Leveraging machine learning to create user-friendly models to mitigate appointment failure at dental school clinics.

PURPOSE/OBJECTIVES: This study had a twofold outcome. The first aim was to develop an efficient, machine learning (ML) model using data from a dental school clinic (DSC) electronic health record (EHR). This model identified patients with a high likelihood of failing an appointment and provided a user-friendly system with a rating score that would alert clinicians and administrators of patients at high risk of no-show appointments. The second aim was to identify key factors with ML modeling that contributed to patient no-show appointments. METHODS: Using de-identified data from a DSC EHR, eight ML algorithms were evaluated: simple decision tree, bagging regressor classifier, random forest classifier, gradient boosted regression, AdaBoost regression, XGBoost regression, neural network, and logistic regression classifier. The performance of each model was assessed using a confusion matrix with different threshold level of probability; precision, recall and predicted accuracy on each threshold; receiver-operating characteristic curve (ROC) and area under curve (AUC); as well as F1 score. RESULTS: The ML models agreed on the threshold of probability score at 0.20-0.25 with Bagging classifier as the model that performed best with a F1 score of 0.41 and AUC of 0.76. Results showed a strong correlation between appointment failure and appointment confirmation, patient's age, number of visits before the appointment, total number of prior failed appointments, appointment lead time, as well as the patient's total number of medical alerts. CONCLUSIONS: Altogether, the implementation of this user-friendly ML model can improve DSC workflow, benefiting dental students learning outcomes and optimizing personalized patient care.

In vitro assessment of antimicrobial potential of low molecular weight chitosan and its ability to mechanically reinforce and control endogenous proteolytic activity of dentine.

AIMS: Chitosan-based biomaterials exhibit several properties of biological interest for endodontic treatment. Herein, a low molecular weight chitosan (CH) solution was tested for its antimicrobial activity against Enterococcus faecalis (E. faecalis) and effects on dentine structure. METHODOLOGY: The root canal of 27 extracted uniradicular teeth were biomechanically prepared, inoculated with a suspension of E. faecalis and randomly assigned to be irrigated with either 5.25% sodium hypochlorite (NaClO), 0.2% CH or sterile ultrapure water (W). Bacteriologic samples were collected from root canals and quantified for of E. faecalis colony-forming units (CFUs). The effectiveness of CH over E. faecalis biofilms was further measured using the MBEC Assay®. Additionally, dentine beams and dentine powder were obtained, respectively, from crowns and roots of 20 extracted third molars. Dentine samples were treated or not with 17% EDTA and immersed in either CH or W for 1 min. The effects of CH on dentine structure were evaluated by assessment of the modulus of elasticity, endogenous proteolytic activity and biochemical modifications. RESULTS: The number of E. faecalis CFUs was significantly lower for samples irrigated with CH and NaClO. No significant differences were found between CH and NaClO treatments. Higher modulus of elasticity and lower proteolytic activity were reported for dentine CH-treated specimens. Chemical interaction between CH and dentine was observed for samples treated or not with EDTA. CONCLUSIONS: Present findings suggest that CH could be used as an irrigant during root canal treatment with the triple benefit of reducing bacterial activity, mechanically reinforcing dentine and inhibiting dentine proteolytic activity.

Treatment challenges of persistent ghost cell odontogenic carcinoma: a case report and literature review.

The aim of this case report is to review and compare the clinical, radiologic, histopathologic, and immunohistochemical features, along with the treatment of a case of ghost cell odontogenic carcinoma. In addition, a report of the existing published literature with an emphasis on treatment will be described to provide information on this rare but aggressive tumor. The family of odontogenic ghost cell tumors comprises a spectrum of lesions characterized by odontogenic epithelium with ghost cell keratinization and calcifications. It appears that early detection is vital in proper treatment due to the high possibility of malignant transformation.

Early detection of oral potentially malignant disorders using machine learning: a retrospective pilot study.

Early diagnosis of oral potentially malignant disorders (OPMDs) may be hindered by similar clinical presentations shared between benign oral lesions and OPMDs. The goal of this retrospective pilot study was to assess the use of machine learning (ML) as an adjunctive evaluation in conjunction with conventional comprehensive oral examination of OMPDs. Digital images of 80 deidentified intraoral lesions (40 benign intraoral lesions and 40 OPMDs) were collected. The images, which were previously identified independently by experienced oral pathologists, were used to create 3 datasets: raw images, grayscale images, and enhanced color images. The datasets were subsequently divided into training (n = 60), test (n = 10), and validation (n = 10) groups so that class labels (benign lesion or OMPD) were distributed equally in each group. A cross-validated grid search was used to optimize the hyperparameters of the Extreme Gradient Boosting (XGBoost) classifications model. Predictions were made on the test group and used to optimize the prediction threshold. The final results were validated by predictions based on the validation group. The XGBoost classification model was able to differentiate between benign intraoral lesions and OPMDs with a mean classification accuracy of 70%, sensitivity of 80%, and specificity of 60% when grayscale and enhanced color intraoral images were used. A mean classification accuracy of 50%, sensitivity of 40%, and specificity of 60% were observed when raw intraoral images were used. The results demonstrated that ML may be a promising tool for the diagnosis of OPMDs when used as an adjunct to conventional comprehensive oral examination.

Significance of chlorine-dioxide-based oral rinses in preventing SARS-CoV-2 cell entry.

OBJECTIVE: This work aims to determine the efficacy of preprocedural oral rinsing with chlorine dioxide solutions to minimize the risk of coronavirus disease 2019 (COVID-19) transmission during high-risk dental procedures. METHODS: The antiviral activity of chlorine-dioxide-based oral rinse (OR) solutions was tested by pre-incubating with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus in a dosage-dependent manner before transducing to human embryonic kidney epithelial (HEK293T-ACE2) cells, which stably expresses ACE-2 receptor. Viral entry was determined by measuring luciferase activity using a luminescence microplate reader. In the cell-to-cell fusion assay, effector Chinese hamster ovary (CHO-K1) cells co-expressing spike glycoprotein of SARS-CoV-2 and T7 RNA polymerase were pre-incubated with the ORs before co-culturing with the target CHO-K1 cells co-expressing human ACE2 receptor and luciferase gene. The luciferase signal was quantified 24 h after mixing the cells. Surface expression of SARS-CoV-2 spike glycoprotein and ACE-2 receptor was confirmed using direct fluorescent imaging and quantitative cell-ELISA. Finally, dosage-dependent cytotoxic effects of ORs were evaluated at two different time points. RESULTS: A dosage-dependent antiviral effect of the ORs was observed against SARS-CoV-2 cell entry and spike glycoprotein mediated cell-to-cell fusion. This demonstrates that ORs can be useful as a preprocedural step to reduce viral infectivity. CONCLUSIONS: Chlorine-dioxide-based ORs have a potential benefit for reducing SARS-CoV-2 entry and spread.

Assessment of communication and physical exam skills: A comparison of students, faculty and standardized patients.

PURPOSE/OBJECTIVES: The objective of this retrospective study was twofold: it aimed to investigate dental students' communication and physical exam self-assessment skills by comparing students' self-evaluations with those completed by faculty and standardized patients (SPs). Second, it aimed to compare faculty and SPs assessment of students' communication skills. METHODS: At the end of their first year of training, students (n = 127), participated in one SP encounter about an initial dental consultation. Students completed self-assessment before receiving feedback from faculty (n = 19) and SPs (n = 19). The data source included evaluation forms submitted by students, faculty and SPs. The Wilcoxon signed rank test was used to compare the overall scores between groups. Agreement between evaluations items were analyzed with McNemar's test (p < 0.05). RESULTS: Overall, there were no statistically significant differences in how students and faculty graded for either communication (p = 0.6724) or physical exam (p = 0.1921) skills. However, both students and faculty provided less favorable marks than SPs for communication skills with a statistically significant difference in the overall grading between both students and SPs (p = 0.0146) and between faculty and SPs (p = 0.0045). CONCLUSIONS: While there was disagreement between students and faculty versus SPs, they weren't meaningful differences in scores and the dissimilarities mainly consisted of ratings of explanation skills. We suggest that, when applicable, dental student's self-evaluations may represent an alternative to faculty assessments of communication and physical exam skills. Nonetheless, we recommend that SPs be included in the assessment of communication skills to provide students with comprehensive feedback that more realistically represents the natural patient-provider relationship.

The role of Nodal and Cripto-1 in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common epithelial malignancy of the oral cavity. Nodal and Cripto-1 (CR-1) are important developmental morphogens expressed in several adult cancers and are associated with disease progression. Whether Nodal and CR-1 are simultaneously expressed in the same tumor and how this affects cancer biology are unclear. We investigate the expression and potential role of both Nodal and CR-1 in human OSCC. Immunohistochemistry results show that Nodal and CR-1 are both expressed in the same human OSCC sample and that intensity of Nodal staining is correlated with advanced-stage disease. However, this was not observed with CR-1 staining. Western blot analysis of lysates from two human OSCC line experiments shows expression of CR-1 and Nodal, and their respective signaling molecules, Src and ERK1/2. Treatment of SCC25 and SCC15 cells with both Nodal and CR-1 inhibitors simultaneously resulted in reduced cell viability and reduced levels of P-Src and P-ERK1/2. Further investigation showed that the combination treatment with both Nodal and CR-1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR-1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.

Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro.

Human Cripto-1 (Cripto-1), the founding member of the EGF-CFC superfamily, is a key regulator of many processes during embryonic development and oncogenesis. Cripto-1 is barely present or even absent in normal adult tissues while it is aberrantly re-expressed in various tumors. Blockade of the CFC domain-mediated Cripto-1 functions is acknowledged as a promising therapeutic intervention point to inhibit the tumorigenic activity of the protein. In this work, we report the generation and characterization of murine monoclonal antibodies raised against the synthetic folded CFC [112-150] domain of the human protein. Through subtractive ELISA assays clones were screened for the ability to specifically recognize "hot spot" residues on the CFC domain, which are crucial for the interaction with Activin Type I receptor (ALK4) and GRP78. On selected antibodies, SPR and epitope mapping studies have confirmed their specificity and have revealed that recognition occurs only on a conformational epitope. Furthermore, FACS analyses have confirmed the ability of 1B4 antibody to recognize the membrane-anchored and soluble native Cripto-1 protein in a panel of human cancer cells. Finally, we have evaluated its functional effects through in vitro cellular signaling assays and cell cycle analysis. These findings suggest that the selected anti-CFC mAbs have the potential to neutralize the protein oncogenic activity and may be used as theranostic molecules suitable as tumor homing agents for Cripto-1-overexpressing cancer cells and tissues and to overcome drug-resistance in routine cancer therapies.

Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma.

OBJECTIVES: The aim of this study was to determine the levels of 5-hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) compared with those in benign, reactive inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a novel biomarker for early diagnosis and prognosis of OSCC. STUDY DESIGN: The study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced with 4-nitroquinoline-1-oxide, were also evaluated. RESULTS: Progressive loss of 5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable in human cell lines. Moreover, we characterized similar alterations in 5-hmC in an animal model of OED/OSCC. CONCLUSIONS: This study demonstrated that 5-hmC distinguishes OED and OSCC from benign lesions with high sensitivity and specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED with potential implications for therapy of OSCC.

Angiopoietin-2 is expressed in oral Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) persists today as a highly prevalent vascular cancer, often found in HIV patients. Studies have shown that angiopoietin 2 (Ang2), a pro-angiogenic protein, is involved in the pathogenesis of this tumor. However, expression of this protein has not been investigated in oral KS lesions. Thus, we aimed to investigate the expression of Ang2 in samples of oral KS. METHODS: Immunohistochemistry was used to evaluate Ang2 expression in 14 oral KS cases, with degrees of expression being analyzed in a semi-quantitative manner. In addition, clinical information such as age, gender, race, tumor location, size, color, and appearance, as well as HIV status, was collected and included in the analysis. RESULTS: All patients were white males, mostly HIV-positive, with a mean age of 40 years. Clinically, the lesions were dark red/blue/purple masses, ranging from 1 to 2.5 cm in diameter, found in various locations such as the tongue, palate, and gingiva. Expression of Ang2 was noted in 72% (10/14) of the samples. Of these, 10% showed weak expression, 60% moderate, and 30% strong expression. CONCLUSIONS: Our results indicate that Ang2 is expressed in oral KS and, consistent with results from previous studies, show that Ang2 may contribute to the pathogenesis of this lesion.