Publications by authors named "Jin Yong Lee"

378 Publications

Changes in DNA-binding activity of transcription factors in the kidney of mice exposed to cadmium.

J Toxicol Sci 2021 ;46(3):125-129

Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin Universityn.

Cadmium (Cd) is a toxic heavy metal, long-term exposure to which causes renal damage associated with disruption in gene expression. Transcription factors whose activities were altered in the kidneys of mice exposed to Cd for 3 months were assessed using protein/DNA-binding assays. Female C57BL/6J mice were exposed to 300 ppm Cd in the diet for 3 months. Nuclear extracts of kidney were used for protein/DNA-binding assays. The concentration of Cd was approximately 100 ppm in mouse kidney, a level that did not induce renal toxicity. Among the 345 transcription factors evaluated, five transcription factors showed over a two-fold increase in their activities and 14 transcription factors showed a half-fold change in their activities after Cd exposure. These findings may provide new information about the causative transcription factors associated with Cd renal toxicity.
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http://dx.doi.org/10.2131/jts.46.125DOI Listing
January 2021

New Obligations of Health Insurance Review and Assessment Service: Taking Full-fledged Action Against the COVID-19 Pandemic.

J Prev Med Public Health 2021 Jan 26;54(1):17-21. Epub 2021 Jan 26.

Health Insurance Review and Assessment Service, Wonju, Korea.

In 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruptions to global health systems. The Korea has taken full-fledged actions against this novel infectious disease, swiftly implementing a testing-tracing-treatment strategy. New obligations have therefore been given to the Health Insurance Review and Assessment Service (HIRA) to devote the utmost effort towards tackling this global health crisis. Thanks to the universal national health insurance and state-of-the-art information communications technology (ICT) of the Korea, HIRA has conducted far-reaching countermeasures to detect and treat cases early, prevent the spread of COVID-19, respond quickly to surging demand for the healthcare services, and translate evidence into policy. Three main factors have enabled HIRA to undertake pandemic control preemptively and systematically: nationwide data aggregated from all healthcare providers and patients, pre-existing ICT network systems, and real-time data exchanges. HIRA has maximized the use of data and pre-existing network systems to conduct rapid and responsive measures in a centralized way, both of which have been the most critical tactics and strategies used by the Korean healthcare system. In the face of new obligations, our promise is to strive for a more responsive and resilient health system during this prolonged crisis.
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http://dx.doi.org/10.3961/jpmph.20.594DOI Listing
January 2021

COVID-19 International Collaborative Research by the Health Insurance Review and Assessment Service Using Its Nationwide Real-world Data: Database, Outcomes, and Implications.

J Prev Med Public Health 2021 Jan 26;54(1):8-16. Epub 2021 Jan 26.

HIRA Research Institute, Health Insurance Review and Assessment Service, Wonju, Korea.

This article aims to introduce the inception and operation of the COVID-19 International Collaborative Research Project, the world's first coronavirus disease 2019 (COVID-19) open data project for research, along with its dataset and research method, and to discuss relevant considerations for collaborative research using nationwide real-world data (RWD). COVID-19 has spread across the world since early 2020, becoming a serious global health threat to life, safety, and social and economic activities. However, insufficient RWD from patients was available to help clinicians efficiently diagnose and treat patients with COVID-19, or to provide necessary information to the government for policy-making. Countries that saw a rapid surge of infections had to focus on leveraging medical professionals to treat patients, and the circumstances made it even more difficult to promptly use COVID-19 RWD. Against this backdrop, the Health Insurance Review and Assessment Service (HIRA) of Korea decided to open its COVID-19 RWD collected through Korea's universal health insurance program, under the title of the COVID-19 International Collaborative Research Project. The dataset, consisting of 476 508 claim statements from 234 427 patients (7590 confirmed cases) and 18 691 318 claim statements of the same patients for the previous 3 years, was established and hosted on HIRA's in-house server. Researchers who applied to participate in the project uploaded analysis code on the platform prepared by HIRA, and HIRA conducted the analysis and provided outcome values. As of November 2020, analyses have been completed for 129 research projects, which have been published or are in the process of being published in prestigious journals.
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http://dx.doi.org/10.3961/jpmph.20.616DOI Listing
January 2021

Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population.

J Dermatol 2021 Feb 19. Epub 2021 Feb 19.

Laboratory of Intestinal Mucosa and Skin Immunology, Seoul, Korea.

Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex-matched non-IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD-specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.
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http://dx.doi.org/10.1111/1346-8138.15676DOI Listing
February 2021

Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study.

Dermatology 2021 Feb 8:1-8. Epub 2021 Feb 8.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited.

Objective: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD.

Methods: Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed.

Results: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results.

Conclusions: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.
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http://dx.doi.org/10.1159/000514030DOI Listing
February 2021

Energetically Preferred Bilayered Coacervation of Oppositely Charged ZrHP Nanoplatelets.

ACS Appl Mater Interfaces 2021 Feb 3;13(6):7664-7671. Epub 2021 Feb 3.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

A platform is introduced for bilayered coacervation of oppositely charged nanoplatelets (NPLs) at the oil-water interface. To this end, we synthesized two types of zirconium hydrogen phosphate (ZrHP) NPLs, cationically charged NPLs (CNPLs), and anionically charged NPLs (ANPLs) by conducting surface-initiated atom transfer radical polymerization. Taking advantage of the platelet geometry and controlled wettability, we demonstrated that ANPLs and CNPLs coacervate themselves to form a bilayered NPL membrane at the interface, which was directly confirmed by confocal laser scanning microscopy. Via theoretical consideration using the hit-and-miss Monte Carlo method, we determined that electrostatic attraction-driven coacervation of ANPLs and CNPLs at the interface shows a minimum attachment energy of ∼ -10T, which is comparable to the cases where NPLs charged with the same type of ions are attached. Finally, this unique and novel interfacial coacervation behavior allowed us to develop a pH-responsive smart Pickering emulsion system.
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http://dx.doi.org/10.1021/acsami.0c18116DOI Listing
February 2021

Power of universal health coverage in the era of COVID-19: A nationwide observational study.

Lancet Reg Health West Pac 2021 Feb 22;7:100088. Epub 2021 Jan 22.

Public Healthcare Center, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

Background: During the COVID-19 pandemic, South Korea has achieved perfect universal health coverage (UHC)-all Koreans receive UHC regardless of their socioeconomic status. The current study investigated whether socioeconomic disparities remained in COVID-19 health outcomes under UHC.

Methods: This retrospective, observational study included all 7,590 confirmed COVID-19 patients in South Korea up to 15 May 2020. We used the official medical claim database, and socioeconomic status was estimated by insurance type (National Health Insurance Service [NHIS] beneficiaries and Medical Aid [MA] recipients). Type of insurance is a well-known indicator of socioeconomic status. Prevalence (per one million), mortality rate (per one million), and case fatality rate were calculated. To determine the factors associated with case fatality rate, multivariable logistic regressions were performed.

Findings: The nationwide prevalence, mortality rate, and case fatality rate of COVID-19 was 144•4, 4•3 and 3•0%, respectively. MA recipients had higher prevalence (424•3 vs 136.3), mortality rate (28•3 vs 3•6), and case fatality rate (6•7 vs 2•7) than NHIS beneficiaries. However, the adjusted analysis showed that the type of insurance was not associated with higher odds of case fatality.

Interpretation: We found socioeconomic disparities in COVID-19 prevalence and fatality despite UHC. However, disparities in fatality were not due to socioeconomic status, but due to the poor underlying health conditions of the people. This result can be explained by a combination of UHC, rapid early testing and treatment, transmission-reducing behaviours, and regional preparedness.

Funding: This research did not receive any funding.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826087PMC
February 2021

New design strategy for chemically-stable blue phosphorescent materials: improving the energy gap between the T and MC states.

Phys Chem Chem Phys 2021 Feb 29;23(5):3543-3551. Epub 2021 Jan 29.

Display Research Center, Samsung Display Co., 1 Samsung-ro, Giheung-gu, Yongin, Gyeonggi, South Korea.

A series of Ir- and Pt-based blue phosphorescent materials were theoretically investigated by means of density functional theory (DFT) calculations to improve their chemical stability in the excited state. High energy splitting between the lowest triplet state (T state), generally a metal-to-ligand charge transfer state (MLCT), and the triplet metal-centred state (MC) can prohibit ligand dissociation and suppress the decomposition reaction from the MC state to the dissociated S. Here, we suggest a new design strategy to improve the chemical stability of blue phosphorescent materials in the excited state. Introducing inter- and intra-ligand interactions in Ir and Pt complexes can dramatically increase the ΔE(MC-T) because attractive or repulsive couplings arising from intra- or inter-ligand interactions can effectively prevent the out-of-plane bending vibrational mode in Ir complexes and the ring deformation vibrational mode in Pt complexes. A ΔE(MC-T) values of 18.62 kcal mol for an Ir complex and 22.86 kcal mol for a Pt complex from the T energy were obtained while the T energy was maintained in the blue region. To the best of our knowledge, these are the highest ΔE(MC-T) values reported to date. We believe that the present research provides profound insights into the excited state chemical stability of deep blue phosphorescent materials that could be implemented to improve device lifetimes.
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http://dx.doi.org/10.1039/c9cp05781aDOI Listing
February 2021

Protein-Activatable Diarylethene Monomer as a Smart Trigger of Noninvasive Control Over Reversible Generation of Singlet Oxygen: A Facile, Switchable, Theranostic Strategy for Photodynamic-Immunotherapy.

J Am Chem Soc 2021 Feb 28;143(5):2413-2422. Epub 2021 Jan 28.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 120-750, Korea.

The development of activatable photosensitizers to allow for the reversible control of singlet oxygen (O) production for photodynamic therapy (PDT) faces great challenges. Fortunately, the flourishing field of supramolecular biotechnology provides more effective strategies for activatable PDT systems. Here, we developed a new reversible PDT on a switch that controls the O generation of self-assembled albumin nanotheranostics in vitro and in vivo. A new molecular design principle of aggregation-induced self-quenching photochromism and albumin on-photoswitching was demonstrated using a new asymmetric, synthetic diarylethene moiety . The photosensitizer porphyrin and were incorporated as building blocks in a glutaraldehyde-induced covalent albumin cross-linking nanoplatform, (NPs). More importantly, the excellent photoswitching property of enables the resultant nanoplatform to act as a facile, switchable strategy for photodynamic-immunotherapy.
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http://dx.doi.org/10.1021/jacs.0c12851DOI Listing
February 2021

Porous CoSe@N-doped carbon nanowires: an ultra-high stable and large-current-density oxygen evolution electrocatalyst.

Chem Commun (Camb) 2021 Feb 21;57(14):1774-1777. Epub 2021 Jan 21.

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.

Nitrogen doped carbon functionalized CoSe nanowires (CoSe@N-C NWs), which act as potential oxygen evolution reaction (OER) catalysts with a large current density and high stability have been reported. Owing to the collaborative optimization of electrical conductivity, free adsorption energy and binding strength of OER intermediates, the prepared CoSe@N-C NWs exhibit an enhanced 6.61-fold catalytic activity compared to the pristine CoSe NW electrode in 1.0 M KOH solution at the overpotential of 340 mV.
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http://dx.doi.org/10.1039/d0cc07647cDOI Listing
February 2021

Development of -Coumaric Acid Analysis in Human Plasma and Its Clinical Application to PK/PD Study.

J Clin Med 2020 Dec 30;10(1). Epub 2020 Dec 30.

Department of Pharmaceutical Engineering, Inje University, Gimhae 50834, Korea.

It has been recognized that -Coumaric acid (-CA) has protective effects as an antioxidant, anti-inflammatory agent. A sensitive and efficient Liquid Chromatography-Mass Spectrometry (LC-MS) method for maximum determination of -CA in human plasma has been established using Ultra-performance liquid Chromatography-tandem mass Spectrometry (UPLC-MS/MS). This study provides the developed analysis of -CA extracted from in Taeniam (BC) to examine the improvement of the treatment -CA, IGF-1 and Osteocalcin level in human children which are important factors on the growth of children's height through Pharmacokinetics/Pharmacodynamics (PK/PD) model. -CA and internal standard in a plasma sample were detected by the Multiple Reaction Monitoring (MRM) scan mode with positive ion detection. The sample participating in the study was made of 34 subjects (placebo = 18, treatment = 16). The subjects were enrolled to be randomized to the control group and BC group. Randomized subjects took tested treatment twice a day, three capsules with oral administration (258 mg/capsule) each time after a meal. Standard calibration curves (reproducibility) were constructed and the lower limit of quantitation (LLOQ) for -CA was found to be 0.2 ng/mL on injection of the sample into the UPLC-MS/MS system. Accuracy and precision were evaluated and the intra-accuracy was 99.2-103.8% with precision of 1.0-5.6% and inter-accuracy was 99.6-108.4% and precision of 1.3-6.4% for -CA. The method has been successfully applied to PK/PD studies of -CA in human plasma. The -CA, BC in Taeniam extract increased the level of IGF-1 and Osteocalcin, and changed the height from baseline, which suggested that the -CA could play an important role in longitudinal bone growth. Therefore, the -CA extracted from BC in Taeniam might be a good alternative medicine to growth hormone (GH) therapy.
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http://dx.doi.org/10.3390/jcm10010108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795779PMC
December 2020

Cadmium toxicity mediated by the inhibition of SLC2A4 expression in human proximal Tubule cells.

FASEB J 2021 Jan;35(1):e21236

Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.

Cadmium (Cd) is an environmental contaminant that causes renal toxicity. We have previously demonstrated that Cd induces renal toxicity by altering transcriptional activities. In this study, we show that Cd markedly inhibited the activity of transcription factor MEF2A in HK-2 human proximal tubule cells, which generated significant cytotoxicity in the cells. This reduction in the nuclear levels of MEF2A protein may be involved in the Cd-induced inhibition of MEF2A activity. We also demonstrate that one of the glucose transporters, GLUT4, was downregulated not only by Cd treatment but also by MEF2A knockdown. Knockdown of SLC2A4, encoding GLUT4, eliminated both cell viability and Cd toxicity. Cd treatment or SLC2A4 deficiency reduced the cellular concentration of glucose. Therefore, the suppression of SLC2A4 expression, which mediates the reduction in cellular glucose, is involved in Cd toxicity. The Cd toxicity induced by the reduction in GLUT4 may be associated with a reduction of cellular ATP levels in HK-2 cells. The levels of Slc2a4 mRNA in the kidney of mice exposed to Cd for 6 or 12 months were significantly lower than those in the control group. These results demonstrate that Cd exerts its cytotoxicity through the suppression in SLC2A4 expression and the subsequent inhibition of MEF2A transcriptional activity. Cd-induced suppression of SLC2A4 expression also reduces cellular ATP levels, partly by reducing glucose levels. This study suggests that the glucose transporter plays an important role in the renal toxicity of Cd, and provides a crucial breakthrough in our understanding of the mechanism of Cd toxicity.
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http://dx.doi.org/10.1096/fj.202001871RDOI Listing
January 2021

NiSn Atomic Pair on Integrated Electrode for Synergistic Electrocatalytic CO2 Reduction.

Angew Chem Int Ed Engl 2020 Dec 14. Epub 2020 Dec 14.

Beijing University of Chemical Technology, Science College, Beisanhuan East Road No.15, 100029, Beijing, CHINA.

Electrochemical CO 2 reduction (CO 2 RR) to value-added chemicals offers an efficient way to mitigate global warming and energy supply issues. However, the development of highly efficient electrocatalysts for CO 2 RR to boost reaction efficiency and guide understanding of catalytic mechanism remains a huge challenge. Herein, we demonstrate a NiSn atomic pair electrocatalyst (NiSn-APC) on a hierarchical integrated electrode, which exhibits a synergistic effect in simultaneously promoting the activity and selectivity of CO 2 RR to formate. The NiSn atomic pair consist of adjacent Ni and Sn coordinated with four nitrogen atoms (N 4 -Ni-Sn-N 4 ) respectively, which is confirmed by high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM) and extended X-ray absorption fine structure (EXAFS). Typically, the as-prepared NiSn-APC displays an exceptional activity toward CO 2 RR to formate with a turnover frequency of 4752 h -1 , a formate productivity of 36.7 mol h -1 g Sn -1 and an utilization degree of active sites (57.9%), which are superior to the previously reported single-atomic catalysts (SACs). Moreover, both in situ attenuated total reflection-infrared (ATR-IR) spectroscopy and density functional theory (DFT) calculation verify the electron redistribution of Sn imposed by adjacent Ni, which reduces the energy barrier of *OCHO intermediate and makes this potential-determining step thermodynamically spontaneous. The NiSn synergistic catalysis for CO 2 RR in this work provides a successful paradigm for rational design and preparation of atomic pair electrocatalysts with largely enhanced performance.
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http://dx.doi.org/10.1002/anie.202014655DOI Listing
December 2020

A microfluidic cathodic photoelectrochemical biosensor chip for the targeted detection of cytokeratin 19 fragments 21-1.

Lab Chip 2021 01 14;21(2):378-384. Epub 2020 Dec 14.

Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, PR China.

A microfluidic chip integrated with a microelectrode and a cathodic photoelectrochemical (PEC) biosensor for the ultrasensitive detection of non-small cell lung cancer cytokeratin fragments based on a signal amplification strategy was designed. The mechanism for signal amplification is developed based on the p-n junction of AgI/BiGaO, with dissolved O as an electron acceptor to produce the superoxide anion radical (˙O) as the working microelectrode. By combining this with a novel superoxide-dismutase-loaded honeycomb manganese oxide nanostructure (SOD@hMnO) as the co-catalyst signal amplification label, ˙O can be catalyzed by SOD via a disproportionation reaction to produce O and HO; then, hMnO is able to trigger the decomposition of HO to generate O and HO. Therefore, the increased O promotes the separation of electron-hole pairs via consuming more electrons, leading to an effective enhancement of the cathodic PEC behavior. Under optimum conditions, with the cytokeratin 19 fragments 21-1 (CYFRA 21-1) as the targeted detection objects, the microfluidic cathodic PEC biosensor chip exhibited excellent linearity from 0.1 pg mL to 100 ng mL, with a detection limit of 0.026 pg mL (S/N = 3). The exciting thing that this work offers is a new strategy for the detection of other important cancer biomarkers for disease diagnosis and prognosis.
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http://dx.doi.org/10.1039/d0lc01063dDOI Listing
January 2021

Application of Testing-Tracing-Treatment Strategy in Response to the COVID-19 Outbreak in Seoul, Korea.

J Korean Med Sci 2020 Nov 23;35(45):e396. Epub 2020 Nov 23.

HIRA Research Institute, Health Insurance Review & Assessment Service, Wonju, Korea.

Background: Following the coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, a total of 637 patients had been diagnosed with the disease in Seoul as of May 2, 2020. Our study aimed to describe the impact of the 3T strategies (preemptive testing, prompt tracing and proper treatment) on the epidemiological characteristics of COVID-19 in Seoul.

Methods: The descriptive and explanatory analysis was carried out on critical indicators such as epidemiological characteristics and key duration of patient status change from January 24 to May 2 in Seoul before and after preemptive testing for patients under investigation associated with COVID-19 clusters.

Results: Preemptive testing increased the positive test rate (3.9% to 4.2%), an asymptomatic case at diagnosis (16.9% to 30.6%), and reduced the time from symptom onset to quarantine (4.0 to 3.0 days). Prompt tracing decreased unknown sources of infection (6.9% to 2.8%), the mean number of contacts (32.2 to 23.6), and the time-varying reproduction number R(t) (1.3 to 0.6). With proper treatment, only 2 cases of mortality occurred, resulting in a fatality rate of just 0.3%.

Conclusion: In the first wave of the COVID-19 pandemic lasting 100 days, the effect of the 3T strategies flattened the curve and decreased the time during which infected individuals were contagious, thereby lowering the R(t) below 1 in Seoul.
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http://dx.doi.org/10.3346/jkms.2020.35.e396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683243PMC
November 2020

Monitoring aromatic ring-currents in Mg-porphyrin by time-resolved circular dichroism.

Phys Chem Chem Phys 2020 Nov;22(45):26605-26613

Department of Chemistry, Physics and Astronomy, University of California, Irvine, 92697-2025, USA.

Time-resolved circular dichroism signals (TRCD) in the X-ray regime can directly probe the magnitude and the direction of ring currents in molecules. The electronic ring currents in Mg-porphyrin, generated by a coherent superposition of electronic states induced by a circularly polarized UV pulse, are tracked by a time-delayed circularly polarized attosecond X-ray pulse. The signals are calculated using the minimal coupling Hamiltonian, which directly makes use of transition current densities. The TRCD signals obtained from the left and right circularly polarized light pump have opposite signs, revealing the direction of the ring current. Molecular aromaticity and its role in photochemical reactions such as ring opening or closure can be studied using this technique.
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http://dx.doi.org/10.1039/d0cp04815aDOI Listing
November 2020

Suboptimal medication adherence in young women living with HIV infection: a Korean nationwide claims study.

AIDS Care 2020 Nov 10:1-5. Epub 2020 Nov 10.

Department of Public Health and Community Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.

The epidemiological characteristics of women living with human immunodeficiency virus (HIV) infection have gained little attention as the numbers are small compared with men living with HIV in the Republic of Korea. However, these data are important to achieve effective HIV infection control and to consider the influence of socioeconomic status on HIV transmission. This study utilized the claims database of the Korean National Health Insurance system to analyze women with a newly diagnosed HIV infection during the period 2009-2016. Adherence to antiretroviral agents was calculated using the medication possession ratio. Among 677 women with a newly diagnosed HIV infection, 219 (32.4%) were over 50 years of age; 291 (43.0%) were identified as having acquired immune deficiency syndrome (AIDS). A total of 99 women (14.6%) were National Medical Aid beneficiaries. Optimal medical adherence >95% was found in 62.2% of subjects. Teenage years (odds ratio(OR) 14.9, 95% confidence interval (95CI) 4.9-44.8), AIDS (OR 1.7, 95CI 1.2-2.3), and low economic status requiring National Medical Aid (OR 3.0, 95CI 2.0-4.6) were associated to adherence. Diagnosis prior to 2012 was also associated with poor adherence. In women, particularly young patients with low economic status, extra attention is required to enhance adherence to prescribed medication.
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http://dx.doi.org/10.1080/09540121.2020.1844863DOI Listing
November 2020

An Ethacrynic Acid-Brominated BODIPY Photosensitizer (EA-BPS) Construct Enhances the Lethality of Reactive Oxygen Species in Hypoxic Tumor-Targeted Photodynamic Therapy.

Angew Chem Int Ed Engl 2021 02 16;60(6):3196-3204. Epub 2020 Dec 16.

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Despite being a clinically approved intervention for cancer, photodynamic therapy (PDT) still suffers from limitations. Prime among these is a therapeutic response that is mostly oxygen dependent. This limits the utility of PDT in treating hypoxic tumors since lower levels of cytotoxic reactive oxygen species (ROS) are generated in regions of low oxygen tension. Glutathione-pi (GST-pi) is a key enzyme that militates against ROS-mediated apoptosis. We report herein a new construct, EA-BPS, that contains both a brominated BODIPY photosensitizer (BPS) and an ethacrynic acid (EA) GST-pi inhibitor. Photoirradiation of EA-BPS induces a synergistic antitumor effect that results from the combination of ROS production and GST-pi inhibition. Relative to BPS alone, an enhanced cell-killing effect is seen under hypoxic conditions both in vitro and in vivo. We conclude that by making better use of the available oxygen in tumor environments, improved therapeutic PDT outcomes should be achievable even under hypoxic conditions.
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http://dx.doi.org/10.1002/anie.202012687DOI Listing
February 2021

Intrinsic Origin of Tau Protein Aggregation: Effects of Histidine Tautomerism on Tau Monomer.

ACS Chem Neurosci 2020 11 4;11(22):3814-3822. Epub 2020 Nov 4.

Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea.

Histidine tautomerism is considered a crucial component that affects the constitutional and accumulation characteristics of the tau monomer in the neutral condition, which are connected with the pathobiology of Alzheimer's disease (AD). Interpreting the organizational characteristics and accumulation procedure is a challenging task because two tautomeric conformations (the N-H or N-H tautomer) can occur in the open neutral condition. In the current work, replica-exchange molecular dynamics (REMD) simulations were performed to investigate the structural properties of the tau monomer considering the histidine tautomeric effect. Based on the simulation outcomes, the histidine 268 (H268) (δ)-H299 (δ) (δδ) isomer had the highest β-sheet content with a value of 26.2%, which acquires a sheet-governing toxic conformer with the first abundant conformational state of 22.6%. In addition, δδ displayed notable antiparallel β-sheets between lysine 8 (K8)-asparagine 13 (N13) and valine 40 (V40)-tyrosine 44 (Y44) as well as between K32-H33 and V40-Y44 (β-meander supersecondary structure), indicating this tautomeric isomer may exist to stimulate tau oligomerization. Furthermore, H299 was found to play an essential role in the structural stabilization of the δδ isomer compared with H268. The present research will aid in obtaining insight into the organizational and accumulation properties of tau protein in the presence of histidine tautomerism to control AD.
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http://dx.doi.org/10.1021/acschemneuro.0c00587DOI Listing
November 2020

N^N Pt(II) Bisacetylide Complexes with Oxoverdazyl Radical Ligands: Preparation, Photophysical Properties, and Magnetic Exchange Interaction between the Two Radical Ligands.

Inorg Chem 2020 Sep 13;59(17):12471-12485. Epub 2020 Aug 13.

Zavoisky Physical-Technical Institute, FRC Kazan Scientific Center of RAS, Kazan 420029, Russia.

To study the effect of a stable radical on the photophysical properties of a phosphorescent Pt(II) coordination framework and the intramolecular magnetic interaction between radical ligands in the N^N Pt(II) bisacetylide complexes, we prepared a series of N^N Pt(II) bis(acetylide) complexes with oxoverdazyl radical acetylide ligands. The linker between the Pt(II) center and the spin carrier was systematically varied, to probe the effect on the sign and magnitude of the spin exchange interactions between the radical ligands and photophysical properties. The complexes were studied with steady-state and femtosecond/nanosecond transient absorption spectroscopy, continuous-wave electron paramagnetic resonance (EPR) spectroscopy, and density functional theory (DFT) computations. The transient absorption spectral studies show that the doublet excited state of the radicals are short-lived (τ ≈ 2 ps) and nonfluorescent. Moreover, the intrinsic long-lived triplet excited state (τ = 1.2 μs) of the Pt(II) coordination center was efficiently quenched by the radical (τ = 6.9 ps for one representative radical Pt(II) complex). The intramolecular magnetic interaction between the radical ligands through the diamagnetic Pt(II) atom was studied with temperature-dependent EPR spectroscopy; antiferromagnetic exchange interaction (- SS, = -5.4 ± 0.1 cm) for the complex with the shortest radical-radical distance through bridge fragments was observed. DFT computations give similar results for the sign and magnitude of the values. For complexes with larger inter-radical distance, however, very weak coupling between the radical ligands was observed (|| < 0.7 cm). Our results are useful for the study of the effect of a radical on the photophysical properties of the phosphorescent transition-metal complexes.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01575DOI Listing
September 2020

Author Correction: Healthcare utilization among children and young people with life-limiting conditions: Exploring palliative care needs using National Health Insurance claims data.

Sci Rep 2020 Aug 11;10(1):13830. Epub 2020 Aug 11.

Department of Paediatrics, Seoul National University Hospital, Seoul, Republic of Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-69836-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417546PMC
August 2020

Tautomeric Effect of Histidine on β-Sheet Formation of Amyloid Beta 1-40: 2D-IR Simulations.

Biophys J 2020 08 18;119(4):831-842. Epub 2020 Jul 18.

Department of Chemistry, Sungkyunkwan University, Suwon, Korea. Electronic address:

Histidine state (protonated or δ or ε tautomer) has been considered the origin of abnormal misfolding and aggregation of β-amyloid (Aβ). Our previous studies reported that the δδδ isomer of Aβ (1-40) has a greater propensity for β-sheet conformation compared to other isomers. However, direct proof of the tautomeric effect has not been reported. In this context, we calculated histidine site-specific two-dimensional infrared spectroscopy of the δδδ, εεε, and πππ (all protonated histidine) systems within the framework of classical molecular dynamics simulations aiming at connecting our previous results with the current experimental observations. Our results showed that β-sheet formation is favored for the δδδ and πππ tautomers compared with the εεε tautomer, consistent with our previous studies. This result was further supported by contact map analyses and the strength of dipole coupling between the amide-I bonds of each residue. The two-dimensional infrared diagonal trace for each tautomer included three distinctive spectrally resolvable peaks near 1680, 1686, and 1693 cm, as was also observed for histidine dipeptides. However, the peak positions at His6, His13, and His14 did not show a consensus trend with the histidine or protonation state but were instead affected by the presence of surrounding hydrogen bonds. Our study provides a deeper insight into the influence of tautomerism and protonation of histidine residues in Aβ (1-40) on amyloid misfolding and provides a connection between our previous simulations and experimental observations.
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http://dx.doi.org/10.1016/j.bpj.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451942PMC
August 2020

Insights into amyotrophic lateral sclerosis linked Pro525Arg mutation in the fused in sarcoma protein through analysis and molecular dynamics simulation.

J Biomol Struct Dyn 2020 Jul 20:1-14. Epub 2020 Jul 20.

Department of Chemistry, Sungkyunkwan University, Suwon, Korea.

A novel heterozygous mutation, Pro525Arg (P525R) in the Fused in Sarcoma (FUS) protein is predominant in young adult females with familial amyotrophic lateral sclerosis (fALS). Investigation of the biophysical characteristics of this mutation through analysis of protein conformation could provide insights into the pathogenic mechanism of amyotrophic lateral sclerosis (ALS). Here, several computational prediction tools were applied to investigate the effect of P525R on the stability, flexibility, and function of FUS. Conservation and biochemical analyses showed that P525 is highly conserved; the mutation of proline to arginine at position 525 in FUS results in a notable increase in molecular weight, number of hydrogen bonds, and loss of hydrophobicity. By performing electrostatic potential, intra-protein interaction, and binding affinity analyses, we found increased electrostatic potential charge in the mutant protein and fewer hydrophobic interactions than the wild-type structure. Binding affinity of the FUS nuclear localization signal (NLS) mutant for transportin (Trn1) was also decreased compared to wild-type. Our molecular dynamics (MD) simulation results highlighted the exchange between hydrophobic and hydrophilic residues from the core to the surface in the mutant structure; also, upon P525R mutation, FUS became less stable, less flexible and more compact and rigid. Overall, this study demonstrated that the Pro525Arg mutation significantly alters the structure and conformation of FUS through loss of nuclear function, thereby likely contributing to its accumulation in the cytoplasm, which has been implicated in the pathogenesis of fALS. Our study can potentially aid in the design of drugs for FUS-associated neurodegenerative diseases.
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http://dx.doi.org/10.1080/07391102.2020.1794967DOI Listing
July 2020

Methylmercury toxic mechanism related to protein degradation and chemokine transcription.

Environ Health Prev Med 2020 Jul 17;25(1):30. Epub 2020 Jul 17.

Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.

Methylmercury is an environmental pollutant that causes neurotoxicity. Recent studies have reported that the ubiquitin-proteasome system is involved in defense against methylmercury toxicity through the degradation of proteins synthesizing the pyruvate. Mitochondrial accumulation of pyruvate can enhance methylmercury toxicity. In addition, methylmercury exposure induces several immune-related chemokines, specifically in the brain, and may cause neurotoxicity. This summary highlights several molecular mechanisms of methylmercury-induced neurotoxicity.
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http://dx.doi.org/10.1186/s12199-020-00868-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469908PMC
July 2020

Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum.

Toxicol Lett 2020 Oct 6;332:130-139. Epub 2020 Jul 6.

Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, 464-8650, Japan. Electronic address:

Cadmium (Cd) is an environmental contaminant that triggers toxic effects in various tissues such as the kidney, liver, and lung. Cd can also cause abnormal iron metabolism, leading to anemia. Iron homeostasis is regulated by intestinal absorption. However, whether Cd affects the iron absorption pathway is unclear. We aimed to elucidate the relationship between the intestinal iron transporter system and Cd-induced iron deficiency anemia. C57BL/6J female and male mice, 129/Sv female mice, and DBA/2 female mice were given a single oral dose of CdCl by gavage. After 3 or 24 h, Cd decreased serum iron concentrations and inhibited the expression of iron transport-related genes in the duodenum. In particular, Cd decreased the levels of divalent metal transporter 1 and ferroportin 1 in the duodenum. In addition, human colon carcinoma Caco-2 cells were treated with CdCl. After 72 h, Cd decreased the expression of iron transport-related factors in Caco-2 cells with a pattern similar to that seen in the murine duodenum. These findings suggest that Cd inhibits iron absorption through direct suppression of iron transport in duodenal enterocytes and contributes to abnormal iron metabolism.
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http://dx.doi.org/10.1016/j.toxlet.2020.07.005DOI Listing
October 2020

Coronavirus Disease Exposure and Spread from Nightclubs, South Korea.

Emerg Infect Dis 2020 Oct 7;26(10):2499-2501. Epub 2020 Jul 7.

At least 246 cases of coronavirus disease (COVID-19) have been linked to nightclubs in Seoul, South Korea. During the April 30-May 5 holiday, young adults from across the country who visited nightclubs in Seoul contracted COVID-19 and spread it nationally. Nightclubs were temporarily closed to limit COVID-19 spread.
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http://dx.doi.org/10.3201/eid2610.202573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510694PMC
October 2020

Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury.

Life Sci 2020 Sep 29;256:118031. Epub 2020 Jun 29.

Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Laboratory of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address:

Aims: We had previously reported that addition of putrescine to the culture medium was reported to reduce methylmercury toxicity in C17.2 neural stem cells. Here, we have examined the inhibition of methylmercury-induced cytotoxicity by putrescine using ODC1-overexpressing C17.2 cells.

Materials And Methods: We established stable ODC1-overexpressing C17.2 cells and evaluated methylmercury-induced apoptosis by examining the TUNEL assay and cleaved caspase-3 levels. Mitochondria-mediated apoptosis was also evaluated by reduction of mitochondrial membrane potential and recruitment of Bax and Bak to the mitochondria.

Key Findings: ODC is encoded by ODC1 gene, and putrescine levels in ODC1-overexpressing cells were significantly higher than in control cells. Overexpression of ODC1 and addition of putrescine to the culture medium suppressed DNA fragmentation and caspase-3 activation, which are observed when apoptosis is induced by methylmercury. Moreover, mitochondrial dysfunction and reactive oxygen species (ROS) generation, caused by methylmercury, were also inhibited by the overexpression of ODC1 and putrescine; pretreatment with ODC inhibitor, however, promoted both ROS generation and apoptosis by methylmercury. Finally, we found that Bax and Bak, the apoptosis-promoting factors, to be increased in mitochondria, following methylmercury treatment, and the same was inhibited by overexpression of ODC1. These results suggest that overexpression of ODC1 may prevent mitochondria-mediated apoptosis by methylmercury via increase of putrescine levels.

Significance: Our findings provide important clues to clarify mechanisms involved in the defense against methylmercury toxicity and suggest novel biological functions of putrescine.
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http://dx.doi.org/10.1016/j.lfs.2020.118031DOI Listing
September 2020

Impact of A2V Mutation and Histidine Tautomerism on Aβ42 Monomer Structures from Atomistic Simulations.

J Chem Inf Model 2020 Jul 30;60(7):3587-3592. Epub 2020 Jun 30.

Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea.

The self-assembly of amyloid-β (Aβ) peptides into senile plaques in the brain is a hallmark of Alzheimer's disease (AD) pathology. Mutation and histidine tautomerism are considered intrinsic origins in the accumulation of Aβ. As a first step toward understanding the impact of A2V mutation and histidine tautomerism on the Aβ42 isoform, we performed replica-exchange molecular dynamics (REMD) simulations to investigate the effects of histidine tautomerism on the structural properties of A2V Aβ42 peptides. There are generally more β-sheet and less α-helix secondary structures in A2V Aβ42 monomers than in WT Aβ42, implying a higher aggregation tendency in A2V Aβ42, which is consistent with previous studies. The current research will help develop the histidine tautomerism hypothesis of misfolded protein aggregation and eventually elucidate the pathogenesis of AD.
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http://dx.doi.org/10.1021/acs.jcim.0c00267DOI Listing
July 2020

Social Distancing and Transmission-reducing Practices during the 2019 Coronavirus Disease and 2015 Middle East Respiratory Syndrome Coronavirus Outbreaks in Korea.

J Korean Med Sci 2020 Jun 15;35(23):e220. Epub 2020 Jun 15.

Department of Health Policy and Management, Seoul National University College of Medicine, Seoul, Korea.

Background: The absence of effective antiviral medications and vaccines increased the focus on non-pharmaceutical preventive behaviors for mitigating against the coronavirus disease 2019 (COVID-19) pandemic. To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea.

Methods: This was a serial cross-sectional population-based study in Korea with four surveys conducted on June 2 and 25, 2015 (MERS-CoV surveys), and February 4, and April 2, 2020 (COVID-19 surveys). Of 25,711 participants selected using random digit dialing numbers, 4,011 participants (aged ≥ 18 years) were successfully interviewed, for the 2020 COVID-19 (n = 2,002) and 2015 MERS-CoV (n = 2,009) epidemics were included. Participants were selected post-stratification by sex, age, and province. The total number of weighted cases in this survey equaled the total number of unweighted cases at the national level. We measured the levels of preventive behaviors (social distancing [avoiding physical contact with others]), and practicing transmission-reducing behaviors such as wearing face mask and handwashing.

Results: Between the surveys, respondents who reported practicing social distancing increased from 41.9%-58.2% (MERS-CoV) to 83.4%-92.3% (COVID-19). The response rate for the four surveys ranged between 13.7% and 17.7%. Practicing transmission-reducing behaviors (wearing face masks and handwashing) at least once during COVID-19 (78.8%, 80.2%) also increased compared to that during MERS-CoV (15.5%, 60.3%). The higher affective risk perception groups were more likely to practice transmission-reducing measures (adjusted odds ratio, 3.24-4.81; 95 confidence interval, 1.76-6.96) during both COVID-19 and MERS-CoV.

Conclusion: The study findings suggest markedly increased proportions of non-pharmaceutical behavioral practices evenly across all subgroups during the two different novel virus outbreaks in Korea. Strategic interventions are needed to attempt based on preventive behavior works.
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http://dx.doi.org/10.3346/jkms.2020.35.e220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295600PMC
June 2020

Quantification of three-dimensional facial asymmetry for diagnosis and postoperative evaluation of orthognathic surgery.

Maxillofac Plast Reconstr Surg 2020 Dec 25;42(1):17. Epub 2020 May 25.

Department of Oral and Maxillofacial Surgery, Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongro-gu, Seoul, 03080 South Korea.

Background: To evaluate the facial asymmetry, three-dimensional computed tomography (3D-CT) has been used widely. This study proposed a method to quantify facial asymmetry based on 3D-CT.

Methods: The normal standard group consisted of twenty-five male subjects who had a balanced face and normal occlusion. Five anatomical landmarks were selected as reference points and ten anatomical landmarks were selected as measurement points to evaluate facial asymmetry. The formula of facial asymmetry index was designed by using the distances between the landmarks. The index value on a specific landmark indicated zero when the landmarks were located on the three-dimensional symmetric position. As the asymmetry of landmarks increased, the value of facial asymmetry index increased. For ten anatomical landmarks, the mean value of facial asymmetry index on each landmark was obtained in the normal standard group. Facial asymmetry index was applied to the patients who had undergone orthognathic surgery. Preoperative facial asymmetry and postoperative improvement were evaluated.

Results: The reference facial asymmetry index on each landmark in the normal standard group was from 1.77 to 3.38. A polygonal chart was drawn to visualize the degree of asymmetry. In three patients who had undergone orthognathic surgery, it was checked that the method of facial asymmetry index showed the preoperative facial asymmetry and the postoperative improvement well.

Conclusions: The current new facial asymmetry index could efficiently quantify the degree of facial asymmetry from 3D-CT. This method could be used as an evaluation standard for facial asymmetry analysis.
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http://dx.doi.org/10.1186/s40902-020-00260-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248163PMC
December 2020