1.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.
3.Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center
Kyung Bok LEE ; Ji Sung LEE ; Jeong-Yoon LEE ; Jun Yup KIM ; Han-Yeong JEONG ; Seong-Eun KIM ; Jonguk KIM ; Do Yeon KIM ; Keon-Joo LEE ; Jihoon KANG ; Beom Joon KIM ; Tae Jung KIM ; Sang Joon AN ; Jang-Hyun BAEK ; Seongheon KIM ; Hyun-Wook NAH ; Jong Yun LEE, ; Jee-Hyun KWON ; Seong Hwan AHN ; Keun-Hwa JUNG ; Hee-Kwon PARK ; Tai Hwan PARK ; Jong-Moo PARK ; Yong-Jin CHO ; Im Seok KOH ; Soo Joo LEE ; Jae-Kwan CHA ; Joung-Ho RHA ; Juneyoung LEE ; Boung Chul LEE ; In Ok BAE ; Gui Ok KIM ; Hee-Joon BAE
Journal of the Korean Neurological Association 2023;41(1):18-30
Background:
Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas.
Methods:
This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis.
Results:
In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively).
Conclusions
There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.
4.Promising Therapeutic Effectsof Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms
Hanna LEE ; Ok-Yi JEONG ; Hee Jin PARK ; Sung-Lim LEE ; Eun-yeong BOK ; Mingyo KIM ; Young Sun SUH ; Yun-Hong CHEON ; Hyun-Ok KIM ; Suhee KIM ; Sung Hak CHUN ; Jung Min PARK ; Young Jin LEE ; Sang-Il LEE
Immune Network 2023;23(6):e45-
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.
5.Annual Case Volume and One-Year Mortality for Endovascular Treatment in Acute Ischemic Stroke
Jun Yup KIM ; Jihoon KANG ; Beom Joon KIM ; Seong-Eun KIM ; Do Yeon SEONG-EUN ; Keon-Joo LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyung Bok LEE ; Jae-Kwan CHA ; Ji Sung LEE ; Juneyoung LEE ; Ki Hwa YANG ; Ock Ran HONG ; Ji Hyeon SHIN ; Jung Hyun PARK ; Philip B. GORELICK ; Hee-Joon BAE
Journal of Korean Medical Science 2022;37(36):e270-
Background:
The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context.
Methods:
National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data.
Results:
We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis.
Conclusion
Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.
6.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
7.Effects of smart-care services program for breast cancer survivors
Bok Yae CHUNG ; Sung Jung HONG
Journal of Korean Academic Society of Nursing Education 2021;27(2):95-106
Purpose:
The purpose of this study was to examine the effects of a smart-care services program for breast cancer survivors on cognitive function and physical health.
Methods:
A quasi-experimental control group pretest posttest design was used. Subjects were recruited in D city, and data were collected from July 2017 to February 2018. The experimental group (n=24) participated in the smart-care services program, whereas the control group (n=26) received conventional management. The smart-care services program consisted of addressing cognitive function problems arising from chemotherapy, diet, exercise, headeck massage and self-monitoring using smartphone applications and smart bands. All participants underwent assessments at baseline, at 6 weeks, and at 12 weeks. Data were analyzed using descriptive statistics (frequency, percentage, mean and standard deviation), a chi-squared test, t-test, and repeated measures ANOVA.
Results:
After the smart-care services program, significant differences were found between the groups in cognitive function (F=18.91, p<.001) and sleep time (F=9.25, p<.001). No significant differences were found between the groups in caloric consumption after the program.
Conclusion
The smart-care services program significantly improved the level of cognitive function and sleep time for breast cancer survivors. The use of this smart-care services program for breast cancer survivors might be an effective nursing intervention tool for improving cognitive function and health behaviors.
8.Effects of Contrast Phases on Automated Measurements of Muscle Quantity and Quality Using CT
Dong Wook KIM ; Kyung Won KIM ; Yousun KO ; Taeyong PARK ; Jeongjin LEE ; Jung Bok LEE ; Jiyeon HA ; Hyemin AHN ; Yu Sub SUNG ; Hong-Kyu KIM
Korean Journal of Radiology 2021;22(11):1909-1917
Objective:
Muscle quantity and quality can be measured with an automated system on CT. However, the effects of contrast phases on the muscle measurements have not been established, which we aimed to investigate in this study.
Materials and Methods:
Muscle quantity was measured according to the skeletal muscle area (SMA) measured by a convolutional neural network-based automated system at the L3 level in 89 subjects undergoing multiphasic abdominal CT comprising unenhanced phase, arterial phase, portal venous phase (PVP), or delayed phase imaging. Muscle quality was analyzed using the mean muscle density and the muscle quality map, which comprises normal and low-attenuation muscle areas (NAMA and LAMA, respectively) based on the muscle attenuation threshold. The SMA, mean muscle density, NAMA, and LAMA were compared between PVP and other phases using paired t tests. Bland-Altman analysis was used to evaluate the inter-phase variability between PVP and other phases. Based on the cutoffs for low muscle quantity and quality, the counts of individuals who scored lower than the cutoff values were compared between PVP and other phases.
Results:
All indices showed significant differences between PVP and other phases (p < 0.001 for all). The SMA, mean muscle density, and NAMA increased during the later phases, whereas LAMA decreased during the later phases. Bland-Altman analysis showed that the mean differences between PVP and other phases ranged -2.1 to 0.3 cm2 for SMA, -12.0 to 2.6 cm2 for NAMA, and -2.2 to 9.9 cm2 for LAMA.The number of patients who were categorized as low muscle quantity did not significant differ between PVP and other phases (p ≥ 0.5), whereas the number of patients with low muscle quality significantly differed (p ≤ 0.002).
Conclusion
SMA was less affected by the contrast phases. However, the muscle quality measurements changed with the contrast phases to greater extents and would require a standardization of the contrast phase for reliable measurement.
9.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
10.Effects of smart-care services program for breast cancer survivors
Bok Yae CHUNG ; Sung Jung HONG
Journal of Korean Academic Society of Nursing Education 2021;27(2):95-106
Purpose:
The purpose of this study was to examine the effects of a smart-care services program for breast cancer survivors on cognitive function and physical health.
Methods:
A quasi-experimental control group pretest posttest design was used. Subjects were recruited in D city, and data were collected from July 2017 to February 2018. The experimental group (n=24) participated in the smart-care services program, whereas the control group (n=26) received conventional management. The smart-care services program consisted of addressing cognitive function problems arising from chemotherapy, diet, exercise, headeck massage and self-monitoring using smartphone applications and smart bands. All participants underwent assessments at baseline, at 6 weeks, and at 12 weeks. Data were analyzed using descriptive statistics (frequency, percentage, mean and standard deviation), a chi-squared test, t-test, and repeated measures ANOVA.
Results:
After the smart-care services program, significant differences were found between the groups in cognitive function (F=18.91, p<.001) and sleep time (F=9.25, p<.001). No significant differences were found between the groups in caloric consumption after the program.
Conclusion
The smart-care services program significantly improved the level of cognitive function and sleep time for breast cancer survivors. The use of this smart-care services program for breast cancer survivors might be an effective nursing intervention tool for improving cognitive function and health behaviors.

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