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Purpose@#BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. @*Materials and Methods@#Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. @*Results@#Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. @*Conclusion@#BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.
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Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an inflammatory dermatosis associated with systemic immune-mediated diseases such as rheumatoid arthritis, systemic sclerosis, lupus erythematosus, and ulcerative colitis. Histologically, serial development of leukocytoclastic vasculitis is shown from an early stage, which can progress to palisading granuloma in the fully developed stage and to fibrosis in the final stage. A 32-yearold man presented with ankylosing spondylitis showing multiple erythematous papules on his fingers, elbows, knees, and left auricle. Histologic examination from his skin lesion revealed a perforating palisading granuloma with leukocytoclastic vasculitis, which was consistent with PNGD. Therefore, this study reported a case of PNGD accompanied by ankylosing spondylitis as an initial presentation.
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Background@#The study aimed to review the initiatives and activities of the Korean Blood Safety Project Group (KBSPG) from 2012 to 2021 to present its work domestically and internationally, and to set up future directions for the KBSPG. @*Methods@#Details of the KBSPG’s projects were organized by task. This project was supported by the Korean Ministry of Health and Welfare. The final annual reports and data posted on the website of the KBSPG were used for analysis. @*Results@#The KBSPG completed 14 tasks, including training and sharing of the latest information with workers of blood centers and transfusion services in medical institutes, external proficiency surveys for donor blood screening tests, and maintenance of a national registration system. The results of these tasks have contributed to the fulfillment of work of the relevant national departments, the establishment and operation of related websites, the publication of annual reports, the implementation of workshops and training programs, the operation of regional networks for blood transfusion management, and the production and distribution of information leaflets and training videos.Additionally, the KBSPG has developed and revised guidelines and standards and published related papers. @*Conclusion@#The KBSPG’s continuous efforts improved the quality of blood centers and transfusion services in medical institutes, thus contributing to the national blood management services. To further improve blood management work and ensure blood safety, the KBSPG must expand its scope and continue to pursue its important mission. (Korean J Blood Transfus 2023;34:1-11)
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Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.
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BACKGROUND@#A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. @*METHODS@#Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+ , CD34+ , CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. @*RESULTS@#As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. @*CONCLUSION@#Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.
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Rheumatoid arthritis (RA) is a common autoimmune disease that mainly affects the joints and systemic organs, such as the skin, eyes, heart, gastrointestinal tract, and lungs. In particular, among various pulmonary involvements, interstitial lung disease (ILD) is closely related to the selection of anti-rheumatic drugs and the long-term prognosis of patients with RA. Although the exact pathogenesis of RA-ILD is not well defined, several mechanistic pathways, similar to those of idiopathic pulmonary fibrosis, have been elucidated recently. Conversely, RA-related autoantibodies, including anti-cyclic citrullinated peptide antibody, are detectable in circulation and in the lungs, even in the absence of articular symptoms. RA-ILD can also predate years before the occurrence of joint symptoms. This evidence supports the fact that local dysregulated mucosal immunity in the lung causes systemic autoimmunity, resulting in clinically evident polyarthritis of RA. Because the early diagnosis of RA-ILD is important, imaging tests, such as computed tomography and pulmonary function tests, are being used for early diagnosis, but there is no clear guideline for the early diagnosis of RA-ILD and selection of optimal disease-modifying anti-rheumatic drugs for the treatment of patients with RA with ILD. In addition, the efficacy of nintedanib, a new anti-fibrotic agent, for RA-ILD treatment, has been investigated recently.This review collectively discusses the basic and clinical aspects, such as pathogenesis, animal models, diagnosis, and treatment, of RA-ILD.
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Background@#Due to the importance of the cold chain related to vaccine transportation, it is necessary to establish a blood cold chain operation strategy by checking the status of blood transportation from blood donation to transfusion. @*Methods@#The blood transportation system and blood storage facilities were checked by inspecting the Korean Red Cross (KRC) Blood Centers and its affiliated supplier and Hanmaeum Blood Center. The status of the cold chain was evaluated through an interview with the quality control manager or blood supply team leader. For the hospital, the status was investigated from the perspective of the 30-min rule. A questionnaire survey was conducted for medical technicians and nurses working at the hospital. @*Results@#Data on temperature during transport of blood components were computerized, and all standards were met. A nationwide network that could supply blood from the blood supply center to the hospitals within 2 hours was established. The frequency of temperature monitoring in the blood transport box and constant temperature check in the transport box during long-distance transport were evaluated. @*Conclusion@#This study confirmed that blood storage and transportation in Korea complied with the cold chain standards of high-income countries or higher. The evaluation of the cold chain is a constantly evolving process requiring continuous attention. When standards for storage and transportation of blood products are established, strict regulations and examinations will be required.
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Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.
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Background@#Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. @*Methods@#We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. @*Results@#A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. @*Conclusion@#Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.
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Background@#Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). @*Methods@#A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. @*Results@#Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). @*Conclusion@#Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.
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Background@#Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. @*Methods@#We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. @*Results@#A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. @*Conclusion@#Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.
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Assuntos
Feminino , Humanos , Adulto Jovem , Anemia , Anticorpos , Transfusão de Sangue , Eritrócitos , Deficiência Intelectual , Ferro , Isoanticorpos , Coreia (Geográfico) , Programas de Rastreamento , Sistema do Grupo Sanguíneo P , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , Reabilitação , Testes SorológicosRESUMO
Background@#We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. @*Methods@#We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. @*Results@#Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. @*Conclusion@#In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.
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Objective@#. To investigate the impact of the amendment of the Korean National Health Insurance (KNHI) reimbursement criteria for anti-tumor necrosis factor-α (TNF-α) agents based on from conventional clinical and laboratory measurements to disease activity score of 28 joints (DAS28) on treatment pattern, clinical response, and persistence rate in patients with rheumatoid arthritis (RA). @*Methods@#. This multicenter retrospective cohort study evaluated 148 RA patients eligible for the initiation of anti- TNF-α agents as the first-line biologics by either the past (n=95) or current (n=53) KNHI reimbursement criteria. Persistence was defined as the duration between the initiation and discontinuation of anti-TNFα agents. @*Results@#. In total, 106 (71.6%), 35 (23.6%), and 7 (4.7%) RA patients started treatment with adalimumab, etanercept, and infliximab, respectively. RA patients who received anti-TNF-α agents under the current reimbursement criteria had a significantly lower mean DAS28-erythrocyte sedimentation rate (ESR) (6.02 vs. 6.95, p<0.001) and daily prednisolone-equivalent glucocorticoid dose (4.51 vs. 6.17 mg, p<0.001) than those who received anti-TNF-α agents under the past reimbursement criteria. No significant differences in the 1-year remission rate defined by DAS28-ESR<2.6 (17.9% vs. 30.2%, p=0.085) and the persistence rate (p=0.703) between the past and current reimbursement criteria was observed. @*Conclusion@#. Our data suggest that less active RA patients can receive reimbursement for anti-TNF-α agents under the current criteria, and the amendment of the KNHI reimbursement criteria may improve access to anti-TNF-α agents without affecting the treatment response and persistence rate.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
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Purpose@#Presently, Korea is facing new challenges associated with an imbalance in blood supply and demand. The purpose ofthis study was to examine trends in blood supply and demand in Korea over the past 10 years through 2018 and to propose whatto prepare in the future. @*Materials and Methods@#Age demographics in Korea were analyzed using data from the Statistics Korea. Blood donation andblood supply data were analyzed using Blood Services Statistics 2018 by the Korean Red Cross. Blood transfusion data from hospitalsin 2018 were obtained from the Health Insurance Review and Assessment Service. @*Results@#In 2018, 2883270 whole blood and apheresis units were collected in Korea. The Korean Red Cross supplied 4277762 bloodcomponents to 2491 hospitals. The overall blood donation rate was 5.6%, and the most frequent donors were young male donors.Leukoreduced red blood cells (RBCs) constituted 25% of all RBCs used, and 40% of all platelets were supplied by single-donorplatelets. The self-sufficiency rate of domestic plasma with which to produce plasma-derived medicinal products was 68.7% in2018. Blood use was the most frequent among patients aged 70–79 years. @*Conclusion@#Blood management in Korea is changing rapidly due to a low birth rate, rapid aging, and an increase in severely illpatients who require most of the blood supply. Therefore, future plans to promote donation at a national level and optimal use ofblood in hospitals is necessary.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
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Background@#Laboratory tests in blood banks vary with respect to methods,equipment, and quality control according to the hospital’s environment. @*Methods@#We surveyed institutions that regularly participated in the Koreanassociation of external quality assessment using a web-based questionnairecomprising 79 questions regarding transfusion laboratory work. @*Results@#A total of 84 institutions were surveyed including 17 senior generalhospitals, 43 general hospitals, 19 hospitals, four clinics, and one commerciallaboratory. ABO cell typing was performed by slide (63, 75.0%), tube (42,50.0%), automated column (19, 22.6%), and automated microplate (7, 8.3%)methods. ABO serum typing was performed by tube (75, 89.3%), automatedcolumn (19, 22.6%), automated microplate (7, 8.3%), and slide (7, 8.3%)methods. Irregular antibody screening test and identification test wasperformed by 58 (69.0%) and 36 (42.9%) institutions, respectively. Irregularantibody screening test and identification test was performed by the columnagglutination method in 34 (40.5%) and 26 (31.0%) institutions, respectively.Room temperature saline, albumin, and anti-globulin reagent crossmatchingtest (three-step method) was the most popular method (48, 57.1%). Theuse of anti-globulin reagent in the crossmatching test did not significantlyvary according to the size of the hospital. A daily quality control programfor ABO, Rh typing, and the crossmatching test was conducted in 58 (69.0%)institutions. @*Conclusions@#There were differences in transfusion-related laboratory testsamong the institutions. Although this survey included a limited number ofinstitutions, it can be helpful to evaluate the routine laboratory tests andtransfusion-related blood bank work in each institution.
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Convalescent plasma therapy has been used to achieve passive immunization against diverse infectious agents by administering pathogen-specific antibodies. Coronavirus disease 19 (COVID-19), which originated in Wuhan, China, has recently become a major concern all over the world. There are no specific treatment recommendations for COVID-19 because of the lack of knowledge and evidence about this virus. Convalescent plasma therapy can be used as an empirical and investigational treatment for COVID-19, and so we briefly describe the main issues related to convalescent plasma therapy from the perspective of transfusion medicine.
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Blood is an essential medical resource for treating diseases and trauma of people, but a limited biological resource for which no artificial production is possible. Therefore, systematic and rational management of its supply and use must be carried out under the national responsibility. On the other hand, the low birthrate and aging population have raised the problem of blood shortages in Korea. To help solve this problem, this study examined proposals for the development of a blood management system in Korea. In addition, the works of blood management bodies were analyzed based on the operation subjects and types of blood projects in the United States, the United Kingdom, France, Germany, the Netherlands, Canada, Australia, Singapore, and Japan. Based on these data, this paper proposes a new organization that can best enhance the specialization of national blood services and strengthen its capacity under the current blood supply system in Korea.