Purpose: Precise registration between intraoral scans (IOSs) and CBCT images is essential for many digital dentistry applications. The purpose of this study was to develop DentalRegiformer, a fully automated, end-to-end deep learning framework that ensures accurate registration between IOS and CBCT images. Materials and Methods: The network was trained on 88 paired CBCT-IOS datasets from 44 patients, with ground-truth alignments obtained through manual registration performed by trained dental students. To enhance clinical accuracy and efficiency, a multi-stage coarse-to-fine strategy is proposed to integrate segmentation, classification, and registration into a unified pipeline. First, tooth segmentation is performed on CBCT volumes using 3D nnU-Net to generate segmented tooth regions for alignment. Simultaneously, IOS datasets are classified as maxillary or mandibular dentition using a hybrid representation that combines geometric descriptors with point cloud features extracted via a DGCNN network. Registration is then conducted in two phases: coarse alignment using a DCP framework for feature encoding and probabilistic correspondence estimation to compute the initial rigid transformation, followed by fine alignment using GeoTransformer’s local-to-global iterative refinement, which alternates between local feature aggregation and global context integration to progressively enhance correspondence accuracy and achieve precise rigid registration. Results The segmentation model achieved robust results, with a Dice coefficient of 0.924, precision of 0.916, and recall of 0.934. The DGCNN classifier perfectly distinguished maxillary and mandibular arches, achieving sensitivity, specificity, ROC, and accuracy of 1.000.For registration, DentalRegiformer accurately predicted transformation between IOS and CBCT images, yielding an overall RMSE of 0.556 mm; MAEs of 0.231mm, 0.329 mm, and 0.283 mm along the x-, y-, and z-axes, respectively; and inference time of 19.623 seconds. In comparison, the manual method based on combined pair-points and ICP had an RMSE of 0.615 mm;MAEs of 0.244 mm, 0.347 mm, and 0.298 mm along the x-, y-, and z-axes, respectively; and processing time of 431.6 seconds.Discussion and Conclusion: Therefore, DentalRegiformer is a fully automated, deep learning–based solution that minimizes manual intervention and improves clinical efficiency. The framework streamlines digital dental workflows, reduces operator-dependent errors, and facilitates automated, personalized dental care.

Background/Aims: Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. Methods: This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. Conclusions Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Background: The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. Methods: We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. Results: We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. Conclusion This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. Conclusion The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Background: The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. Methods: We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. Results: We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. Conclusion This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Background: This study was performed to identify acute tinnitus and evaluate the efficacy of steroids for noise-induced acute tinnitus by measuring the gap-prepulse inhibition of the acoustic startle (GPIAS) value in an animal model. Methods: Nineteen rats (the noise group [n = 7] and the noise + dexamethasone [DEX] group [n = 12]) were exposed to narrow-band noise centered at 16 kHz from a sound generator for 4 hours. The noise + DEX group received intraperitoneal steroid administration daily for 5 days (1.5 mg/kg/day) after completing noise exposure. Auditory brainstem response and GPIAS value were measured just prior to, and 1 day after noise exposure and on days 1 and 10 days after completing steroid administration. The changes in cochlear structure were evaluated by histological analysis. Results: The threshold shift was checked 1 and 10 days after intraperitoneal steroid injection, and no differences in threshold shift were observed between the two groups in each frequency except for 32 kHz 1 day after steroid injection. The mean GPIAS value in the noise + DEX group (36.4% ± 14.1%) was significantly higher than that in the noise group (16.4% ± 18.8%) 10 days after intraperitoneal steroid administration (P = 0.017). There were no pathological changes associated with noise trauma in the two groups as determined on hematoxylin and eosin and immunohistochemical staining. Conclusion An acute tinnitus model with minimal structural changes by noise exposure was set up, and used to verify tinnitus objectively by measuring the GPIAS value. Steroid therapy for control of tinnitus was validated in this animal model.

PURPOSE: This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. MATERIALS AND METHODS: Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. RESULTS: We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were “very satisfied” and “satisfied,” respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. CONCLUSION: The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.
Clinical Decision-Making ; Dissent and Disputes ; Hospitals, General ; Korea* ; Specialization ; Surveys and Questionnaires

OBJECTIVE: Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. MATERIALS AND METHODS: This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. RESULTS: A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). CONCLUSION: The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.
Aged ; Alzheimer Disease* ; Dementia* ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Neurodegenerative Diseases ; Parkinson Disease* ; Parkinsonian Disorders ; Retrospective Studies ; Substantia Nigra*

BACKGROUND/OBJECTIVES: Citrus flavonoids have a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated whether bioconversion of Citrus unshiu with cytolase (CU-C) ameliorates the anti-adipogenic effects by modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 cells. MATERIALS/METHODS: Glycoside forms of Citrus unshiu (CU) were converted into aglycoside forms with cytolase treatment. Cell viability of CU and CU-C was measured at various concentrations in 3T3L-1 cells. The anti-adipogenic and lipolytic effects were examined using Oil red O staining and free glycerol assay, respectively. We performed real time-polymerase chain reaction and western immunoblotting assay to detect mRNA and protein expression of adipogenic transcription factors, respectively. RESULTS: Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and instead, increased flavanone aglycoside forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with CU or CU-C at a dose of 0.5 mg/ml. Adipocyte differentiation was inhibited in CU-C group, but not in CU group. CU-C markedly suppressed the insulin-induced protein expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) as well as the mRNA levels of CEBPalpha, PPARgamma, and sterol regulatory element binding protein 1c (SREBP1c). Both CU and CU-C groups significantly increased the adipolytic activity with the higher release of free glycerol than those of control group in differentiated 3T3-L1 adipocytes. CU-C is particularly superior in suppression of adipogenesis, whereas CU-C has similar effect to CU on stimulation of lipolysis. CONCLUSIONS: These results suggest that bioconversion of Citrus unshiu peel extracts with cytolase enhances aglycoside flavonoids and improves the anti-adipogenic metabolism via both inhibition of key adipogenic transcription factors and induction of adipolytic activity.
3T3-L1 Cells* ; Adipocytes ; Adipogenesis ; Blotting, Western ; Cell Survival ; Citrus* ; Flavonoids ; Glycerol ; Lipid Metabolism ; Lipolysis ; Metabolism ; PPAR gamma ; RNA, Messenger ; Sterol Regulatory Element Binding Protein 1 ; Transcription Factors