Automatic mandibular canal detection using a deep convolutional neural network

The practicability of deep learning techniques has been demonstrated by their successful implementation in varied fields, including diagnostic imaging for clinicians. In accordance with the increasing demands in the healthcare industry, techniques for automatic prediction and detection are being widely researched. Particularly in dentistry, for various reasons, automated mandibular canal detection has become highly desirable. The positioning of the inferior alveolar nerve (IAN), which is one of the major structures in the mandible, is crucial to prevent nerve injury during surgical procedures. However, automatic segmentation using Cone beam computed tomography (CBCT) poses certain difficulties, such as the complex appearance of the human skull, limited number of datasets, unclear edges, and noisy images. Using work-in-progress automation software, experiments were conducted with models based on 2D SegNet, 2D and 3D U-Nets as preliminary research for a dental segmentation automation tool. The 2D U-Net with adjacent images demonstrates higher global accuracy of 0.82 than naïve U-Net variants. The 2D SegNet showed the second highest global accuracy of 0.96, and the 3D U-Net showed the best global accuracy of 0.99. The automated canal detection system through deep learning will contribute significantly to efficient treatment planning and to reducing patients’ discomfort by a dentist. This study will be a preliminary report and an opportunity to explore the application of deep learning to other dental fields.Peer reviewe

Microbial and molecular differences according to the location of head and neck cancers

Microbiome has been shown to substantially contribute to some cancers. However, the diagnostic implications of microbiome in head and neck squamous cell carcinoma (HNSCC) remain unknown. To identify the molecular difference in the microbiome of oral and non-oral HNSCC, primary data was downloaded from the Kraken-TCGA dataset. The molecular differences in the microbiome of oral and non-oral HNSCC were identified using the linear discriminant analysis effect size method. In the study, the common microbiomes in oral and non-oral cancers were Fusobacterium, Leptotrichia, Selenomonas and Treponema and Clostridium and Pseudoalteromonas, respectively. We found unique microbial signatures that positively correlated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in oral cancer and positively and negatively correlated KEGG pathways in non-oral cancer. In oral cancer, positively correlated genes were mostly found in prion diseases, Alzheimer disease, Parkinson disease, Salmonella infection, and Pathogenic Escherichia coli infection. In non-oral cancer, positively correlated genes showed Herpes simplex virus 1 infection and Spliceosome and negatively correlated genes showed results from PI3K-Akt signaling pathway, Focal adhesion, Regulation of actin cytoskeleton, ECM-receptor interaction and Dilated cardiomyopathy. These results could help in understanding the underlying biological mechanisms of the microbiome of oral and non-oral HNSCC. Microbiome-based oncology diagnostic tool warrants further exploration.This work was supported by the National Research Foundation of Korea (NRF-2018R1A5A2023879, 2020R1A2C1005203, 2020R1C1C1003741, and 2021R1A2C4001466). This research was supported by a grant of the Medical data-driven hospital support project through the Korea Health Information Service (KHIS), funded by the Ministry of Health & Welfare, Republic of Korea. A portion of the data used for this study were obtained from the GenomeInfraNet (IDs: 1711020733, 1711032008, and 1711028992) of the Korea Bioinformation Center

Drosophila Homolog of Human KIF22 at the Autism-Linked 16p11.2 Loci Influences Synaptic Connectivity at Larval Neuromuscular Junctions

Copy number variations at multiple chromosomal loci, including 16p11.2, have recently been implicated in the pathogenesis of autism spectrum disorder (ASD), a neurodevelopmental disease that affects 1~3% of children worldwide. The aim of this study was to investigate the roles of human genes at the 16p11.2 loci in synaptic development using Drosophila larval neuromuscular junctions (NMJ), a well-established model synapse with stereotypic innervation patterns. We conducted a preliminary genetic screen based on RNA interference in combination with the GAL4-UAS system, followed by mutational analyses. Our result indicated that disruption of klp68D, a gene closely related to human KIF22, caused ectopic innervations of axon branches forming type III boutons in muscle 13, along with less frequent re-routing of other axon branches. In addition, mutations in klp64D, of which gene product forms Kinesin-2 complex with KLP68D, led to similar targeting errors of type III axons. Mutant phenotypes were at least partially reproduced by knockdown of each gene via RNA interference. Taken together, our data suggest the roles of Kinesin-2 proteins, including KLP68D and KLP64D, in ensuring proper synaptic wiring.Pusan National University (2013 Research Grant)Simons Foundation Autism Research Initiative (Infrastructure Grant Program, 2009

The potential use of bromelain as a natural oral medicine having anticarcinogenic activities

Bromelain (BR), a protease extracted from Ananas comosus, reportedly possesses pharmacological activities including the reduction of thrombogenesis, and antihypertensive, and antimicrobial effects. This study aimed to investigate the potential effects of BR on oral cancer cells. The effect of BR on the viability of Ca9‐22 and SCC25 cells was determined using the MTT assay. These cells were also treated with different doses of BR, and Western blotting was conducted to monitor apoptosis. Finally, flow cytometry analysis was performed to identify sub‐G1 populations of oral cancer cells. After treatment, the viability of both Ca9‐22 and SCC25 cells was markedly reduced, in a dose‐dependent manner. BR induced poly (ADP‐ribose) polymerase (PARP) and lamin A/C degradation, and generated cleavage products. Flow cytometry analysis showed that BR treatment significantly increased the sub‐G1 population. Our findings therefore indicate that BR has potential as a novel, natural anticarcinogenic medicine

Reconstruction of cheek mucosal defect with a buccal fat pad flap in a squamous cell carcinoma patient: a case report and literature review

Abstract Background Squamous cell carcinoma (SCC) is the most commonly occurring malignant tumor in the oral cavity. In South Korea, it occurs most frequently in the mandible, tongue, maxilla, buccal mucosa, other areas of the oral cavity, and lips. Radial forearm free flap (RFFF) is the most widely used reconstruction method for the buccal mucosal defect. The scar of the forearm donor, however, is highly visible and unsightly, and a secondary surgical site is needed when such technique is applied. For these reasons, buccal fat pad (BFP) flap has been commonly used for closing post-surgical excision sites since the recent decades because of its reliability, ease of harvest, and low complication rate. Case presentation In the case reported herein, BFP flap was used to reconstruct a cheek mucosal defect after excision. The defect was completely covered by the BFP flap, without any complications. Conclusion Discussed herein is the usefulness of BFP flap for the repair of the cheek mucosal defect. Also, further studies are needed to determine the possibility of using BFP flap when the defect is deep, and the maximum volume that can be harvested considering the changes in volume with age

Promoter Methylation of Cancer Stem Cell Surface Markers as an Epigenetic Biomarker for Prognosis of Oral Squamous Cell Carcinoma

Growing evidence suggests that genetic and epigenetic factors, including environmental factors, contribute to the development of oral squamous cell carcinoma (OSCC). Here, we investigated the transcriptional silencing of the CD24, CD44, CD133, and CD147 genes, which are well-known cancer stem cell surface markers in various cancer types, including OSCC. We first examined the correlation between the transcriptional expression level and reactivation by 5-aza-2′-deoxycytidine (5-aza-dC) and the promoter methylation levels of the four genes in several OSCC cell lines. We observed promoter hypermethylation for the CD24, CD133, and CD147 genes at 70%, 75%, and 70%, respectively, in OSCC cell lines compared to normal oral mucosa tissues (CD133 and CD147 extracted from The Cancer Genome Atlas (TCGA) database were negatively correlated, supporting their epigenetic regulation in primary OSCC tumors. The methylation status of CD133 and CD147 was associated with poor survival in patients with OSCC using the TCGA database. Our findings provide additional insight into the abnormal DNA methylation of CD133 and that CD147 could be used for the diagnosis and therapeutic treatment of patients with OSCC

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell cycle), wound-healing assay, invasion assay, Western blot analysis, gelatin zymography, and immunofluorescence. To investigate whether quercetin also inhibits transforming growth factor β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) in human keratinocyte cells, HaCaT cells were treated with TGF-β1. Overall, our results strongly suggest that quercetin suppressed the viability of OSCC cells by inducing cell cycle arrest at the G2/M phase. However, quercetin did not affect cell viability of human keratinocytes such as HaCaT (immortal keratinocyte) and nHOK (primary normal human oral keratinocyte) cells. Additionally, quercetin suppresses cell migration through EMT and matrix metalloproteinase (MMP) in OSCC cells and decreases TGF-β1-induced EMT in HaCaT cells. In conclusion, this study is the first, to our knowledge, to demonstrate that quercetin can inhibit the survival and metastatic ability of OSCC cells via the EMT-mediated pathway, specifically Slug. Quercetin may thus provide a novel pharmacological approach for the treatment of OSCCs

Infection of Porphyromonas gingivalis Increases Phosphate-Induced Calcification of Vascular Smooth Muscle Cells

Accumulating evidence suggests a link between periodontal disease and cardiovascular diseases. Vascular calcification is the pathological precipitation of phosphate and calcium in the vasculature and is closely associated with increased cardiovascular risk and mortality. In this study, we have demonstrated that the infection with Porphyromonas gingivalis (P. gingivalis), one of the major periodontal pathogens, increases inorganic phosphate-induced vascular calcification through the phenotype transition, apoptosis, and matrix vesicle release of vascular smooth muscle cells. Moreover, P. gingivalis infection accelerated the phosphate-induced calcium deposition in cultured rat aorta ex vivo. Taken together, our findings indicate that P. gingivalis contributes to the periodontal infection-related vascular diseases associated with vascular calcification

Oral Administration of <i>Porphyromonas gingivalis</i>, a Major Pathogen of Chronic Periodontitis, Promotes Resistance to Paclitaxel in Mouse Xenografts of Oral Squamous Cell Carcinoma

Chemotherapy is not a first-line therapy for oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer, because most OSCC shows resistance to chemotherapeutic reagents. Inflammatory signals are suggested to be associated with chemoresistance as well as carcinogenesis in many different cancers, and thus chronic periodontitis, the most common chronic inflammatory disease of the oral cavity, could modulate responsiveness to chemotherapeutic agents used against oral cancer. This study was performed to define the role of chronic periodontitis in oral cancer progression and to determine the responsiveness of oral cancer to a chemotherapeutic reagent. First, we quantified the tumor growth rate and changes in serum cytokine profiles of mice administered Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Compared with uninfected mice, the mice that were chronically administered P. gingivalis showed increased resistance to paclitaxel and a decreased tumor growth rate. In addition, P. gingivalis-treated mice exhibited higher serum levels of interleukin-6 (IL-6) than uninfected mice. Furthermore, the sensitivity of tumor xenografts to paclitaxel in mice administered P. gingivalis was dramatically increased when the mice were administered ibuprofen, an anti-inflammatory drug which supports the modulatory effect of periodontal pathogen-induced inflammation in chemoresistance