1.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
2.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
3.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
4.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
5.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
6.Moderators of the Association Between Contact Frequency With Non-Cohabitating Adult Children and Depressive Symptoms Among Community-Dwelling Older Adults
Yujin RHO ; Minji KIM ; Jungeun BEON ; Yeojin KIM ; Sunwoo YOON ; You Jin NAM ; Sunhwa HONG ; Yong Hyuk CHO ; Sang Joon SON ; Chang Hyung HONG ; Hyun Woong ROH
Psychiatry Investigation 2023;20(8):758-767
Objective:
Contact frequency with adult children plays a critical role in late-life depression. However, evidence on possible moderators of this association remains limited. Moreover, considering alterations in contact modes after the coronavirus disease-2019 pandemic, there is a need to investigate this association post-pandemic to develop effective therapeutic interventions.
Methods:
This study included 7,573 older adults who completed the Living Profiles of the Older People Survey in Korea. Participants’ contact frequency and depressive symptoms were analyzed. Regression analysis was performed after adjusting for covariates. The moderating effects of variables were verified using a process macro.
Results:
Multivariable logistic regression analysis revealed that infrequent face-to-face (odd ratio [OR]=1.86, 95% confidence interval [CI]=1.55–2.22) and non-face-to-face contact (OR=1.23, 95% CI=1.04–1.45) in the non-cohabitating adult children group was associated with a higher risk of late-life depression compared to that in the frequent contact group. Linear regression analysis indicated consistent results for face-to-face and non-face-to-face contact (estimate=0.458, standard error [SE]=0.090, p<0.001 and estimate=0.236, SE= 0.074, p=0.001, respectively). Moderation analysis revealed that the association between late-life depression and frequency of face-toface contact was moderated by age, household income quartiles, number of chronic diseases, physical activity frequency, presence of spouse, nutritional status, and whether the effect of frequency of non-face-to-face contact on late-life depression was increased by participation in social activity, frequent physical activity, and good cognitive function (p for interaction<0.05).
Conclusion
Frequent contact with non-cohabitating children lowers the risk of depression later in life. Several variables were identified as significant moderators of contact frequency and depression symptoms.
7.Artificial Intelligence Computer-Assisted Diagnosis for Thyroid Nodules: Comparison of Diagnostic Performance Using Original and Mobile Ultrasonography Images
Sangwoo CHO ; Eunjung LEE ; Hyunju LEE ; Hye Sun LEE ; Jung Hyun YOON ; Vivian Youngjean PARK ; Miribi RHO ; Jiyoung YOON ; Jin Young KWAK
International Journal of Thyroidology 2023;16(1):111-119
Background and Objectives:
This study investigated whether an artificial intelligence computer-assisted diagnosis (AI-CAD) software recently developed in our institution named the Severance Artificial intelligence program (SERA) could show similar diagnostic performance for thyroid cancers using ultrasonographic (US) images from a mobile phone (SERA_M) compared to using images directly downloaded from the pictures archive and communication system (PACS) (SERA_P).
Materials and Methods:
From October 2019 to December 2019, 259 thyroid nodules from 259 patients were included. SERA was run on original and mobile images to evaluate SERA_P and SERA_M. Nodules were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). To compare diagnostic performance, a logistic regression analysis was conducted using the Generalized Estimating Equation. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve, and compared using the Delong Method.
Results:
There were 40 cancers (15.4%) and 219 benign lesions (84.6%). The AUC and sensitivity of SERA_M (0.82 and 85%, respectively) were not statistically different from SERA_P (0.8 and 75%, respectively) (p=0.526 and p=0.091, respectively). The AUC of radiologists (0.856) was not significantly different compared to SERA_P and SERA_M (p=0.163 and p=0.414, respectively). The sensitivity of radiologists (77.5%) was not statistically different compared to SERA_P and SERA_M (p=0.739 and p=0.361, respectively).
Conclusion
AI-CAD software using pictures taken by a mobile phone showed comparable diagnostic performance with the same software using images directly from PACS.
8.Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2
Enkhmend ENKHTAIVAN ; Hyun Ji KIM ; Boram KIM ; Hyung Jung BYUN ; Lu YU ; Tuan Minh NGUYEN ; Thi Ha NGUYEN ; Phuong Anh DO ; Eun Ji KIM ; Kyung Sung KIM ; Hiệu Phùng HUY ; Mostafizur RAHMAN ; Ji Yun JANG ; Seung Bae RHO ; Ho LEE ; Gyeoung Jin KANG ; Mi Kyung PARK ; Nan-Hyung KIM ; Chang Ick CHOI ; Kyeong LEE ; Hyo Kyung HAN ; Jungsook CHO ; Ai Young LEE ; Chang Hoon LEE
Biomolecules & Therapeutics 2022;30(2):203-211
Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.
9.PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase
Gyeoung Jin KANG ; Jung Ho PARK ; Hyun Ji KIM ; Eun Ji KIM ; Boram KIM ; Hyun Jung BYUN ; Lu YU ; Tuan Minh NGUYEN ; Thi Ha NGUYEN ; Kyung Sung KIM ; Hiệu Phùng HUY ; Mostafizur RAHMAN ; Ye Hyeon KIM ; Ji Yun JANG ; Mi Kyung PARK ; Ho LEE ; Chang Ick CHOI ; Kyeong LEE ; Hyo Kyung HAN ; Jungsook CHO ; Seung Bae RHO ; Chang Hoon LEE
Biomolecules & Therapeutics 2022;30(4):340-347
Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.
10.Developing national level high alert medication lists for acute care setting in Korea
Ji Min HAN ; Kyu-Nam HEO ; Ah Young LEE ; Sang il MIN ; Hyun Jee KIM ; Jin-Hee BAEK ; Juhyun RHO ; Sue In KIM ; Ji yeon KIM ; Haewon LEE ; Eunju CHO ; Young-Mi AH ; Ju-Yeun LEE
Korean Journal of Clinical Pharmacy 2022;32(2):116-124
Background:
High-alert medications (HAMs) are medications that bear a heightened risk of causing significant patient harm if used in error. To facilitate safe use of HAMs, identifying specific HAM lists for clinical setting is necessary. We aimed to develop the national level HAM list for acute care setting.
Methods:
We used three-step process. First, we compiled the pre-existing lists referring HAMs. Second, we analyzed medication related incidents reported from national patient safety incident report data and adverse events indicating medication errors from the Korea Adverse Event Reporting System (KAERS).We also surveyed the assistant staffs to support patient safety tasks and pharmacist in charge of medication safety in acute care hospital. From findings from analysis and survey results we created additional candidate list of HAMs. Third, we derived the final list for HAMs in acute care settings through expert panel surveys.
Results:
From pre-existing HAM list, preliminary list consisting of 42 medication class/ingredients was derived. Eight assistant staff to support patient safety tasks and 39 pharmacists in charge of medication safety responded to the survey. Additional 44 medication were listed from national patient safety incident report data, KAERS data and common medications involved in prescribing errors and dispensing errors from survey data. A list of mandatory and optional HAMs consisting of 10 and 6 medication classes, respectively, was developed by consensus of the expert group.
Conclusion
We developed national level HAM list for Korean acute care setting from pre-existing lists, analyzing medication error data, survey and expert panel consensus.

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