Publications by authors named "Myung-Geun Shin"

178 Publications

Phospholipase C Beta 2 Protein Overexpression Is a Favorable Prognostic Indicator in Newly Diagnosed Normal Karyotype Acute Myeloid Leukemia.

Ann Lab Med 2021 Jul;41(4):409-413

Brain Korea 21 Plus Program, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.

Phospholipase C beta 2 (PLC-β2) regulates various essential functions in cell signaling, differentiation, growth, and mobility. We investigated the clinical implications of PLC-β2 protein expression in newly diagnosed normal karyotype acute myeloid leukemia (NK-AML). The PLC-β2 expression status in bone marrow tissues obtained from 101 patients with NK-AML was determined using semiquantitative immunohistochemistry (IHC). IHC results were compared with those for known prognostic markers. Using a cutoff score for positivity of 7.0, the PLC-β2 overexpression group showed superior overall survival (OS) (72.6% vs. 26.5%; =0.016) and low hazard ratio (HR) (0.453; =0.019) compared with the PLC-β2 low-expression group. The PLC-β2 overexpression group showed no significant gain in event-free survival (50.6% vs. 43.0%, =0.465) and HR (0.735; =0.464). Among the known prognostic markers, only positivity was associated with a significantly low OS and high HR. In conclusion, PLC-β2 overexpression was associated with favorable OS in NK-AML patients. Our results suggest that PLC-β2 expression assessment using IHC allows prognosis prediction in NK-AML.
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http://dx.doi.org/10.3343/alm.2021.41.4.409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884198PMC
July 2021

Evaluation of a Fully Automated Antinuclear Antibody Indirect Immunofluorescence Assay in Routine Use.

Front Immunol 2020 4;11:607541. Epub 2020 Dec 4.

Department of Laboratory Medicine, Chonnam National University Hospital, Gwangju, South Korea.

Indirect immunofluorescence assay (IFA) using HEp-2 cells as a substrate is the gold standard for detecting antinuclear antibodies (ANA) in patient serum. However, the ANA IFA has labor-intensive nature of the procedure and lacks adequate standardization. To overcome these drawbacks, the automation has been developed and implemented to the clinical laboratory. The purposes of this study were to evaluate the analytical performance of a fully automated Helios ANA IFA analyzer in a real-life laboratory setting, and to compare the time and the cost of ANA IFA testing before and after adopting the Helios system. A total of 3,276 consecutive serum samples were analyzed for ANA using the Helios system from May to August 2019. The positive/negative results, staining patterns, and endpoint titers were compared between Helios and visual readings. Furthermore, the turnaround time and the number of wells used were compared before and after the introduction of Helios system. Of the 3,276 samples tested, 748 were positive and 2,528 were negative based on visual readings. Using visual reading as the reference standard, the overall relative sensitivity, relative specificity, and concordance of Helios reading were 73.3, 99.4, and 93.4% ( = 0.80), respectively. For pattern recognition, the overall agreement was 70.1% (298/425) for single patterns, and 72.4% (89/123) for mixed patterns. For titration, there was an agreement of 75.9% (211/278) between automated and classical endpoint titers by regarding within ± one titer difference as acceptable. Helios significantly shortened the median turnaround time from 100.6 to 55.7 h ( < 0.0001). Furthermore, routine use of the system reduced the average number of wells used per test from 4 to 1.5. Helios shows good agreement in distinguishing between positive and negative results. However, it still has limitations in positive/negative discrimination, pattern recognition, and endpoint titer prediction, requiring additional validation of results by human observers. Helios provides significant advantages in routine laboratory ANA IFA work in terms of labor, time, and cost savings. We hope that upgrading and developing softwares with more reliable capabilities will allow automated ANA IFA analyzers to be fully integrated into the routine operations of the clinical laboratory.
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http://dx.doi.org/10.3389/fimmu.2020.607541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746920PMC
December 2020

Changing the frequency and spectra of chromosomal aberrations in Korean patients with acute leukemia in a tertiary care hospital.

Blood Res 2020 Dec;55(4):225-245

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.

Background: Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies.

Methods: We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA.

Results: The incidence of CA changed in the leukemia subgroups during the two time periods. Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL.

Conclusion: The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.
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http://dx.doi.org/10.5045/br.2020.2020255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784131PMC
December 2020

MEF2D-BCL9 B-Lymphoblastic Leukemia Blast Morphology Does Not Always Mimic Mature B-Cell Leukemia.

J Pediatr Hematol Oncol 2021 Apr;43(3):112-113

Department of Pediatrics, Chonnam National University Hwasun Hospital, Hwasun.

MEF2D (myocyte enhancer factor 2D)-rearranged acute lymphoblastic leukemia (ALL) has recently been documented by transcriptome sequencing in B-cell precursor ALL. It is associated with older age of onset (median: 14 y), and characterized by very early relapse and poorer outcomes than other B-cell precursor ALL groups. According to report by Suzuki and colleagues, all 4 cases of MEF2D-BCL9-fusion ALL among 59 children with relapsed or primary refractory ALL had leukemic blasts morphologically mimicking mature B-cell leukemia cells. However, we display morphologically different blast populations in 2 patients with MEF2D-BCL9-rearranged ALL. Mature B-cell leukemia-like morphology would aid the detection of MEF2D-BCL9 fusion, but not all cases might have typical morphology.
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http://dx.doi.org/10.1097/MPH.0000000000002009DOI Listing
April 2021

RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia.

Sci Rep 2020 11 18;10(1):20119. Epub 2020 Nov 18.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P < 6.3e-05 and P < 2.2e-13). The level of reduction of RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R = 0.74, P < 5.4e-05). A decision tree analysis, based on 3-log reduction of RUNX1-RUNX1T1 and cKIT-D816 at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P < 0.08) and 2-year relapse incidence rates at 13%, 42%, and 67% (P < 0.05). On the other hand, although low residual allelic burden was common, it was not associated with long-term outcome, indicating that mutation clearance alone cannot be interpreted as MRD-negative. Overall, our study demonstrates that the clinical utility of RNA sequencing as a potential tool for MRD monitoring in fusion gene-driven AML such as RUNX1-RUNX1T1 AML.
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http://dx.doi.org/10.1038/s41598-020-76933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674449PMC
November 2020

Utility of an Automatic Vision-Based Examination System (AVE-562) for the Detection of Eggs in Stool.

Ann Lab Med 2021 Mar;41(2):221-224

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

Stool examination is the gold standard for the detection of intestinal parasites. We assessed the performance of a newly developed AVE-562 analyzer (AVE Science & Technology Co., Hunan, China) for the vision-based detection of eggs of -the most common intestinal parasite in Korea-in stool samples. In total, 30 stool samples with a high or low egg count or without eggs (as negative control samples) (N=10 each) were prepared and analyzed. The performance of the AVE-562 analyzer was compared with that of the formalin-ether concentration (FEC) method. The overall correct identification rate of the AVE-562 analyzer based on FEC results was 66.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of the AVE-562 analyzer for detecting C. sinensis eggs were 36.4%, 100.0%, 100.0%, and 73.1%, respectively. The average time required to run five tests simultaneously was 27 min using the AVE-562 analyzer and 58 min using the FEC method. Although the AVE-562 analyzer enables rapid and convenient stool examination, its sensitivity needs to be improved, particularly considering the prevalence of low-burden infection in Korea.
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http://dx.doi.org/10.3343/alm.2021.41.2.221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591289PMC
March 2021

Performance Evaluation of VITEK MS for the Identification of a Wide Spectrum of Clinically Relevant Filamentous Fungi Using a Korean Collection.

Ann Lab Med 2021 Mar;41(2):214-220

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l'Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed "no identification" or "multiple species identification" results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for , dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed "no identification" and "misidentification" results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification.
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http://dx.doi.org/10.3343/alm.2021.41.2.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591280PMC
March 2021

tRNA-Derived Small RNAs: Novel Epigenetic Regulators.

Cancers (Basel) 2020 Sep 27;12(10). Epub 2020 Sep 27.

Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

An epigenetic change is a heritable genetic alteration that does not involve any nucleotide changes. While the methylation of specific DNA regions such as CpG islands or histone modifications, including acetylation or methylation, have been investigated in detail, the role of small RNAs in epigenetic regulation is largely unknown. Among the many types of small RNAs, tRNA-derived small RNAs (tsRNAs) represent a class of noncoding small RNAs with multiple roles in diverse physiological processes, including neovascularization, sperm maturation, immune modulation, and stress response. Regarding these roles, several pioneering studies have revealed that dysregulated tsRNAs are associated with human diseases, such as systemic lupus, neurological disorder, metabolic disorder, and cancer. Moreover, recent findings suggest that tsRNAs regulate the expression of critical genes linked with these diseases by a variety of mechanisms, including epigenetic regulation. In this review, we will describe different classes of tsRNAs based on their biogenesis and will focus on their role in epigenetic regulation.
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http://dx.doi.org/10.3390/cancers12102773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599909PMC
September 2020

The HLA-A*02:01:175 allele newly identified in a Korean hematopoietic stem cell donor by next-generation sequencing.

HLA 2021 Jan 27;97(1):62-64. Epub 2020 Sep 27.

Department of Laboratory Medicine, Chonnam National University Hospital and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.

HLA-A*02:01:175 has a single synonymous nucleotide polymorphism when compared with HLA-A*02:01:01:01 [c165.G>C].
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http://dx.doi.org/10.1111/tan.14071DOI Listing
January 2021

Evaluation of Two Commercial Broth Microdilution Methods Using Different Interpretive Criteria for the Detection of Molecular Mechanisms of Acquired Azole and Echinocandin Resistance in Four Common Species.

Antimicrob Agents Chemother 2020 10 20;64(11). Epub 2020 Oct 20.

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea.

The abilities of the new Vitek 2 AST-YS08 (YS08) and Sensititre YeastOne (SYO) systems to detect the resistances of isolates to azoles and echinocandins were evaluated. In total, 292 isolates, including 28 (6 Erg11 and 2 Fks mutants), 57 (26 Erg11 mutants), 24 (10 Erg11 and 1 Fks mutants), and 183 (39 Pdr1 and 13 Fks mutants) isolates, were tested. The categorical agreements (CAs) between the Clinical and Laboratory Standards Institute (CLSI) method and YS08 fluconazole MICs obtained using clinical breakpoints were 92.4% (), 96.5% (), and 87.0% (), and the CAs between the CLSI and SYO MICs were 92.3% (), 77.2% (), 100% (), and 98.9% (). For , the CAs with the CLSI micafungin MICs were 92.4% and 55.5% for the YS08 micafungin and caspofungin MICs, respectively; they were 100%, 95.6%, and 98.9% for the SYO micafungin, caspofungin, and anidulafungin MICs, respectively. YS08 does not provide fluconazole data for ; the CA with the CLSI fluconazole MIC was 97.8% for the YS08 voriconazole MIC, using an epidemiological cutoff value (ECV) of 0.5 μg/ml. Increased CAs with the CLSI MIC were observed for the YS08 MIC using CLSI ECVs (for fluconazole and , 100%; for micafungin and , 98.9%) and for the SYO MIC using method-specific ECVs (for fluconazole and , 91.2%; for caspofungin and , 98.9%). Therefore, the YS08 and SYO systems may have different abilities to detect mechanisms of azole and echinocandin resistance in four species; the use of method-specific ECVs may improve the performance of both systems.
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http://dx.doi.org/10.1128/AAC.00740-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577149PMC
October 2020

One-step immunoassay without washing steps for influenza A virus detection using ISFET.

Biosens Bioelectron 2020 Oct 11;165:112341. Epub 2020 Jun 11.

Department of Materials Science and Engineering, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea. Electronic address:

A one-step immunoassay for influenza A virus detection was developed using two different microbeads and a filter-inserted bottle. Two bead types with diameters of 15 (capture bead) and 3 (detection bead) μm were prepared to specifically detect influenza A virus. Anti-influenza A virus antibodies were coated on both bead types, whereas urease was immobilized only on the detection bead. An influenza A-positive sample could form a sandwich complex with the capture and detection beads; this complex would not pass through the filter, which had a controlled pore size. As the detection bead was used at a limiting concentration, it would be prevented from crossing the filter; thus, it would further react with the substrate urea and consequently increase the pH. An influenza A-negative sample would fail to form the sandwich complex in the presence of the capture and detection beads. Accordingly, the detection bead would pass through the filter into the urea buffer and increase the pH. The pH change in the urease reaction could be quantitatively measured by an indicator such as phenol red or using ion-selective field-effect transistor (ISFET). This one-step immunoassay was used for the detection of influenza A virus in real samples. The receiver operating characteristic (ROC) plot analysis showed an area under the curve (AUC) value of 0.931; the sensitivity and specificity of the assay was 80% and 90%, respectively, at a cutoff value of 0.9986. These results demonstrate that the one-step immunoassay could increase the sensitivity of influenza A virus detection in real samples.
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http://dx.doi.org/10.1016/j.bios.2020.112341DOI Listing
October 2020

Coronavirus disease-19 and its hematological manifestations.

Blood Res 2020 Jun;55(2):71-74

Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Korea.

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http://dx.doi.org/10.5045/br.2020.2020121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343544PMC
June 2020

The novel HLA-DRB1 allele, HLA-DRB1*01:108, identified in a Korean individual.

HLA 2020 09 20;96(3):364-366. Epub 2020 Jun 20.

Department of Laboratory Medicine, Chonnam National University Hospital and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.

HLA-DRB1*01:108 has a nucleotide polymorphism (c346.G>A) compared with HLA-DRB1*01:01:01:01, causing an amino acid substitution (p.Glu87Lys).
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http://dx.doi.org/10.1111/tan.13963DOI Listing
September 2020

Antifungal Susceptibility Tests and the Mutant Strains among Clinical Isolates from Korean Multicenters.

Mycobiology 2020 10;48(2):148-152. Epub 2020 Apr 10.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

We investigated the antifungal susceptibilities and the mutant strains among clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions Nine isolates harbored one to five mutations in with high polymorphism, and 11 isolates exhibited the same Q42L mutation in . Overall, a low azole resistance rate and high frequency of amino acid substitutions were observed in the azole-susceptible isolates in Korea.
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http://dx.doi.org/10.1080/12298093.2020.1744955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178884PMC
April 2020

Detection of the novel HLA-B allele, HLA-B*27:199, in a Korean individual.

HLA 2020 09 21;96(3):345-347. Epub 2020 Apr 21.

Department of Laboratory Medicine, Chonnam National University Hospital and Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.

HLA-B*27:199 differs from HLA-B*27:05:02:01 by one nucleotide substitution (c.814G>T) with one amino acid change (p.V248L).
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http://dx.doi.org/10.1111/tan.13895DOI Listing
September 2020

Synergistic effects of depression and NR3C1 methylation on prognosis of acute coronary syndrome.

Sci Rep 2020 03 26;10(1):5519. Epub 2020 Mar 26.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.

High levels of methylation in the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) have been associated with depression and cardiovascular risk. This study aimed to investigate whether NR3C1 methylation status was associated with the long-term prognosis of acute coronary syndrome (ACS) considering depression and cardiovascular status at the early phase of ACS. A total of 969 patients with recent ACS were recruited at a tertiary university hospital in Korea. Baseline evaluations were made from 2007 to 2012, including DSM-IV depressive disorder, NR3C1 methylation, and various demographic and clinical characteristics such as cardiovascular risk markers. Over a 5~12 year follow-up after the index ACS, time to major adverse cardiac event (MACE) was investigated using Cox regression models. Higher NR3C1 methylation status was associated with depression and several cardiovascular risk markers at baseline. NR3C1 hypermethylation predicted worse long-term prognosis of ACS only in the presence of depressive disorder with significant synergistic interaction terms and independent of potential confounding factors. Synergistic effects of depressive disorder and NR3C1 hypermethylation on long-term cardiac outcomes in ACS were found. NR3C1 methylation status represents a candidate prognostic biomarker for ACS in combination with a diagnosis of depressive disorder. Further research is needed to ascertain the generalisability of these findings.
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http://dx.doi.org/10.1038/s41598-020-62449-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099028PMC
March 2020

Potential biomarkers and antagonists for fluoranthene-induced cellular toxicity of bone marrow derived mesenchymal stem cells.

Blood Res 2019 Dec 20;54(4):253-261. Epub 2019 Dec 20.

Department of Laboratory Medicine and Mitochondrial Research Laboratory, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Background: Fluoranthene (FR) is a common environmental pollutant that exists in a complex mixture with other polycyclic aromatic hydrocarbons (PAHs). We identified biomarkers for monitoring FR exposure and investigated the rescue effect of FR-induced cellular toxicity via aryl hydrocarbon receptor (AHR) antagonist activity in bone marrow derived mesenchymal stem cells (BM-MSCs).

Methods: Morphological changes, viability, and rescue effects of an AHR antagonist (CH223191) were examined in BM-MSCs after exposure to FR. Cytotoxic effects were assayed using the tetrazolium-based colorimetric assay. Apoptosis was measured by annexin V and propidium iodide dye-based flowcytometry assay, mitochondrial membrane potential assay, and nuclear DNA fragmentation assay. Molecular signaling pathways of apoptosis and autophagy were investigated using immunoblotting. Proteomics were performed in order to reveal the spectra of cellular damage and identify biomarkers for FR exposure.

Results: Exposing BM-MSCs to FR (IC=50 µM) induced cell death and morphological changes, while the AHR antagonist showed rescue effects. Autophagy was activated and mitochondrial membrane potential was decreased. Proteomic analysis identified 48 deregulated proteins (26 upregulated and 22 downregulated). Among them, annexin A6, pyruvate kinase, UDP-glucose dehydrogenase, and phospholipase A2 could be potential biomarkers for FR exposure.

Conclusion: The exposure of BM-MSCs to FR induced remarkable alterations in cellular biology and the proteome, allowing for identification of novel biomarkers for FR exposure. Furthermore, AHR antagonists might be able to prevent cellular damage due to FR exposure.
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http://dx.doi.org/10.5045/br.2019.54.4.253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942141PMC
December 2019

Characterization of the new HLA-DQB1*06:344 allele by next-generation sequencing in a Korean individual.

HLA 2020 02 17;95(2):155-156. Epub 2019 Nov 17.

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Korea.

DQB1*06:344 differs from DQB1*06:02:01:01 by one nucleotide substitution at codon 211 in exon 3.
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http://dx.doi.org/10.1111/tan.13739DOI Listing
February 2020

First Case of Nosocomial Fungemia Caused by .

Ann Lab Med 2020 Mar;40(2):177-179

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.2.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821997PMC
March 2020

The MAKE Biomarker Discovery for Enhancing anTidepressant Treatment Effect and Response (MAKE BETTER) Study: Design and Methodology.

Psychiatry Investig 2019 Oct 16;16(10):791-792. Epub 2019 Oct 16.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.

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http://dx.doi.org/10.30773/pi.2017.10.2.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801320PMC
October 2019

A longitudinal study of the associations of BDNF genotype and methylation with poststroke anxiety.

Int J Geriatr Psychiatry 2019 11 7;34(11):1706-1714. Epub 2019 Aug 7.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.

Background: Although the precise etiology of poststroke anxiety (PSA) has yet to be fully elucidated, it is known that brain-derived neurotrophic factor (BDNF) is important for neural plasticity and long-term potentiation, associated with the pathophysiology of anxiety. The expression of BDNF is regulated by epigenetic and genetic profiles. Thus, we investigated the association between BDNF methylation status and PSA at 2 weeks and 1 year after stroke while accounting for interactions with the BDNF Val66Met polymorphism.

Methods: The baseline sample comprised 286 patients who were assessed at 2 weeks after stroke; of these patients, 222 (78%) were followed up with at 1 year after stroke. The presence of PSA was determined using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), and the effects of BDNF methylation status and polymorphisms on PSA status were assessed with multivariate logistic regression models.

Results: The prevalence of PSA was slightly lower (27 [9.4%]) at baseline, and 35 (15.8%) patients were identified as having PSA at the 1-year follow-up. Stroke patients with a higher average methylation status were more likely to have PSA at 1 year. The BDNF Val66Met polymorphism was not independently associated with PSA during either the acute or chronic phase after stroke, but there was a significant interactive effect between BDNF methylation and genotype on PSA at 2 weeks.

Conclusions: In this study, BDNF methylation in combination with the met/met BDNF polymorphism (Val66Met polymorphism) was associated with PSA. These findings may help identify patients at higher risk for PSA.
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http://dx.doi.org/10.1002/gps.5185DOI Listing
November 2019

Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model.

Bioorg Med Chem 2019 10 18;27(19):115014. Epub 2019 Jul 18.

Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea. Electronic address:

A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.
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http://dx.doi.org/10.1016/j.bmc.2019.07.030DOI Listing
October 2019

Fluoranthene-Induced Cytotoxicity and Direct Effect of Aryl Hydrocarbon Receptor Antagonist on Hematopoietic Stem Cell Differentiation.

Ann Lab Med 2019 Nov;39(6):580-583

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.

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http://dx.doi.org/10.3343/alm.2019.39.6.580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660337PMC
November 2019

Remission clone in acute myeloid leukemia shows growth advantage after chemotherapy but is distinct from leukemic clone.

Exp Hematol 2019 07 12;75:26-30. Epub 2019 Jun 12.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.

In a previously published case study of acute myeloid leukemia, we tracked the dynamics of somatic mutations over 9 years. Interestingly, we observed a group of mutations that expanded during remission, which we named the "remission clone." To determine the nature of the remission clones, we performed flow cytometry-based cell sorting followed by ultradeep sequencing. The remission clone repeatedly expanded after chemotherapeutic cycles and was suppressed during relapse in the myeloid lineage (multipotent hematopoietic stem, progenitor, and myeloid cells). On the other hand, the remission clone was consistently observed in lymphoid lineages (B and T cells) regardless of the disease state. When transfected into the HEK-293 cell line, the NR2C2(A93V) mutant exhibited a growth advantage (all p values < 0.05). The results indicate that the remission clone seems to be another form of clonal hematopoiesis, but without a clear association with leukemia. As the remission clone is present in both myeloid and lymphoid lineages, it likely originates from ancestral hematopoietic cell lineages. More importantly, the remission clone is distinct from the leukemic clone; therefore, mutations expanded during remission require special interpretation when performing next-generation sequencing-based measurable residual disease assessment.
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http://dx.doi.org/10.1016/j.exphem.2019.06.001DOI Listing
July 2019

Candida auris Clinical Isolates from South Korea: Identification, Antifungal Susceptibility, and Genotyping.

J Clin Microbiol 2019 04 28;57(4). Epub 2019 Mar 28.

Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea.

is an emerging worldwide fungal pathogen. Over the past 20 years, 61 patient isolates of (4 blood and 57 ear) have been obtained from 13 hospitals in Korea. Here, we reanalyzed those molecularly identified isolates using two matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, including Biotyper and Vitek MS, followed by antifungal susceptibility testing, sequencing of the gene, and genotyping. With a research-use-only (RUO) library, 83.6% and 93.4% of the isolates were correctly identified by Biotyper and Vitek MS, respectively. Using an diagnostic (IVD) library of Vitek MS, 96.7% of the isolates were correctly identified. Fluconazole-resistant isolates made up 62.3% of the isolates, while echinocandin- or multidrug-resistant isolates were not found. Excellent essential (within two dilutions, 96.7%) and categorical agreements (93.4%) between the Clinical and Laboratory Standards Institute (CLSI) and Vitek 2 (AST-YS07 card) methods were observed for fluconazole. Sequencing for all 61 isolates revealed that only 3 fluconazole-resistant isolates showed the Erg11p amino acid substitution K143R. All 61 isolates showed identical multilocus sequence typing (MLST). Pulsed-field gel electrophoresis (PFGE) analyses revealed that both blood and ear isolates had the same or similar patterns. These results show that MALDI-TOF MS and Vitek 2 antifungal susceptibility systems can be reliable diagnostic tools for testing isolates from Korean hospitals. The Erg11p mutation was seldom found among Korean isolates of , and multidrug resistance was not found. Both MLST and PFGE analyses suggest that these isolates are genetically similar.
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http://dx.doi.org/10.1128/JCM.01624-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440790PMC
April 2019

Increased Prevalence of Thalassemia in Young People in Korea: Impact of Increasing Immigration.

Ann Lab Med 2019 Mar;39(2):133-140

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Thalassemia is highly prevalent in Southeast Asia but is rare in Korea; however, Southeast Asian immigrant population is recently rising in Korea. We investigated the prevalence of thalassemia in Korea in the context of increasing immigration.

Methods: This prospective, observational, multicenter study was conducted between September 2015 and August 2017. A total of 669 subjects <30 years living in Korea were grouped into the multiethnic (N=314) and Korean (N=355) groups. Hb electrophoresis and complete blood count (CBC) were performed. If low mean corpuscular volume with high red blood cell distribution width coefficient of variation or a high fetal Hb (HbF) or Hb alpha 2 (HbA₂) level was observed, genetic testing of the α- and β-globin genes was performed. In addition, the number of potential thalassemia carriers in Korea was estimated by multiplying the prevalence of thalassemia in a specific ethnicity by the number of immigrants of that ethnicity.

Results: Twenty-six multiethnic and 10 Korean subjects showed abnormal results for Hb electrophoresis and CBC. Eighteen multiethnic subjects and four Korean subjects were tested for α-globin and β-globin gene mutations. Within the multiethnic group, five subjects (1.5%) were α-thalassemia carriers, and six (1.9%) were β-thalassemia minor. The deletion in and , and c. 126_129delCTTT (p.Phe42Leufs*19) mutation of were the dominant inherited mutations.

Conclusions: The prevalence of thalassemia in young people in Korea is increasing due to the increasing number of Southeast Asian immigrants.
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http://dx.doi.org/10.3343/alm.2019.39.2.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240526PMC
March 2019

Methylation of the glucocorticoid receptor gene associated with depression in patients with acute coronary syndrome.

Psychoneuroendocrinology 2019 03 29;101:42-49. Epub 2018 Oct 29.

Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address:

Objective: The present study investigated the longitudinal effects of NR3C1 1 F exon methylation on the risk of depression following ACS and treatment outcomes.

Methods: In total, 969 patients admitted for recent ACS were recruited within 2 weeks of ACS; 711 of these patients were followed up at 1 year. Depressive disorder was diagnosed according to DSM-IV criteria and included prevalent depressive disorder at baseline and incident or persistent depressive disorder at follow-up based on depression status at the two examinations. Of the 378 baseline participants who were diagnosed with depression, 255 participated in a randomized double-blind placebo-controlled trial of escitalopram, while the remaining 123 were managed with the usual medical treatment for ACS.NR3C1 1 F exon methylation was measured using peripheral blood samples, and various demographic and clinical characteristics were assessed as covariates.

Results: Higher NR3C1 1 F exon methylation levels were independently associated with prevalent depressive disorder at baseline but not with incident or persistent depressive disorder at follow-up based on logistic regression analyses adjusted for covariates. The effects of escitalopram on the remission of depressive symptoms was not influenced by NR3C1 1 F exon methylation status in ACS patients, but a placebo effect on the remission of depressive symptoms was observed, particularly in patients with lower methylation levels.

Conclusions: ACS patients with higher NR3C1 1 F exon methylation levels were at higher risk of developing depressive disorder within 2 weeks of ACS. Additionally, adequate antidepressant treatment may be effective for the remission of depressive symptoms regardless of NR3C1 1 F exon methylation status.
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http://dx.doi.org/10.1016/j.psyneuen.2018.10.024DOI Listing
March 2019

Microsatellite Typing and Resistance Mechanism Analysis of Voriconazole-Resistant Isolates in South Korean Hospitals.

Antimicrob Agents Chemother 2019 02 29;63(2). Epub 2019 Jan 29.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

A recent surveillance study in South Korea revealed that 14% (7/50) of clinical isolates had a voriconazole minimum inhibitory concentration of ≥4 μg/ml. Of seven non-wild-type (non-WT) isolates, six ear isolates from four hospitals shared the same microsatellite genotype. None of the non-WT isolates showed mutations associated with azole resistance. However, the mean expression levels of efflux pump (, , and ) and target () genes exhibited significant differences between non-WT and other isolates.
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http://dx.doi.org/10.1128/AAC.01610-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355573PMC
February 2019

Xpert MTB/RIF Assay as a Substitute for Smear Microscopy in an Intermediate-Burden Setting.

Am J Respir Crit Care Med 2019 03;199(6):784-794

2 Department of Laboratory Medicine and.

Rationale: Use of Xpert MTB/RIF assay as a substitute for smear microscopy in routine clinical practice remains unexplored in an intermediate-tuberculosis-burden setting.

Objectives: To compare the diagnostic performance of Xpert and smear microscopy, based on sampling time and location, correlation of Xpert semiquantitative category with smear grade and time to culture positivity, and compliance of reporting time with defined standard time.

Methods: Consecutive sputum samples collected from 2,952 suspected pulmonary tuberculosis patients over a 3-year period were tested by Xpert, smear microscopy, and liquid culture as part of routine diagnostics in South Korea.

Measurements And Main Results: Based on the analysis of a single sputum specimen per patient, of 2,952 samples, 263 (8.9%) were culture-confirmed tuberculosis and 265 (9.0%) were nontuberculous mycobacteria. The overall sensitivity and specificity were 74.1% and 97.5% for Xpert versus 38.8% and 96.7% for smear microscopy, respectively (P < 0.0001; P > 0.05). Of 82 smear-positive nontuberculous mycobacteria, 81 (98.8%) were accurately excluded by Xpert. Sampling time and location significantly affected the performance of smear microscopy but not that of Xpert. Xpert semiquantitative category strongly correlated with smear grade (γ = 0.982; P < 0.0001) and time to culture positivity (γ = -0.962; P < 0.0001). Median reporting time and its compliance rate within 24 hours were 3.1 hours and 96.3% for Xpert versus 19.1 hours and 88.7% for smear microscopy, respectively (P < 0.0001; P < 0.05).

Conclusions: Xpert provides faster, more stable, and superior results compared with smear microscopy, in addition to its strong correlation with smear grade. Xpert might replace smear microscopy as the first-line diagnostic test for pulmonary tuberculosis in routine clinical practice in an intermediate-burden setting.
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http://dx.doi.org/10.1164/rccm.201804-0654OCDOI Listing
March 2019