• Title/Summary/Keyword: alternative sensitivity

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Toxicity Prediction using Three Quantitative Structure-activity Relationship (QSAR) Programs (TOPKAT®, Derek®, OECD toolbox) (TOPKAT®, Derek®, OECD toolbox를 활용한 화학물질 독성 예측 연구)

  • Lee, Jin Wuk;Park, Seonyeong;Jang, Seok-Won;Lee, Sanggyu;Moon, Sanga;Kim, Hyunji;Kim, Pilje;Yu, Seung Do;Seong, Chang Ho
    • Journal of Environmental Health Sciences
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    • v.45 no.5
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    • pp.457-464
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    • 2019
  • Objectives: Quantitative structure-activity relationship (QSAR) is one of the effective alternatives to animal testing, but its credibility in terms of toxicity prediction has been questionable. Thus, this work aims to evaluate its predictive capacity and find ways of improving its credibility. Methods: Using $TOPKAT^{(R)}$, OECD toolbox, and $Derek^{(R)}$, all of which have been applied world-wide in the research, industrial, and regulatory fields, an analysis of prediction credibility markers including accuracy (A), sensitivity (S), specificity (SP), false negative (FN), and false positive (FP) was conducted. Results: The multi-application of QSARs elevated the precision credibility relative to individual applications of QSARs. Moreover, we found that the type of chemical structure affects the credibility of markers significantly. Conclusions: The credibility of individual QSAR is insufficient for both the prediction of chemical toxicity and regulation of hazardous chemicals. Thus, to increase the credibility, multi-QSAR application, and compensation of the prediction deviation by chemical structure are required.

CDRgator: An Integrative Navigator of Cancer Drug Resistance Gene Signatures

  • Jang, Su-Kyeong;Yoon, Byung-Ha;Kang, Seung Min;Yoon, Yeo-Gha;Kim, Seon-Young;Kim, Wankyu
    • Molecules and Cells
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    • v.42 no.3
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    • pp.237-244
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    • 2019
  • Understanding the mechanisms of cancer drug resistance is a critical challenge in cancer therapy. For many cancer drugs, various resistance mechanisms have been identified such as target alteration, alternative signaling pathways, epithelial-mesenchymal transition, and epigenetic modulation. Resistance may arise via multiple mechanisms even for a single drug, making it necessary to investigate multiple independent models for comprehensive understanding and therapeutic application. In particular, we hypothesize that different resistance processes result in distinct gene expression changes. Here, we present a web-based database, CDRgator (Cancer Drug Resistance navigator) for comparative analysis of gene expression signatures of cancer drug resistance. Resistance signatures were extracted from two different types of datasets. First, resistance signatures were extracted from transcriptomic profiles of cancer cells or patient samples and their resistance-induced counterparts for >30 cancer drugs. Second, drug resistance group signatures were also extracted from two large-scale drug sensitivity datasets representing ~1,000 cancer cell lines. All the datasets are available for download, and are conveniently accessible based on drug class and cancer type, along with analytic features such as clustering analysis, multidimensional scaling, and pathway analysis. CDRgator allows meta-analysis of independent resistance models for more comprehensive understanding of drug-resistance mechanisms that is difficult to accomplish with individual datasets alone (database URL: http://cdrgator.ewha.ac.kr).

Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice

  • Kim, Suji;Song, No-Joon;Chang, Seo-Hyuk;Bahn, Gahee;Choi, Yuri;Rhee, Dong- Kwon;Yun, Ui Jeong;Choi, Jinhee;Lee, Jeon;Yoo, Jae Hyuk;Shin, Donghan;Park, Ki-Moon;Kang, Hee;Lee, Sukchan;Ku, Jin-Mo;Cho, Yoon Shin;Park, Kye Won
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.107-116
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    • 2019
  • The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

Odds curve for two classification distributions (두 분류 분포를 위한 오즈 곡선)

  • Hong, Chong Sun;Oh, Se Hyeon;Oh, Tae Gyu
    • The Korean Journal of Applied Statistics
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    • v.34 no.2
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    • pp.225-238
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    • 2021
  • The ROC, TOC, and TROC curves, which are visually descriptive methods of exploring the performance of the binary classification model, are implemented with TP, TN, FP, FN which consist of the confusion matrix, as well as their ratios TPR, TNR, FPR, FNR. In this study, we consider two types odds and then propose an odds curve representing these odds. And show the relationship between the odds curve and ROC curve. Based on the odds curve, we propose not only two statistics that measure the discriminant power of the odds curve but also the criteria for validation ratings of the odds curve. According to the shape of the odds curves, two classification distributions can be estimated and a criterion for validation ratings can be determined. The odds curve can be meaningfully used like other visual methods, and two kinds of measures for the discriminant power can be also applied together as an alternative criterion.

Assessment and Comparison of Three Dimensional Exoscopes for Near-Infrared Fluorescence-Guided Surgery Using Second-Window Indocyanine-Green

  • Cho, Steve S.;Teng, Clare W.;Ravin, Emma De;Singh, Yash B.;Lee, John Y.K.
    • Journal of Korean Neurosurgical Society
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    • v.65 no.4
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    • pp.572-581
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    • 2022
  • Objective : Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with near-infrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed. Methods : Serial dilutions of indocyanine-green (1-2000 ㎍/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison. Results : Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 ㎍/L and >31.3 ㎍/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadolinium-enhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis. Conclusion : Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

Can indirect magnetic resonance arthrography be a good alternative to magnetic resonance imaging in diagnosing glenoid labrum lesions?: a prospective study

  • Mardani-Kivi, Mohsen;Alizadeh, Ahmad;Asadi, Kamran;Izadi, Amin;Leili, Ehsan Kazemnejad;arzpeyma, Sima Fallah
    • Clinics in Shoulder and Elbow
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    • v.25 no.3
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    • pp.182-187
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    • 2022
  • Background: This study was designed to evaluate and compare the diagnostic value of magnetic resonance imaging (MRI) and indirect magnetic resonance arthrography (I-MRA) imaging with those of arthroscopy and each other. Methods: This descriptive-analytical study was conducted in 2020. All patients who tested positive for labrum lesions during that year were included in the study. The patients underwent conservative treatment for 6 weeks. In the event of no response to conservative treatment, MRI and I-MRA imaging were conducted, and the patients underwent arthroscopy to determine their ultimate diagnosis and treatment plan. Imaging results were assessed at a 1-week interval by an experienced musculoskeletal radiologist. Image interpretation results and arthroscopy were recorded in the data collection form. Results: Overall, 35 patients comprised the study. Based on the kappa coefficient, the results indicate that the results of both imaging methods are in agreement with the arthroscopic findings, but the I-MRA consensus rate is higher than that of MRI (0.612±0.157 and 0.749±0.101 vs. 0.449±0.160 and 0.603±0.113). The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of MRI in detecting labrum tears were 77.77%, 75.00%, 91.30%, 50.00%, and 77.14%, respectively, and those of I-MRA were 88.88%, 75.00%, 92.30%, 66.66%, and 85.71%. Conclusions: Here, I-MRA showed higher diagnostic value than MRI for labral tears. Therefore, it is recommended that I-MRA be used instead of MRI if there is an indication for potential labrum lesions.

Combination of multiplex reverse transcription recombinase polymerase amplification assay and capillary electrophoresis provides high sensitive and high-throughput simultaneous detection of avian influenza virus subtypes

  • Tsai, Shou-Kuan;Chen, Chen-Chih;Lin, Han-Jia;Lin, Han-You;Chen, Ting-Tzu;Wang, Lih-Chiann
    • Journal of Veterinary Science
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    • v.21 no.2
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    • pp.24.1-24.11
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    • 2020
  • The pandemic of avian influenza viruses (AIVs) in Asia has caused enormous economic loss in poultry industry and human health threat, especially clade 2.3.4.4 H5 and H7 subtypes in recent years. The endemic chicken H6 virus in Taiwan has also brought about human and dog infections. Since wild waterfowls is the major AIV reservoir, it is important to monitor the diversified subtypes in wildfowl flocks in early stage to prevent viral reassortment and transmission. To develop a more efficient and sensitive approach is a key issue in epidemic control. In this study, we integrate multiplex reverse transcription recombinase polymerase amplification (RT-RPA) and capillary electrophoresis (CE) for high-throughput detection and differentiation of AIVs in wild waterfowls in Taiwan. Four viral genes were detected simultaneously, including nucleoprotein (NP) gene of all AIVs, hemagglutinin (HA) gene of clade 2.3.4.4 H5, H6 and H7 subtypes. The detection limit of the developed detection system could achieve as low as one copy number for each of the four viral gene targets. Sixty wild waterfowl field samples were tested and all of the four gene signals were unambiguously identified within 6 h, including the initial sample processing and the final CE data analysis. The results indicated that multiplex RT-RPA combined with CE was an excellent alternative for instant simultaneous AIV detection and subtype differentiation. The high efficiency and sensitivity of the proposed method could greatly assist in wild bird monitoring and epidemic control of poultry.

Establishment and application of a solid-phase blocking ELISA method for detection of antibodies against classical swine fever virus

  • Cao, Yuying;Yuan, Li;Yang, Shunli;Shang, Youjun;Yang, Bin;Jing, Zhizhong;Guo, Huichen;Yin, Shuanghui
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.32.1-32.11
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    • 2022
  • Background: Classical swine fever (CSF) is a severe infectious disease of pigs that causes significant economic losses to the swine industry. Objectives: This study developed a solid-phase blocking enzyme-linked immunosorbent assay (spbELISA) method for the specific detection of antibodies against the CSF virus (CSFV) in porcine serum samples. Methods: A spbELISA method was developed based on the recombinant E2 expressed in Escherichia coli. The specificity of this established spbELISA method was evaluated using reference serum samples positive for antibodies against other common infectious diseases. The stability and sensitivity were evaluated using an accelerated thermostability test. Results: The spbELISA successfully detected the antibody levels in swine vaccinated with the C-strain of CSFV. In addition, the detection ability of spbELISA for CSFV antibodies was compared with that of other commercial ELISA kits and validated using an indirect immunofluorescence assay. The results suggested that the spbELISA provides an alternative, stable, and rapid serological detection method suitable for the large-scale screening of CSFV serum antibodies. Conclusions: The spbELISA has practical applications in assessing the vaccination status of large pig herds.

A Sensitive, Efficient, and Cost-Effective Method to Determine Rotigotine in Rat Plasma Using Liquid-Liquid Extraction (LLE) and LC-MRM

  • Kim, Ji Seong;Jang, Yong Jin;Kim, Jin Hee;Kim, Jin Hwan;Seo, Jae Hee;Park, Il-Ho;Kang, Myung Joo;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.13 no.4
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    • pp.146-151
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    • 2022
  • Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson's disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH-DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over previous methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00-115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the development of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

Prediction of Wave Transmission Characteristics of Low Crested Structures Using Artificial Neural Network

  • Kim, Taeyoon;Lee, Woo-Dong;Kwon, Yongju;Kim, Jongyeong;Kang, Byeonggug;Kwon, Soonchul
    • Journal of Ocean Engineering and Technology
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    • v.36 no.5
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    • pp.313-325
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    • 2022
  • Recently around the world, coastal erosion is paying attention as a social issue. Various constructions using low-crested and submerged structures are being performed to deal with the problems. In addition, a prediction study was researched using machine learning techniques to determine the wave attenuation characteristics of low crested structure to develop prediction matrix for wave attenuation coefficient prediction matrix consisting of weights and biases for ease access of engineers. In this study, a deep neural network model was constructed to predict the wave height transmission rate of low crested structures using Tensor flow, an open source platform. The neural network model shows a reliable prediction performance and is expected to be applied to a wide range of practical application in the field of coastal engineering. As a result of predicting the wave height transmission coefficient of the low crested structure depends on various input variable combinations, the combination of 5 condition showed relatively high accuracy with a small number of input variables defined as 0.961. In terms of the time cost of the model, it is considered that the method using the combination 5 conditions can be a good alternative. As a result of predicting the wave transmission rate of the trained deep neural network model, MSE was 1.3×10-3, I was 0.995, SI was 0.078, and I was 0.979, which have very good prediction accuracy. It is judged that the proposed model can be used as a design tool by engineers and scientists to predict the wave transmission coefficient behind the low crested structure.