An Update on the Use of Artificial Intelligence in Digital Pathology for Oral Epithelial Dysplasia Research.

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.

Performance of AI chatbots on controversial topics in oral medicine, pathology, and radiology.

OBJECTIVES: In this study, we assessed 6 different artificial intelligence (AI) chatbots (Bing, GPT-3.5, GPT-4, Google Bard, Claude, Sage) responses to controversial and difficult questions in oral pathology, oral medicine, and oral radiology. STUDY DESIGN: The chatbots' answers were evaluated by board-certified specialists using a modified version of the global quality score on a 5-point Likert scale. The quality and validity of chatbot citations were evaluated. RESULTS: Claude had the highest mean score of 4.341 ± 0.582 for oral pathology and medicine. Bing had the lowest scores of 3.447 ± 0.566. In oral radiology, GPT-4 had the highest mean score of 3.621 ± 1.009 and Bing the lowest score of 2.379 ± 0.978. GPT-4 achieved the highest mean score of 4.066 ± 0.825 for performance across all disciplines. 82 out of 349 (23.50%) of generated citations from chatbots were fake. CONCLUSIONS: The most superior chatbot in providing high-quality information for controversial topics in various dental disciplines was GPT-4. Although the majority of chatbots performed well, it is suggested that developers of AI medical chatbots incorporate scientific citation authenticators to validate the outputted citations given the relatively high number of fabricated citations.

Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples. Through iterative training, the generator allows the creation of images that are indistinguishable from real ones, leading to high-quality image generation. Considering their success in computer vision, GANs hold great potential for medical diagnostic applications. In the medical field, GANs can generate images of rare diseases, aid in learning, and be used as visualization tools. GANs can leverage unlabeled medical images, which are large in size, numerous in quantity, and challenging to annotate manually. GANs have demonstrated remarkable capabilities in image synthesis and have the potential to significantly impact digital histopathology. This review article focuses on the emerging use of GANs in digital histopathology, examining their applications and potential challenges. Histopathology plays a crucial role in disease diagnosis, and GANs can contribute by generating realistic microscopic images. However, ethical considerations arise because of the reliance on synthetic or pseudogenerated images. Therefore, the manuscript also explores the current limitations and highlights the ethical considerations associated with the use of this technology. In conclusion, digital histopathology has seen an emerging use of GANs for image enhancement, such as color (stain) normalization, virtual staining, and ink/marker removal. GANs offer significant potential in transforming digital pathology when applied to specific and narrow tasks (preprocessing enhancements). Evaluating data quality, addressing biases, protecting privacy, ensuring accountability and transparency, and developing regulation are imperative to ensure the ethical application of GANs.

Prosthodontic implications of saliva and salivary gland dysfunction.

PURPOSE: To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented. MATERIALS AND METHODS: English-language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information. RESULTS: Saliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations. CONCLUSION: This review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction.

Isolated Congenital Camptodactyly and Temporomandibular Joint Articular Disc Displacement.

The development of craniofacial structures is complex and involves multiple cellular and molecular interactions. We report a case of congenital camptodactyly in a female who subsequently developed chronic tinnitus and temporomandibular joint dysfunction. This report describes the clinicoradiographic features and surgical management of the facial skeletal manifestations, along with postoperative rehabilitation. Furthermore, a concise review of similar literature raises the question of whether this complex of manifestations represents a new entity or a minimal manifestation of a previously characterized syndrome. As such, a possible developmental association between camptodactyly and temporomandibular joint dysfunction is suggested.

Oral Epithelial Dysplasia Grading Systems: A Systematic Review & Meta-Analysis.

This systematic review and meta-analysis aims to provide a robust qualitative and quantitative analysis of the different systems used to assess the grade of oral epithelial dysplasia (OED). This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA) statement. Six electronic databases were searched for primary research published over the past four decades. Overall quality and level of evidence were based on the Johns Hopkins Research Evidence Appraisal Tool, while evidence of heterogeneity was determined by the Q-statistic and I^2 statistic. Evidence of publication bias was determined using Egger's regression and the Rank correlation tests. A total of 170 records were identified. Only 9 primary research articles were included in the qualitative systematic review. Four studies (4/9) were included in the final quantitative meta-analysis. The grading systems analyzed included the WHO, binary, Ljubljana, Smith and Pindborg, Brothwell, and the oral intraepithelial neoplasia. The results demonstrate the binary system to be superior to the WHO system in grading OED, by providing better inter-observer agreement, however, the substantial error among the inter-observer κ values analyzed indicates the significance of this finding to be of minimal impact. Lack of reliable reproducibility of the grading systems and lack of common effect size (heterogeneity analysis) were noted.

The influence of antiretroviral therapy on HIV-related oral manifestations.

PURPOSE: This review aims to provide primary medical and dental healthcare professionals with the current state of information on the oral manifestations of HIV infection in the era of antiretroviral therapy (ART) advancements. RESULTS: Infection with the human immunodeficiency virus (HIV) is associated with an increased risk of infectious, neoplastic, and immune-mediated oral complications that are regarded as a major constituent of this global epidemic. HIV-related oral manifestations have been subject to changes in their prevalence with the employment of ART, particularly in this period of enhanced patient accessibility to ART. Available antiretroviral medications (ARVs), the clinical presentation of common HIV-related oral manifestations, and patients and healthcare providers' perceptions are also discussed. CONCLUSIONS: Screening, diagnosing, and treating patients with HIV/Acquired immunodeficiency syndrome (AIDS) has improved drastically since the isolation and characterization of HIV. Oral manifestations have been acknowledged to correlate with treatment responses and disease progression. Healthcare providers should be familiar with HIV-related oral manifestations and comfortable in managing and referring patients with HIV/AIDS, they are also key stakeholders in facilitating the elimination of the stigma associated with the infection.

The state of Oral Medicine and Oral Pathology in the Arab Middle East.

The Arab World consists of 22 countries with more than half located in the Arab Middle East. Whereas the current state of Oral Medicine and Oral Pathology in the Western World is well known, available information on the current state of Oral Medicine and Oral Pathology across the Arab Middle East is lacking. This concise communication sheds light on the current state of these two specialties with specific reference to specialty training programs, board certification, and future directions. This piece provides valuable information to the general public and other disciplines to raise awareness and guide clinicians in making appropriate referrals. Additionally, it is of importance to newly graduated dentists interested in pursuing a career in either of these two disciplines.

The role of primary care providers in oral health education for patients with diabetes.

OBJECTIVE: In this manuscript, we provide information and guidance on oral health education for diabetes care management, which will be beneficial to primary care providers and educators as it serves to fill a current knowledge gap. RESULTS: There is a lack of awareness on the relationship between diabetes mellitus and oral health complications along with less frequent dental visits by adult patients with diabetes, which can be attributed to the great variation in the volume and intensity of training on oral health information between current diabetes education programs. CONCLUSIONS: There is a general lack of reliable oral health assessment tools incorporated in diabetes education curricula in addition to a lack of familiarity and time to complete the existing tools among diabetes patient educators in the busy primary care setting. PRACTICE IMPLICATIONS: We propose a simplified, more feasible oral health assessment tool that can be incorporated in office visits of primary care educators and providers. The intention of this manuscript is to generate sufficient awareness to motivate a follow-up effectiveness study to test the validity and use of the proposed tool.

What every dentist should know about oral mucosal wound healing.

The oral mucosa has superior wound healing potential compared to other mucosal tissues. The objective of this article is to review the current state of evidence on the mechanisms that govern accelerated oral mucosal wound healing and explore clinical approaches that facilitate the natural course of these processes.

The Role of Candida albicans Secreted Polysaccharides in Augmenting Streptococcus mutans Adherence and Mixed Biofilm Formation: In vitro and in vivo Studies.

The oral cavity is a complex environment harboring diverse microbial species that often co-exist within biofilms formed on oral surfaces. Within a biofilm, inter-species interactions can be synergistic in that the presence of one organism generates a niche for another enhancing colonization. Among these species are the opportunistic fungal pathogen Candida albicans and the bacterial species Streptococcus mutans, the etiologic agents of oral candidiasis and dental caries, respectively. Recent studies have reported enhanced prevalence of C. albicans in children with caries indicating potential clinical implications for this fungal-bacterial interaction. In this study, we aimed to specifically elucidate the role of C. albicans-derived polysaccharide biofilm matrix components in augmenting S. mutans colonization and mixed biofilm formation. Comparative evaluations of single and mixed species biofilms demonstrated significantly enhanced S. mutans retention in mixed biofilms with C. albicans. Further, S. mutans single species biofilms were enhanced upon exogenous supplementation with purified matrix material derived from C. albicans biofilms. Similarly, growth in C. albicans cell-free spent biofilm culture media enhanced S. mutans single species biofilm formation, however, the observed increase in S. mutans biofilms was significantly affected upon enzymatic digestion of polysaccharides in spent media, identifying C. albicans secreted polysaccharides as a key factor in mediating mixed biofilm formation. The enhanced S. mutans biofilms mediated by the various C. albicans effectors was also demonstrated using confocal laser scanning microscopy. Importantly, a clinically relevant mouse model of oral co-infection was adapted to demonstrate the C. albicans-mediated enhanced S. mutans colonization in a host. Analyses of harvested tissue and scanning electron microscopy demonstrated significantly higher S. mutans retention on teeth and tongues of co-infected mice compared to mice infected only with S. mutans. Collectively, the findings from this study strongly indicate that the secretion of polysacharides from C. albicans in the oral environment may impact the development of S. mutans biofilms, ultimately increasing dental caries and, therefore, Candida oral colonization should be considered as a factor in evaluating the risk of caries.

Tele-Oral Oncology: Reinvigorating Telemedicine in Oral Cancer Care.

Introduction: In recent years, we have witnessed significant growth in the employment of technological advancements in health-care practices. These advancements have increased the practicality and utility of telemedicine applications. The aim of this focused review is to provide in-depth insights into the current state of telemedicine in oral oncology. Observations: Tele-oral oncology (TOO) is a rapidly emerging field and has provided new opportunities to transform oral cancer care into the 22nd century. This review will explore topics related to TOO as they pertain to consultation, oral cancer management in underserved areas, patient education and e-learning applications. Conclusion and Relevance: The utilisation of TOO is hindered by many challenges and this review addresses the potential limitations that prevent the integration of TOO in routine oral cancer care. A working model that circumvents the potential shortcomings of TOO is also proposed.

Combination Nivolumab/Ipilimumab Immunotherapy For Melanoma With Subsequent Unexpected Cardiac Arrest: A Case Report and Review of Literature.

The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis with high-dose steroids, which should be tapered over 6 weeks, further cardiology care is needed, and a defibrillator might have to be implanted. Understanding the pathophysiology of immune-related adverse events could make cancer immunotherapy both more effective and safer.

The effect of embryonic origin on the osteoinductive potential of bone allografts.

STATEMENT OF PROBLEM: Allografts with osteoinduction potential are widely used to augment bone in surgical and prosthetic rehabilitations. However, osteoinduction potential varies among commercially available allografts. Donor bones are derived from different embryonic origins, either the neural crest or mesoderm. Whether the origin of the bones affects the osteoinductivity of allograftsis is unclear. PURPOSE: The purpose of this ex vivo study was to investigate the osteoinduction potential of allografts derived from bones with distinct embryonic origins. MATERIAL AND METHODS: Allografts were obtained from human frontal and parietal bones at 2 different ages (fetal and adult). The specimens were divided into 4 groups: adult frontal (n=5), adult parietal (n=5), fetal frontal (n=10), and fetal parietal (n=10). Two investigations were conducted to assess the osteoinductive potential of these allografts. First, the osteogenesis of human osteoblasts exposed to these allografts were evaluated by analyzing the expression of runt-related transcription factor 2 (RUNX2), collagen type 1 alpha 2 chain (COL1A2), and bone gamma-carboxyglutamate protein (BGLAP) genes using quantitative real-time polymerase chain reaction (qRT-PCR). Second, the protein content of the adult frontal and parietal bone matrices was analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). One-way ANOVA and the t test were used for statistical analyses of the gene and protein expression of the groups (α=.05). RESULTS: No difference was found in the gene expression of the cells exposed to frontal or parietal bones. However, all 3 genes were significantly overexpressed in cells treated with fetal bones compared with adult bones. No difference was found in protein expression between adult frontal and adult parietal bones. CONCLUSIONS: No difference was found in the osteoinductive capacity of frontal and parietal bones used as allografts. However, the osteoinductivity of fetal bones can be higher than that of adult bones. Further microanalyses are needed to determine the protein content of fetal bones.

Central xanthoma of the mandible associated with hyperlipidemia: A rare presentation.

Xanthoma is a common, self-limiting cutaneous lesion of non-Langerhans cell, lipid-laden foamy histiocytes that is often concomitant with hyperlipidemia. The intraosseous counterpart is rarely encountered and typically presents as a painless, expansile osteolytic process in the context of hyperlipidemia or normolipidemia. Only a scant number of gnathic xanthomas have been reported in the otolaryngologic literature. We report the clinical, laboratory, radiographic, histopathologic, immunohistochemical, and ultrastructural studies of a mandibular lesion discovered in an asymptomatic 16-year-old male, and associated with 2 previously unreported comorbidities, namely hyperlipidemia and vitamin D deficiency.

Recurrent Gingival Squamous Papilloma: A Rare Finding in a Child.

Gingival squamous papilloma (SP) is a mucocutanous, benign proliferation rarely seen in the pediatric population. The majority of publications of affected younger patients have been confined to datasets from clinicopathologic investigations. A limited number of case reports in this age group have appeared in the literature, usually featuring primary gingival lesions. Recognition of recurrent gingival SPs in pediatric patients has been underappreciated. The purpose of this report is to present the case of a four-year-old boy with a gingival SP that recurred twice within 18 months and to increase awareness of this entity in children.

Glycogen-Rich Clear Cell Squamous Cell Carcinoma Originating in the Oral Cavity.

Clear cell squamous cell carcinoma (CCSCC) is a rare histological subtype of squamous cell carcinoma (SCC) that was originally described in the skin. Here, we report a case of a 66-year-old female patient who presented with a fungating ulcerative mass of the left lateral tongue extending anteriorly to the floor of the mouth, and posteriorly to the left retromolar fossa and the oropharynx. The patient had a history of SCC of the left posterior tongue that was treated with partial glossectomy and adjuvant radiotherapy. Representative biopsies were obtained from the floor of the mouth, tongue and retromolar fossa. The examined biopsies showed various degrees of dysplastic surface epithelium with transition into infiltrating epithelial tumor nests and cords with clear cytoplasm and malignant cellular features. Pancytokeratin, CK5/6, and p63 were all diffusely positive. S-100, Calponin, and smooth muscle actin (SMA) were negative. PAS stain was diffusely positive and diastase labile in the tumor clear cells. Sparse areas of mucicarmine positivity were noted. Based on these findings a final diagnosis of a glycogen-rich CCSCC was given. This case represents a very rare histological variant of oral SCC, which is significant for the histological differential diagnosis of clear cell tumors of the oral cavity.