.6 years (range 3–81 years), mean size 1.9 ± 0.9 cm (range 1–5 cm). Receiver operating curve (ROC) showed that a cut-off age of 13.5 years and below [area under the curve (AUC) 0.902, 95%CI 0.859–0.945; p

We assessed age-related excisional palatal mucoperiosteal wound closure in rats. A 4.2 mm diameter punch was used to create a secondary healing defect in the palate of Wistar rats. Study group—21, 18-month-old vs. control 21, 2-month-old males. The 2-dimensional area, maximum length and width of the soft tissue defect served as clinical outcome parameters. The dynamics of the initial three healing weeks were assessed. Semi-quantitative histomorphometric analysis of inflammation and myofibroblasts served for the evaluation of the inflammatory and proliferative wound healing phases. Complete wound closure was faster in the old rats. A dimensional related wound closure was observed in the young rats versus a symmetrical wound closure in the old rats. Inflammatory response was significantly delayed and of lower intensity in the old rats. Myofibroblastic response, representing the proliferative stage, was delayed and of lower intensity in the old rats, albeit not statistically significant. Reduced initial tissue damage due to decreased and delayed inflammatory response in the old rats ultimately led to faster clinical wound healing compared to the young rats, despite a statistically non-significant lower proliferative response in the old rats.

This study aimed to characterize the demographic and clinical features of underreported surgical ciliated cysts developing after sinus floor augmentation, based on a series of cases from our files and a systematic review of the literature. A series of five cases (four patients) of microscopically confirmed surgical ciliated cysts following sinus floor augmentation procedures from our files are described. A systematic literature search (1991–2020) with strict clinical-, radiological- and microscopic-based exclusion and inclusion criteria was performed to detect additional similar cases. The systematic review revealed only five cases that fulfilled the inclusion criteria. Altogether, surgical ciliated cysts associated with sinus floor augmentation have been rarely reported in the literature, and have not been characterized either demographically or clinically. Graft materials were diverse, implants were placed simultaneously, or up to two years post-augmentation. The associated surgical ciliated cysts developed between 0.5 and 10 years post-augmentation. Although limited in its extent, this study is the first series to characterize possible underreported sequelae of surgical ciliated cysts associated with sinus floor augmentation. It emphasizes the need for long post-operative follow-up and confirmation of lesion by microscopic examination.

Curcumin is known as an anti-tumor, anti-aging, and wound healing promoter. The aim this study was to examine the effect of 2% curcumin paste application on primary wound healing in a palatal rat model. A mid-crestal incision was initiated on the maxillary alveolar ridge. A full thickness flap was raised on either side of the incision and was then repositioned and sutured. Experimental groups consisted of 2% curcumin (Cur), orabase (O), cut only (C), and intact control-no incision, no paste (N). Curcumin 2% and orabase were applied postoperatively every 12 h for 3 consecutive days. Rats were equally killed after 1 and 2 weeks. Histological data included-epithelial gap, inflammatory infiltrate, myofibroblasts, epithelial and connective tissue stem cell-related markers. Data were collected at two time points-1 and 2 weeks. There was no residual epithelial gap 1 week from incision in the Cur and O group vs. residual gap in the C group (

Objective: To apply the technique of deep learning on a small dataset of panoramic images for the detection and segmentation of the mental foramen (MF). Study design: In this study we used in-house dataset created within the School of Dental Medicine, Tel Aviv University. The dataset contained randomly chosen and anonymized 112 digital panoramic X-ray images and corresponding segmentations of MF. In order to solve the task of segmentation of the MF we used a single fully convolution neural network, that was based on U-net as well as a cascade architecture. 70% of the data were randomly chosen for training, 15% for validation and accuracy was tested on 15%. The model was trained using NVIDIA GeForce GTX 1080 GPU. The SPSS software, version 17.0 (Chicago, IL, USA) was used for the statistical analysis. The study was approved by the ethical committee of Tel Aviv University. Results: The best results of the dice similarity coefficient ( DSC), precision, recall, MF-wise true positive rate (MFTPR) and MF-wise false positive rate (MFFPR) in single networks were 49.51%, 71.13%, 68.24%, 87.81% and 14.08%, respectively. The cascade of networks has shown better results than simple networks in recall and MFTPR, which were 88.83%, 93.75%, respectively, while DSC and precision achieved the lowest values, 31.77% and 23.92%, respectively. Conclusions: Currently, the U-net, one of the most used neural network architectures for biomedical application, was effectively used in this study. Methods based on deep learning are extremely important for automatic detection and segmentation in radiology and require further development.

Background and objectives: Subepithelial connective tissue graft (SCTG) from the palate has been considered as the &ldquo, gold standard&rdquo, for the treatment of deep gingival recessions. A single-incision technique was reported to allow primary wound healing. A palatal single incision was performed in a rat model. The present study assessed the histology and histomorphometry of palatal wound healing following surgical closure with primary intention. Materials and Methods: Twenty-six 6-month-old male Wistar rats weighing 427&ndash, 650 g. An incision was made on the maxillary palate. A full thickness flap was raised palatally, and then repositioned and sutured. Two experimental groups: S&mdash, Study group, I&mdash, Intact control group. Half of the animals were sacrificed 7 days and the remaining 14 days postoperatively. Outcome parameters included&mdash, epithelial gap, inflammatory infiltration, vascular fraction, expression of myofibroblasts and stem cell markers within the oral epithelium and stromal cells and physical properties of stromal collagen fibers. Investigations were performed at two time-points (7 and 14 days) during the wound healing process. Results: The epithelial gap closed completely after 14 days. The inflammatory reaction and vascular fraction were relatively low. Surgical trauma downregulated the expression of cytokeratin (CK) 14 and CK 15, which returned to normal after 14 days. Epithelial differentiation was mediated through upregulation of connective tissue sex- determining-region-Y-box2 (SOX2). Epithelial SOX2, CD34, alpha smooth muscle actin (&alpha, SMA) and physical properties of stromal collagen fibers were not influenced by the surgical trauma. Conclusions: Surgical trauma followed by palatal wound healing with primary intention in a rat model heals within 14 days. It induces minimal inflammatory infiltration and vascular proliferation. Epithelization is exerted through promotion of epithelial differentiation from stem cells by connective tissue SOX2.

BACKGROUND The stroma of odontogenic cysts/tumors may confer them differential biological behavior. We aimed to investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, and CD34) in the stroma of odontogenic cysts and tumors. CD34 was investigated exclusively as a marker for stromal fibroblast/fibrocyte cells (CD34 + SFCs). CD34 + SFCs were also investigated ultrastructurally. METHODS Ten cases each of primary odontogenic keratocyst (OKC), recurrent OKC, dentigerous cyst, ameloblastoma, unicystic ameloblastoma, odontogenic myxoma, and 7 syndromic OKC were included. Results were represented as the mean score (%) of positive cells/field for each marker for each study group. For CD34 + SFCs, results are presented as the mean number of cells/field for each type of lesion. Kruskal-Wallis and Spearman's correlation statistical tests were used; significance was set at P

Background: Oral tongue squamous cell carcinoma (OTSCC) cells are highly proliferative and invasive. Lingonberry contains several polyphenolic compounds similar to curcumin. We hypothesize that fermented lingonberry juice (FLJ) has an anti-invasive and anti-proliferative effect on OTSCC cells similarly to curcumin, which is known to be anti-carcinogenic. Materials and methods: FLJ, curcumin dissolved in ethanol, or curcumin loaded in Candida extracellular vesicles (EVs) were added to more (HSC-3) and less aggressive (SCC-25) OTSCC cells. Cell proliferation was measured with a 5-bromo-2’-deoxyuridine kit and invasion in the three-dimensional Myogel spheroid assay. Statistical analyses were completed with one-way ANOVA and Bonferroni post-hoc testing. Results: Both FLJ and curcumin significantly reduced the proliferation and invasion of HSC-3 and SCC-25 cells. The effects of curcumin were not improved when cells were treated with curcumin loaded within EVs. Conclusions: Our results suggest that FLJ, like curcumin, has an anti-carcinogenic effect on aggressive OTSCC cells in vitro.

The aim of the present study was to compare the clinical, radiological and histomorphometrical outcome of simultaneous implant placement following augmentation of atrophic maxillary sinuses using allograft (block or particles). Consecutive patients with maxillary residual alveolar ridge height ≤3 mm, scheduled for sinus floor augmentation with simultaneous implant placement, were randomly included. Allograft bone-block or bone-particles served as grafting material. Simultaneously, dental implants were inserted. Biopsies were taken at second stage surgery (after 9 months) for histomorphometric evaluation. Initially 38 sinus augmentations (29 individuals) were allocated for the study. In 4 out of 21(19%) sinuses using particles it was impossible to stabilize the implants and a second stage insertion was preferred, leaving 34 sinuses for histomorphometric evaluation. The difference in the ability to perform simultaneous implant placement was statistically significant (p 0.05). Ninety implants were inserted simultaneously. All implants osseointegrated. None of the implants was lost up to the end of follow-up time (Range 50-120 months, Mean 74.5 ± 13.5 months). Bone gain radiographically 12.3 ± 1 mm vs. 11.2 ± 1 mm (block vs. particles respectively) and new bone formation histomorphometrically 27.7 ± 15% vs. 32.1 ± 19% (block vs. particles respectively) showed no statistically significant differences between the two groups. Sinus augmentation using allograft (particles or block) and simultaneous implant placement is predictable. All outcome parameters are similar when sinus bone-blocks augmentation is compared to bone-particles augmentation (radiological new bone gain, implant survival, hisomorphometricly new bone formation) despite the ability to stabilize implants, when placed simultaneously with sinus augmentation. Blocks may be advisable when simultaneous implant placement is imperative in cases with residual alveolar bone height ≤3 mm.

Objective To investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, CD34) in odontogenic cysts and tumors. CD34 was investigated as a marker for stromal fibroblast/fibrocyte cells (CD34+SFCs). CD34+SFCs were also investigated ultrastructurally. The physical aggregation of collagen fibers was examined by picrosirius red stain and polarized light. Methods Ten cases each of primary odontogenic keratocysts (OKC), recurrent OKC, dentigerous cysts, ameloblastoma, unicystic ameloblastoma, and odontogenic myxoma and 7 syndromic OKC (sOKC) were included. Results were expressed as the mean number of positive cells per field. Changes (%) in polarization colors of the collagen fibers were assessed pending 90° rotation of the microscope table. Significance was set at P Results All markers except Oct4 were expressed by stromal cells in all lesions. Expression of SOX2 but not Nanog was significantly higher in tumors than in cysts (P Conclusions Stromal cells in odontogenic cysts and tumors seem to contribute to their biological behavior.

Introduction White/red lesions, exophytic masses with or without ulceration, are well-recognized typical presentations of oral squamous cell carcinoma (OSCC). Rarely, clinical characteristics may mimic benign lesions. Objective To report an unusual case of OSCC of the anterior maxillary gingiva and hard palate, with an initial nonspecific clinical and histologic presentation mimicking benign inflammatory lesions. Case Presentation A 58-year-old, otherwise healthy woman was referred with mild pain and a reddish, papillary, gingivopalatal, inflammatory-like lesion of 6 months’ duration. Medications, systemic medical conditions, tobacco use, and parafunctional habits that could generate the appearance were excluded. Radiographs did not reveal any bone involvement. Repeated periodontal treatment, improvement of oral hygiene, topical applications of disinfectant, an antifungal, and corticosteroids all failed to yield any improvement. During a period of 18 months, 3 biopsies were taken from the affected gingiva, showing only benign epithelial hyperplasia with dense chronic inflammation devoid of any evidence of malignancy. Following rapidly progressing tooth mobility of the lateral incisor concomitant with accelerated overgrowth of the anterior palatal gingiva, dental radiography was repeated, and computed tomography was performed. Both revealed an extensive osteolytic lesion in the premaxilla. A new biopsy taken from the affected gingiva and adjacent maxillary alveolar bone yielded a diagnosis of OSCC. Treatment included resection of the premaxilla and floor of the nose with bilateral neck dissection. Conclusions This case emphasizes the possibility of a deceptive initial appearance of OSCC, the sudden burst and rapid disease progression, and the importance of close follow-up of unusual nonspecific inflammatory-like processes in the oral cavity.

BACKGROUND An age-related decrease in the number of osteogenic progenitor cells may compromise bone augmentation. PURPOSE Histomorphometrical assessment of age-related new bone formation, following atrophic alveolar ridge reconstruction, using cancellous bone-block allografts. MATERIAL AND METHODS Ninety-three consecutive patients (58 females and 35 males) were referred for implant-supported restoration of 122 severe atrophic alveolar ridges. Alveolar ridge deficiency locations were classified as anterior maxilla (n = 58), posterior maxilla (n= 32), and posterior mandible (n = 32). A bony deficiency of at least 3 mm horizontally and up to 3 mm vertically according to computerized tomography (CT) in the posterior mandible and anterior maxilla, served as inclusion criteria. In the posterior maxilla, a residual alveolar ridge up to 4 mm vertically according to CT served as inclusion criteria. Augmentation was performed by the use of cancellous bone-block allografts. Bone biopsies (9-month posterior maxilla, 4 months anterior maxilla and posterior mandible) of young (≤40 years) versus older (>40 years) patients were histomorphometrically evaluated. RESULTS In the posterior maxilla, no statistically significant histomorphometric differences were noted. While at the anterior maxilla and posterior mandible, statistically significant more newly formed bone was found in young versus older individuals, respectively (38.6% vs 19.8%, P = 0.04 and 69% vs 31%, P = .05). CONCLUSION New bone formation following residual alveolar ridge bone grafting is age-related. Longer bone consolidation and healing time may be recommended for older individuals.