LEAPSE: Learning Environment Affordances for 3D Human Pose and Shape Estimation.

We live in a 3D world where people interact with each other in the environment. Learning 3D posed humans therefore requires us to perceive and interpret these interactions. This paper proposes LEAPSE, a novel method that learns salient instance affordances for estimating a posed body from a single RGB image in a non-parametric manner. Existing methods mostly ignore the environment and estimate the human body independently from the surroundings. We capture the influences of non-contact and contact instances on a posed body as an adequate representation of the "environment affordances". The proposed method learns the global relationships between 3D joints, body mesh vertices, and salient instances as environment affordances on the human body. LEAPSE achieved state-of-the-art results on the 3DPW dataset with many affordance instances, and also demonstrated excellent performance on Human3.6M dataset. We further demonstrate the benefit of our method by showing that the performance of existing weak models can be significantly improved when combined with our environment affordance module.

Diagnosing oral and maxillofacial diseases using deep learning.

The classification and localization of odontogenic lesions from panoramic radiographs is a challenging task due to the positional biases and class imbalances of the lesions. To address these challenges, a novel neural network, DOLNet, is proposed that uses mutually influencing hierarchical attention across different image scales to jointly learn the global representation of the entire jaw and the local discrepancy between normal tissue and lesions. The proposed approach uses local attention to learn representations within a patch. From the patch-level representations, we generate inter-patch, i.e., global, attention maps to represent the positional prior of lesions in the whole image. Global attention enables the reciprocal calibration of path-level representations by considering non-local information from other patches, thereby improving the generation of whole-image-level representation. To address class imbalances, we propose an effective data augmentation technique that involves merging lesion crops with normal images, thereby synthesizing new abnormal cases for effective model training. Our approach outperforms recent studies, enhancing the classification performance by up to 42.4% and 44.2% in recall and F1 scores, respectively, and ensuring robust lesion localization with respect to lesion size variations and positional biases. Our approach further outperforms human expert clinicians in classification by 10.7 % and 10.8 % in recall and F1 score, respectively.

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion.

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-ß signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-ß signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells.

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.

Improved time-varying reproduction numbers using the generation interval for COVID-19.

Estimating key epidemiological parameters, such as incubation period, serial interval (SI), generation interval (GI) and latent period, is essential to quantify the transmissibility and effects of various interventions of COVID-19. These key parameters play a critical role in quantifying the basic reproduction number. With the hard work of epidemiological investigators in South Korea, estimating these key parameters has become possible based on infector-infectee surveillance data of COVID-19 between February 2020 and April 2021. Herein, the mean incubation period was estimated to be 4.9 days (95% CI: 4.2, 5.7) and the mean generation interval was estimated to be 4.3 days (95% CI: 4.2, 4.4). The mean serial interval was estimated to be 4.3, with a standard deviation of 4.2. It is also revealed that the proportion of presymptomatic transmission was ~57%, which indicates the potential risk of transmission before the disease onset. We compared the time-varying reproduction number based on GI and SI and found that the time-varying reproduction number based on GI may result in a larger estimation of Rt, which refers to the COVID-19 transmission potential around the rapid increase of cases. This highlights the importance of considering presymptomatic transmission and generation intervals when estimating the time-varying reproduction number.

Heterogeneity is a key factor describing the initial outbreak of COVID-19.

Assessing the transmission potential of emerging infectious diseases, such as COVID-19, is crucial for implementing prompt and effective intervention policies. The basic reproduction number is widely used to measure the severity of the early stages of disease outbreaks. The basic reproduction number of standard ordinary differential equation models is computed for homogeneous contact patterns; however, realistic contact patterns are far from homogeneous, specifically during the early stages of disease transmission. Heterogeneity of contact patterns can lead to superspreading events that show a significantly high level of heterogeneity in generating secondary infections. This is primarily due to the large variance in the contact patterns of complex human behaviours. Hence, in this work, we investigate the impacts of heterogeneity in contact patterns on the basic reproduction number by developing two distinct model frameworks: 1) an SEIR-Erlang ordinary differential equation model and 2) an SEIR stochastic agent-based model. Furthermore, we estimated the transmission probability of both models in the context of COVID-19 in South Korea. Our results highlighted the importance of heterogeneity in contact patterns and indicated that there should be more information than one quantity (the basic reproduction number as the mean quantity), such as a degree-specific basic reproduction number in the distributional sense when the contact pattern is highly heterogeneous.

Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.

The possible anticancer activity of combination (M + E + F) of metformin (M), efavirenz (E), and fluoxetine (F) was investigated in normal HDF cells and HCT116 human colon cancer cells. Metformin increased cellular FOXO3a, p-FOXO3a, AMPK, p-AMPK, and MnSOD levels in HDFs but not in HCT116 cells. Cellular ATP level was decreased only in HDFs by metformin. Metformin increased ROS level only in HCT116 cells. Transfection of si-FOXO3a into HCT116 reversed the metformin-induced cellular ROS induction, indicating that FOXO3a/MnSOD is the key regulator for cellular ROS level. Viability readout with M, E, and F alone decreased slightly, but the combination of three drugs dramatically decreased cell survival in HCT116, A549, and SK-Hep-1 cancer cells but not in HDF cells. ROS levels in HCT116 cells were massively increased by M + E + F combination, but not in HDF cells. Cell cycle analysis showed that of M + E + F combination caused cell death only in HCT116 cells. The combination of M + E + F reduced synergistically mitochondrial membrane potential and mitochondrial electron transport chain complex I and III activities in HCT116 cells when compared with individual treatments. Western blot analysis indicated that DNA damage, apoptosis, autophagy, and necroptosis-realated factors increased in M + E + F-treated HCT116 cells. Oral administration with M + E + F combination for 3 weeks caused dramatic reductions in tumor volume and weight in HCT116 xenograft model of nude mice when compared with untreated ones. Our results suggest that M + E + F have profound anticancer activity both in vitro and in vivo via a cancer cell-specific ROS amplification (CASRA) through ROS-induced DNA damage, apoptosis, autophagy, and necroptosis.

FOXO3a Mediates Homologous Recombination Repair (HRR) via Transcriptional Activation of MRE11, BRCA1, BRIP1, and RAD50.

To test whether homologous recombination repair (HRR) depends on FOXO3a, a cellular aging model of human dermal fibroblast (HDF) and tet-on flag-h-FOXO3a transgenic mice were studied. HDF cells transfected with over-expression of wt-h-FOXO3a increased the protein levels of MRE11, BRCA1, BRIP1, and RAD50, while knock-down with siFOXO3a decreased them. The protein levels of MRE11, BRCA1, BRIP1, RAD50, and RAD51 decreased during cellular aging. Chromatin immunoprecipitation (ChIP) assay was performed on FOXO3a binding accessibility to FOXO consensus sites in human MRE11, BRCA1, BRIP1, and RAD50 promoters; the results showed FOXO3a binding decreased during cellular aging. When the tet-on flag-h-FOXO3a mice were administered doxycycline orally, the protein and mRNA levels of flag-h-FOXO3a, MRE11, BRCA1, BRIP1, and RAD50 increased in a doxycycline-dose-dependent manner. In vitro HRR assays were performed by transfection with an HR vector and I-SceI vector. The mRNA levels of the recombined GFP increased after doxycycline treatment in MEF but not in wt-MEF, and increased in young HDF comparing to old HDF, indicating that FOXO3a activates HRR. Overall, these results demonstrate that MRE11, BRCA1, BRIP1, and RAD50 are transcriptional target genes for FOXO3a, and HRR activity is increased via transcriptional activation of MRE11, BRCA1, BRIP1, and RAD50 by FOXO3a.

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2.

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

Estimation of Serial Interval and Reproduction Number to Quantify the Transmissibility of SARS-CoV-2 Omicron Variant in South Korea.

The omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the predominant variant in South Korea from late January 2022. In this study, we aimed to report the early estimates of the serial interval distribution and reproduction number to quantify the transmissibility of the omicron variant in South Korea between 25 November 2021 and 31 December 2021. We analyzed 427 local omicron cases and reconstructed 73 transmission pairs. We used a maximum likelihood estimation to assess serial interval distribution from transmission pair data and reproduction numbers from 74 local cases in the first local outbreak. We estimated that the mean serial interval was 3.78 (standard deviation, 0.76) days, which was significantly shorter in child infectors (3.0 days) compared to adult infectors (5.0 days) (p < 0.01). We estimated the mean reproduction number was 1.72 (95% CrI, 1.60−1.85) for the omicron variant during the first local outbreak. Strict adherence to public health measures, particularly in children, should be in place to reduce the transmission risk of the highly transmissible omicron variant in the community.

Discovering spatiotemporal patterns of COVID-19 pandemic in South Korea.

A novel severe acute respiratory syndrome coronavirus 2 emerged in December 2019, and it took only a few months for WHO to declare COVID-19 as a pandemic in March 2020. It is very challenging to discover complex spatial-temporal transmission mechanisms. However, it is crucial to capture essential features of regional-temporal patterns of COVID-19 to implement prompt and effective prevention or mitigation interventions. In this work, we develop a novel framework of compatible window-wise dynamic mode decomposition (CwDMD) for nonlinear infectious disease dynamics. The compatible window is a selected representative subdomain of time series data, in which compatibility between spatial and temporal resolutions is established so that DMD can provide meaningful data analysis. A total of four compatible windows have been selected from COVID-19 time-series data from January 20, 2020, to May 10, 2021, in South Korea. The spatiotemporal patterns of these four windows are then analyzed. Several hot and cold spots were identified, their spatial-temporal relationships, and some hidden regional patterns were discovered. Our analysis reveals that the first wave was contained in the Daegu and Gyeongbuk areas, but it spread rapidly to the whole of South Korea after the second wave. Later on, the spatial distribution is seen to become more homogeneous after the third wave. Our analysis also identifies that some patterns are not related to regional relevance. These findings have then been analyzed and associated with the inter-regional and local characteristics of South Korea. Thus, the present study is expected to provide public health officials helpful insights for future regional-temporal specific mitigation plans.

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract.

Arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC). The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner. Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. Conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.

Combined inhibition of STAT and Notch signalling effectively suppresses tumourigenesis by inducing apoptosis and inhibiting proliferation, migration and invasion in glioblastoma cells.

Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer and this is due to cancer cells being apoptosis-resistant and having increased cell proliferation, migration, invasion, and angiogenesis properties. Previous studies have indicated both STAT and Notch pathways being important for initiation and progression in GBM. In this work, we first studied the effects of STAT inhibitors on Notch signalling using small molecule STAT inhibitors. It was observed that STAT inhibitors surprisingly activated Notch signalling by inducing NICD and Notch target genes in GBM cells. Thus, we aimed to combine STAT inhibitor treatment with a Notch pathway inhibitor and study effects on GBM tumourigenesis. STAT5 inhibitor (Pimozide) and STAT3 inhibitor (S3I-201) were individually used in combination with γ-secretase inhibitor (DAPT), an inhibitor of Notch signalling, in a panel of GBM cells for cell proliferation and epithelial plasticity changes. Compared with single-agent treatments, combinatorial treatments with the STAT and Notch inhibitors significantly increased apoptosis in the treated cells, impairing cell proliferation, migration, and invasion. These findings suggest that concurrent blocking of STAT and Notch signalling pathways could provide added therapeutic benefit for the treatment of glioblastoma.

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells.

Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts. Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells. Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells. p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells. Transfection of si-FOXO3a in HDF increased ROS levels, while wt-FOXO3a-transfected AsPC-1 cells decreased ROS levels. Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect. Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells. Metformin/apigenin combination in AsPC-1 cells increased DNA damage-, apoptosis-, autophagy- and necroptosis-related factors, but not in HDF cells. Oral administration with metformin/apigenin caused dramatic blocks tumor size in AsPC-1-xenografted nude mice. Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.

Zn2+-Imidazole Coordination Crosslinks for Elastic Polymeric Binders in High-Capacity Silicon Electrodes.

Recent research has built a consensus that the binder plays a key role in the performance of high-capacity silicon anodes in lithium-ion batteries. These anodes necessitate the use of a binder to maintain the electrode integrity during the immense volume change of silicon during cycling. Here, Zn2+-imidazole coordination crosslinks that are formed to carboxymethyl cellulose backbones in situ during electrode fabrication are reported. The recoverable nature of Zn2+-imidazole coordination bonds and the flexibility of the poly(ethylene glycol) chains are jointly responsible for the high elasticity of the binder network. The high elasticity tightens interparticle contacts and sustains the electrode integrity, both of which are beneficial for long-term cyclability. These electrodes, with their commercial levels of areal capacities, exhibit superior cycle life in full-cells paired with LiNi0.8Co0.15Al0.05O2 cathodes. The present study underlines the importance of highly reversible metal ion-ligand coordination chemistries for binders intended for high capacity alloying-based electrodes.

Purple corn extract (PCE) alleviates cigarette smoke (CS)-induced DNA damage in rodent blood cells by activation of AMPK/Foxo3a/MnSOD pathway.

Purple corn extract (PCE) is a nutraceutical, an activator of AMPK, and it has antioxidants and anticancer properties. Therefore, PCE could be a candidate for alleviating cigarette smoke (CS)-induced oxidative DNA damage. This study examined whether PCE can have a protective effect on blood cells in an animal model of cigarette smoke (CS)-induced DNA damage. PCE was orally administered to CS-inhaled Spraque-Dawley (SD) rats, followed by the target cells being examined for markers of DNA damage. The study also sought to elucidate the mechanism of PCE action in the PCE treated animals. SD rat inhalation of CS was for once a day for 30 min, repeated for 7 days. PCE was administered orally before CS inhalation. Pretreatment of the animals with oral PCE kept the numbers of white blood cells (WBC) as well as neutrophils (NE), lymphocytes (LY), monocytes (Mo), eosinophils (EO), abd jasophils (BA) from increasing as those were increased in the CS-inhaling SD rats. The amount of phosphorylated γ-H2AX, a DNA damage marker, was assayed in the circulating blood cells collected from the animals and western blot analysis with anti-Foxo3a, p-Foxo3a, p-AMPK, MnSOD antibodies were performed on those cells. PCE protected the circulating blood cells from CS inhalation-induced DNA damage by 44% as assayed by increases in γ-H2AX. PCE also increased the nuclear localization of Foxo3a by 52% over control cells. Mechanistically, PCE appears to efficiently protect various blood cell types from CS-induced DNA damage through removal of ROS via activation of the AMPK/Foxo3a/MnSOD pathway.

Explaining Neural Networks Using Attentive Knowledge Distillation.

Explaining the prediction of deep neural networks makes the networks more understandable and trusted, leading to their use in various mission critical tasks. Recent progress in the learning capability of networks has primarily been due to the enormous number of model parameters, so that it is usually hard to interpret their operations, as opposed to classical white-box models. For this purpose, generating saliency maps is a popular approach to identify the important input features used for the model prediction. Existing explanation methods typically only use the output of the last convolution layer of the model to generate a saliency map, lacking the information included in intermediate layers. Thus, the corresponding explanations are coarse and result in limited accuracy. Although the accuracy can be improved by iteratively developing a saliency map, this is too time-consuming and is thus impractical. To address these problems, we proposed a novel approach to explain the model prediction by developing an attentive surrogate network using the knowledge distillation. The surrogate network aims to generate a fine-grained saliency map corresponding to the model prediction using meaningful regional information presented over all network layers. Experiments demonstrated that the saliency maps are the result of spatially attentive features learned from the distillation. Thus, they are useful for fine-grained classification tasks. Moreover, the proposed method runs at the rate of 24.3 frames per second, which is much faster than the existing methods by orders of magnitude.

Bmp Signal Gradient Modulates Convergent Cell Movement via Xarhgef3.2 during Gastrulation of Xenopus Embryos.

Gastrulation is a critical step in the establishment of a basic body plan during development. Convergence and extension (CE) cell movements organize germ layers during gastrulation. Noncanonical Wnt signaling has been known as major signaling that regulates CE cell movement by activating Rho and Rac. In addition, Bmp molecules are expressed in the ventral side of a developing embryo, and the ventral mesoderm region undergoes minimal CE cell movement while the dorsal mesoderm undergoes dynamic cell movements. This suggests that Bmp signal gradient may affect CE cell movement. To investigate whether Bmp signaling negatively regulates CE cell movements, we performed microarray-based screening and found that the transcription of Xenopus Arhgef3.2 (Rho guanine nucleotide exchange factor) was negatively regulated by Bmp signaling. We also showed that overexpression or knockdown of Xarhgef3.2 caused gastrulation defects. Interestingly, Xarhgef3.2 controlled gastrulation cell movements through interacting with Disheveled (Dsh2) and Dsh2-associated activator of morphogenesis 1 (Daam1). Our results suggest that Bmp gradient affects gastrulation cell movement (CE) via negative regulation of Xarhgef3.2 expression.

A Tumor-Immune Interaction Model for Synergistic Combinations of Anti PD-L1 and Ionizing Irradiation Treatment.

Combination therapy with immune checkpoint blockade and ionizing irradiation therapy (IR) generates a synergistic effect to inhibit tumor growth better than either therapy does alone. We modeled the tumor-immune interactions occurring during combined IT and IR based on the published data from Deng et al. The mathematical model considered programmed cell death protein 1 and programmed death ligand 1, to quantify data fitting and global sensitivity of critical parameters. Fitting of data from control, IR and IT samples was conducted to verify the synergistic effect of a combination therapy consisting of IR and IT. Our approach using the model showed that an increase in the expression level of PD-1 and PD-L1 was proportional to tumor growth before therapy, but not after initiating therapy. The high expression level of PD-L1 in T cells may inhibit IT efficacy. After combination therapy begins, the tumor size was also influenced by the ratio of PD-1 to PD-L1. These results highlight that the ratio of PD-1 to PD-L1 in T cells could be considered in combination therapy.

Evaluation of COVID-19 epidemic outbreak caused by temporal contact-increase in South Korea.

OBJECTIVES: On March 15, 2020, 61.3% of the confirmed cases of COVID-19 infection in South Korea are associated with the worship service that was organized on February 9 in the Shincheonji Church of Jesus in Daegu. We aim to evaluate the effects of mass infection in South Korea and assess the preventive control intervention. METHOD: Using openly available data of daily cumulative confirmed cases and deaths, the basic and effective reproduction numbers was estimated using a modified susceptible-exposed-infected-recovered-type epidemic model. RESULTS: The basic reproduction number was estimated to be R0=1.77. The effective reproduction number increased approximately 20 times after the mass infections from the 31 st patient, which was confirmed on February 9 in the Shincheonji Church of Jesus, Daegu. However, the effective reproduction number decreased to less than unity after February 28 owing to the implementation of high-level preventive control interventions in South Korea, coupled with voluntary prevention actions by citizens. CONCLUSION: Preventive action and control intervention were successfully established in South Korea.