Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea®).

INTRODUCTION: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. METHODS: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. RESULTS: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. CONCLUSIONS: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.

Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis.

PURPOSE: This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer. METHODS: We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib's anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4'-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model. RESULTS: Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights. CONCLUSION: Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.

Neuropilin-2 acts a critical determinant for epithelial-to-mesenchymal transition and aggressive behaviors of human head and neck cancer.

PURPOSE: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. METHODS: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. RESULTS: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. CONCLUSIONS: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.

Dental students' perception of their educational environment in relation to their satisfaction with dentistry major: a cross-sectional study.

BACKGROUND: Students' perception of their educational environment and satisfaction with their major can reveal the extent of their readiness to practice their profession after graduation. This study aimed to evaluate dental students' perception of their educational environment and satisfaction with their major in dentistry, as well as the relationship between these two factors. METHODS: An online survey was conducted in 2022 among first- to fourth-year students across 11 dental schools in Korea. The Dundee Ready Education Environment Measure (DREEM) and Academic Major Satisfaction Scale (AMSS) were used to measure the students' perception of the educational environment and satisfaction with their major in dentistry, respectively. RESULTS: A total of 539 students participated in the survey (response rate = 18.1%). The overall mean scores of the DREEM and AMSS were 125.03 (maximum score 200) and 22.01 (maximum score 30), respectively. Fourth-year students had the lowest scores in the overall DREEM, DREEM subscales (excluding students' perceptions of atmosphere), and AMSS. The overall DREEM scores and all DREEM subscales showed statistically significant positive and moderate correlations with AMSS (p < 0.001). CONCLUSION: Using the DREEM, we identified areas that need improvement and the academic year (fourth year) that require proactive support. Considering the positive correlation between all DREEM subscales and the AMSS, measures to comprehensively improve the educational environment are needed to improve dental students' satisfaction with their major.

Reappraisal of tubulopapillary hidradenoma-like tumor of the mandible: Suggested change in nomenclature to reflect tumor origin.

Several cases of intraosseous mandibular tumors have been reported under the name "tubulopapillary hidradenoma-like tumor of the mandible (TPHLTM)." However, the intraosseous occurrence of sweat gland tumors needs to be reappraised. The aim of this review was to propose a new name for these tumors to reflect the possible tumor origin. In view of the incidence and the tissue of origin, TPHLTM is more likely to be a salivary gland tumor than a sweat gland tumor. Among salivary gland tumors, a recently described salivary neoplasm called "sialadenoma papilliferum-like intraductal papillary tumor (SP-IPT)" seems to be histologically and genetically identical to tubulopapillary hidradenoma. Therefore, we proposed that the term TPHLTM be replaced by "SP-IPT of the mandible," which better explains its origin and could help in clarifying the nature of SP-IPT.

Nationwide Surveillance for Infectious Bronchitis Virus in South Korea from 2020 to 2021.

Infectious bronchitis virus (IBV) is a major pathogen in poultry. The genotypes of IBV vary considerably, and their antigenicity may differ. Nationwide surveillance in South Korea was performed to determine the prevalence and distribution of IBV and its genotypes. By both active and passive surveillance, a total of 939 samples were collected and tested for IBV detection by pathogen-specific reverse transcriptase-PCR. IBV RNA-positive samples were inoculated in embryonated eggs for virus isolation. IBV was genotyped and analyzed phylogenetically based on a partial nucleotide sequence of the S1 gene. A total of 114 IBV strains were isolated; 34 (30.9%) of the 110 samples obtained by passive surveillance, and 80 (9.7%) of the 829 samples obtained by active surveillance, were positive. Most IBVs in both groups were isolated from broilers. Five genotypes (QX-like, B4-like, KM91-like, K40/09-like, and 20AD17-like) were observed in South Korea, with the QX-like genotype being the most common, and the 20AD17-like genotype being a novel genotype. These findings will help to maximize protection against IBV infection by providing a reference for the selection of an avian vaccine for IBV in South Korea.

Vigilancia nacional del virus de la bronquitis infecciosa en Corea del Sur del año 2020 al 2021. El virus de la bronquitis infecciosa (IBV) es un patógeno importante en la avicultura. Los genotipos del virus de la bronquitis varían considerablemente y su antigenicidad puede ser diversa. Se realizó un estudio de vigilancia a nivel nacional en Corea del Sur para determinar la prevalencia y distribución del virus de bronquitis y sus genotipos. Mediante vigilancia activa como pasiva, se recolectaron un total de 939 muestras y se analizaron para la detección del virus de la bronquitis infecciosa mediante transcripción reversa y PCR específica para este patógeno. Se inocularon muestras positivas para ARN del virus de bronquitis en huevos embrionados para el aislamiento del virus. Los virus de bronquitis se genotipificaron y analizaron filogenéticamente basándose en una secuencia parcial de nucleótidos del gene S1. Se aislaron un total de 114 cepas del virus de bronquitis; 34 (30.9%) de las 110 muestras obtenidas por vigilancia pasiva y 80 (9.7%) de las 829 muestras obtenidas por vigilancia activa resultaron positivas. La mayoría de los virus de bronquitis en ambos grupos se aislaron de pollos de engorde. Se observaron cinco genotipos (similares a QX, similares a B4, similares a KM91, similares a K40/09 y similares a 20AD17) en Corea del Sur, siendo el genotipo similar a QX el más común y el genotipo similar a 20AD17 que ha sido un genotipo de nueva aparición. Estos hallazgos ayudarán a maximizar la protección contra la infección por el virus de la bronquitis infecciosa al proporcionar una referencia para la selección de vacunas aviares para bronquitis infecciosa en Corea del Sur.

Impact of inland waters on highly pathogenic avian influenza outbreaks in neighboring poultry farms in South Korea.

BACKGROUND: Since 2003, the H5 highly pathogenic avian influenza (HPAI) subtype has caused massive economic losses in the poultry industry in South Korea. The role of inland water bodies in avian influenza (AI) outbreaks has not been investigated. Identifying water bodies that facilitate risk pathways leading to the incursion of the HPAI virus (HPAIV) into poultry farms is essential for implementing specific precautionary measures to prevent viral transmission. OBJECTIVES: This matched case-control study (1:4) examined whether inland waters were associated with a higher risk of AI outbreaks in the neighboring poultry farms. METHODS: Rivers, irrigation canals, lakes, and ponds were considered inland water bodies. The cases and controls were chosen based on the matching criteria. The nearest possible farms located within a radius of 3 km of the case farms were chosen as the control farms. The poultry farms were selected randomly, and two HPAI epidemics (H5N8 [2014-2016] and H5N6 [2016-2017]) were studied. Conditional logistic regression analysis was applied. RESULTS: Statistical analysis revealed that inland waters near poultry farms were significant risk factors for AI outbreaks. The study speculated that freely wandering wild waterfowl and small animals contaminate areas surrounding poultry farms. CONCLUSIONS: Pet birds and animals raised alongside poultry birds on farm premises may wander easily to nearby waters, potentially increasing the risk of AI infection in poultry farms. Mechanical transmission of the AI virus occurs when poultry farm workers or visitors come into contact with infected water bodies or their surroundings. To prevent AI outbreaks in the future, poultry farms should adopt strict precautions to avoid contact with nearby water bodies and their surroundings.

BRAF V600E and previously unidentified KRAS G12C mutations in odontogenic tumors may affect MAPK activation differently depending on tumor type.

Although several types of odontogenic tumors share the same mutations in MAPK pathway genes, their effects on MAPK activation remain unclarified. This study aimed to evaluate the associations between these mutations and ERK phosphorylation in ameloblastoma and mixed odontogenic tumors (MOTs) and to analyze the expression pattern of phosphorylated ERK (p-ERK) for determining the involvement of MAPK activation in the development and progression of odontogenic tumors. Forty-three odontogenic tumors consisting of 18 ameloblastomas and 25 MOTs were analyzed for BRAF, KRAS, and NRAS mutations by Sanger sequencing. The expressions of BRAFV600E protein and p-ERK were detected by immunohistochemistry. The associations between mutation status and p-ERK expression were statistically analyzed. The effect of BRAFV600E inhibition on MAPK activation was investigated in ameloblastoma cells. In benign MOTs, BRAFV600E mutations were neither expressed at the protein level nor associated with p-ERK expression. In contrast, BRAFV600E -mutant ameloblastic fibrosarcoma showed co-expression of BRAF V600E protein and p-ERK, especially in the sarcomatous component. In ameloblastoma, p-ERK was predominantly expressed in the tumor periphery showing a significant correlation with BRAFV600E mutations, and in vitro BRAFV600E inhibition decreased ERK phosphorylation. KRASG12C mutations, previously unidentified in odontogenic tumors, were detected in one case each of benign MOT and ameloblastoma; only the latter was high-p-ERK. In conclusion, unlike in benign MOTs, BRAFV600E and KRASG12C mutations lead to MAPK activation in ameloblastoma, suggesting their role as therapeutic targets. p-ERK intratumoral heterogeneity indicates that MAPK pathway activation may be associated with sarcomatous proliferation of ameloblastic fibrosarcoma and infiltrative behavior of ameloblastoma.

Spatial Variation in Risk for Highly Pathogenic Avian Influenza Subtype H5N6 Viral Infections in South Korea: Poultry Population-Based Case-Control Study.

Given the substantial economic damage caused by the continual circulation of highly pathogenic avian influenza (HPAI) outbreaks since 2003, identifying high-risk locations associated with HPAI infections is essential. In this study, using affected and unaffected poultry farms' locations during an HPAI H5N6 epidemic in South Korea, we identified places where clusters of HPAI cases were found. Hotspots were defined as regions having clusters of HPAI cases. With the help of the statistical computer program R, a kernel density estimate and a spatial scan statistic were employed for this purpose. A kernel density estimate and detection of significant clusters through a spatial scan statistic both showed that districts in the Chungcheongbuk-do, Jeollabuk-do, and Jeollanam-do provinces are more vulnerable to HPAI outbreaks. Prior to the migration season, high-risk districts should implement particular biosecurity measures. High biosecurity measures, as well as improving the cleanliness of the poultry environment, would undoubtedly aid in the prevention of HPAIV transmission to poultry farms in these high-risk regions of South Korea.

Interpolation of Point Prevalence Rate of the Highly Pathogenic Avian Influenza Subtype H5N8 Second Phase Epidemic in South Korea.

Humans and animals are both susceptible to highly pathogenic avian influenza (HPAI) viruses. In the future, HPAI has the potential to be a source of zoonoses and pandemic disease drivers. It is necessary to identify areas of high risk that are more vulnerable to HPAI infections. In this study, we applied unbiased predictions based on known information to find points of localities with a high probability of point prevalence rate. To carry out such predictions, we utilized the inverse distance weighting (IDW) and kriging method, with the help of the R statistical computing program. The provinces of Jeollanam-do, Gyeonggi-do, Chungcheongbuk-do and Ulsan have high anticipated risk. This research might aid in the management of avian influenza threats associated with various potential risks.

Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma.

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Orthokeratinized odontogenic cyst: A large series and comprehensive literature review with emphasis on synchronous multiple occurrence and neoplastic transformation.

OBJECTIVES: The objective of this study was to demonstrate the clinical, radiologic, and histologic features of orthokeratinized odontogenic cyst (OOC); determine the characteristics of multiple OOCs; and present rare but significant manifestations of OOC. STUDY DESIGN: A clinical, radiologic, and histopathologic study of 65 primary and 2 recurrent OOC cases was performed retrospectively along with a comprehensive literature review. RESULTS: OOCs shared similar radiologic findings with odontogenic keratocyst, yet some showed features that have not been previously described: root resorption and radiopaque foci. Histologic review revealed a unique histiocytic lining and some findings suggestive of the multipotentiality of the odontogenic epithelium. The analysis of patients with multiple OOCs demonstrated that multiple OOCs occurred synchronously with a marked predilection for young male adults. Two unusual cases were also identified: an OOC combined with a BRAFV600E ameloblastoma and a recurrent OOC with malignant transformation. CONCLUSIONS: This largest series presents previously unreported radiographic and histopathologic features that can be seen in OOC. Multiple OOCs have clinical characteristics distinct from those of solitary cases. The first reported OOC associated with ameloblastoma suggests the involvement of oncogenic mutations in odontogenic tumorigenesis. Although OOC shows a low recurrence rate, the possibility of malignant transformation of recurrent OOCs should be emphasized.

Methanol extract of Sedum oryzifolium and its constituent, trehalose, impede the invasiveness of oral squamous cell carcinoma cell lines via downregulation of Slug.

BACKGROUND: Sedum species are reported to possess diverse pharmacological activities in various solid tumors. However, the anticancer functions of Sedum orizyfolium and its constituents have never been determined in human cancers. PURPOSE: The present study focused on addressing the inhibition efficacy of the methanol extract of S. orizyfolium (MESO) and its constituents and the molecular mechanism underlying invasion and epithelial-to-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) cell lines. STUDY DESIGN/METHODS: After MESO treatment, a wound-healing assay, an invasion assay, and immunocytochemistry were performed in OSCC cell lines, coupled with in silico analysis and immunohistochemistry in OSCC patient samples, to investigate the role of the EMT transcription factor Slug. Trehalose, an active component of MESO, was identified through gas chromatography-mass spectrometry. RESULTS: Among the methanol extracts of 18 various wild plants from South Korea, MESO exhibited the highest anticancer functionality in OSCC cells by downregulating Slug expression. In silico analysis and immunohistochemistry indicated that elevated Slug levels are remarkably associated with tumor progression and invasion in patients with OSCC, suggesting that changes in Slug expression alter EMT progression and invasion in OSCC. Notably, treatment with trehalose, a sugar component of MESO, inhibited invasiveness and Slug expression in OSCC cells. CONCLUSION: Cumulatively, this study highlighted the beneficial role of MESO and trehalose in the inhibition of invasiveness of OSCC cells via suppression of Slug expression and suggested a new design for potential chemotherapeutic drugs against OSCC.

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma.

BACKGROUND: Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells. METHODS: CD31/PAS staining was performed to evaluate VM in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. The correlation between SOX7 levels and cancer cohorts was investigated using in silico analysis. VM formation assay was performed to observe VM in vitro. To investigate the role of SOX7 in VM formation, SOX7 was transiently over-expressed in SCC-9 cells. VM-modulating genes were identified by Western blotting. RESULTS: We found a positive correlation between VM and lymph node metastasis and patient survival in OSCC (p = 0.003). In silico analysis from The Cancer Genome Atlas and Gene Expression Omnibus database showed that down-regulation of SOX7 expression was significantly correlated with OSCC patients (p = 0.0187) and lymph node metastasis (p = 0.0017). We also found that the presence of VM in OSCC tissue was inversely associated with SOX7 expression (p = 0.020). We observed that overexpression of SOX7 impaired VM formation by reducing the expression of VE-cadherin, thereby inhibiting cell migration and invasion. CONCLUSION: These results suggest that SOX7 plays an important role in the regulation of VM formation and may inhibit OSCC metastasis.

Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates.

Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell-mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.

Discrepancy between immunohistochemistry and sequencing for BRAF V600E in odontogenic tumours: Comparative analysis of two VE1 antibodies.

BACKGROUND: Although immunohistochemistry (IHC) along with molecular tests has been investigated in ameloblastoma for BRAF V600E detection, VE1 IHC has not been studied in odontogenic carcinomas (OCs) and benign mixed epithelial and mesenchymal odontogenic tumours (BMOTs). Here, we performed BRAF V600E mutation analysis, examined the expression pattern of VE1 IHC, and comparatively evaluated the performance of two VE1 antibodies in ameloblastomas, OCs and BMOTs. METHODS: BRAF V600E detection was performed using Sanger sequencing in a total of 47 odontogenic tumours: 28 ameloblastomas, 6 OCs and 13 BMOTs. VE1 IHC was conducted using two different antibodies (IHC-A and IHC-V), and their performance was analysed by calculating the sensitivity and specificity compared with sequencing. RESULTS: BRAF V600E mutations were identified in 24/28 (85.7%) ameloblastomas, 2/5 (40.0%) ameloblastic carcinomas (ACs), 3/7 (42.9%) ameloblastic fibromas and 1/2 (50.0%) ameloblastic fibro-odontomas. In the presence of the mutation, VE1 showed diffuse cytoplasmic staining in ameloblastomas and ACs, whereas all BMOTs were negative for VE1. IHC-A and IHC-V yielded a sensitivity of 76.7% and 60.0%, respectively, although both antibodies showed 100% specificity. CONCLUSION: OCs and BMOTs have BRAF V600E mutations in common at lower frequencies than ameloblastoma. Diffuse VE1 cytoplasmic staining in AC suggests the utility of MAPK-targeted therapy as selectively applied in ameloblastoma, and consistent VE1 false-negative expression in BMOTs requires further investigation. Considering the high specificity but low sensitivity of VE1 IHC, molecular tests should be performed to determine the presence of BRAF V600E mutations in odontogenic tumours.

Leiomyosarcoma of the jaw: case series.

OBJECTIVES: Leiomyosarcoma is a malignant neoplasm that affects smooth muscle tissue and it is very rare in the field of oral and maxillofcial surgery. The purpose of this study was to obtain information on diagnosis of and treatment methods for leiomyosarcoma by retrospectively reviewing of the cases. PATIENTS AND METHODS: The study included nine patients who were diagnosed with leiomyosarcoma in the Department of Oral and Maxillofacial Surgery at Seoul National University Dental Hospital. The subjects were analyzed with respect to sex, age, clinical features, primary site of disease, treatment method, recurrence, and metastasis. RESULTS: Particular clinical features included pain, edema, mouth-opening limitations, dysesthesia, and enlarged lymph nodes. All cases except one were surgically treated, and recurrence was found in two cases. Four of nine patients were followed up without recurrence and one patient underwent additional surgery due to recurrence. CONCLUSION: In our case series, notable symptoms included pain, edema, mouth-opening limitations, and dysesthesia; however, it was difficult to label these as specific symptoms of leiomyosarcoma. Considering the aggressive characteristics of the disease and poor prognosis, surgical treatment is necessary with careful consideration of postoperative radiotherapy and chemotherapy.

Social Distancing and Outdoor Physical Activity During the COVID-19 Outbreak in South Korea: Implications for Physical Distancing Strategies.

The novel coronavirus disease (COVID-19) outbreak has put the entire world in a pandemic situation. In response, strict screening, quarantine protocols, and contact tracing have been conducted in South Korea. The purpose of this study was to examine effects of social distancing on the Public Bicycle Sharing System (PBSS) during the COVID-19 outbreak. We used the PBSS public dataset of Seoul, South Korea. Difference-in-differences (DID) analysis was used. In the DID approach, the 2 groups are distinguished based on designated year. Cases of PBSS use were observed in 2 time periods: pre- and post-strict social distancing in Seoul, Korea. Average PBSS usage per day doubled during 2019-2020 (30 697 vs 77 996, P < .001). Commuters and weekend users increased during the social distancing period in 2020 compared with the same period in 2019. DID analysis showed statistically significant positive effects of high levels of social distancing on PBSS usage, commuters, weekend users, and new subscribers. In conclusion, social distancing during the COVID-19 outbreak increased outdoor physical activity. Meaningful outdoor physical activity during the COVID-19 pandemic can be safe from infection and psychologically stabilized as long as keeping meticulous physical distancing, such as hand hygiene, wearing facial masks, and surface cleaning of public resources.