Yonsei University College of Dentistry

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.

PURPOSE: The aim of the current study was to develop a computer-assisted detection system based on a deep convolutional neural network (CNN) algorithm and to evaluate the potential usefulness and accuracy of this system for the diagnosis and prediction of periodontally compromised teeth (PCT). METHODS: Combining pretrained deep CNN architecture and a self-trained network, periapical radiographic images were used to determine the optimal CNN algorithm and weights. The diagnostic and predictive accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve, area under the ROC curve, confusion matrix, and 95% confidence intervals (CIs) were calculated using our deep CNN algorithm, based on a Keras framework in Python. RESULTS: The periapical radiographic dataset was split into training (n=1,044), validation (n=348), and test (n=348) datasets. With the deep learning algorithm, the diagnostic accuracy for PCT was 81.0% for premolars and 76.7% for molars. Using 64 premolars and 64 molars that were clinically diagnosed as severe PCT, the accuracy of predicting extraction was 82.8% (95% CI, 70.1%-91.2%) for premolars and 73.4% (95% CI, 59.9%-84.0%) for molars. CONCLUSIONS: We demonstrated that the deep CNN algorithm was useful for assessing the diagnosis and predictability of PCT. Therefore, with further optimization of the PCT dataset and improvements in the algorithm, a computer-aided detection system can be expected to become an effective and efficient method of diagnosing and predicting PCT.

Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-kappaB (NF-kappaB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 micromol/L, EGCG abrogates p300-induced p65 acetylation in vitro and in vivo, increases the level of cytosolic IkappaBalpha, and suppresses tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. We also showed that EGCG prevents TNFalpha-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-kappaB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-kappaB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of interleukin-6 gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-kappaB-mediated inflammatory signaling pathway. Importantly, EGCG at 50 micromol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases.

The Cox proportional hazards model commonly used to evaluate prognostic variables in survival of cancer patients may be too simplistic to properly predict a cancer patient's outcome since it assumes that the outcome is a linear combination of covariates. In this retrospective study including 255 patients suitable for analysis who underwent surgical treatment in our department from 2000 to 2017, we applied a deep learning-based survival prediction method in oral squamous cell carcinoma (SCC) patients and validated its performance. Survival prediction using DeepSurv, a deep learning based-survival prediction algorithm, was compared with random survival forest (RSF) and the Cox proportional hazard model (CPH). DeepSurv showed the best performance among the three models, the c-index of the training and testing sets reaching 0.810 and 0.781, respectively, followed by RSF (0.770/0.764), and CPH (0.756/0.694). The performance of DeepSurv steadily improved with added features. Thus, deep learning-based survival prediction may improve prediction accuracy and guide clinicians both in choosing treatment options for better survival and in avoiding unnecessary treatments.

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.

The ability of insects to detect and avoid ingesting naturally occurring repellents and insecticides is essential for their survival. Nevertheless, the gustatory receptors enabling them to sense toxic botanical compounds are largely unknown. The only insect gustatory receptor shown to be required for avoiding noxious compounds is the Drosophila caffeine receptor, Gr66a. However, this receptor is not sufficient for the caffeine response, suggesting that Gr66a may be a subunit of a larger receptor. Here, we report that mutations in the gene encoding the gustatory receptor, Gr93a, result in a phenotype identical to that caused by mutations in Gr66a. This includes an inability to avoid caffeine or the related methylxanthine present in tea, theophylline. Caffeine-induced action potentials were also eliminated in Gr93a-mutant animals, while the flies displayed normal responses to other aversive compounds or to sugars. The Gr93a protein was coexpressed with Gr66a in avoidance-gustatory receptor neurons (GRNs), and functioned in the same GRNs as Gr66a. However, misexpression of both receptors in GRNs that normally do not express either Gr93a or Gr66a does not confer caffeine sensitivity to these GRNs. Because Gr93a- and Gr66a-mutant animals exhibit the identical phenotypes and function in the same cells, we propose that they may be caffeine coreceptors. In contrast to mammalian and Drosophila olfactory receptors and mammalian taste receptors, which are monomeric or dimeric receptors, we propose that Drosophila taste receptors that function in avoidance of bitter compounds are more complex and require additional subunits that remain to be identified.

Three-dimensional (3D) printing is increasingly being utilized in the dental field. After fabricating a prosthesis using a 3D printed resin, a post-curing process is required to improve its mechanical properties, but there has been insufficient research on the optimal post-curing conditions. We used various 3D printed crown and bridge materials in this study, and evaluated the changes in their properties according to post-curing time by evaluating the flexural strength, Weibull modulus, Vickers hardness, color change, degree of conversion, and biocompatibility. The obtained results confirmed that the strength of the 3D printed resin increased when it was post-cured for 60–90 min. The Vickers hardness, the degree of conversion, and biocompatibility of the 3D printed resins increased significantly around the beginning of the post-curing time, and then increased more gradually as the post-curing time increased further. It was observed that the color tone also changed as the post-curing time increased, with some groups showing a ΔE00 value of ≥ 2.25, which can be recognized clinically. This study has confirmed that, after the printing process of a 3D printed resin was completed, a sufficient post-curing time of at least 60 min is required to improve the overall clinical performance of the produced material.

It is well-known that microbiota dysbiosis is closely associated with numerous diseases in the human body. The oral cavity and gut are the two largest microbial habitats, playing a major role in microbiome-associated diseases. Even though the oral cavity and gut are continuous regions connected through the gastrointestinal tract, the oral and gut microbiome profiles are well-segregated due to the oral-gut barrier. However, the oral microbiota can translocate to the intestinal mucosa in conditions of the oral-gut barrier dysfunction. Inversely, the gut-to-oral microbial transmission occurs as well in inter- and intrapersonal manners. Recently, it has been reported that oral and gut microbiomes interdependently regulate physiological functions and pathological processes. Oral-to-gut and gut-to-oral microbial transmissions can shape and/or reshape the microbial ecosystem in both habitats, eventually modulating pathogenesis of disease. However, the oral-gut microbial interaction in pathogenesis has been underappreciated to date. Here, we will highlight the oral-gut microbiome crosstalk and its implications in the pathogenesis of the gastrointestinal disease and cancer. Better understanding the role of the oral-gut microbiome axis in pathogenesis will be advantageous for precise diagnosis/prognosis and effective treatment.

Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.

BACKGROUND: Asians increasingly seek non-surgical facial esthetic treatments, especially at younger ages. Published recommendations and clinical evidence mostly reference Western populations, but Asians differ from them in terms of attitudes to beauty, structural facial anatomy, and signs and rates of aging. A thorough knowledge of the key esthetic concerns and requirements for the Asian face is required to strategize appropriate facial esthetic treatments with botulinum toxin and hyaluronic acid (HA) fillers. METHODS: The Asian Facial Aesthetics Expert Consensus Group met to develop consensus statements on concepts of facial beauty, key esthetic concerns, facial anatomy, and aging in Southeastern and Eastern Asians, as a prelude to developing consensus opinions on the cosmetic facial use of botulinum toxin and HA fillers in these populations. RESULTS: Beautiful and esthetically attractive people of all races share similarities in appearance while retaining distinct ethnic features. Asians between the third and sixth decades age well compared with age-matched Caucasians. Younger Asians' increasing requests for injectable treatments to improve facial shape and three-dimensionality often reflect a desire to correct underlying facial structural deficiencies or weaknesses that detract from ideals of facial beauty. CONCLUSIONS: Facial esthetic treatments in Asians are not aimed at Westernization, but rather the optimization of intrinsic Asian ethnic features, or correction of specific underlying structural features that are perceived as deficiencies. Thus, overall facial attractiveness is enhanced while retaining esthetic characteristics of Asian ethnicity. Because Asian patients age differently than Western patients, different management and treatment planning strategies are utilized. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

RANKL (receptor activator of NF-kappaB ligand) induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca(2+) ([Ca(2+)](i)). The [Ca(2+)](i) oscillations activate calcineurin, which activates the transcription factor NFATc1. The pathway by which RANKL induces [Ca(2+)](i) oscillations and osteoclastogenesis is poorly understood. Here we report the discovery of a novel pathway induced by RANKL to cause a long lasting increase in reactive oxygen species (ROS) and [Ca(2+)](i) oscillations that is essential for differentiation of bone marrow-derived monocytes into osteoclasts. The pathway includes RANKL-mediated stimulation of Rac1 to generate ROS, which stimulate phospholipase Cgamma1 to evoke [Ca(2+)](i) oscillations by stimulating Ca(2+) release from the inositol 1,4,5-trisphosphate pool and STIM1-regulated Ca(2+) influx. Induction and activation of the pathway is observed only after 24-h stimulation with RANKL and lasts for at least 3 days. The physiological role of the pathway is demonstrated in mice with deletion of the Peroxiredoxin II gene and results in a mark increase is ROS and, consequently, a decrease in bone density. Moreover, bone marrow-derived monocytes in PrxII(-/-) primary culture show increased ROS and spontaneous [Ca(2+)](i) oscillations. These findings identify the primary RANKL-stimulated pathway to trigger the late stages of osteoclastogenesis and regulate bone resorption.

OBJECTIVE: To propose a safe and reproducible injection point for botulinum toxin-A (BTX-A) as a supplementary method for the treatment of gummy smile, as determined by assessment of the morphologic characteristics of three lip elevator muscles. MATERIALS AND METHODS: A total of 50 hemi-faces from 25 adult cadavers (male 13, female 12; ages, 47 to 88 years) were used in this study. Topographic relations and the directions of the lip elevator muscles (ie, levator labii superioris [LLS], levator labii superioris alaeque nasi [LLSAN], and zygomaticus minor [ZMi]), were investigated. Possible injection points were examined through the study of predetermined surface landmarks. RESULTS: The insertion of the LLS was covered partially or entirely by the LLSAN and the ZMi, and the three muscles converged on the area lateral to the ala. The mean angle between the facial midline and each muscle vector was 25.8 +/- 4.8 degrees for the LLS, 55.7 +/- 6.4 degrees for the ZMi, and -20.2 +/- 3.2 degrees for the LLSAN; no significant differences were noted between male and female subjects or between left and right sides. The three vectors passed near a triangular region formed by three surface landmarks. The center of this triangle, named the "Yonsei point", was suggested as an appropriate injection point for BTX-A. The clinical effectiveness of the injection point was demonstrated in selected cases with or without orthodontic treatment. CONCLUSIONS: Under careful case selection, BTX-A may be an effective treatment alternative for patients with excessive gingival display caused by hyperactive lip elevator muscles.

Energy expenditure and energy intake need to be balanced to maintain proper energy homeostasis. Energy homeostasis is tightly regulated by the central nervous system, and the hypothalamus is the primary center for the regulation of energy balance. The hypothalamus exerts its effect through both humoral and neuronal mechanisms, and each hypothalamic area has a distinct role in the regulation of energy expenditure. Recent studies have advanced the understanding of the molecular regulation of energy expenditure and thermogenesis in the hypothalamus with targeted manipulation techniques of the mouse genome and neuronal function. In this review, we elucidate recent progress in understanding the mechanism of how the hypothalamus affects basal metabolism, modulates physical activity, and adapts to environmental temperature and food intake changes.

Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-1alpha was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy.

), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

The epithelial-mesenchymal transition (EMT) comprises an essential biological process involving cancer progression as well as initiation. While the EMT has been regarded as a phenotypic conversion from epithelial to mesenchymal cells, recent evidence indicates that it plays a critical role in stemness, metabolic reprogramming, immune evasion and therapeutic resistance of cancer cells. Interestingly, several transcriptional repressors including Snail (SNAI1), Slug (SNAI2) and the ZEB family constitute key players for EMT in cancer as well as in the developmental process. Note that the dynamic conversion between EMT and epithelial reversion (mesenchymal-epithelial transition, MET) occurs through variable intermediate-hybrid states rather than being a binary process. Given the close connection between oncogenic signaling and EMT repressors, the EMT has emerged as a therapeutic target or goal (in terms of MET reversion) in cancer therapy. Here we review the critical role of EMT in therapeutic resistance and the importance of EMT as a therapeutic target for human cancer.

Patients with odontogenic cysts and tumors may have to undergo serious surgery unless the lesion is properly detected at the early stage. The purpose of this study is to evaluate the diagnostic performance of the real-time object detecting deep convolutional neural network You Only Look Once (YOLO) v2-a deep learning algorithm that can both detect and classify an object at the same time-on panoramic radiographs. In this study, 1602 lesions on panoramic radiographs taken from 2010 to 2019 at Yonsei University Dental Hospital were selected as a database. Images were classified and labeled into four categories: dentigerous cysts, odontogenic keratocyst, ameloblastoma, and no cyst. Comparative analysis among three groups (YOLO, oral and maxillofacial surgeons, and general practitioners) was done in terms of precision, recall, accuracy, and F1 score. While YOLO ranked highest among the three groups (precision = 0.707, recall = 0.680), the performance differences between the machine and clinicians were statistically insignificant. The results of this study indicate the usefulness of auto-detecting convolutional networks in certain pathology detection and thus morbidity prevention in the field of oral and maxillofacial surgery.

Three-dimensional (3D) printing is an attractive technology in dentistry. Acrylic-based 3D printed resin parts have to undergo postcuring processes to enhance their mechanical and biological properties, such as UV-light and thermal polymerization. However, no previous studies have revealed how the postcuring temperature influences the biocompatibility of the produced parts. Therefore, we postprocessed 3D printed denture teeth resin under different postcuring temperatures (40, 60 and 80 °C) for different periods (15, 30, 60, 90 and 120 min), and evaluated their flexural properties, Vickers hardness, cell cytotoxicity, cell viability, and protein adsorption. In addition, confocal laser scanning was used to assess the condition of human gingival fibroblasts. It was found that increasing the postcuring temperature significantly improved the flexural strength and cell viability. The flexural strength and cell viability were 147.48 ± 5.82 MPa (mean ± standard deviation) and 89.51 ± 7.09%, respectively, in the group cured at 80 °C for 120 min, which were higher than the values in the 40 and 60 °C groups. The cell cytotoxicity increased in the 40 °C groups and for longer cultivation time. Confocal laser scanning revealed identifiable differences in the morphology of fibroblasts. This study has confirmed that the postcuring temperature influences the final mechanical and biological properties of 3D printed resin.

OBJECTIVE: The aim of this systematic multiscale analysis was to evaluate the effects of thermoforming on the physical and mechanical properties of thermoplastic materials used to fabricate transparent orthodontic aligners (TOAs). METHODS: -test. RESULTS: After thermoforming, the transparency of Duran and Essix A+ decreased, while the water absorption ability of all materials; the water solubility of Duran, Essix A+, and Essix ACE; and the surface hardness of Duran and Essix A+ increased. The flexure modulus for the 0.5-mm-thick Duran, Essix A+, and eCligner specimens increased, whereas that for the 0.75-/1.0-mm-thick Duran and eClginer specimens decreased. In addition, the elastic modulus increased for the 0.5-mm-thick Essix A+ specimens and decreased for the 0.75-mm-thick Duran and Essix ACE and the 1.0-mm-thick Essix ACE specimens. CONCLUSIONS: Our findings suggest that the physical and mechanical properties of thermoplastic materials used for the fabrication of TOAs should be evaluated after thermoforming in order to characterize their properties for clinical application.