Publications by authors named "Sungjin Park"

172 Publications

Leaderboard Design Principles to Enhance Learning and Motivation in a Gamified Educational Environment: Development Study.

JMIR Serious Games 2021 Apr 20;9(2):e14746. Epub 2021 Apr 20.

Department of Industrial Engineering, Kangwon National University, Chuncheon, Republic of Korea.

Background: Gamification in education enhances learners' motivation, problem-solving abilities, decision-making abilities, and social skills such as communication. Numerous ongoing studies are examining the application of gamification design methodology and game mechanics to a learning environment. Leaderboards are a type of game mechanic that assist learners in goal setting and unleash the motivation for learning.

Objective: The aim of this study was to develop leaderboard design principles to assist learners in efficient goal setting, improve learning motivation, and promote learning in gamified learning environments.

Methods: This study implemented 2 different strategies. First, we analyzed previous research on leaderboards that focus on educational efficacy and influence on social interactions. Second, we collected and analyzed data related to cases of leaderboards being used in educational and sport environments.

Results: This study determined 4 leaderboard design objectives from previous studies. Based on these objectives, we developed 3 leaderboard design principles. First, macro leaderboards and micro leaderboards should be designed and used together. Second, all the elements used to measure learners' achievements in an educational environment should be incorporated into the micro leaderboard. Third, leaderboards should be designed and considered for application in contexts other than learning environments. This study further analyzes best practices considering the 3 leaderboard design principles.

Conclusions: This study contributes toward resolving problems associated with leaderboard design for the application of gamification in educational environments. Based upon our results, we strongly suggest that when teachers consider applying gamification in classrooms, the leaderboard design principles suggested in this research should be incorporated.
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http://dx.doi.org/10.2196/14746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097522PMC
April 2021

Associations Between General Perceptions of COVID-19 and Posttraumatic Stress Disorder in Korean Hospital Workers: Effect Modification by Previous Middle East Respiratory Syndrome Coronavirus Experience and Occupational Type.

J Prev Med Public Health 2021 Mar 19;54(2):86-95. Epub 2021 Jan 19.

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.

Objectives: This study investigated associations between perceptions of coronavirus disease 2019 (COVID-19) and the prevalence of posttraumatic stress disorder (PTSD) in workers at hospitals designated to treat COVID-19, as well as the difference in the magnitude of these associations by occupational type and previous Middle East respiratory syndrome coronavirus (MERS-CoV) experience.

Methods: The participants were workers at hospitals designated to treat COVID-19 who completed a questionnaire about their perceptions related to COVID-19, work experience during the previous MERS-CoV outbreak, and symptoms of PTSD ascertained by the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders. Participants' characteristics were compared using the chi-square test. Multivariable logistic regression was performed to evaluate the associations between perceptions and the prevalence of PTSD, stratified by occupational type and previous MERS-CoV experience.

Results: Non-medical personnel showed stronger associations with PTSD than medical personnel according to general fear (odds ratio [OR], 6.67; 95% confidence interval [CI], 1.92 to 23.20), shortages of supplies (OR, 1.29; 95% CI, 1.07 to 1.56), and issue-specific fear (OR, 1.29; 95% CI, 1.05 to 1.59). Those with prior MERS-CoV quarantine experience were more prone to PTSD than those without such experience in terms of general fear (OR, 1.70; 95% CI, 1.22 to 2.37), shortages of supplies (OR, 1.24; 95% CI, 1.10 to 1.40), and issue-specific fear (OR, 1.21; 95% CI, 1.06 to 1.38).

Conclusions: During the COVID-19 pandemic, non-medical personnel tended to have higher odds of being categorized as having PTSD. Workers with prior MERS-CoV experience were more susceptible than those without such experience. These findings suggest the need for timely interventions to manage human resources for a sustainable quarantine system.
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http://dx.doi.org/10.3961/jpmph.20.540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046607PMC
March 2021

A temperature-sensitive FERONIA mutant allele that alters root hair growth.

Plant Physiol 2021 Mar;185(2):405-423

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.

In plants, root hairs undergo a highly polarized form of cell expansion called tip-growth, in which cell wall deposition is restricted to the root hair apex. In order to identify essential cellular components that might have been missed in earlier genetic screens, we identified conditional temperature-sensitive (ts) root hair mutants by ethyl methanesulfonate mutagenesis in Arabidopsis thaliana. Here, we describe one of these mutants, feronia-temperature sensitive (fer-ts). Mutant fer-ts seedlings were unaffected at normal temperatures (20°C), but failed to form root hairs at elevated temperatures (30°C). Map based-cloning and whole-genome sequencing revealed that fer-ts resulted from a G41S substitution in the extracellular domain of FERONIA (FER). A functional fluorescent fusion of FER containing the fer-ts mutation localized to plasma membranes, but was subject to enhanced protein turnover at elevated temperatures. While tip-growth was rapidly inhibited by addition of rapid alkalinization factor 1 (RALF1) peptides in both wild-type and fer-ts mutants at normal temperatures, root elongation of fer-ts seedlings was resistant to added RALF1 peptide at elevated temperatures. Additionally, at elevated temperatures fer-ts seedlings displayed altered reactive oxygen species (ROS) accumulation upon auxin treatment and phenocopied constitutive fer mutant responses to a variety of plant hormone treatments. Molecular modeling and sequence comparison with other Catharanthus roseus receptor-like kinase 1L (CrRLK1L) receptor family members revealed that the mutated glycine in fer-ts is highly conserved, but is not located within the recently characterized RALF23 and LORELI-LIKE-GLYCOPROTEIN 2 binding domains, perhaps suggesting that fer-ts phenotypes may not be directly due to loss of binding to RALF1 peptides.
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http://dx.doi.org/10.1093/plphys/kiaa051DOI Listing
March 2021

Trajectories of objectively measured physical activity and mood states in older Japanese adults: longitudinal data from the Nakanojo Study.

Biopsychosoc Med 2021 Feb 23;15(1). Epub 2021 Feb 23.

Exercise Sciences Research Group, Tokyo Metropolitan Institute of Gerontology, 35-1 Sakecho, Itabashi-ku, Tokyo, Japan.

Background: Japan, like many developed countries, now faces fiscal problems from the escalating health-care expenditures associated with an aging population. Mental health problems such as depression contribute as much to these growing demands as physical disease, and measures to prevent depression are important to controlling costs. There are few longitudinal studies examining the relation between objectively measured physical activity and depressive symptoms. Therefore, the aims of our study were to explore the patterns of change of physical activity in older Japanese adults for 5 years through the use of trajectory analysis and to examine the relation between physical activity trajectories and depressive mood states.

Main Body: Ninety-two male and 99 female volunteers aged 65-85 years were asked to equip themselves with an electronic accelerometer with a 60-day storage capacity for at least 5 years. The parameters calculated each July for the 5 years were the average daily step count and the average daily duration of activity > 3 METs (moderate to vigorous physical activity: MVPA). Hospital Anxiety and Depression Scale (HADS) assessed corresponding mood states (HADS-A and HADS-D). Trajectories of the accelerometer data were analyzed and fifth-year HADS-D and HADS-A scores were compared among trajectory groups using an analysis of covariance (ANCOVA) that controlled for baseline scores and for baseline scores and age. Six and five distinct trajectories were identified for daily step count and for daily duration of MVPA, respectively. Using ANCOVA controlling for baseline scores, HADS-D scores differed significantly among trajectory groups classed by daily duration of MVPA (p = 0.04), and Tukey's multiple comparison tests showed significant differences between group 2, whose pattern was stable with the middle duration of MVPA, and group 1, whose pattern was stable with the lowest duration of MVPA (p = 0.02), while the results were not significant controlling for both baseline scores and age.

Conclusions: Older people with less MVPA continued to do less MVPA over the 5 years of study, which may be related to a future more depressive mood. Further clinical studies will be necessary to clarify these findings.
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http://dx.doi.org/10.1186/s13030-021-00207-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903728PMC
February 2021

Acid-activated carbon nitrides as photocatalysts for degrading organic pollutants under visible light.

Chemosphere 2021 Jun 23;273:129731. Epub 2021 Jan 23.

Department of Chemistry and Chemical Engineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea. Electronic address:

Three-dimensional (3D) carbon nitride (CN) can be used as a promising platform for visible-light-active photocatalysts because of its suitable band positions. This study reports that HNO activation improves the photocatalytic activity of 3D melamine-derived CN (MCN) materials, which degrade the organic pollutant rhodamine B (RhB). HNO treatment under reflux removes the carbonaceous impurities in MCN and introduces oxygen-containing functional groups on its surface. Under visible light irradiation, the nitric acid treated MCN (NT-MCN) completely degrades RhB within 30 min. Photophysical characterizations and control experiments with radical scavengers reveal that MCN and NT-MCN follow different reaction mechanisms. Because NT-MCN exhibits a longer photoluminescence lifetime, smaller electrochemical resistance, and larger photocurrent than those of MCN, it enables a better transfer of charge carriers during the catalytic reaction.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129731DOI Listing
June 2021

Strategies for Manipulating Phonon Transport in Solids.

ACS Nano 2021 Feb 28;15(2):2182-2196. Epub 2021 Jan 28.

School of Mechanical Engineering, Yonsei University, Seoul 03722, Korea.

In this review, we summarize the recent efforts on manipulating phonon transport in solids by using specific techniques that modify their phonon thermal conductivity (, specific heat, phonon group velocity, and mean free path) and phonon thermal conductance (, transmission probability and density of states). The strategies discussed for tuning thermal conductivity are as follows: large unit cell approach and liquid-like conduction for maneuvering specific heat; rattler, mini-bandgap, and phonon confinement for manipulating phonon group velocity; nanoparticles, nanosized grains, coated grains, alloy (isotope) scattering, selection rules in phonon dispersion, Grüneisen parameter, lone-pair electronics, dynamic disorder, and local static distortion for restricting mean free path. We have also included the discussion on tuning phonon thermal conductance, as thermal conduction can be viewed as a transmission process. Additionally, phonon filtering, ballistic transport, and waveguiding are discussed to alter density of states and transmission probability. We hope this review can bring meaningful insights to the researchers in the field of phonon transport in solids.
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http://dx.doi.org/10.1021/acsnano.0c10411DOI Listing
February 2021

Alpha-Methylacyl-CoA Racemase (AMACR), a Potential New Biomarker for Glioblastoma.

Front Oncol 2020 13;10:550673. Epub 2020 Oct 13.

Department of Pharmacology, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, South Korea.

Alpha-Methylacyl-CoA racemase (AMACR), which was initially discovered as a prostate cancer marker, is critical for the chiral inversion mechanism of branched-chain fatty acids. However, the function of AMACR in brain tumors has not been investigated. In this study, AMACR appeared to be involved in glioblastoma. The protein and mRNA levels of AMACR were highly elevated in glioblastoma. Downregulation of AMACR inhibited cell proliferation. Comprehensive analysis of the public REMBRANDT GBM dataset also confirmed that the level of AMACR expression was correlated with the clinical prognosis of glioma patients. In summary, these findings indicate that AMACR expression is increased in a glioblastoma cell line and glioma patients, suggesting that AMACR might be a potential diagnostic marker and therapeutic target for cancer, including glioma.
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http://dx.doi.org/10.3389/fonc.2020.550673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590573PMC
October 2020

Precarious Employment as Compared With Unemployment Reduces the Risk of Depression in the Elderly in Korea.

J Occup Environ Med 2020 10;62(10):e559-e566

Department of Occupational and Environmental Medicine, Cheonan Medical Center, Cheonan (Dr Park); Department of Occupational and Environmental Medicine, The Catholic University College of Medicine (Dr Kang); Department of Occupational and Environmental Medicine, Soonchunhyang University College of Medicine (Dr Lee), Seoul, Republic of Korea.

Objective: To compare how depression develops in precarious employment and in unemployment, as how precarious jobs impact unemployment-related depression is relatively unknown.

Methods: Using the 1st to 4th Korean Longitudinal Study of Aging survey data, 5638 older people were analyzed to measure depression incidence in relation to employment status. A Center for Epidemiological Studies-Depression Scale form was chosen to identify depression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from Cox proportional hazards models adjusted for a number of variables.

Results: Unemployment-related depression risk was significantly higher than for precarious employment. Depression risk was significantly lower for male full-time permanent workers than precarious workers, but was not significantly different in women.

Conclusions: To prevent the deterioration of mental health in the elderly, an extensive job promotion campaign including precarious work is required.
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http://dx.doi.org/10.1097/JOM.0000000000001981DOI Listing
October 2020

The negative impact of long working hours on mental health in young Korean workers.

PLoS One 2020 4;15(8):e0236931. Epub 2020 Aug 4.

Division of Cardiology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea.

Long working hours are known to have a negative effect on health. However, there is no clear evidence for a direct link between mental health and long working hours in the young adult populations. Therefore, we aimed to determine whether long working hours are associated with mental health in young adult workers. Data were collected from a 2012 follow-up survey of the Youth Panel 2007. A total of 3,332 young adult employees (aged 20 to 35) were enrolled in the study. We analyzed stress, depression, and suicidal thoughts by multivariate logistic regression analysis based on working hours (41 to 50, 51 to 60 and over 60 hours, compared to 31 to 40 hours per week), which was adjusted for sex, age, marriage status, region, and educational level. From the 3,332 young adult employees, about 60% of the workers worked more than 40 hours and 17% of the workers worked more than 50 hours per week. In a Chi-square test, stress level, depression, and suicidal thoughts increased with increasing working hours (p-value <0.001, 0.007, and 0.018, respectively). The multivariate logistic regression model showed that, compared to the 31 to 40 hours per week group, the adjusted odds ratios of the 41 to 50, 51 to 60, and over 60 hours per week groups for stress were 1.46(1.23-1.74), 2.25(1.79-2.83) and 2.55(1.72-3.77), respectively. A similar trend was shown in depression [odds ratios: 2.08(1.23-3.53), 2.79(1.44-5.39) and 4.09(1.59-10.55), respectively] and suicidal ideation [odds ratios: 1.98(0.95-4.10), 3.48(1.48-8.19) and 5.30(1.61-17.42), respectively]. We concluded that long working hours were associated with stress, depression, and suicidal ideation in young employees, aged 20 to 35.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236931PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402483PMC
October 2020

Yin Yang 1 is required for PHD finger protein 20-mediated myogenic differentiation in vitro and in vivo.

Cell Death Differ 2020 12 18;27(12):3321-3336. Epub 2020 Jun 18.

Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015, South Korea.

The development of skeletal muscle requires progression of a highly ordered cascade of events comprising myogenic lineage commitment, myoblast proliferation, and terminal differentiation. The process of myogenesis is controlled by several myogenic transcription factors that act as terminal effectors of signaling cascades and produce appropriate developmental stage-specific transcripts. PHD finger protein 20 (PHF20) is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53, but its function is unclear. Notably, it has been reported that PHF20 knockout mice die shortly after birth and display a wide variety of phenotypes within the skeletal and hematopoietic systems. Therefore, the putative role of PHF20 in myogenic differentiation was further investigated. In the present study, we found that protein and mRNA expression levels of PHF20 were decreased during myogenic differentiation in CC cells. At the same time, Yin Yang 1 (YY1) was also decreased during myogenic differentiation. PHF20 overexpression increased YY1 expression during myogenic differentiation, together with a delay in MyoD expression. PHF20 expression enhanced the transcriptional activity of YY1 while shRNA-mediated depletion of PHF20 resulted in the reduction of YY1 promoter activity in CC cells. In addition, PHF20 directly bounds to the YY1 promoter in CC cells. In a similar manner, YY1 expression was elevated while myosin heavy chain expression was decreased in PHF20 transgenic (TG) mice. Histological analysis revealed abnormalities in the shape and length of muscles in PHF20-TG mice. Furthermore, PHF20-TG muscles slowly regenerated after cardiotoxin injection, indicating that PHF20 affected muscle differentiation and regeneration after injury in vivo. Taken together, these results suggested that PHF20 plays an important role in myogenic differentiation by regulating YY1.
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http://dx.doi.org/10.1038/s41418-020-0580-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853144PMC
December 2020

The N-terminal zinc finger of CELLULOSE SYNTHASE6 is critical in defining its functional properties by determining the level of homodimerization in Arabidopsis.

Plant J 2020 08 1;103(5):1826-1838. Epub 2020 Jul 1.

Department of Plant Biology, Michigan State University, 612 Wilson Road, East Lansing, MI, 48824, USA.

Primary cell wall cellulose is synthesized by the cellulose synthase complex (CSC) containing CELLULOSE SYNTHASE1 (CESA1), CESA3 and one of four CESA6-like proteins in Arabidopsis. It has been proposed that the CESA6-like proteins occupy the same position in the CSC, but their underlying selection mechanism remains unclear. We produced a chimeric CESA5 by replacing its N-terminal zinc finger with its CESA6 counterpart to investigate the consequences for its homodimerization, a crucial step in forming higher-order structures during assembly of the CSC. We found that the mutant phenotypes of prc1-1, a cesa6 null mutant, were rescued by the chimeric CESA5, and became comparable to the wild type (WT) and prc1-1 complemented by WT CESA6 in regard to plant growth, cellulose content, cellulose microfibril organization, CSC dynamics and subcellular localization. Bimolecular fluorescence complementation assays were employed to evaluate pairwise interactions between the N-terminal regions of CESA1, CESA3, CESA5, CESA6 and the chimeric CESA5. We verified that the chimeric CESA5 explicitly interacted with all the other CESA partners, comparable to CESA6, whereas interaction between CESA5 with itself was significantly weaker than that of all other CESA pairs. Our findings suggest that the homodimerization of CESA6 through its N-terminal zinc finger is critical in defining its functional properties, and possibly determines its intrinsic roles in facilitating higher-order structures in CSCs.
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http://dx.doi.org/10.1111/tpj.14870DOI Listing
August 2020

FCHO1 peptide, a PKB kinase motif, inhibits tumor progression.

Biochem Biophys Res Commun 2020 07 4;528(3):478-484. Epub 2020 Jun 4.

Department of Pharmacology, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, 35015, South Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, South Korea. Electronic address:

Background: Cell division is regulated by protein kinase B (PKB)-mediated FCH domain only 1 (FCHO1) phosphorylation.

Methods: FCHO1, a synthetic water-soluble peptide, was generated from the PKB substrate motif PPRRLRSRKVSC found in the human FCHO1 protein.

Results: In this study, we found that in vitro FCHO1 inhibits cell proliferation via PKB/ERK/SMAD4 pathways in K-mutated A549 lung cancer cells. In addition, FCHO1, at effective doses of 15 and 30 mg/kg, significantly suppressed tumor growth and decreased the size and weight of tumors in A549-xenograft mice.

Conclusion: These results suggest that the FCHO1 peptide could be a potential therapy for lung cancer.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.173DOI Listing
July 2020

Increased risk of atherosclerosis associated with pesticide exposure in rural areas in Korea.

PLoS One 2020 1;15(5):e0232531. Epub 2020 May 1.

Institute of Genomic Cohort, Wonju College of Medicine, Yonsei University, Wonju, Korea.

Atherosclerosis is a progressive inflammation in systemic vessels, and pesticide exposure has been emerging as its risk factor. This cross-sectional study investigated the association between pesticide exposure and the risk of atherosclerosis in a rural population in Korea using carotid intima-media thickness (CIMT). This study used dataset from the baseline survey of the Korea Farmers Cohort Study between November 2005 and January 2008, and the final analysis included 477 participants. Well-structured questionnaires were used to estimate pesticide exposure. CIMT ≥ 0.9 mm was established for carotid atherosclerosis. Multiple logistic regression analyses were undertaken to evaluate the association between pesticide exposure and atherosclerosis, adjusting demographic and health-related confounders. Even after adjustments, the increased risk of atherosclerosis was significantly associated with pesticide exposure, such as a lifetime history of farming (odds ratio [OR] 3.25 95% confidence interval [CI] 1.51-6.98), a history of using pesticide (OR 3.42 95% CI 1.63-7.16), using pesticide 10 times or more annually (OR 2.55 95% CI 1.21-5.39), and higher cumulative exposure index level (OR 3.63 95% CI 1.65-7.97). Further prospective studies are required to elucidate effects of pesticide exposure on the risk of atherosclerosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232531PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194402PMC
July 2020

Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death.

Toxicol Res 2020 Apr 7;36(2):123-130. Epub 2020 Feb 7.

5Department of Neurosurgery, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, 35015 Korea.

Lung cancer is the most common cause of cancer-associated death worldwide. Most patients with non-small cell lung cancer die within several years of the initial diagnosis, and new therapies are desperately needed. Transmembrane protein (TMEM) 39AS41, a synthetic peptide, was generated from the protein kinase B substrate motif GLRNRNGSAIGLPVP found in the human TMEM39A protein. Myristic acid was conjugated to the N-terminus of the peptide to confer cell permeability. In this study, we found that in vitro TMEM39AS41 peptide led to cell death via inhibition of inflammation/autophagy pathways in KRAS-mutated cell and tissues. In addition, TMEM39A, at a dose of 30 mg/kg, significantly suppressed tumor growth in KRAS non-small cell lung cancer mice. These results suggest that the TMEM39AS41 peptide could have therapeutic potential for lung cancer.
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http://dx.doi.org/10.1007/s43188-020-00038-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099121PMC
April 2020

HER2 as a potential biomarker of lymph node metastasis in undifferentiated early gastric cancer.

Sci Rep 2020 03 24;10(1):5270. Epub 2020 Mar 24.

Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Republic of Korea.

Human epidermal growth factor receptor 2 (HER2) is implicated in several cancers, including gastric cancer. However, limited data are available regarding its clinical significance in early gastric cancer (EGC). We evaluated the clinical significance of HER2 overexpression in patients with EGC. We retrospectively reviewed 727 patients who underwent surgical treatment for EGC between October 2010 and August 2017. HER2 expression was analysed in 680 EGC cases by immunohistochemistry and classified as negative (0 and 1+), equivocal (2+), or positive [overexpression (3+)]. Among patients with differentiated EGC, the number of patients with HER2 overexpression was not significantly different from that of HER2-negative patients in terms of age, sex, tumour size, location, gross type, depth of invasion, presence of lymphovascular invasion (LVI), and presence of lymph node metastasis (LNM). However, in patients with undifferentiated EGC, HER2 overexpression was significantly correlated with LVI and presence of LNM compared with HER2-negative patients. Multivariate analysis indicated HER2 overexpression as a good predictive marker of LNM in patients with undifferentiated EGC. HER2 expression is associated with LNM in undifferentiated EGC. Therefore, the importance of HER2 overexpression in EGC should not be overlooked, and further studies are needed to identify its clinical significance.
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http://dx.doi.org/10.1038/s41598-020-61567-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093413PMC
March 2020

Rational design of small molecule RHOA inhibitors for gastric cancer.

Pharmacogenomics J 2020 08 4;20(4):601-612. Epub 2020 Feb 4.

Department of Biomedical Science, Hanyang Biomedical Research Institute, Hanyang University, Seoul, 04763, Korea.

Previously, we identified Ras homologous A (RHOA) as a major signaling hub in gastric cancer (GC), the third most common cause of cancer death in the world, prompting us to rationally design an efficacious inhibitor of this oncogenic GTPase. Here, based on that previous work, we extend those computational analyses to further pharmacologically optimize anti-RHOA hydrazide derivatives for greater anti-GC potency. Two of these, JK-136 and JK-139, potently inhibited cell viability and migration/invasion of GC cell lines, and mouse xenografts, diversely expressing RHOA. Moreover, JK-136's binding affinity for RHOA was >140-fold greater than Rhosin, a nonclinical RHOA inhibitor. Network analysis of JK-136/-139 vs. Rhosin treatments indicated downregulation of the sphingosine-1-phosphate, as an emerging cancer metabolic pathway in cell migration and motility. We assert that identifying and targeting oncogenic signaling hubs, such as RHOA, represents an emerging strategy for the design, characterization, and translation of new antineoplastics, against gastric and other cancers.
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http://dx.doi.org/10.1038/s41397-020-0153-6DOI Listing
August 2020

The profiles of microRNAs from urinary extracellular vesicles (EVs) prepared by various isolation methods and their correlation with serum EV microRNAs.

Diabetes Res Clin Pract 2020 Feb 24;160:108010. Epub 2020 Jan 24.

Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; Department of Internal Medicine, Gachon University College of Medicine, Incheon, Republic of Korea; Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, Republic of Korea. Electronic address:

Aims: MicroRNAs (miRNAs) that circulate in biological fluids are frequently enclosed in extracellular vesicles (EVs). However, urinary EVs and their cargo miRNAs have not been systematically studied according to their EV isolation methods.

Methods: In type 2 diabetes mellitus persons with diabetic nephropathy (n = 4), we compared miRNA species in urine EVs prepared by ultracentrifugation (UC), qEV original size exclusion column (qEV), ExoQuick-TC Plus (ExoQuick), and ultrafiltration using Amicon Ultra centrifugal filter devices (Amicons) 10 K and 100 K. EV miRNAs were profiled by next-generation sequencing (NGS). Additionally, we evaluated the correlations of EV miRNA expression between the urine and serum samples isolated by UC.

Results: From each of 100 ml of urine, the UC method yielded the highest number of EV miRNA species (233 ± 37.3), with the ExoQuick yielded the lowest (103 ± 17.4). Urine EV miRNA profiles were highly correlated between UC, qEV, ExoQuick and Amicon 10 K methods. EV miRNA profiles between the urine and serum samples showed variable correlations between the patients (paired sample number = 3, r = 0.39-0.72).

Conclusions: UC, qEV, ExoQuick, and Amicon 10 K are acceptable for urinary EV isolation to profile miRNAs. Urine- and serum-derived EV miRNA profiles have variable correlations depending on specific patients.
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http://dx.doi.org/10.1016/j.diabres.2020.108010DOI Listing
February 2020

Retina-Inspired Carbon Nitride-Based Photonic Synapses for Selective Detection of UV Light.

Adv Mater 2020 Mar 27;32(11):e1906899. Epub 2020 Jan 27.

Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

Photonic synapses combine sensing and processing in a single device, so they are promising candidates to emulate visual perception of a biological retina. However, photonic synapses with wavelength selectivity, which is a key property for visual perception, have not been developed so far. Herein, organic photonic synapses that selectively detect UV rays and process various optical stimuli are presented. The photonic synapses use carbon nitride (C N ) as an UV-responsive floating-gate layer in transistor geometry. C N nanodots dominantly absorb UV light; this trait is the basis of UV selectivity in these photonic synapses. The presented devices consume only 18.06 fJ per synaptic event, which is comparable to the energy consumption of biological synapses. Furthermore, in situ modulation of exposure to UV light is demonstrated by integrating the devices with UV transmittance modulators. These smart systems can be further developed to combine detection and dose-calculation to determine how and when to decrease UV transmittance for preventive health care.
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http://dx.doi.org/10.1002/adma.201906899DOI Listing
March 2020

GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα.

Development 2020 01 23;147(2). Epub 2020 Jan 23.

The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe Street, PCTB 1004, Baltimore, MD 21205, USA

Oligodendrocyte development is tightly controlled by extrinsic signals; however, mechanisms that modulate cellular responses to these factors remain unclear. Six-transmembrane glycerophosphodiester phosphodiesterases (GDEs) are emerging as central regulators of cellular differentiation via their ability to shed glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface. We show here that GDE3 controls the pace of oligodendrocyte generation by negatively regulating oligodendrocyte precursor cell (OPC) proliferation. GDE3 inhibits OPC proliferation by stimulating ciliary neurotrophic factor (CNTF)-mediated signaling through release of CNTFRα, the ligand-binding component of the CNTF-receptor multiprotein complex, which can function as a soluble factor to activate CNTF signaling. GDE3 releases soluble CNTFRα by GPI-anchor cleavage from the plasma membrane and from extracellular vesicles (EVs) after co-recruitment of CNTFRα in EVs. These studies uncover new physiological roles for GDE3 in gliogenesis and identify GDE3 as a key regulator of CNTF-dependent regulation of OPC proliferation through release of CNTFRα.
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http://dx.doi.org/10.1242/dev.180695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983723PMC
January 2020

The Effects of Workplace Rest Breaks on Health Problems Related to Long Working Hours and Shift Work among Male Apartment Janitors in Korea.

Saf Health Work 2019 Dec 6;10(4):512-517. Epub 2019 Nov 6.

Department of Occupational and Environmental Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.

Background: Rest breaks at work are reported to reduce fatigue and job stress. Apartment janitors in Korea who perform night shift work and work long hours can be exposed to various health problems (HPs). However, few studies have evaluated relationships between their rest breaks and HPs. This study was conducted to examine the relationships between long working hours, shift work, and insufficient rest breaks and HPs among Korean apartment janitors.

Methods: Data on 1,212 selected male apartment janitors were obtained from the 3rd and 4th Korean Working Conditions Surveys. Demographic and occupational characteristics were collected using self-reported questionnaires. Rest breaks at work were classified as "sufficient" or "insufficient." Long working hours were considered as working more than 60 hours per week. Zero-inflated negative binomial (ZINB) regression was performed to investigate the effects of shift work and long working hours on HPs and the effects of rest breaks on relationships between HPs and long working hours and shift work.

Results: Among those with insufficient rest breaks at work, significant associations were found between long working hours and the risk of HPs [odds ratio (OR) = 1.489; 95% confidence interval (CI) = 1.038-2.136] and work-related HPs (WRHPs) [OR 1.621; 95% CI = 1.156-2.272], and between shift work and HPs [OR = 1.603; 95% CI = 1.084-2.372]. These relationships became nonsignificant when sufficient rest breaks were provided.

Conclusion: It is important to provide breaks at work to reduce HPs because of long working hours and shift work among aged workers such as apartment janitors.
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http://dx.doi.org/10.1016/j.shaw.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933219PMC
December 2019

The release of surface-anchored α-tectorin, an apical extracellular matrix protein, mediates tectorial membrane organization.

Sci Adv 2019 11 27;5(11):eaay6300. Epub 2019 Nov 27.

Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of α-tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
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http://dx.doi.org/10.1126/sciadv.aay6300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881170PMC
November 2019

Can Workplace Rest Breaks Prevent Work-Related Injuries Related to Long Working Hours?

J Occup Environ Med 2020 03;62(3):179-184

Department of Occupational and Environmental Medicine, Cheonan Medical Center, Cheonan (Dr Park); Department of Occupational and Environmental Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon (Dr Lee); Department of Occupational and Environmental Medicine, Soonchunhyang University College of Medicine, Seoul (Dr Lee), Republic of Korea.

Objective: This study examined the relationship between long working hours, rest breaks, and work-related injuries.

Methods: A total of 25,439 employees were examined from the 4th Korean Working Conditions Survey. Rest breaks were divided into two groups and working hours were divided into four groups. Multiple logistic regression was conducted to estimate the relationship between long working hours, rest breaks, and work-related injuries.

Results: Work-related injuries were significantly associated with long working hours. Stratified by rest breaks, the risk of work-related injuries increased with increasing working hours in a dose-response pattern among those with insufficient rest breaks, while the risk was not significant among those with sufficient rest breaks.

Conclusion: It is important to provide sufficient rest breaks to prevent work-related injuries among workers with long working hours.
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http://dx.doi.org/10.1097/JOM.0000000000001772DOI Listing
March 2020

Systematic mutation analysis in rare colorectal cancer presenting ovarian metastases.

Sci Rep 2019 11 18;9(1):16990. Epub 2019 Nov 18.

College of Medicine, Gachon University, Incheon, Korea.

Although colorectal cancer is one of the most lethal cancer types in the world, its metastasis to the ovary is rare, compared to metastasis to other organs. Consequently, the genomic basis for colon-to-ovary metastasis remains unstudied, due to limited available patients, and thus there have been no attempts to construct individual-specific networks. Due to its rarity, the small sample size makes common mutations difficult to find. To overcome this problem, we herein attempted to apply a biological connectivity map called a sample-specific network (SSN), to reveal common biological functions in three samples. Our three samples were compared to a clinical dataset contained in The Cancer Genome Atlas (TCGA) Colorectal Adenocarcinoma (COAD), showing different mutational spectra, compared to matched samples based on age, gender, microsatellite instability (MSI) status, and tumor, node, metastasis (TNM) stage. The SSNs for the three samples revealed significant correlations of the mutation statuses of several apoptosis genes, in contrast to the TCGA-matched samples. Further analysis of a targeted-gene panel sequencing dataset for colon-to-ovary metastasis of primary tumor samples also confirmed significant correlations of the mutational statuses among apoptosis genes. In summary, using SSN, we successfully identified a common function (apoptosis) among our three patients having colon-to-ovary metastasis, despite no common mutations in the three patients. Such computational analyses could facilitate productive study of rare cancers and other diseases.
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http://dx.doi.org/10.1038/s41598-019-53182-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861287PMC
November 2019

miR2Diabetes: A Literature-Curated Database of microRNA Expression Patterns, in Diabetic Microvascular Complications.

Genes (Basel) 2019 10 9;10(10). Epub 2019 Oct 9.

College of Medicine, Gachon University, Incheon 21565, Korea.

microRNAs (miRNAs) have been established as critical regulators of the pathogenesis of diabetes mellitus (DM), and diabetes microvascular complications (DMCs). However, manually curated databases for miRNAs, and DM (including DMCs) association studies, have yet to be established. Here, we constructed a user-friendly database, "miR2Diabetes," equipped with a graphical web interface for simple browsing or searching manually curated annotations. The annotations in our database cover 14 DM and DMC phenotypes, involving 156 miRNAs, by browsing diverse sample origins (e.g., blood, kidney, liver, and other tissues). Additionally, we provide miRNA annotations for disease-model organisms (including rats and mice), of DM and DMCs, for the purpose of improving knowledge of the biological complexity of these pathologies. We assert that our database will be a comprehensive resource for miRNA biomarker studies, as well as for prioritizing miRNAs for functional validation, in DM and DMCs, with likely extension to other diseases.
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http://dx.doi.org/10.3390/genes10100784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826485PMC
October 2019

A mutation in the catalytic domain of cellulose synthase 6 halts its transport to the Golgi apparatus.

J Exp Bot 2019 11;70(21):6071-6083

Department of Plant Biology, Michigan State University, 612 Wilson Road, East Lansing, MI, USA.

Cellulose microfibrils, which form the mechanical framework of the plant cell wall, are synthesized by the cellulose synthase complex in the plasma membrane. Here, we introduced point mutations into the catalytic domain of cellulose synthase 6 (CESA6) in Arabidopsis to produce enhanced yellow fluorescent protein (EYFP)-tagged CESA6D395N, CESA6Q823E, and CESA6D395N+Q823E, which were exogenously produced in a cesa6 null mutant, prc1-1. Comparison of these mutants in terms of plant phenotype, cellulose content, cellulose synthase complex dynamics, and organization of cellulose microfibrils showed that prc1-1 expressing EYFP:CESA6D395N or CESA6D395N+Q823E was nearly the same as prc1-1, whereas prc1-1 expressing EYFP:CESA6Q823E was almost identical to wild type and prc1-1 expressing EYFP:WT CESA6, indicating that CESA6D395N and CESA6D395N+Q823E do not function in cellulose synthesis, while CESA6Q823E is still functionally active. Total internal reflection fluorescence microscopy and confocal microscopy were used to monitor the subcellular localization of these proteins. We found that EYFP:CESA6D395N and EYFP:CESA6D395N+Q823E were absent from subcellular regions containing the Golgi and the plasma membrane, and they appeared to be retained in the endoplasmic reticulum. By contrast, EYFP:CESA6Q823E had a normal localization pattern, like that of wild-type EYFP:CESA6. Our results demonstrate that the D395N mutation in CESA6 interrupts its normal transport to the Golgi and its eventual participation in cellulose synthase complex assembly.
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http://dx.doi.org/10.1093/jxb/erz369DOI Listing
November 2019

Control of CO Capture Process on Transition-Metal-Porphyrin-like Graphene with Mechanical Strain.

ACS Omega 2018 Sep 5;3(9):10554-10563. Epub 2018 Sep 5.

Department of Physics, Konkuk University, Seoul 05029, Republic of Korea.

Nanomaterials, such as zeolites and metal-organic frameworks, have been studied for CO capture and sequestration. However, this application of nanomaterials has been limited largely due to their poor selectivity for flue gases as well as low capture capacity under low pressures. The first-principle density-functional theory calculations for porphyrin-like graphene decorated with a transition metal were performed to investigate the effects of mechanical strain on its CO capture capacity. We found that Sc- and V-decorated porphyrin-like graphenes could capture CO molecules selectively from gaseous mixtures under low CO pressure with compressive strain and release them with tensional strain at room temperatures. The CO binding to these transition metals was understood to be mostly due to the Dewar interaction involving hybridization of the metal d orbitals with π orbitals of CO. These results elucidate a novel approach to the CO capture process with the application of the mechanical strain to nanomaterials.
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http://dx.doi.org/10.1021/acsomega.8b01371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645585PMC
September 2018

Independent and Interactive Effects of Habitually Ingesting Fermented Milk Products Containing Strain Shirota and of Engaging in Moderate Habitual Daily Physical Activity on the Intestinal Health of Older People.

Front Microbiol 2019 31;10:1477. Epub 2019 Jul 31.

Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.

Infrequent bowel movements decrease the number of beneficial bacteria in the human intestines, thereby potentially increasing the individual's risk of colorectal cancer. The correction of such bowel problems could therefore make an important contribution to improving population health and quality-adjusted lifespan. We examined independent and interactive effects upon the fecal microbiota of two potentially favorable determinants of intestinal motility: the intake frequency of a fermented milk product containing strain Shirota (LcS) and the quantity/quality of habitual physical activity in 338 community-living Japanese aged 65-92 years. Subjects were arbitrarily grouped on the basis of questionnaire estimates of LcS intake (0-2, 3-5, and 6-7 days/week) and pedometer/accelerometer-determined patterns of physical activity [<7000 and ≥7000 steps/day, or <15 and ≥15 min/day of activity at an intensity >3 metabolic equivalents (METs)]. After adjustment for potential confounders, the respective numbers of various beneficial fecal bacteria tended to be larger in more frequent consumers of LcS-containing products, this trend being statistically significant (mostly < 0.001) for total , the subgroup, and the cluster; in contrast, there were no statistically significant differences in fecal bacterial counts between the physical activity groups. A multivariate-adjusted logistic regression analysis estimated that the risk of infrequent bowel movements (arbitrarily defined as defecating ≤3 days/week) was significantly lower ( < 0.05) in subjects who ingested LcS-containing products 6-7 rather than 0-2 days/week [odds ratio (95% confidence interval) 0.382 (0.149-0.974)] and was also lower in those who took ≥7000 rather than <7000 steps/day [0.441 (0.201-0.971)] or spent ≥15 rather than <15 min/day of physical activity at an intensity >3 METs [0.412 (0.183-0.929)]. The risk of infrequent bowel movements in subjects who combined 6-7 days/week of LcS with ≥7000 steps/day or ≥15 min/day of activity at >3 METs was only a tenth of that for individuals who combined 0-2 days/week of LcS with <7000 steps/day or <15 min/day at >3 METs. These results suggest that elderly individuals can usefully ingest LcS-containing supplements regularly (≥6 days/week) and also engage in moderate habitual physical activity (≥7000 steps/day and/or ≥15 min/day at >3 METs) in order to enhance their gastrointestinal health.
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http://dx.doi.org/10.3389/fmicb.2019.01477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684969PMC
July 2019

A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts.

J Ginseng Res 2019 Jul 31;43(3):431-441. Epub 2018 Jul 31.

Department of Pharmacology, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.

Background: The efficacy of ginseng, the representative product of Korea, and its chemical effects have been well investigated. The ginsenoside RG3 has been reported to exhibit apoptotic, anticancer, and antidepressant-like effects.

Methods: In this report, the putative effect of RG3 on several cellular function including cell survival, differentiation, development and aging process were evaluated by monitoring each specific marker. Also, mitochondrial morphology and function were investigated in ultraviolet (UV)-irradiated normal human dermal fibroblast cells.

Results: RG3 treatment increased the expression of extracellular matrix proteins, growth-associated immediate-early genes, and cell proliferation genes in UV-irradiated normal human dermal fibroblast cells. And, RG3 also resulted in enhanced expression of antioxidant proteins such as nuclear factor erythroid 2-related factor-2 and heme oxygenase-1. In addition, RG3 affects the morphology of UV-induced mitochondria and plays a role in protecting mitochondrial dysfunction.

Conclusioin: RG3 restores mitochondrial adenosine triphosphate (ATP) and membrane potential via its antioxidant effects in skin cells damaged by UV irradiation, leading to an increase in proteins linked with the extracellular matrix, cell proliferation, and antioxidant activity.
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http://dx.doi.org/10.1016/j.jgr.2018.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606973PMC
July 2019

A Badge Design Framework for a Gamified Learning Environment: Cases Analysis and Literature Review for Badge Design.

JMIR Serious Games 2019 May 29;7(2):e14342. Epub 2019 May 29.

Management of Technology Lab, Kangwon National University, Chuncheon, Republic of Korea.

Background: In the past, the educational badge was an extrinsic means of rewarding the motivation to learn. Based on continued research, however, the badge began to be recognized as a scale to measure the learner's knowledge and skill and an important means of helping learners to gradually build intrinsic motivation by using certain extrinsic motivators. As the badge's value has grown, the importance of its design has garnered attention.

Objective: The objective of this research was to establish a badge design framework that can be used in a gamified learning environment.

Methods: Data were collected from previous studies on badge design, 943 badge cases were extracted from 11 online and offline gamification in education contents, and their patterns and features were analyzed.

Results: Based on the analysis of results from previous studies and 943 collected badge cases, our study suggests three conditions for badge design. Through the literature review and collected badge cases, our study designed a badge design framework. First, it is necessary to distinguish whether the type of learning activity required for earning badges is physical or conceptual. Second, it is necessary to distinguish whether the scale of an activity required for earning badges requires individual learning or interaction-induced learning. Third, it is important to review whether the time and effort invested in earning badges is simple, repetitive, and short-term or continuous and long-term. Based on these three conditions, collected badge cases were analyzed. To verify self-developed badge types, we conducted a chi-square test on the collected cases and confirmed that there was a significant difference for each of the eight badge types (Pearson chi-square 1117.7, P<.001).

Conclusions: Through its literature review on previous studies, this study demonstrated the badge's educational effectiveness. The badge design framework suggested in our study is expected to resolve some of the difficulties experienced during the badge design process in a gamified learning environment, encourage efficient badge design, and maximize learning effect.
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http://dx.doi.org/10.2196/14342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658268PMC
May 2019