• Information Systems Review
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• v.24 no.1
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• pp.21-37
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• 2022

Drug repositioning, one of the methods of developing new drugs, is a useful way to discover new indications by allowing drugs that have already been approved for use in people to be used for other purposes. Recently, with the development of machine learning technology, the case of analyzing vast amounts of biological information and using it to develop new drugs is increasing. The use of machine learning technology to drug repositioning will help quickly find effective treatments. Currently, the world is having a difficult time due to a new disease caused by coronavirus (COVID-19), a severe acute respiratory syndrome. Drug repositioning that repurposes drugsthat have already been clinically approved could be an alternative to therapeutics to treat COVID-19 patients. This study intends to examine research trends in the field of drug repositioning using machine learning techniques. In Pub Med, a total of 4,821 papers were collected with the keyword 'Drug Repositioning'using the web scraping technique. After data preprocessing, frequency analysis, LDA-based topic modeling, random forest classification analysis, and prediction performance evaluation were performed on 4,419 papers. Associated words were analyzed based on the Word2vec model, and after reducing the PCA dimension, K-Means clustered to generate labels, and then the structured organization of the literature was visualized using the t-SNE algorithm. Hierarchical clustering was applied to the LDA results and visualized as a heat map. This study identified the research topics related to drug repositioning, and presented a method to derive and visualize meaningful topics from a large amount of literature using a machine learning algorithm. It is expected that it will help to be used as basic data for establishing research or development strategies in the field of drug repositioning in the future.

• Journal of Cardiovascular Imaging
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• v.31 no.1
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• pp.18-23
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• 2023

BACKGROUND: Three-dimensional (3D) transesophageal echocardiogram (TEE) is the gold standard for the diagnosis of degenerative mitral regurgitation (dMR) and preoperative planning for transcatheter mitral valve repair (TMVr). TEE is an invasive modality requiring anesthesia and esophageal intubation. The severe acute respiratory syndrome coronavirus 2 pandemic has limited the number of elective invasive procedures. Multi-detector computed tomographic angiography (MDCT) provides high-resolution images and 3D reconstructions to assess complex mitral anatomy. We hypothesized that MDCT would reveal similar information to TEE relevant to TMVr, thus deferring the need for a preoperative TEE in certain situations like during a pandemic. METHODS: We retrospectively analyzed data on patients who underwent or were evaluated for TMVr for dMR with preoperative MDCT and TEE between 2017 and 2019. Two TEE and 2 MDCT readers, blinded to patient outcome, analyzed: leaflet pathology (flail, degenerative, mixed), leaflet location, mitral valve area (MVA), flail width/gap, anterior-posterior (AP) and commissural diameters, posterior leaflet length, leaflet thickness, presence of mitral valve cleft and degree of mitral annular calcification (MAC). RESULTS: A total of 22 (out of 87) patients had preoperative MDCT. MDCT correctly identified the leaflet pathology in 77% (17/22), flail leaflet in 91% (10/11), MAC degree in 91% (10/11) and the dysfunctional leaflet location in 95% (21/22) of patients. There were no differences in the measurements for MVA, flail width, commissural or AP diameter, posterior leaflet length, and leaflet thickness. MDCT overestimated the measurements of flail gap. CONCLUSIONS: For preoperative TMVr planning, MDCT provided similar measurements to TEE in our study.

• KSBB Journal
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• v.22 no.6
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• pp.371-377
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• 2007

Polyhydroxyalkanoates (PHAs) are a family of microbial polyesters that can be produced by fermentation from renewable resources. PHAs can be used as completely biodegradable plastics or elastomers. In this paper, novel applications of PHAs in biosensor are described. A general platform technology was developed by using the substrate binding domain (SBD) of PHA depolymerase as a fusion partner to immobilize proteins of interest on PHA surface. It could be shown that the proteins fused to the SBD of PHA depolymerase could be specifically immobilized onto PHA film, PHA microbead, and microcontact printed PHA surface. We review the results obtained for monitoring the specific interaction between the SBO and PHA by using enhanced green fluorescent protein, red fluorescent protein, single chain antibody against hepatitis B virus preS2 surface protein and severe acute respiratory syndrome coronavirus surface antigen as model proteins. Thus, this system can be efficiently used for studying protein-protein and possibly protein-biomolecule interactions for various biotechnological applications.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.284-295
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• 2020

In December 2019, the first coronavirus disease- 2019 (COVID-19) patient was reported in Wuhan, Hubei Province, China. Since then, the number of patients who suffered severe acute respiratory syndrome caused by the novel Coronavirus (SARS-CoV-2 or 2019-nCoV) has increased dramatically in Korea. This new variant virus induces pulmonary diseases, including cough, sore throat, rhinorrhea, dyspnea, and pneumonia. Because SARS-CoV-2 is an RNA virus, real-time reverse-transcriptase PCR has been used widely to diagnose COVID-19. As the Korea Centers for Disease Prevention and Control (KCDC) and Ministry of Food & Drug Safety (MFDS) approved emergency use authorization, clinical specimens collected from COVID-19 patients and even healthy people have been clinically diagnosed by laboratory medicine. Based on a literature search, this paper reviews the epidemiology, symptoms, molecular diagnostics approved by KCDC, a current diagnosis of COVID-19 in the laboratories, the difference between molecular and serological diagnosis, and guidelines for clinical specimens. In addition, the Korean guidelines of biosafety for clinical laboratory scientists are evaluated to prevent healthcare-associated infection. The author's experience and lessons as clinical laboratory scientists will provide valuable insights to protect the domestic and international health community in this COVID-19 pandemic around the world.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.7.1-7.19
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• 2024

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10⁵ plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10² PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10² PFU-virus-infected lungs from 2 dpi, but not in 1×10⁵ PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10⁵ PFU; however, 1×1² PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.12-24
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• 2024

The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination. We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22-0.37; I² =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01-0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97-5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.