1.Guidelines for Manufacturing and Application of Organoids: Heart
Hyang-Ae LEE ; Dong-Hun WOO ; Do-Sun LIM ; Jisun OH ; C-Yoon KIM ; Ok-Nam BAE ; Sun-Ju AHN
International Journal of Stem Cells 2024;17(2):130-140
Cardiac organoids have emerged as invaluable tools for assessing the impact of diverse substances on heart function.This report introduces guidelines for general requirements for manufacturing cardiac organoids and conducting cardiac organoid-based assays, encompassing protocols, analytical methodologies, and ethical considerations. In the quest to employ recently developed three-dimensional cardiac organoid models as substitutes for animal testing, it becomes imperative to establish robust criteria for evaluating organoid quality and conducting toxicity assessments. This guideline addresses this need, catering to regulatory requirements, and describes common standards for organoid quality and toxicity assessment methodologies, commensurate with current technological capabilities. While acknowledging the dynamic nature of technological progress and the potential for future comparative studies, this guideline serves as a foundational framework. It offers a comprehensive approach to standardized cardiac organoid testing, ensuring scientific rigor, reproducibility, and ethical integrity in investigations of cardiotoxicity, particularly through the utilization of human pluripotent stem cell-derived cardiac organoids.
2.Mortality Burden Due to Short-term Exposure to Fine Particulate Matter in Korea
Jongmin OH ; Youn-Hee LIM ; Changwoo HAN ; Dong-Wook LEE ; Jisun MYUNG ; Yun-Chul HONG ; Soontae KIM ; Hyun-Joo BAE
Journal of Preventive Medicine and Public Health 2024;57(2):185-196
Objectives:
Excess mortality associated with long-term exposure to fine particulate matter (PM2.5) has been documented. However, research on the disease burden following short-term exposure is scarce. We investigated the cause-specific mortality burden of short-term exposure to PM2.5 by considering the potential non-linear concentration–response relationship in Korea.
Methods:
Daily cause-specific mortality rates and PM2.5 exposure levels from 2010 to 2019 were collected for 8 Korean cities and 9 provinces. A generalized additive mixed model was employed to estimate the non-linear relationship between PM2.5 exposure and cause-specific mortality levels. We assumed no detrimental health effects of PM2.5 concentrations below 15 μg/m3. Overall deaths attributable to short-term PM2.5 exposure were estimated by summing the daily numbers of excess deaths associated with ambient PM2.5 exposure.
Results:
Of the 2 749 704 recorded deaths, 2 453 686 (89.2%) were non-accidental, 591 267 (21.5%) were cardiovascular, and 141 066 (5.1%) were respiratory in nature. A non-linear relationship was observed between all-cause mortality and exposure to PM2.5 at lag0, whereas linear associations were evident for cause-specific mortalities. Overall, 10 814 all-cause, 7855 non-accidental, 1642 cardiovascular, and 708 respiratory deaths were attributed to short-term exposure to PM2.5. The estimated number of all-cause excess deaths due to short-term PM2.5 exposure in 2019 was 1039 (95% confidence interval, 604 to 1472).
Conclusions
Our findings indicate an association between short-term PM2.5 exposure and various mortality rates (all-cause, non-accidental, cardiovascular, and respiratory) in Korea over the period from 2010 to 2019. Consequently, action plans should be developed to reduce deaths attributable to short-term exposure to PM2.5.
3.The Ethanolic Extract of Chrysanthemum morifolium Ramat Flower Activates Parasympathomimetic and Anti-inflammatory Effects for Prevention of Presbyopia
Amitesh SHARMA ; Shivani DEVI ; Kartic ; Nattan STALIN ; Jiwon LIM ; Jiwon CHOI ; Jisun KIM ; Mi-Young JEONG ; Sung-Joon LEE ; Tae-Sik PARK
Natural Product Sciences 2024;30(1):20-29
Presbyopia is characterized by a loss of the accommodative ability of the eye that negatively affects vision-aided health-related quality of life. Local inflammation in the eye diminishes parasympathetic cholinergic stimulation and contraction of the iris and ciliary muscle in the eyes via the muscarinic (cholinergic) receptor.Along with the cholinergic agent, a non-steroidal anti-inflammatory agent is often integrated to ameliorate presbyopia. Chrysanthemum morifolium belongs to the Asteraceae. We examined whether Chrysanthemum morifolium flower extract (CME) has parasympathomimetic and anti-inflammatory activity in HLE-B3 human lens epithelial cells and RAW 264.7 macrophages. CME induced time- and dose-dependent production of IP 1 and Ca 2+ accumulation in HLE-B3 cells. In the LPS-induced inflammatory response, CME treatment downregulated inducible nitric oxide synthase (iNOS) and nitric oxide in RAW 264.7 macrophages. CME downregulated the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) with no change in TNF-α levels. In addition, the phosphorylation of JNK and p38 was reduced with no change in ERK by CME in LPS-treated cells. These findings suggest that the parasympathetic and anti-inflammatory efficacy of CME can be applied to develop therapeutics against presbyopia.
4.Forecasting of the COVID-19 pandemic situation of Korea
Taewan GOO ; Catherine APIO ; Gyujin HEO ; Doeun LEE ; Jong Hyeok LEE ; Jisun LIM ; Kyulhee HAN ; Taesung PARK
Genomics & Informatics 2021;19(1):e11-
For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values’ comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.
5.Forecasting of the COVID-19 pandemic situation of Korea
Taewan GOO ; Catherine APIO ; Gyujin HEO ; Doeun LEE ; Jong Hyeok LEE ; Jisun LIM ; Kyulhee HAN ; Taesung PARK
Genomics & Informatics 2021;19(1):e11-
For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values’ comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.
6.Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study
Eun LEE ; Dae Jin SONG ; Woo Kyung KIM ; Dong In SUH ; Hey Sung BAEK ; Meeyong SHIN ; Young YOO ; Jin Tack KIM ; Ji Won KWON ; Gwang Cheon JANG ; Dae Hyun LIM ; Hyeon Jong YANG ; Hwan Soo KIM ; Ju Hee SEO ; Sung Il WOO ; Hyung Young KIM ; Youn Ho SHIN ; Ju Suk LEE ; Jisun YOON ; Sungsu JUNG ; Minkyu HAN ; Eunjin EOM ; Jinho YU
Allergy, Asthma & Immunology Research 2020;12(1):86-98
PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.
Air Filters
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Air Pollution
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Animals
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Asthma
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Child
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Dander
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Dogs
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Education
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Environmental Exposure
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Humans
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Logistic Models
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Odds Ratio
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Ownership
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Risk Factors
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Smoke
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Social Change
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Tobacco
7.A small window into the status of malaria in North Korea: estimation of imported malaria incidence among visitors from South Korea
Jisun SUNG ; Hae-Kwan CHEONG ; Ah-Young LIM ; Jong-Hun KIM
Epidemiology and Health 2020;42(1):e2020068-
OBJECTIVES:
This study aimed to develop hypotheses on trends in malaria incidence in North Korea using malaria incidence among South Korean visitors to North Korea.
METHODS:
The number of South Korean tourists who visited Mount Kumgang from 2000 to 2008 and the number of South Korean employees at the Kaesong Industrial Complex from 2005 to 2015 were obtained from the Korean Statistical Information Service. The number of malaria cases among South Koreans who visited North Korea was obtained from a previous report. The incidence of malaria per 100,000 person-years was calculated using these data and compared with the malaria incidence in North Korea derived from published articles.
RESULTS:
A high incidence of malaria in 2001 and a sharp decline in the following years were observed in both South and North Korean data. Since then, North Korean data showed a relatively low and stable incidence, but the incidence among South Koreans visiting North Korea increased in 2006. Considering the trends in mass primaquine preventive treatment, floods, and economic growth rate, the incidence of malaria may have increased in North Korea in 2006. Since 2009, the incidence of malaria decreased gradually according to both South and North Korean data.
CONCLUSIONS
The trends of malaria incidence in North Korea could be reflected through its incidence among South Koreans who visited North Korea. For future inter-Korean collaboration aiming to eradicate malaria, we propose that a North Korean malaria monitoring system be established applying this method.
8.Religion and Health Behaviors in Primary Care Patients
Mina KANG ; La Young PARK ; Seo Young KANG ; Jisun LIM ; Young Sik KIM
Korean Journal of Family Medicine 2020;41(2):105-110
Background:
Few studies have investigated the association between religion and health behaviors in Korea, where various religions coexist. The present study aimed to investigate the association between religion and health behaviors among primary care patients in Korea.
Methods:
We analyzed data from the Family Cohort Study in Primary Care. Among the 1,040 participants in the cohort, 973 of those who had reported their religion were included in the analysis. Participants completed standardized questionnaires that included religious status and lifestyle factors, such as physical activity, smoking status, drinking status, and dietary habits. The association between religion and health behaviors was analyzed using multivariate logistic regression models.
Results:
Among the 973 participants, 345 (35.5%) were Christian, 153 (15.7%) were Roman Catholic, 308 (31.7%) were Buddhist, and 163 (16.8%) did not have any religion. Compared with those without a religion, the odds ratio (OR) for vigorous physical activity (OR, 1.52; 95% confidence interval [CI], 1.01–2.28) increased, and that for binge drinking (OR, 0.67; 95% CI, 0.46–0.78) and problematic drinking (OR, 0.59; 95% CI, 0.35–0.99) decreased among participants with a religion. Compared with those without a religion, Catholics were more likely to engage in vigorous physical activity (OR, 2.20; 95% CI, 1.31–3.67), whereas Christians were less likely to engage in heavy (OR, 0.50; 95% CI, 0.30–0.84), binge (OR, 0.35; 95% CI, 0.22–0.54), and problematic drinking (OR, 0.46; 95% CI, 0.25–0.86). Smoking, meal regularity, and breakfast consumption were not associated with religion.
Conclusion
The status of drinking and physical activities were different according to religion. As religion is one of the psychosocial characteristics of patients, knowing patients’ religion can be helpful for primary physicians.
9.A small window into the status of malaria in North Korea: estimation of imported malaria incidence among visitors from South Korea
Jisun SUNG ; Hae-Kwan CHEONG ; Ah-Young LIM ; Jong-Hun KIM
Epidemiology and Health 2020;42(1):e2020068-
OBJECTIVES:
This study aimed to develop hypotheses on trends in malaria incidence in North Korea using malaria incidence among South Korean visitors to North Korea.
METHODS:
The number of South Korean tourists who visited Mount Kumgang from 2000 to 2008 and the number of South Korean employees at the Kaesong Industrial Complex from 2005 to 2015 were obtained from the Korean Statistical Information Service. The number of malaria cases among South Koreans who visited North Korea was obtained from a previous report. The incidence of malaria per 100,000 person-years was calculated using these data and compared with the malaria incidence in North Korea derived from published articles.
RESULTS:
A high incidence of malaria in 2001 and a sharp decline in the following years were observed in both South and North Korean data. Since then, North Korean data showed a relatively low and stable incidence, but the incidence among South Koreans visiting North Korea increased in 2006. Considering the trends in mass primaquine preventive treatment, floods, and economic growth rate, the incidence of malaria may have increased in North Korea in 2006. Since 2009, the incidence of malaria decreased gradually according to both South and North Korean data.
CONCLUSIONS
The trends of malaria incidence in North Korea could be reflected through its incidence among South Koreans who visited North Korea. For future inter-Korean collaboration aiming to eradicate malaria, we propose that a North Korean malaria monitoring system be established applying this method.
10.Genetic Alterations in Preinvasive Lung Synchronous Lesions
Soyeon AHN ; Jisun LIM ; Soo Young PARK ; Hyojin KIM ; Hyun Jung KWON ; Yeon Bi HAN ; Choon-Taek LEE ; Sukki CHO ; Jin-Haeng CHUNG
Cancer Research and Treatment 2020;52(4):1120-1134
Purpose:
Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD)
Materials and Methods:
We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing.
Results:
Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions.
Conclusion
Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

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