Artificial intelligence in salivary biomarker discovery and validation for oral diseases.

Salivary biomarkers can improve the efficacy, efficiency, and timeliness of oral and maxillofacial disease diagnosis and monitoring. Oral and maxillofacial conditions in which salivary biomarkers have been utilized for disease-related outcomes include periodontal diseases, dental caries, oral cancer, temporomandibular joint dysfunction, and salivary gland diseases. However, given the equivocal accuracy of salivary biomarkers during validation, incorporating contemporary analytical techniques for biomarker selection and operationalization from the abundant multi-omics data available may help improve biomarker performance. Artificial intelligence represents one such advanced approach that may optimize the potential of salivary biomarkers to diagnose and manage oral and maxillofacial diseases. Therefore, this review summarized the role and current application of techniques based on artificial intelligence for salivary biomarker discovery and validation in oral and maxillofacial diseases.

Exosomes derived from mesenchymal stromal cells promote bone regeneration by delivering miR-182-5p-inhibitor.

Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182-5p, miR-335-3p, miR-382-5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182-5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. DATA AVAILABILITY STATEMENT: Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo).

Bone-Targeted Dual Functional Lipid-coated Drug Delivery System for Osteosarcoma Therapy.

PURPOSE OR OBJECTIVE: Osteosarcoma is well-known for its high incidence in children and adolescents and long-term bone pain, which seriously reduces the life quality of patients. Cisplatin (CDDP), as the first-line anti-osteosarcoma drug, has been used in many anticancer treatments. At the same time, the serious side effects of platinum (Pt) drugs have also attracted widespread attention. To accurately deliver Pt drugs to the lesion site and realize controlled release of Pt drugs, certain modified delivery systems have been extensively studied. METHODS: Among them, liposomes have been approved for clinical cancer treatment due to their highly biocompatibility and superior modifiability. Here, we developed a bone-targeted dual functional lipid-coated drug delivery system, lipid-coated CDDP alendronate nanoparticles (LCA NPs) to target the bone and precisely deliver the drugs to the tumor site. Cell toxicity, apoptosis and cellular uptake were detected to evaluate the anticancer effect for LCA NPs. Furthermore, transwell assay and wound healing assay were conducted to estimate the osteosarcoma cell migration and invasion. Hemolysis assay was utilized to assess the biocapitibility of the kind of NPs. RESULTS: With the aim of bone-targeted unit alendronate (ALD), LCA NPs serve as a rich bone homing Pt delivery system to exert efficient anticancer effects and synergistically reduce bone resorption and bone loss potentially. CONCLUSIONS: By providing a highly biocompatible platform for osteosarcoma therapy, LCA NPs may help to significantly enhance the anticancer effect of Pt and greatly reduce the systemic toxicity and side effects of Pt towards osteosarcoma.

Validity of nomograms for predicting cancer risk in oral leukoplakia and oral lichen planus.

OBJECTIVES: This study assessed the validity of nomograms for predicting malignant transformation (MT) among patients with oral leukoplakia (OL) and oral lichen planus (OLP). MATERIALS AND METHODS: Two nomograms were identified following a systematic search. Variables to interrogate both nomograms were obtained for a retrospective OL/OLP cohort. Then, the nomograms were applied to estimate MT probabilities twice and their average was used to calculate the discriminatory performance, calibration, and potential net benefit of the models. Subgroup analyses were performed for patients with OL, OLP, and oral epithelial dysplasia. RESULTS: Predicted probabilities were mostly significantly higher among OL/OLP patients who developed MT compared to those who did not (p = <0.001-0.034). AUC values and Brier scores of the nomograms were 0.644-0.844 and 0.040-0.088 among OL patients and 0.580-0.743 and 0.008-0.072 among OLP patients. Decision curve analysis suggested that the nomograms had some net benefit for risk stratification. However, the models did not best binary dysplasia grading in discriminatory validity and net benefit among patients with OL and oral epithelial dysplasia. CONCLUSION: Nomograms for predicting MT may have satisfactory validity among patients with OL than OLP, but they do not outperform binary dysplasia grading in risk stratification of OL.

The contralateral-based submental artery island flap: feasibility and oncological safety in oral cancer-related defect reconstruction.

OBJECTIVES: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects. METHODS: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients. RESULTS: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival. CONCLUSION: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety.

Accuracy and safety of in-house surgeon-designed three-dimensional-printed patient-specific implants for wafer-less Le Fort I osteotomy.

OBJECTIVES: The design and fabrication of three-dimensional (3D)-printed patient-specific implants (PSIs) for orthognathic surgery are customarily outsourced to commercial companies. We propose a protocol of designing PSIs and surgical guides by orthognathic surgeons-in-charge instead for wafer-less Le Fort I osteotomy. The aim of this prospective study was to evaluate the accuracy and post-operative complications of PSIs that are designed in-house for Le Fort I osteotomy. MATERIALS AND METHODS: The post-operative cone beam computer tomography (CBCT) model of the maxilla was superimposed to the virtual surgical planning to compare the discrepancies of pre-determined landmarks, lines, and principal axes between the two models. Twenty-five patients (12 males, 13 females) were included. RESULTS: The median linear deviations of the post-operative maxilla of the x, y, and z axes were 0.74 mm, 0.75 mm, and 0.72 mm, respectively. The deviations in the principal axes for pitch, yaw, and roll were 1.40°, 0.90°, and 0.60°, respectively. There were no post-operative complications related to the PSIs in the follow-up period. CONCLUSIONS: The 3D-printed PSIs designed in-house for wafer-less Le Fort I osteotomy are accurate and safe. CLINICAL RELEVANCE: Its clinical outcomes and accuracy are comparable to commercial PSIs for orthognathic surgery. TRIAL REGISTRATION: Clinical trial registration number: HKUCTR-2113. Date of registration: 29 July 2016.

Performance of a simplified scoring system for risk stratification in oral cancer and oral potentially malignant disorders screening.

BACKGROUND: Impact and efficiency of oral cancer and oral potentially malignant disorders screening are most realized in "at-risk" individuals. However, tools that can provide essential knowledge on individuals' risks are not applied in risk-based screening. This study aims to optimize a simplified risk scoring system for risk stratification in organized oral cancer and oral potentially malignant disorders screening. METHODS: Participants were invited to attend a community-based oral cancer and oral potentially malignant disorders screening program in Hong Kong. Visual oral examination was performed for all attendees and information on sociodemographic characteristics as well as habitual, lifestyle, familial, and comorbidity risk factors were obtained. Individuals' status of those found to have suspicious lesions following biopsy and histopathology were classified as positive/negative and this outcome was used in a multiple logistic regression analysis with variables collected during screening. Odds ratio weightings were then used to develop a simplified risk scoring system which was validated in an external cohort. RESULTS: Of 979 participants, 4.5% had positive status following confirmatory diagnosis. A 12-variable simplified risk scoring system with weightings was generated with an AUC, sensitivity, and specificity of 0.82, 0.71, and 0.78 for delineating high-risk cases. Further optimization on the validation cohort of 491 participants yielded a sensitivity and specificity of 0.75 and 0.87 respectively. CONCLUSIONS: The simplified risk scoring system was able to stratify oral cancer and oral potentially malignant disorders risk with satisfactory sensitivity and specificity and can be applied in risk-based disease screening.

A neural-related gene risk score for head and neck squamous cell carcinoma.

OBJECTIVES: This study aimed to establish a neural-related gene risk score (NRGRS) for the prediction of head and neck squamous cell carcinoma prognosis and explore its predictive value on the benefit of immune checkpoint inhibitor therapy. METHODS: Based on the transcriptome data of HNSCC patients (n = 546) from The Cancer Genome Atlas database, 37 neural-related hub genes were identified by weighted gene co-expression network analysis. Four genes (ITGA5, PYGM, GNG7 and ATP2A3) were identified to construct NRGRS using Lasso-Cox regression method based on the derivation cohort and validated in the Gene Expression Omnibus cohort (n = 109). The survival analysis was performed to validate the prognostic value of NRGRS and immune characteristics in NRGRS-defined subgroups were analyzed. RESULTS: NRGRS-high patients had a worse overall survival than NRGRS-low patients. Tumors with high NRGRS were more likely to have high infiltration of naive CD4+ T cells, M0, M2 macrophages and resting mast cells, which illustrated suppressive immunity and less benefit from immunotherapy therapy. CONCLUSION: NRGRS strongly correlates with survival and is a promising biomarker to predict immunotherapy benefits for head and neck cancer patients. This study provides evidence for the potential correlation between neural-related transcriptome alteration and immune activity.

Accuracy of self-designed 3D-printed patient-specific surgical guides and fixation plates for advancement genioplasty.

AIM: A prospective study was conducted to evaluate the accuracy and complications of 3D-printed patient-specific surgical guides and plates that were designed and finished in-house. MATERIALS AND METHODS: Eighteen patients who required advancement genioplasty, with or without concomitant orthognathic surgery, were enrolled in the study. Virtual surgical movements were simulated using the patient's CBCT scans, and the computer-aided designing of patient-specific surgical guides and fixation plates was performed in the authors' department. CBCT scans were taken at 1-month postoperatively, and stereolithographic models of the preoperative virtual plan and the postoperative CBCT scan were registered. Part comparisons were performed to assess the accuracy of the movements. The median, minimum, and maximum differences were measured. Two landmarks, the Menton (Me) and Pogonion (Pog), were also used to compare the differences locally. RESULTS: The median deviation for the 18 cases was 0.19 mm. The median deviation at the Me and Pog were 0.67 and 0.41 mm, respectively. There was no significant correlation between the surgical movement of < 7 mm advancement and the transfer accuracy (P = 0.77). No adverse events or complications were reported within the postoperative 6-month period. CONCLUSION: The protocol of self-designed 3D-printed patient-specific surgical guides and plates provided an accurate method to transfer the virtual surgical plan to the operating theater. (Int J Comput Dent 2022;25(4):369-0; doi: 10.3290/j.ijcd.b2599791).

Three-Dimensionally Printed Patient-Specific Surgical Plates Increase Accuracy of Oncologic Head and Neck Reconstruction Versus Conventional Surgical Plates: A Comparative Study.

BACKGROUND: Surgeons are pursuing accurate head and neck reconstruction to enhance aesthetic and functional outcomes after oncologic resection. This study aimed to investigate whether accuracy of head and neck reconstruction is improved with the use of three-dimensionally (3D)-printed patient-specific surgical plates compared with conventional plates. METHODS: In this comparative study, patients were prospectively recruited into the study group (3DJP16) with 3D-printed patient-specific surgical plates. The patients in control group with conventional surgical plates were from a historic cohort in the same unit. The primary end point of the study was the accuracy of head and neck reconstruction. The secondary end points were accuracy of osteotomy, intraoperative blood loss, total operative time, and length of hospital stay. RESULTS: The study recruited of 33 patients, including 17 in the study group and 16 in the control group. The patients' baseline characteristics were similar between the two groups. The absolute distance deviation of the maxilla or mandible was 1.5 ± 0.5 mm in the study group and 2.1 ± 0.7 mm in the control group [mean difference, - 0.7 mm; 95% confidence interval (CI) - 1.1 to - 0.3; p = 0.003], showing superior accuracy of reconstruction for the patients with 3D-printed patient-specific surgical plates. Improved accuracy of reconstruction also was detected in terms of bilateral mandibular angles and bone grafts. Concerning the secondary end points, the accuracy of the osteotomy was similar in the two groups. No difference was found regarding intraoperative blood loss, total operative time, or length of hospital stay. CONCLUSIONS: This is the first study to prove that compared with conventional plates, 3D-printed patient-specific surgical plates improve the accuracy of oncologic head and neck reconstruction.

Nature and Diffusion of COVID-19-related Oral Health Information on Chinese Social Media: Analysis of Tweets on Weibo.

BACKGROUND: Social media has become increasingly important as a source of information for the public and is widely used for health-related information. The outbreak of the coronavirus disease (COVID-19) has exerted a negative impact on dental practices. OBJECTIVE: The aim of this study is to analyze the nature and diffusion of COVID-19-related oral health information on the Chinese social media site Weibo. METHODS: A total of 15,900 tweets related to oral health and dentistry information from Weibo during the COVID-19 outbreak in China (December 31, 2019, to March 16, 2020) were included in our study. Two researchers coded 1000 of the total tweets in advance, and two main thematic categories with eight subtypes were refined. The included tweets were analyzed over time and geographic region, and coded into eight thematic categories. Additionally, the time distributions of tweets containing information about dental services, needs of dental treatment, and home oral care during the COVID-19 epidemic were further analyzed. RESULTS: People reacted rapidly to the emerging severe acute respiratory syndrome coronavirus 2 threat to dental services, and a large amount of COVID-19-related oral health information was tweeted on Weibo. The time and geographic distribution of tweets shared similarities with epidemiological data of the COVID-19 outbreak in China. Tweets containing home oral care and dental services content were the most frequently exchanged information (n=4803/15,900, 30.20% and n=4478, 28.16%, respectively). Significant differences of public attention were found between various types of bloggers in dental services-related tweets (P<.001), and the tweets from the government and media engaged the most public attention. The distributions of tweets containing information about dental services, needs of dental treatment, and home oral care information dynamically changed with time. CONCLUSIONS: Our study overviewed and analyzed social media data on the dental services and oral health information during the COVID-19 epidemic, thus, providing insights for government organizations, media, and dental professionals to better facilitate oral health communication and efficiently shape public concern through social media when routine dental services are unavailable during an unprecedented event. The study of the nature and distribution of social media can serve as a useful adjunct tool to help make public health policies.

Synergistic effects of ischemic preconditioning and immediate post-conditioning in the protection against ischemia/reperfusion injury in rabbit submandibular glands.

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post-conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post-conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post-conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post-conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post-conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post-conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands.

Microvascular Submandibular Gland Transplantation for Severe Keratoconjunctivitis Sicca: A Single-Institution Experience of 61 Grafts.

PURPOSE: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS. PATIENTS AND METHODS: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins. RESULTS: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%). CONCLUSIONS: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS.

Reconstruction of Tongue Defects With the Contralateral Nasolabial Island Flap.

PURPOSE: Reconstruction of tongue defects after cancer resection is challenging for reconstructive surgeons. Conventional local flaps are usually compromised in patients with suspected ipsilateral neck metastasis. To extend the application of the nasolabial flap, especially in circumstances in which a free flap is unavailable, the contralateral nasolabial island flap was used, with favorable outcomes. PATIENTS AND METHODS: Seven patients presenting with tongue carcinoma underwent surgical resection and neck dissection. Tongue defects were simultaneously reconstructed using a contralateral nasolabial island flap. Clinical outcomes, including locoregional recurrence and distant metastasis, were recorded. Subjective functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. RESULTS: All flaps survived without partial or complete necrosis. All patients survived without locoregional recurrence or distant metastasis during follow-up (6 months to 2 years). Functional outcomes were satisfactory, especially swallowing and speech functions. Donor-site morbidity was minimal and the scars were inconspicuously hidden in the nasolabial fold. CONCLUSIONS: The contralateral nasolabial island flap is technically feasible and can be an excellent option for tongue reconstruction without compromising oncologic safety.

Current concepts in odontohypophosphatasia form of hypophosphatasia and report of two cases.

BACKGROUND: Hypophosphatasia is a rare inherited disease derived from mutations in tissue non-specific alkaline phosphatase genes, with typical oral symptoms including short root anomaly and dysplasia of dentin or cementum. CASE PRESENTATION: Two young female patients presented with short root anomaly with a history of premature loss of deciduous and/or permanent teeth. The laboratory and imaging investigations were performed. One case was diagnosed as odontohypophosphatasia concurrent with hyperthyroidism, the other was odontohypophosphatasia concurrent with multiple radicular cysts. CONCLUSION: This report presents two cases of odontohypophosphatasia, a rare disease which is difficult to be diagnosed, and highlights that the history of premature loss of deciduous and/or permanent teeth, oral manifestation and laboratory tests are crucial for clinical diagnosis.

Risk Factors and Prognosis for Myoepithelial Carcinoma of the Major Salivary Glands.

BACKGROUND: The clinical behavior and treatment outcomes of salivary gland myoepithelial carcinoma have yet to be clearly defined. The current study investigated risk factors and prognoses for this tumor. METHODS: A retrospective review of the medical records for 32 patients with myoepithelial carcinoma of the major salivary glands was performed. Their clinical parameters were assessed to identify correlations with local-regional recurrence, distant metastasis, and survival. RESULTS: The 5-year survival rate was 71 %. Of the reviewed patients, 41 % had local-regional recurrences, and 22 % had distant metastases. Age of 60 years or younger was a predictive factor for distant metastasis. Patients with neck lymph nodes clinically positive for carcinoma had shorter overall survival durations than those with nodes negative for carcinoma. CONCLUSIONS: Myoepithelial carcinoma of the major salivary glands is characterized by a high incidence of local-regional recurrence and distant metastasis. Adjuvant therapy is indicated for selected patients with high-risk disease.

Reinnervated nerves contribute to the secretion function and regeneration of denervated submandibular glands in rabbits.

This study aimed to investigate the contribution of redistributed nerves in the secretory function and regeneration of a denervated submandibular gland (SMG). The postganglionic parasympathetic and sympathetic denervated SMGs of rabbits were wrapped in polyester or acellular dermal matrices to block nerve regeneration either partially or completely. Submandibular glands were removed 4, 8, 16, and 24 wk after the operation and examined histologically. Furthermore, the aquaporin-5 (AQP5), muscarinic-3 (M3), and ß1-adrenergic receptors were evaluated by immunofluorescence and western blot analysis. After denervation, salivary flow was decreased and acinar cells were atrophic, and the expression levels of the M3, ß1-adrenergic, and AQP5 receptors were decreased. However, both impaired secretion function and atrophic parenchyma were gradually ameliorated with the growing redistribution of parasympathetic and sympathetic nerves. Apoptosis was markedly inhibited and expression of the M3, ß1-adrenergic, and AQP5 receptors was increased after reinnervation. In contrast, SMGs without reinnervated nerves maintained hyposecretion and atrophic parenchyma. In conclusion, reinnervated nerves in a rabbit's denervated SMG played an important role in the secretion function and regeneration of SMGs via up-regulation of the expression of neurotransmitter receptors and AQP5.

Leveraging artificial intelligence for perioperative cancer risk assessment of oral potentially malignant disorders.

Oral potentially malignant disorders (OPMDs) are mucosal conditions with an inherent disposition to develop oral squamous cell carcinoma. Surgical management is the most preferred strategy to prevent malignant transformation in OPMDs, and surgical approaches to treatment include conventional scalpel excision, laser surgery, cryotherapy, and photodynamic therapy. However, in reality, since all patients with OPMDs will not develop oral squamous cell carcinoma in their lifetime, there is a need to stratify patients according to their risk of malignant transformation to streamline surgical intervention for patients with the highest risks. Artificial intelligence (AI) has the potential to integrate disparate factors influencing malignant transformation for robust, precise, and personalized cancer risk stratification of OPMD patients than current methods to determine the need for surgical resection, excision, or re-excision. Therefore, this article overviews existing AI models and tools, presents a clinical implementation pathway, and discusses necessary refinements to aid the clinical application of AI-based platforms for cancer risk stratification of OPMDs in surgical practice.