Publications by authors named "Joon Seo Lim"

36 Publications

Circulating and renal fibrocytes are associated with interstitial fibrosis in lupus nephritis.

Rheumatology (Oxford) 2022 Jun 15. Epub 2022 Jun 15.

Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: Fibrocytes, the extracellular matrix (ECM)-producing cells derived from bone marrow progenitors, contribute to organ fibrosis. We investigated the presence and characteristics of fibrocytes in the peripheral blood and kidney of patients with lupus nephritis (LN), and the association of the abundance of fibrocytes with renal tubular epithelial cells (RTECs) in LN fibrogenesis.

Methods: Fibrocytes were identified with type I collagen (colI), alpha-smooth muscle actin (α-SMA), CD34, and CD45 using flow cytometry and confocal imaging. The associations between the levels of fibrocytes and pathologic features of patients with LN were analyzed. The contribution of RTECs in the fibrocyte generation was determined using LN sera-treated HK-2 cells.

Results: Spindle-shaped fibrocytes (colI+α-SMA+CD34+CD45+ cells) were present in the peripheral blood and their abundance was especially high in LN patients with interstitial fibrosis compared with healthy control. Renal fibrocytes (colI+α-SMA+CD45+ cells) were found in the tubulointerstitium in patients with LN, and their numbers were significantly associated with the degrees of chronicity indices including interstitial fibrosis and renal dysfunction. Stimulation of peripheral blood mononuclear cells with supernatants from LN sera treated HK-2 cells led to a significant generation of fibrocytes, which was abrogated by the addition of IL-6 neutralizing antibody.

Conclusion: Fibrocytes were significantly increased in the blood and kidney tissue of patients with LN, especially those with interstitial fibrosis. Fibrocytes could be differentiated from blood cells, with an active contribution from RTECs. Our results show a possible link between fibrocytes and tubulointerstitial fibrosis, which may serve as a novel therapeutic target for LN fibrogenesis.
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http://dx.doi.org/10.1093/rheumatology/keac345DOI Listing
June 2022

Transmission and Infectious SARS-CoV-2 Shedding Kinetics in Vaccinated and Unvaccinated Individuals.

JAMA Netw Open 2022 May 2;5(5):e2213606. Epub 2022 May 2.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Importance: Data are limited on whether patients with breakthrough COVID-19 infection have the potential to significantly contribute to the spread of SARS-CoV-2.

Objective: To compare the secondary attack rate and infectious viral shedding kinetics of SARS-CoV-2 between fully vaccinated individuals (breakthrough infection group) and partially or unvaccinated individuals (nonbreakthrough infection group).

Design, Setting, And Participants: This cohort study assessed secondary transmission by analyzing the epidemiologic data of health care workers, inpatients, and caregivers diagnosed with COVID-19 during hospitalization or residence in a tertiary care hospital between March 1, 2020, and November 6, 2021. To evaluate viral shedding kinetics, the genomic RNA of SARS-CoV-2 was measured using polymerase chain reaction and performed virus culture from daily saliva samples of individuals with mild COVID-19 infected with the Delta variant who were isolated in a community facility in Seoul, South Korea, between July 20 and August 20, 2021.

Exposures: COVID-19 vaccination.

Main Outcomes And Measures: The secondary attack rate and infectious viral shedding kinetics according to COVID-19 vaccination status.

Results: A total of 173 individuals (median [IQR] age, 47 [32-59] years; 100 female [58%]) with COVID-19 were included in the secondary transmission study, of whom 50 (29%) had a breakthrough infection. Secondary transmission was significantly less common in the breakthrough infection group than in the nonbreakthrough infection group (3 of 43 [7%] vs 29 of 110 [26%]; P = .008). In the viral shedding kinetics study, 45 patients (median age, 37 years [IQR, 25-49 years]; 14 female [31%]) infected with the Delta variant were included, of whom 6 (13%) were fully vaccinated and 39 (87%) were partially or unvaccinated. Although the initial genomic viral load was comparable between the 2 groups, viable virus in cell culture was detected for a notably longer duration in partially vaccinated (8 days after symptom onset) or unvaccinated (10 days after symptom onset) individuals compared with fully vaccinated individuals (4 days after symptom onset).

Conclusions And Relevance: In this cohort study, although the initial genomic viral load was similar between vaccinated and unvaccinated individuals, fully vaccinated individuals had a shorter duration of viable viral shedding and a lower secondary attack rate than partially vaccinated or unvaccinated individuals. Data from this study provide important evidence that despite the possibility of breakthrough infections, COVID-19 vaccinations remain critically useful for controlling the spread of SARS-CoV-2.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.13606DOI Listing
May 2022

Clinical and virological characteristics of SARS-CoV-2 B.1.617.2 (Delta) variant: a prospective cohort study.

Clin Infect Dis 2022 Apr 1. Epub 2022 Apr 1.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Data on the clinical and virological characteristics of the delta variant of SARS-CoV-2 are limited. This prospective cohort study compared the characteristics of the delta variant to other variants.

Methods: Adult patients with mild COVID-19 who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcriptase-PCR. Cell cultures were performed on saliva samples with positive genomic RNA results.

Results: A total of 141 patients (delta group, n = 108 [77%]; non-delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the delta group than in the non-delta group (52% vs. 27%, P = .03). Total symptom scores were significantly higher in the delta group between days 3 to 10 after symptom onset. Initial genomic RNA titers were similar between the two groups; however, during the late course of disease, genomic RNA titers were higher in the delta group. Negative conversion of subgenomic RNA was slower in the delta group (median 9 vs. 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the delta group (median 5 vs. 3 days; P = .002).

Conclusions: COVID-19 patients infected with the delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-delta variants.
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http://dx.doi.org/10.1093/cid/ciac239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047158PMC
April 2022

Subretinal fluid disturbs the retinal venous blood flow in central serous chorioretinopathy.

Sci Rep 2022 03 22;12(1):4903. Epub 2022 Mar 22.

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

The significance of subretinal fluid in the retinal blood flow is unclear. Here, we evaluated the association between subretinal fluid (SRF) and retinal blood flow in eyes with central serous chorioretinopathy (CSC) using a retinal functional imager (RFI) and optical coherence tomography angiography (OCTA). In this retrospective case-control study involving 26 eyes from 18 CSC patients and 25 eyes from 21 age- and sex-matched controls, we found that the CSC group showed significant differences from the control group in terms of the retinal venule blood flow velocity (3.60 ± 0.43 vs 3.96 ± 0.56 mm/s; p = 0.030), retinal venule blood flow rate (8.75 ± 2.67 vs 12.51 ± 7.12 nl/s; p = 0.040), and the diameter of retinal venules (118.26 ± 14.25 vs 126.92 ± 35.31 μm; p = 0.045). Linear regression analysis showed that SRF thickness accounted for a 36.9% reduction in venous BFR (p = 0.013). The difference in the O saturation between retinal arteries and veins was greater in the CSC group. There was no correlation between SRF thickness and capillary densities in OCTA. Our findings suggest that disturbance in venous return and the associated altered oxygen may be significant changes in the retinal blood flow dynamics in eyes with SRF.
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http://dx.doi.org/10.1038/s41598-022-08865-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941082PMC
March 2022

Correlation between Reactogenicity and Immunogenicity after the ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccination.

Immune Netw 2021 Dec 17;21(6):e41. Epub 2021 Dec 17.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.
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http://dx.doi.org/10.4110/in.2021.21.e41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733188PMC
December 2021

Sphingosine 1-Phosphate Receptor 4 Promotes Nonalcoholic Steatohepatitis by Activating NLRP3 Inflammasome.

Cell Mol Gastroenterol Hepatol 2022 8;13(3):925-947. Epub 2021 Dec 8.

Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background & Aims: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear.

Methods: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n -octylphenyl)ethyl]-1,3- propanediol hydrochloride)-like sphingolipid-focused library.

Results: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4 mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca release and deactivated the Nod-like receptor pyrin domain-containning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4 mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome.

Conclusions: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages.
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http://dx.doi.org/10.1016/j.jcmgh.2021.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810559PMC
April 2022

Lipid signatures reflect the function of the murine primary placentation†.

Biol Reprod 2022 03;106(3):583-596

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our findings highlight the importance of the nutrient transport function of the primary placenta in the early gestational period and the role of lipids in embryonic development.

Summary Sentence: The placenta is activated characteristically in terms of lipid transport during primary placentation, and the lipid-related signatures closely reflect the functional state of the placenta.
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http://dx.doi.org/10.1093/biolre/ioab219DOI Listing
March 2022

Dynamics of Viral Shedding and Symptoms in Patients with Asymptomatic or Mild COVID-19.

Viruses 2021 10 22;13(11). Epub 2021 Oct 22.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.
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http://dx.doi.org/10.3390/v13112133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625453PMC
October 2021

Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

Neurotherapeutics 2021 10 20;18(4):2692-2706. Epub 2021 Sep 20.

Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

In intracerebral hemorrhage (ICH), delayed secondary neural damages largely occur from perihematomal edema (PHE) resulting from the disruption of the blood-brain barrier (BBB). PHE is often considered the principal cause of morbidity and mortality in patients with ICH. Nevertheless, the main cellular mechanism as well as the specific BBB component involved in the formation of PHE after ICH remains elusive. Herein, we evaluated the role of AQP4, a water channel expressed on the astrocytes of the BBB, in the formation of PHE in ICH. The static and dynamic functions of the BBB were evaluated by analyzing the microstructure and leakage assay. Protein changes in the PHE lesion were analyzed and the control mechanism of AQP4 expression by reactive oxygen species was also investigated. Delayed PHE formation due to BBB disruption after ICH was confirmed by the decreased coverage of multiple BBB components and increased dynamic leakages. Microstructure assay showed that among the BBB components, AQP4 showed a markedly decreased expression in the PHE lesions. The decrease in AQP4 was due to microenvironmental ROS derived from the hemorrhage and was restored by treatment with ROS scavenger. AQP4-deficient mice had significantly larger PHE lesions and unfavorable survival outcomes compared with wild-type mice. Our data identify AQP4 as a specific BBB-modulating target for alleviating PHE in ICH. Further comprehensive studies are needed to form the preclinical basis for the use of AQP4 enhancers as BBB modulators for preventing delayed cerebral edema after ICH.
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http://dx.doi.org/10.1007/s13311-021-01126-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804112PMC
October 2021

CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm.

PLoS One 2021 24;16(8):e0245361. Epub 2021 Aug 24.

Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.

Objective: The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways.

Methods: Twenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n = 7) and those with weak, focal, and junctional CRP immunopositivity (n = 3).

Results: mCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity.

Conclusions: AAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245361PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384196PMC
November 2021

SARS-CoV-2-Specific Antibody and T Cell Response Kinetics According to Symptom Severity.

Am J Trop Med Hyg 2021 Jun 17;105(2):395-400. Epub 2021 Jun 17.

1Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.
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http://dx.doi.org/10.4269/ajtmh.20-1594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437179PMC
June 2021

Adverse Reactions of the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine in Healthcare Workers in Korea.

J Korean Med Sci 2021 May 31;36(21):e153. Epub 2021 May 31.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

We conducted a prospective, mobile-based survey on the self-reported adverse reactions in healthcare workers (HCWs) who received both doses of the BNT162b2 mRNA vaccine. Of the 342 HCWs who completed the two-dose vaccination, 265 (77.5%) responded to the survey at least once. Overall, the rates of adverse reactions were higher after the second dose compared with the first dose (89.1% vs. 80.1%, = 0.006). The most common systemic reactions were muscle ache (69.1%), fatigue (65.7%), headache (48.7%), chills (44.2%), and fever (32.1%), and were notably more common after the second dose vaccine as well. We also noted a sex difference in which the frequency of adverse reactions after the second dose of the vaccine was significantly higher in females, which was not observed after the first dose. The rates of adverse reactions were lower in older age groups, and the rates and severities of the adverse reactions decreased during the 3-day period following vaccination.
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http://dx.doi.org/10.3346/jkms.2021.36.e153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167406PMC
May 2021

Pitfall of Universal Pre-Admission Screening for SARS-CoV-2 in a Low Prevalence Country.

Viruses 2021 04 30;13(5). Epub 2021 Apr 30.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

It is unclear whether universal PCR screening for SARS-CoV-2 in asymptomatic individuals prior to admission is useful. From April to December 2020, the positive rate of universal pre-admission screening was 0.005% (4/76,521) in a tertiary care hospital in Korea. The positive rates were not different between the periods (period 1 (daily new patients of <1 per million inhabitants) vs. period 2 (1-8.3 per million inhabitants) vs. period 3 (10.3 to 20 per million inhabitants); = 0.45). Universal pre-admission screening for SARS-CoV-2 had a lower positive rate than that of symptom-based screening (0.005% vs. 0.049% (53/109,257), < 0.001). In addition, seven patients with negative pre-admission test results had subsequent positive PCR during hospitalization, and four patients had secondary transmission. Universal pre-admission PCR screening may not be practical in settings of low prevalence of COVID-19, and negative PCR results at admission should not serve as a basis for underestimating the risk of nosocomial spread from asymptomatic patients.
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http://dx.doi.org/10.3390/v13050804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145721PMC
April 2021

Adverse Reactions Following the First Dose of ChAdOx1 nCoV-19 Vaccine and BNT162b2 Vaccine for Healthcare Workers in South Korea.

J Korean Med Sci 2021 May 3;36(17):e115. Epub 2021 May 3.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea.

Methods: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination.

Results: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%]; BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group ( < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age.

Conclusion: In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.
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http://dx.doi.org/10.3346/jkms.2021.36.e115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093607PMC
May 2021

Effects of Ginsenoside Rg3 on Inhibiting Differentiation, Adipogenesis, and ER Stress-Mediated Cell Death in Brown Adipocytes.

Evid Based Complement Alternat Med 2021 16;2021:6668665. Epub 2021 Mar 16.

College of Korean Medicine, Dongguk University, Goyang, Republic of Korea.

Objectives: Ginsenoside Rg3 (Rg3), a main active component of , has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes.

Methods: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored.

Results: Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs.

Conclusions: Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.
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http://dx.doi.org/10.1155/2021/6668665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990545PMC
March 2021

Transmission Characteristics of SARS-CoV-2 That Hinder Effective Control.

Immune Netw 2021 Feb 22;21(1):e9. Epub 2021 Feb 22.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

The most important characteristics of coronavirus disease 2019 (COVID-19) transmission that makes it difficult to control are 1) asymptomatic and presymptomatic transmission, 2) low incidence or lack of dominant systemic symptoms such as fever, 3) airborne transmission that may need a high infectious dose, and 4) super-spread events (SSEs). Patients with COVID-19 have high viral loads at symptom onset or even a few days prior to symptom onset, and most patients with COVID-19 have only mild respiratory symptoms or merely pauci-/null-symptoms. These characteristics of the virus enable it to easily spread to the community because most patients are unaware of their potential infectivity, and symptom-based control measures cannot prevent this type of transmission. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also capable of airborne transmission in conditions such as aerosol-generating procedures, under-ventilated indoor spaces, and over-crowded areas. In this context, universal mask-wearing is important to prevent both outward and inward transmission until an adequate degree of herd immunity is achieved through vaccination. Lastly, the SSEs of SARS-CoV-2 transmission emphasize the importance of reducing contacts by limiting social gatherings. The above-mentioned transmission characteristics of SARS-CoV-2 have culminated in the failure of long-lasting quarantine measures, and indicate that only highly effective vaccines can keep the communities safe from this deadly, multifaceted virus.
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http://dx.doi.org/10.4110/in.2021.21.e9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937505PMC
February 2021

Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea.

Viruses 2021 02 20;13(2). Epub 2021 Feb 20.

Asan Medical Center, Department of Infectious Diseases, University of Ulsan College of Medicine, Seoul 05505, Korea.

Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been tested using nationwide health-insurance data of South Korea.

Methods: All adults tested for SARS-CoV-2 from 20 January 2020 to 15 May 2020 were identified. HCQ users were defined as patients who had been pretreated with HCQ for at least 30 days until the date of SARS-CoV-2 testing. The prevalence of positive PCR results for SARS-CoV-2 was compared between HCQ users and nonusers.

Results: Of a total of 216,686 individuals who had been tested for SARS-CoV-2, 743 (0.3%) were pretreated with HCQ. The prevalence of positive results was not significantly different between HCQ users (2.2%) and nonusers (2.7%; = 0.35), with an odds ratio of 0.79 (95% confidence interval (CI), 0.48-1.30). Propensity score-matched-cohort analysis showed similar results in terms of the prevalence of positive results (2.2% in HCQ users vs. 3.1% in nonusers; = 0.18), with an odds ratio of 0.69 (95% CI, 0.40-1.19). The rate of positive PCR was not significantly different in long-term HCQ users (more than 3 or 6 months) compared with nonusers.

Conclusions: In this population-based study, recent exposure to HCQ was not significantly associated with a lower risk of SARS-CoV-2 infection. Our data do not support the use of HCQ as pre-exposure prophylaxis against COVID-19.
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http://dx.doi.org/10.3390/v13020329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924588PMC
February 2021

Effects of Recent Use of Renin-Angiotensin System Inhibitors on Mortality of Patients With Coronavirus Disease 2019.

Open Forum Infect Dis 2020 Nov 27;7(11):ofaa519. Epub 2020 Oct 27.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: There is growing concern about the potential harmful effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19) and cardiovascular diseases (CVDs). The aim of this study was to evaluate the association between recent exposure to ACEIs/ARBs and in-hospital mortality in patients with COVID-19.

Methods: We used data from a nationwide cohort of patients with COVID-19 from the health insurance claims data of South Korea, which were released for research purposes for public health by the Ministry of Health and Welfare of South Korea. Patients with COVID-19 were identified using the relevant diagnostic code. Propensity score matching (1:1) was carried out among patients with CVD according to the type of medication (ACEIs/ARBs vs other), and the risk of death was assessed.

Results: A total of 4936 patients with COVID-19 were analyzed, of whom 1048 (21.2%) had CVD. Of the 1048 patients with CVD, 864 (82.4%) received at least 1 antihypertensive medication before the diagnosis of COVID-19, including 359 (41.6%) who received ACEIs/ARBs and 505 (58.4%) who received drugs other than ACEIs/ARBs. Using the propensity scores for ACEI/ARB use, we matched 305 pairs of patients receiving ACEIs/ARBs and patients receiving other drugs. Recent use of ACEIs/ARBs was not significantly associated with in-hospital mortality in unadjusted analysis (odds ratio [OR], 0.62; 95% CI, 0.33-1.14) or propensity score matching analysis (OR, 1.00; 95% CI, 0.46-2.16).

Conclusions: In patients with COVID-19 and underlying CVDs, the recent use of ACEIs/ARBs was not significantly associated with in-hospital mortality. These findings do not support stopping or modifying ACEIs/ARBs in patients during the current COVID-19 pandemic.
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http://dx.doi.org/10.1093/ofid/ofaa519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665750PMC
November 2020

Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis.

Gut 2021 10 18;70(10):1954-1964. Epub 2020 Nov 18.

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Objective: Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.

Design: Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4).

Results: HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of but not was higher in mouse models and patients with NASH. FC in hepatocytes induced expression, and knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis.

Conclusion: SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
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http://dx.doi.org/10.1136/gutjnl-2020-322509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458090PMC
October 2021

Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection.

Thorax 2021 01 22;76(1):61-63. Epub 2020 Sep 22.

Department of Infectious Diseases, Asan Medical Center, Songpa-gu, Seoul, Republic of Korea

Background: Asymptomatic individuals with SARS-CoV-2 infection have viable viral loads and have been linked to several transmission cases. However, data on the viral loads in such individuals are lacking. We assessed the viral loads in asymptomatic individuals with SARS-CoV-2 infection in comparison with those in symptomatic patients with COVID-19.

Methods: Study participants were recruited from a community facility designated for the isolation of patients with mild COVID-19 in South Korea. The presence of symptoms was evaluated with a questionnaire-based survey. Viral loads in the upper respiratory tract were measured with real-time reverse transcription-PCR (RT-PCR) targeting the , and genes of SARS-CoV-2, with a cycle threshold (Ct) value of 40 for determining positivity.

Results: In 213 patients with SARS-CoV-2 infection, 41 (19%) had remained asymptomatic from potential exposure to laboratory confirmation and admission; of them, 39 (95%) underwent follow-up RT-PCR testing after a median 13 days. In 172 symptomatic patients, 144 (84%) underwent follow-up RT-PCR testing. Twenty-one (54%) asymptomatic individuals and 92 (64%) symptomatic patients tested positive for SARS-CoV-2 at follow-up. Asymptomatic individuals and symptomatic patients did not show any significant differences in the mean Ct values of the (31.15 vs 31.43; p>0.99), (32.26 vs 32.93; p=0.92) and (33.05 vs 33.28; p>0.99) genes.

Conclusion: Approximately one-fifth of the individuals without severe symptoms were asymptomatic, and their viral loads were comparable to those in symptomatic patients. A large proportion of mildly symptomatic patients with COVID-19 or asymptomatic individuals with SARS-CoV-2 showed persistent positive upper respiratory RT-PCR results at follow-up.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462047PMC
January 2021

Inconsistency in the use of the term "validation" in studies reporting the performance of deep learning algorithms in providing diagnosis from medical imaging.

PLoS One 2020 11;15(9):e0238908. Epub 2020 Sep 11.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: The development of deep learning (DL) algorithms is a three-step process-training, tuning, and testing. Studies are inconsistent in the use of the term "validation", with some using it to refer to tuning and others testing, which hinders accurate delivery of information and may inadvertently exaggerate the performance of DL algorithms. We investigated the extent of inconsistency in usage of the term "validation" in studies on the accuracy of DL algorithms in providing diagnosis from medical imaging.

Methods And Findings: We analyzed the full texts of research papers cited in two recent systematic reviews. The papers were categorized according to whether the term "validation" was used to refer to tuning alone, both tuning and testing, or testing alone. We analyzed whether paper characteristics (i.e., journal category, field of study, year of print publication, journal impact factor [JIF], and nature of test data) were associated with the usage of the terminology using multivariable logistic regression analysis with generalized estimating equations. Of 201 papers published in 125 journals, 118 (58.7%), 9 (4.5%), and 74 (36.8%) used the term to refer to tuning alone, both tuning and testing, and testing alone, respectively. A weak association was noted between higher JIF and using the term to refer to testing (i.e., testing alone or both tuning and testing) instead of tuning alone (vs. JIF <5; JIF 5 to 10: adjusted odds ratio 2.11, P = 0.042; JIF >10: adjusted odds ratio 2.41, P = 0.089). Journal category, field of study, year of print publication, and nature of test data were not significantly associated with the terminology usage.

Conclusions: Existing literature has a significant degree of inconsistency in using the term "validation" when referring to the steps in DL algorithm development. Efforts are needed to improve the accuracy and clarity in the terminology usage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238908PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485764PMC
November 2020

Effectiveness of surgical, KF94, and N95 respirator masks in blocking SARS-CoV-2: a controlled comparison in 7 patients.

Infect Dis (Lond) 2020 Nov - Dec;52(12):908-912. Epub 2020 Aug 26.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Data on the filtration efficacies of various masks against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. We thus evaluate the effectiveness of the surgical mask, the N95 respirator mask, and its equivalent (KF94 mask) in filtering SARS-CoV-2.

Methods: Patients hospitalised with SARS-CoV-2 infection were instructed to cough five times each while wearing (1) no mask, (2) surgical mask, (3) KF94 mask, and (4) N95 mask. The coughs were separated by 20-second intervals, and the patients were rested for at least 5 min between each setting. SARS-CoV-2 viral loads in patient samples (i.e. nasopharyngeal swabs and saliva), petri dishes placed in front of the patients during coughing, and swabs from the outer and inner surfaces of the masks were analysed with PCR.

Results: A total of 7 patients with SARS-CoV-2 infection participated in the mask test. SARS-CoV-2 was detected on the petri dishes after coughing in 3 out of 7 cases with the surgical mask or no mask. Viral particles were not found in the petri dishes after coughing while wearing the N95 mask or the KF94 mask. While viral particles were detected in both the inner and outer surfaces of the surgical masks, those were detected only in the inner surfaces of the N95 and K94 masks.

Conclusion: Surgical masks were less effective in filtering viral particles from coughing patients with SARS-CoV-2 infection. N95 masks and its equivalents efficiently blocked SARS-CoV-2 particles from coughing patients.
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http://dx.doi.org/10.1080/23744235.2020.1810858DOI Listing
October 2020

Feasibility of a Hybrid Risk-Adapted Monitoring System in Investigator-Sponsored Trials in Cancer.

Ther Innov Regul Sci 2021 01 18;55(1):180-189. Epub 2020 Aug 18.

Clinical Trial Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: We assessed the feasibility of a hybrid monitoring system (minimal on-site monitoring + strategic central monitoring) used at the academic research office at Asan Medical Center (Seoul, Korea) in monitoring investigator-sponsored oncology trials.

Methods: Monitoring findings in three oncology trials conducted between 2014 and 2017 were compared. A confirmatory source data verification (SDV) was carried out in the low-risk trial and compared with the central monitoring findings. The economic advantages of central monitoring were tested by calculating the monitoring hours per patient.

Results: A total of 50, 118, 228 patients were enrolled in the high-, intermediate-, and low-risk trials, respectively. The high-risk trial was monitored through 42 on-site visits (1299 findings); the intermediate-risk trial had 79 monitorings (on-site, 24%; central, 76%; 1464 findings); the low-risk trial had 197 monitorings (on-site, 4%; central, 96%; 3364 findings). Central monitoring was more effective than on-site monitoring in revealing minor errors such as "missing case report forms" and "data outliers" (both P < 0.0001), and showed comparable results in revealing major issues such as investigational product compliance and delayed reporting of serious adverse events (both P > 0.05). Confirmatory SDV in the low-risk trial revealed more findings than central monitoring in the "inconsistent data" and "inappropriate adverse event" categories. The total monitoring hours per patient were lower in the intermediate- and low-risk trials than in the high-risk trial (8.1 and 7.3 vs. 14.3 h, respectively).

Conclusion: Our hybrid monitoring system showed acceptable feasibility in revealing both major and minor issues in multi-center oncology investigator-sponsored trials.
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http://dx.doi.org/10.1007/s43441-020-00204-5DOI Listing
January 2021

Clinical and histological significance of urinary CD11c macrophages in lupus nephritis.

Arthritis Res Ther 2020 07 17;22(1):173. Epub 2020 Jul 17.

Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Infiltration of immune cells into the kidney is one of the key features of lupus nephritis (LN). The presence of immune cells in the urine may be used as a non-invasive biomarker of LN. Here, we aimed to analyze the clinicopathologic significance of urinary CD11c macrophages in patients with LN.

Methods: The numbers and proportions of CD11c macrophages in the urine samples of patients with LN at the time of kidney biopsy were examined using flow cytometry. We also examined the association between the levels of urinary CD11c macrophages and the clinical and pathologic features of patients with LN.

Results: Compared with patients without LN or those with non-proliferative LN, patients with proliferative LN had significantly higher numbers and proportions of urinary CD11c macrophages, which were strongly correlated with the serum anti-dsDNA antibody titer. The numbers and proportions of urinary CD11c macrophages were significantly associated with the values of chronicity indices such as tubular atrophy and interstitial fibrosis. No significant relationships were found between the levels of urinary CD11c macrophages and the activity scores, degree of proteinuria, or lupus disease activity. Urinary CD11c macrophages were more abundant in patients who did not achieve renal response to induction treatment with immunosuppressants than in those who achieved complete or partial response. The receiver operating characteristic (ROC) curve analysis showed that the number of urinary CD11c macrophages was the most powerful predictor of renal response at 6 months (ROC-AUC = 1.00, p = 0.0004).

Conclusion: The urinary levels of CD11c macrophages were closely associated with the chronic pathologic changes of LN and renal response and may thus be used as a novel biomarker in LN.
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http://dx.doi.org/10.1186/s13075-020-02265-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368794PMC
July 2020

Association of herpes zoster with dementia and effect of antiviral therapy on dementia: a population-based cohort study.

Eur Arch Psychiatry Clin Neurosci 2021 Aug 1;271(5):987-997. Epub 2020 Jul 1.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro-43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

We investigated the association between herpes zoster (HZ) and dementia, and the effects of antiviral therapy on the risk of dementia. We used the National Health Insurance Service-National Sample Cohort in South Korea to identify individuals that were followed from January 1, 2002, to December 31, 2013. Occurrences of HZ and dementia were identified using the relevant diagnostic codes. Dementia was defined as the presence of diagnostic codes and history of anti-dementia drug prescription. Propensity score matching (1:1) was carried out among HZ patients according to antiviral therapy. A total of 229,594 individuals aged ≥50 years were analyzed. The incidences of the first-diagnosed HZ and dementia were 16.69 and 4.67 per 1000 person-years (PY), respectively. HZ patients had a higher risk of dementia (incidence rate ratio [IRR], 1.94 [95% CI 1.83-2.06]; adjusted hazard ratio [HR], 1.12 [95% CI 1.05-1.19]). Of the 34,505 patients with HZ, 28,873 (84%) had received antiviral treatment. The crude incidence rates of subsequent dementia in the treated and untreated groups were 7.79 and 12.27 per 1000 PY, respectively, resulting in an IRR of 0.64 (95% CI 0.56-0.72) and covariate-adjusted HR of 0.79 (95% CI 0.69-0.90). After propensity score matching, the treated group showed a significantly lower risk of dementia (HR 0.76; 95% CI 0.65-0.90). In this large population-based cohort study, HZ was associated with a higher risk of dementia. The use of antiviral agents in HZ patients was associated with lower risks of dementia.
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http://dx.doi.org/10.1007/s00406-020-01157-4DOI Listing
August 2021

Effectiveness of Surgical and Cotton Masks in Blocking SARS-CoV-2: A Controlled Comparison in 4 Patients.

Ann Intern Med 2020 07 6;173(1):W22-W23. Epub 2020 Apr 6.

Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (S.B., J.Y.K., H.C., J.J., M.K., D.K.O., S.H., S.K.).

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http://dx.doi.org/10.7326/M20-1342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153751PMC
July 2020

Immunological characteristics and possible pathogenic role of urinary CD11c+ macrophages in lupus nephritis.

Rheumatology (Oxford) 2020 08;59(8):2135-2145

Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: Kidney-infiltrating immune cells can contribute to the pathogenesis of lupus nephritis (LN). We investigated the immunological characteristics of CD11c+ macrophages and their functions associated with the pathogenesis of LN.

Methods: CD11c+ macrophages were examined in the urine samples of patients with LN. Phenotypic markers and pro-inflammatory cytokine expression levels were analysed by flow cytometry. To determine the origin of urinary macrophages, peripheral monocytes were treated with sera from patients with systemic lupus erythematosus (SLE). The pathogenic role of CD11c+ macrophages in tubulointerstitial damage was investigated using SLE sera-treated monocytes and HK-2 cells.

Results: Urinary CD11c+ macrophages expressed pro-inflammatory cytokines, such as IL-6 and IL-1β, and resembled infiltrated monocytes rather than tissue-resident macrophages with respect to surface marker expression. CD11c+ macrophages had high expression levels of the chemokine receptor CXCR3, which were correlated with cognate chemokine IP-10 expression in urinary tubular epithelial cells. When treated with sera from SLE patients, peripheral monocytes acquired the morphological and functional characteristics of urinary CD11c+ macrophages, which was blocked by DNase treatment. Finally, SLE sera-treated monocytes induced fibronectin expression, apoptosis and cell detachment in HK-2 cells via production of IL-6.

Conclusion: CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.
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http://dx.doi.org/10.1093/rheumatology/keaa053DOI Listing
August 2020

Effects of providing manuscript editing through a combination of in-house and external editing services in an academic hospital.

PLoS One 2019 9;14(7):e0219567. Epub 2019 Jul 9.

Scientific Publications Team, Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: English editing services are effective for improving manuscript quality as well as providing learning opportunities for non-native English-speaking authors. Herein, we describe the effects of a combined system of in-house and external editing services for handling large volumes of editing requests and providing personalized editing service in academic hospitals.

Methods: We established the Scientific Publications Team (SPT), an in-house editing team in Asan Medical Center in Seoul, Korea. The SPT is composed of two professional editors who manage editing requests sent to external companies while also providing one-on-one in-house editing services. We gathered author satisfaction data from 936 surveys between July 2017 and December 2018 and analyzed the number of editing requests and research publications by segmented regression analysis of interrupted time series data.

Results: The SPT processed 3931 editing requests in 2017-2018, which was a marked increase compared with prior to its establishment (P = 0.0097). The authors were generally satisfied with the quality of editing services from both in-house and external editors. Upon conducting regular quality control, overall author satisfaction with one external company gradually increased over the course of one year (P for trend = 0.086). Author satisfaction survey results revealed that overall satisfaction of editing service was most strongly correlated with how well the edits conformed to the authors' intentions (R = 0.796), and was only weakly correlated with quick turnaround time (R = 0.355). We also observed a significant increase in the trend of the number of research publications (P = 0.0007) at one year after the establishment of the SPT.

Conclusion: Providing a combination of in-house and external editing services resulted in high author satisfaction and subsequent hospital-wide increases in manuscript writing and publication. Our model system may be adapted in academic hospitals to better address the editing needs of non-native English-speaking researchers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219567PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615627PMC
March 2020
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