• Genomics & Informatics
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• v.16 no.4
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• pp.37.1-37.3
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• 2018

Gene-gene interaction is a key factor for explaining missing heritability. Many methods have been proposed to identify gene-gene interactions. Multifactor dimensionality reduction (MDR) is a well-known method for the detection of gene-gene interactions by reduction from genotypes of single-nucleotide polymorphism combinations to a binary variable with a value of high risk or low risk. This method has been widely expanded to own a specific objective. Among those expansions, fuzzy-MDR uses the fuzzy set theory for the membership of high risk or low risk and increases the detection rates of gene-gene interactions. Fuzzy-MDR is expanded by a maximum likelihood estimator as a new membership function in empirical fuzzy MDR (EFMDR). However, EFMDR is relatively slow, because it is implemented by R script language. Therefore, in this study, we implemented EFMDR using RCPP ($c^{{+}{+}}$ package) for faster executions. Our implementation for faster EFMDR, called EMMDR-Fast, is about 800 times faster than EFMDR written by R script only.

• The Korean journal of internal medicine
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• v.39 no.3
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• pp.448-457
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• 2024

Background/Aims: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. Methods: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. Results: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). Conclusions: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1179-1188
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• 2023

Escherichia coli, particularly multidrug-resistant (MDR) strains, is a serious cause of healthcare-associated infections. Development of novel antimicrobial agents or restoration of drug efficiency is required to treat MDR bacteria, and the use of natural products to solve this problem is promising. We investigated the antimicrobial activity of dried green coffee (DGC) beans, coffee pulp (CP), and arabica leaf (AL) crude extracts against 28 isolated MDR E. coli strains and restoration of ampicillin (AMP) efficiency with a combination test. DGC, CP, and AL extracts were effective against all 28 strains, with a minimum inhibitory concentration (MIC) of 12.5-50 mg/ml and minimum bactericidal concentration of 25-100 mg/ml. The CP-AMP combination was more effective than CP or AMP alone, with a fractional inhibitory concentration index value of 0.01. In the combination, the MIC of CP was 0.2 mg/ml (compared to 25 mg/ml of CP alone) and that of AMP was 0.1 mg/ml (compared to 50 mg/ml of AMP alone), or a 125-fold and 500-fold reduction, respectively, against 13-drug resistant MDR E. coli strains. Time-kill kinetics showed that the bactericidal effect of the CP-AMP combination occurred within 3 h through disruption of membrane permeability and biofilm eradication, as verified by scanning electron microscopy. This is the first report indicating that CP-AMP combination therapy could be employed to treat MDR E. coli by repurposing AMP.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.342-348
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• 2020

Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs), which is one of the most common infectious diseases in humans worldwide. Since UPEC is increasingly gaining resistance to many antimicrobial agents, antibiotic therapy of UTI has recently become a great concern. This study examined the epidemiological relationship, and antimicrobial resistance patterns of 84 UPEC isolates obtained from UTI patients in Daejeon, from March to December 2017. Molecular epidemiology was investigated by multilocus sequence typing (MLST), and an antimicrobial susceptibility test was determined using an E-test. In this study, UTI was more common in females (73.8%) than in males (26.2%), and the highest incidence of UTI was observed in the age group in their 70s. Among the 84 UPEC isolates, 59 isolates (70.2%) were multidrug-resistant (MDR), and the major sequence type was ST131 (44 isolates, 52.4%). Interestingly, the rates of MDR in non-ST131 isolates (72.5%) were higher compared to ST131 isolates (68.2%). These results indicate the possibility of the development and spread of MDR in non-ST131 isolates. Effective surveillance networks and continuous research need to be conducted globally to prevent the emergence and international spread of MDR non-ST131 isolates.

• The KIPS Transactions:PartD
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• v.18D no.3
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• pp.149-156
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• 2011

Recently, enterprise systems require the necessity of integration for data sharing and cooperation. As a methodology for integration, Service-Oriented Architecture for service integration and Master Data for integration of data, which is used for service, were appeared. This paper suggests a method that operates BP(Business Process) efficiently. We make XMDR(eXtended Meta Data Registry) as knowledge-repository to support the BP and construct data hubs to operate it. XMDR manages MDM(Master Data Management) to integrate the data, resolves heterogeneity between the data and provides relationship to the business efficiently. This is composed of MDR(Meta Data Registry), ontology and BR(Business Relations). MDR describes relationship between meta data to solve structured heterogeneity. Ontology describes semantic heterogeneity and relationship between data. BR describes relationship between tasks. XMDR data hub supports the management of master data and interaction of different process effectively.

• Bulletin of the Korean Chemical Society
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• v.30 no.1
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• pp.43-48
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• 2009

The synthesis of coumarin-based natural products and their derivatives is described. In vitro MDR reversal activities of the synthesized compounds were evaluated in P-glycoprotein over-expressing human sarcoma cell line MES-SA/DX5. Some of the coumarin derivatives were found to show potent MDR reversal activity. In particular, pyridyl derivative (15e) exhibited more potency than verapamil.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.114-120
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• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.180-189
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• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.111-121
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• 2022

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

• Korean Journal of Food Science and Technology
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• v.54 no.2
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• pp.209-217
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• 2022

In this study, Enterococcus faecalis BMSE-HMP005 isolated from human breast milk demonstrated antimicrobial effects against multidrug-resistant (MDR) bacterial strains. The bacteriocin produced by E. faecalis BMSE-HMP005 was fractionated using reverse-phase high-performance liquid chromatography. This fraction showed antimicrobial effects against both gram-positive and gram-negative MDR bacteria. No hemolytic reactions were observed. E. faecalis BMSEHMP005 was resistant to vancomycin; however, kanamycin, ampicillin, and erythromycin showed minimum inhibitory concentrations that were lower than the acceptable range provided by the European Food Safety Authority. For artificial gastric juice and bile acid, the survival rates were 98.67% and 95.70%, respectively. These results show the potential utility of E. faecalis BMSE-HMP005 as a probiotic with remarkable antimicrobial effects against MDR bacteria.