Dephasing Dynamics Accessed by High Harmonic Generation: Determination of Electron-Hole Decoherence of Dirac Fermions.

We reveal the critical effect of ultrashort dephasing on the polarization of high harmonic generation in Dirac fermions. As the elliptically polarized laser pulse falls in or slightly beyond the multiphoton regime, the elliptically polarized high harmonic generation is produced and exhibits a characteristic polarimetry of the polarization ellipse, which is found to depend on the decoherence time T2. T2 could then be determined to be a few femtoseconds directly from the experimentally observed polarimetry of high harmonics. This shows a sharp contrast with the semimetal regime of higher pump intensity, where the polarimetry is irrelevant to T2. An access to the dephasing dynamics would extend the prospect of high harmonic generation into the metrology of a femtosecond dynamic process in the coherent quantum control.

Selective Aster inhibitors distinguish vesicular and nonvesicular sterol transport mechanisms.

The Aster proteins (encoded by the Gramd1a-c genes) contain a ligand-binding fold structurally similar to a START domain and mediate nonvesicular plasma membrane (PM) to endoplasmic reticulum (ER) cholesterol transport. In an effort to develop small molecule modulators of Asters, we identified 20α-hydroxycholesterol (HC) and U18666A as lead compounds. Unfortunately, both 20α-HC and U18666A target other sterol homeostatic proteins, limiting their utility. 20α-HC inhibits sterol regulatory element-binding protein 2 (SREBP2) processing, and U18666A is an inhibitor of the vesicular trafficking protein Niemann-Pick C1 (NPC1). To develop potent and selective Aster inhibitors, we synthesized a series of compounds by modifying 20α-HC and U18666A. Among these, AI (Aster inhibitor)-1l, which has a longer side chain than 20α-HC, selectively bound to Aster-C. The crystal structure of Aster-C in complex with AI-1l suggests that sequence and flexibility differences in the loop that gates the binding cavity may account for the ligand specificity for Aster C. We further identified the U18666A analog AI-3d as a potent inhibitor of all three Aster proteins. AI-3d blocks the ability of Asters to bind and transfer cholesterol in vitro and in cells. Importantly, AI-3d also inhibits the movement of low-density lipoprotein (LDL) cholesterol to the ER, although AI-3d does not block NPC1. This finding positions the nonvesicular Aster pathway downstream of NPC1-dependent vesicular transport in the movement of LDL cholesterol to the ER. Selective Aster inhibitors represent useful chemical tools to distinguish vesicular and nonvesicular sterol transport mechanisms in mammalian cells.

SAR Image Generation Method Using DH-GAN for Automatic Target Recognition.

In recent years, target recognition technology for synthetic aperture radar (SAR) images has witnessed significant advancements, particularly with the development of convolutional neural networks (CNNs). However, acquiring SAR images requires significant resources, both in terms of time and cost. Moreover, due to the inherent properties of radar sensors, SAR images are often marred by speckle noise, a form of high-frequency noise. To address this issue, we introduce a Generative Adversarial Network (GAN) with a dual discriminator and high-frequency pass filter, named DH-GAN, specifically designed for generating simulated images. DH-GAN produces images that emulate the high-frequency characteristics of real SAR images. Through power spectral density (PSD) analysis and experiments, we demonstrate the validity of the DH-GAN approach. The experimental results show that not only do the SAR image generated using DH-GAN closely resemble the high-frequency component of real SAR images, but the proficiency of CNNs in target recognition, when trained with these simulated images, is also notably enhanced.

Fully automated deep learning approach to dental development assessment in panoramic radiographs.

BACKGROUND: Dental development assessment is an important factor in dental age estimation and dental maturity evaluation. This study aimed to develop and evaluate the performance of an automated dental development staging system based on Demirjian's method using deep learning. METHODS: The study included 5133 anonymous panoramic radiographs obtained from the Department of Pediatric Dentistry database at Seoul National University Dental Hospital between 2020 and 2021. The proposed methodology involves a three-step procedure for dental staging: detection, segmentation, and classification. The panoramic data were randomly divided into training and validating sets (8:2), and YOLOv5, U-Net, and EfficientNet were trained and employed for each stage. The models' performance, along with the Grad-CAM analysis of EfficientNet, was evaluated. RESULTS: The mean average precision (mAP) was 0.995 for detection, and the segmentation achieved an accuracy of 0.978. The classification performance showed F1 scores of 69.23, 80.67, 84.97, and 90.81 for the Incisor, Canine, Premolar, and Molar models, respectively. In the Grad-CAM analysis, the classification model focused on the apical portion of the developing tooth, a crucial feature for staging according to Demirjian's method. CONCLUSIONS: These results indicate that the proposed deep learning approach for automated dental staging can serve as a supportive tool for dentists, facilitating rapid and objective dental age estimation and dental maturity evaluation.

Correlation between dental and skeletal maturity in Korean children based on dental maturity percentile: a retrospective study.

BACKGROUND: The correlation between dental maturity and skeletal maturity has been proposed, but its clinical application remains challenging. Moreover, the varying correlations observed in different studies indicate the necessity for research tailored to specific populations. AIM: To compare skeletal maturity in Korean children with advanced and delayed dental maturity using dental maturity percentile. DESIGN: Dental panoramic radiographs and cephalometric radiographs were obtained from 5133 and 395 healthy Korean children aged between 4 and 16 years old. Dental maturity was assessed with Demirjian's method, while skeletal maturity was assessed with the cervical vertebral maturation method. Standard percentile curves were developed through quantile regression. Advanced (93 boys and 110 girls) and delayed (92 boys and 100 girls) dental maturity groups were defined by the 50th percentile. RESULTS: The advanced group showed earlier skeletal maturity in multiple cervical stages (CS) in both boys (CS 1, 2, 3, 4, and 6) and girls (CS 1, 3, 4, 5, and 6). Significant differences, as determined by Mann-Whitney U tests, were observed in CS 1 for boys (p = 0.004) and in CS 4 for girls (p = 0.037). High Spearman correlation coefficients between dental maturity and cervical vertebral maturity exceeded 0.826 (p = 0.000) in all groups. CONCLUSION: A correlation between dental and skeletal maturity, as well as advanced skeletal maturity in the advanced dental maturity group, was observed. Using percentile curves to determine dental maturity may aid in assessing skeletal maturity, with potential applications in orthodontic diagnosis and treatment planning.

Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Criteria for early diagnosis of mandibular third molar agenesis based on the developmental stages of mandibular canine, first and second premolars, and second molar: a retrospective cohort study.

BACKGROUND: Permanent first molars with severe dental caries, developmental defects, or involved in oral pathologies are at risk of poor prognosis in children. Accordingly, using the third molar to replace the first molar can be a good treatment option when third molar agenesis is predicted early. Thus, this retrospective cohort study aimed to develop criteria for early detection of mandibular third molar (L8) agenesis based on the developmental stages of mandibular canine (L3), first premolar (L4), second premolar (L5), and second molar (L7). METHOD: Overall, 1,044 and 919 panoramic radiographs of 343 males and 317 females, respectively, taken between the ages of 6 and 12 years were included. All developmental stages of L3, L4, L5, L7, and L8 were analyzed based on the dental age, as suggested by Demirjian et al. The independent t-test was used to assess age differences between males and females. The rank correlation coefficients were examined using Kendall's tau with bootstrap analysis and Bonferroni's correction to confirm the teeth showing developmental stages most similar to those of L8s. Finally, a survival analysis was performed to determine the criteria for the early diagnosis of mandibular third molar agenesis. RESULTS: Some age differences were found in dental developmental stages between males and females. Correlation coefficients between all stages of L3, L4, L5, and L7 and L8 were high. In particular, the correlation coefficient between L7 and L8 was the highest, whereas that between L3 and L8 was the lowest. CONCLUSION: If at least two of the following criteria (F stage of L3, F stage of L4, F stage of L5, and E stage of L7) are met in the absence of L8 crypt, agenesis of L8 can be confirmed.

Increased adolescent game usage and health-related risk behaviors during the COVID-19 pandemic.

This study examines adolescent game usage and corresponding health-related risk behaviors during a period of limited social interaction and activity due to the COVID-19 pandemic. Participants included 225 middle- and 225 high-school students in Seoul who completed a survey online from October 1 to 30, 2021. The study measured participants' game usage level and the health-related risk behavior index. Findings showed that participants who engaged in excessive gaming showed higher levels of health-related risk behaviors. A multivariate analysis of variance was conducted to compare the health-related risk behaviors of students in the general, potential, and high-risk groups on excessive gaming. Results indicated that female students in the high-risk group showed higher stress levels and fatigue (f = 5.549, p < .01, Cohen's d = 0.016) than the males of the same group. However, male students showed higher physical inactivity levels (f = 3.195, p > .05, Cohen's d = 0.009) than females. The post hoc test indicated clear sex distinctions among the general, potential, and high-risk groups on excessive gaming (p < .001). Among the high-risk game usage group, female students displayed a higher level of risk behaviors than males. Adolescent gaming addiction should be considered an emotional and behavioral disorder for which parental guidance and support are needed, and counseling experts and professionals must come together to provide a cure and reform program.

Soil microbial communities-mediated bioattenuation in simulated aquifer storage and recovery (ASR) condition: Long-term study.

This study evaluated the long-term organic removal performance and microbial community shift in simulated aquifer storage and recovery (ASR) conditions. For this purpose, anoxic soil box systems were operated at 15 °C for one year. The results showed that the assimilable organic carbon (AOC) concentration in the anoxic soil box systems was successfully decreased by 79.1%. The dissolved organic carbon (DOC) concentration increased during the initial operational periods; however, it subsequently decreased during long-term operation. Readily biodegradable organic fractions (i.e., low-molecular weight (LMW) neutrals and LMW acids) decreased along with time elapsed, whereas non-biodegradable fraction (i.e., humic substances) increased. Proteobacteria and Acidobacteriota were predominant in the anoxic box systems throughout the operational periods. Firmicutes and Bacteroidota suddenly increased during the initial operational period while Gemmatimonadota slightly increased during prolonged long-term operation. Interestingly, the microbial community structures were significantly shifted with respect to the operational periods while the effects of AOC/NO3- addition were negligible. Various bacterial species preferring low temperature or anoxic conditions were detected as predominant bacteria. Some denitrifying (i.e., Noviherbaspirillum denitrificans) and iron reducing bacteria (i.e., Geobacter spp.) appeared during the long-term operation; these bacterial communities also acted as organic degraders in the simulated ASR systems. The findings of this study suggest that the application of natural bioattenuation using indigenous soil microbial communities can be a promising option as an organic carbon management strategy in ASR systems.

Automatic Pancreatic Cyst Lesion Segmentation on EUS Images Using a Deep-Learning Approach.

The automatic segmentation of the pancreatic cyst lesion (PCL) is essential for the automated diagnosis of pancreatic cyst lesions on endoscopic ultrasonography (EUS) images. In this study, we proposed a deep-learning approach for PCL segmentation on EUS images. We employed the Attention U-Net model for automatic PCL segmentation. The Attention U-Net was compared with the Basic U-Net, Residual U-Net, and U-Net++ models. The Attention U-Net showed a better dice similarity coefficient (DSC) and intersection over union (IoU) scores than the other models on the internal test. Although the Basic U-Net showed a higher DSC and IoU scores on the external test than the Attention U-Net, there was no statistically significant difference. On the internal test of the cross-over study, the Attention U-Net showed the highest DSC and IoU scores. However, there was no significant difference between the Attention U-Net and Residual U-Net or between the Attention U-Net and U-Net++. On the external test of the cross-over study, all models showed no significant difference from each other. To the best of our knowledge, this is the first study implementing segmentation of PCL on EUS images using a deep-learning approach. Our experimental results show that a deep-learning approach can be applied successfully for PCL segmentation on EUS images.

Dual Resonant Sum Frequency Generations from Two-Dimensional Materials.

We propose dual resonant optical sum frequency generation (SFG), where the two most singular resonances could be selected, and report for the monolayer (1L-) WSe2 when one (ω1) of two excitation pulses is resonant to A exciton and their sum frequency (ω1 + ω2) to D exciton. The dual resonant SFG confirms that, under an irradiation of ω1 and ω2 pulses with the same fluence of ∼1.4 × 1010 W/m2, its signal intensity could be enhanced about 20 times higher than the resonant SHG (i.e., 2ω1 to the D excitonic absorption). Further, the dual resonant SFG intensity of 1L-WSe2 is found to be 1 order of magnitude higher than the single resonant SFG intensity of 1L-WS2 under the same condition of two-pulse irradiation. Finally, observations of the dual resonant SFG are thoroughly examined using real-time time-dependent density functional theory (rt-TDDFT), and the relevant nonlinear optical characteristics are scrutinized using the Greenwood-Kubo formalism.

Developing a clinical presentation dental education model and a pilot test.

INTRODUCTION: Accurate clinical decision-making of dentists should be based on their knowledge and experience. In the past 10 years, interest in competency-based dentistry education has rapidly increased, but there has been little attention paid to methods of improving dental education competency. The purpose of this study was to develop a clinical presentation education model that provides opportunities for students to practice problem-solving from the moment they greet the patient so that students can obtain the practical experience of competency-based education and the effectiveness of this model can be confirmed through pilot test. METHODS: This article is divided two parts: First, developing the clinical presentation dental education model (CPDEM) and Second, a pilot study adopted CPDEM. To confirm the effectiveness of this model, the students' satisfaction, their perception of self-achievement were analysed. RESULTS: Clinical presentation dental education model has been developed to provide practice-related education experience and provide linkage between basic science and clinical science. The result of applying this education model to 10 students as a pilot test was shown an overall high satisfaction level. In addition, self-achievement students' reported of all intended competencies was higher than for non-participating students of this model. CONCLUSIONS: This study focuses on practical education centring on clinical presentation. This model could get a meaningful and realistic experiences through the practice using clinical presentation of patients, use their metacognition for organizing and memorizing the patient's case by using concept map. It can be used as a future instructional method to enhance students' competency.

Restructuring of Porphyrin Networks Driven by Self-Assembled Octanoic Acid Monolayer on Au(111).

We report time-dependent surface restructuring of bicomponent domain structures of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (H2OEP) and cobalt(II) 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (CoOEP) (H2/Co OEP) driven by self-assembled octanoic acid on the surface of Au(111). Scanning tunneling microscopy (STM) visualized molecular adsorption/desorption and rearrangement of supramolecular architectures in real-time in a solution of octanoic acid. We found that unique domain structures emerged at an initial state guided by adsorbed octanoic acid on the Au surface. Moreover, the desorption of octanoic acid occurred in solution, leading to the surface restructuring of porphyrin molecular networks. This molecular evidence is well-manifested in the time-dependent phase transitions, monitored by in situ STM.

Assimilable organic carbon removal strategy for aquifer storage and recovery applications.

Aquifer storage and recovery (ASR) technology has been adopted as a strategic water management tool. However, during the injection of oxic and organic carbon-containing water to the underground aquifers, severe phenomena such as clogging and groundwater deterioration have been reported. To prevent these severe phenomena, assimilable organic carbon (AOC) concentration has been controlled in the ASR applications by supporting bacteria growth potential. In this study, the AOC removal strategy was investigated in a simulated ASR system using an indigenous bacterium, Pseudomonas jinjuensis. AOC removal was evaluated under three different experimental conditions: (i) 30 °C and aerobic, (ii) 15 °C and aerobic, and (iii) 15 °C and anoxic. The effects of contact media such as sand and granular activated carbon on AOC removal efficiency were also investigated. Results show that under the 30 °C aerobic condition, P. jinjuensis could remove 99.8% (13 µg L-1) of AOC with soil. The variations in the organic fractions determined by liquid chromatography with organic carbon detector analysis were observed and showed trends similar to those of AOC determined by the flow cytometry method. The indirect injection method in ASR application was recommended due to the AOC removal benefit by soil indigenous bacterium.

Anomalous Electron Dynamics Induced through the Valley Magnetic Domain: A Pathway to Valleytronic Current Processing.

An interplay between an applied strain and the Berry curvature reconstruction in the uniaxially strained monolayer MoS2 is explored that leads to the unbalanced Berry curvatures centered at K and -K points and, eventually, the valley magnetization under an external electric field. This is shown to explain a recent experimental observation of the valley magnetoelectric effect and develop a novel concept of the valley magnetic domain (VMD), i.e., a real-space homogeneous distribution of the valley magnetization. A realization of VMD guarantees a sufficient number of stable valley-polarized carriers, one of the most essential prerequisites of the valleytronics. Furthermore, we discover the anomalous electron dynamics through the VMD activation and achieve a manipulation of the anomalous transverse current perpendicular to the electric field, directly accessible to the signal processing [for instance, the current modulation under the VMD (i.e., the VMD wall) moving and the terahertz current rectification under the VMD switching]. This suggests a concept of VMD for use in providing new physical insight into the valleytronic functionality and its manipulation as a key ingredient of potential device applications.

Clinical Considerations for Dental Management of Children with Molar-Root Incisor Malformations.

Molar root-incisor malformation (MRIM) or molar-incisor malformation (MIM) is a new type of dental anomaly characterized by dysplastic roots of permanent first molars, occasionally second primary molars, and the crowns of maxillary central incisors. MRIM involving permanent first molars and second primary molars is characterized by normal crowns with short, thin, and narrow roots, whereas MRIM involving permanent maxillary central incisors exhibits constrictions of the crown in the cervical area. In the first case, we extracted the affected first permanent molars at the optimal timing to minimize space deficiencies and induce space closure. In addition, composite resin restorations were performed on the anterior central incisors. In the second case, a mandibular lingual arch was used to stabilize the affected teeth in order to mitigate discomfort by reducing rotational biting forces.

Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.

Ovonic threshold switching in polycrystalline zinc telluride thin films deposited by RF sputtering.

Chalcogenide materials of the amorphous phase with low band gaps were reported to show Ovonic threshold switching (OTS), making them suitable for selection devices in cross-point memory arrays. Herein, we report that ZnTe films with polycrystalline structures show OTS behavior. Nearly stoichiometric ZnTe thin films were deposited by an RF sputtering method. X-ray diffraction analysis indicated that the films were polycrystalline. The optical band gaps of the ZnTe films were estimated as 2.2 eV from UV-visible spectroscopy transmittance measurements. Photoluminescence measurements indicated the existence of deep-level defects in the ZnTe thin films. Although these ZnTe films have a polycrystalline structure with a relatively high band gap, I-V profiles show OTS characteristics, with a selectivity of over 104, fast threshold switching time in the sub-10 ns scale, and thermal stability up to 400 °C. ZnTe also shows switching endurance for more than 109 cycles without Vth drift, maintaining its selectivity of 104. Thus, we improved the threshold switching characteristics by using a wide band-gap and polycrystalline-structured ZnTe-based chalcogenide material. Post-annealing experiments indicated that the thermal budget of the ZnTe thin film was sufficient for stacked cross-point array structures, thereby overcoming a previous limitation of chalcogenide switching materials. This material is promising for application in high-density cross-point memory arrays as the selection device.

Candidate gene sequencing reveals mutations causing hypoplastic amelogenesis imperfecta.

OBJECTIVE: Amelogenesis imperfecta (AI) is a rare hereditary disorder affecting the quality and quantity of the tooth enamel. The purpose of this study was to identify the genetic etiology of hypoplastic AI families based on the candidate gene approach. MATERIALS AND METHODS: We recruited three Turkish families with hypoplastic AI and performed a candidate gene screening based on the characteristic clinical feature to find the pathogenic genetic etiology. RESULTS: The candidate gene sequencing of the LAMB3 gene for family 1 revealed a heterozygous nonsense mutation in the last exon [c.3431C > A, p.(Ser1144*)]. FAM20A gene sequencing for families 2 and 3 identified a homozygous deletion [c.34_35delCT, p.(Leu12Alafs*67)] and a homozygous deletion-insertion (c.1109 + 3_1109 + 7delinsTGGTC) mutation, respectively. CONCLUSION: The candidate gene approach can be successfully used to identify the genetic etiology of the AI in some cases with characteristic clinical features. CLINICAL RELEVANCE: Identification of the genetic etiology of the AI will help both the family members and dentist understand the nature of the disorder. Characteristic clinical feature can suggest possible genetic causes.

Effects of dental treatment and systemic disease on oral health-related quality of life in Korean pediatric patients.

BACKGROUND: The findings that not only dental caries but also systemic disease can exert a negative effect on oral health-related quality of life (OHRQoL), and that dental treatment can improve OHRQoL have been confirmed in multiple studies. The purpose of this study is to investigate the impact of dental treatment on OHRQoL of Korean pediatric patients and the differences in OHRQoL between patients with and without systemic disease. METHODS: All the primary caregivers of pediatric patients who underwent dental treatments under either general anesthesia or intravenous deep sedation at Seoul National University Dental Hospital completed abbreviated versions of the Child Oral Health Impact Profile (COHIP-14) and Family Impact Scale (FIS-12) surveys on OHRQOL pre- and post-treatment (average: 2.4 ± 1.7 months after dental treatment). This is a case control study with patients divided into two groups according to the presence or absence of systemic disease. RESULTS: Data from 93 pediatric patients (46 male and 47 female, average patient age: 5.0 ± 3.4 years) were analyzed to compare OHRQoL before and after treatment with the Wilcoxon signed-rank test and to calculate the effect size using Cohen's d. All of the patients exhibited an improvement in OHRQoL (COHIP-14: p <  0.001, effect size = 1.0; FIS-12: p <  0.001, effect size = 0.7). Patients with systemic diseases demonstrated lower OHRQoL in both pre- and post-treatment surveys than patients without systemic diseases (Wilcoxon Rank-sum test, both COHIP-14 and FIS-12: p <  0.05). The COHIP-14 appears to have a greater impact on the FIS-12 in patients with systemic disease than those without (explanatory power of 65.3 and 44.6%, respectively). CONCLUSIONS: Based on the primary caregivers' perceptions, dental treatment can improve the OHRQoL in Korean pediatric patients. Systemic disease results in a reduced OHRQoL, and the awareness of patients' oral health appeared to have a greater impact on OHRQoL for family members of patients with a systemic disease. TRIAL REGISTRATION: KCT0002473 (Clinical Research Information Service, Republic of Korea) and 22 Sep 2017, retrospectively registered.