• 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.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1985-1995
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• 2021

Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and Methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.

• Korean Journal of Radiology
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• v.22 no.4
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• pp.584-595
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• 2021

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

• Korean Journal of Radiology
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• v.22 no.11
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• pp.1875-1885
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• 2021

Objective: Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19. Materials and Methods: A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality. Results: A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; p = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings. Conclusion: Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.

• Korean Journal of Radiology
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• v.22 no.4
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• pp.652-662
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• 2021

Objective: To investigate the association between CT imaging features and survival outcomes in patients with primary invasive mucinous adenocarcinoma (IMA). Materials and Methods: Preoperative CT image findings were consecutively evaluated in 317 patients with resected IMA from January 2011 to December 2015. The association between CT features and long-term survival were assessed by univariate analysis. The independent prognostic factors were identified by the multivariate Cox regression analyses. The survival comparison of IMA patients was investigated using the Kaplan-Meier method and propensity scores. Furthermore, the prognostic impact of CT features was assessed based on different imaging subtypes, and the results were adjusted using the Bonferroni method. Results: The median follow-up time was 52.8 months; the 5-year disease-free survival (DFS) and overall survival rates of resected IMAs were 68.5% and 77.6%, respectively. The univariate analyses of all IMA patients demonstrated that 15 CT imaging features, in addition to the clinicopathologic characteristics, significantly correlated with the recurrence or death of IMA patients. The multivariable analysis revealed that five of them, including imaging subtype (p = 0.002), spiculation (p < 0.001), tumor density (p = 0.008), air bronchogram (p < 0.001), emphysema (p < 0.001), and location (p = 0.029) were independent prognostic factors. The subgroup analysis demonstrated that pneumonic-type IMA had a significantly worse prognosis than solitary-type IMA. Moreover, for solitary-type IMAs, the most independent CT imaging biomarkers were air bronchogram and emphysema with an adjusted p value less than 0.05; for pneumonic-type IMA, the tumors with mixed consolidation and ground-glass opacity were associated with a longer DFS (adjusted p = 0.012). Conclusion: CT imaging features characteristic of IMA may provide prognostic information and individual risk assessment in addition to the recognized clinical predictors.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.233-242
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• 2021

Objective: To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs). Materials and Methods: We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase (IDH)-mutation, IDH mutation and a chromosome arm 1p/19q-codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q-nondeleted (IDHmut1p/19qnondel), and IDH wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared. Results: IDHmut G3 gliomas showed a larger volume (p = 0.017), lower nCBF (p = 0.048), and higher nADC (p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV (p = 0.024) and lower nADC (p = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas (p < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs. Conclusion: We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to IDH mutation and 1p/19q codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.159-167
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• 2021

Objective: The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. Materials and Methods: This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. Results: Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001-0.705) compared to the mammography group. Conclusion: Our study found that Korean females aged 40-49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.

• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• Research in Plant Disease
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• v.29 no.4
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• pp.414-419
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• 2023

In 2023, a number of seeds suspected to be discolored black oat seeds on oat farms in Gangjin were observed and examined for fungal infection. The species Alternaria alternata was predominant, accounting for 84% of all fungal infections. The appearance and quality of seeds harvested in 2022 were compared with seeds harvested in 2023 from the same field. The lightness value was lower in the seeds harvested in 2023, while the electrical conductivity was higher in the seeds harvested in 2023. The content of avenanthramide was found to be 10 times higher in the 2023 seeds than in those harvested in 2022. The accumulated precipitation in Gangjin in May 2023 was 230 times higher than that in May 2022, and the average relative humidity was high. These conditions created an environment suitable for infection of A. alternata, which were thought to have caused discolored black oat seeds.

• Research in Plant Disease
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• v.30 no.2
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• pp.148-156
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• 2024

Ralstonia pseudosolanacearum, a plant pathogenic bacterium that can survive for a long time in soil and water, causes lethal wilt in the Solanaceae family. Sigma S is a part of the RNA polymerase complex, which regulates gene expression during bacterial stress response or stationary phase. In this study, we investigated the role of sigma S in R. pseudosolanacearum under stress conditions using a rpoS-defective mutant strain of R. pseudosolanacearum and its wild-type strain. The phenotypes of rpoS-defective mutant were complemented by introducing the original rpoS gene. There were no differences observed in bacterial growth rate and exopolysaccharide production between the wild-type strain and the rpoS mutant. However, the wild-type strain responded more sensitively to nutrient deficiency compared to the mutant strain. Under the nutrient deficiency, the rpoS mutant maintained a high bacterial viability for a longer period, while the viability of the wild-type strain declined rapidly. Furthermore, a significant difference in pH was observed between the culture supernatant of the wild-type strain and the mutant strain. The pH of the culture supernatant for the wild-type strain decreased rapidly during bacterial growth, leading to medium acidification. The rapid decline in the wild-type strain's viability may be associated with medium acidification and bacterial sensitivity to acidity during transition to the stationary phase. Interestingly, the rpoS mutant strain cannot utilize acetic acid, D-alanine, D-trehalose, and L-histidine. These results suggest that sigma S of R. pseudosolanacearum regulates the production or utilization of organic acids and controls cell death during stationary phase under nutrient deficiency.