• Title/Summary/Keyword: CiPA

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An Artificial Neural Network-Based Drug Proarrhythmia Assessment Using Electrophysiological Characteristics of Cardiomyocytes (심근 세포의 전기생리학적 특징을 이용한 인공 신경망 기반 약물의 심장독성 평가)

  • Yoo, Yedam;Jeong, Da Un;Marcellinus, Aroli;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.42 no.6
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    • pp.287-294
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    • 2021
  • Cardiotoxicity assessment of all drugs has been performed according to the ICH guidelines since 2005. Non-clinical evaluation S7B has focused on the hERG assay, which has a low specificity problem. The comprehensive in vitro proarrhythmia assay (CiPA) project was initiated to correct this problem, which presented a model for classifying the Torsade de pointes (TdP)-induced risk of drugs as biomarkers calculated through an in silico ventricular model. In this study, we propose a TdP-induced risk group classifier of artificial neural network (ANN)-based. The model was trained with 12 drugs and tested with 16 drugs. The ANN model was performed according to nine features, seven features, five features as an individual ANN model input, and the model with the highest performance was selected and compared with the classification performance of the qNet input logistic regression model. When the five features model was used, the results were AUC 0.93 in the high-risk group, AUC 0.73 in the intermediate-risk group, and 0.92 in the low-risk group. The model's performance using qNet was lower than the ANN model in the high-risk group by 17.6% and in the low-risk group by 29.5%. This study was able to express performance in the three risk groups, and it is a model that solved the problem of low specificity, which is the problem of hERG assay.

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

  • Amit K. Rath;Dibakar Sahu;Sajal De
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.2
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    • pp.165-175
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    • 2024
  • Background: The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. Methods: We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz > upper limit of normal or respiratory system reactance at 5 Hz < lower limit of normal. Results: The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p<0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p<0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p<0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p<0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). Conclusion: SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

Breast Feeding and Breast Cancer Risk: A Case-control Study in Korea

  • Do, Min-Hee;Lee, Sang-Sun;Jung, Pa-Jong;M.D.;Lee, Min-Hyuk;M.B.
    • Nutritional Sciences
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    • v.3 no.2
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    • pp.77-82
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    • 2000
  • We carried out a case-control study to investigate protective effect of lactating against breast cancer in Korea. Cases (n=108) were the newly histologically identified breast cancer between December 1997 and August 1999. Hospital-based controls were selected by frequency matching method with age ($\pm$4 age) and menopausal status from the patients at the same hospital in the plastic surgery, general surgery and opthalmology department. Interviews included information on general characteristics of subjects, disease history, family history of breast cancer, vitamin supplementation, alcohol intake, food intake, and reproductive factors as well as lactation history. Odds ratio (OR) and 95% Confidence Intervals (CI) were calculated by using unconditional logistic regression. Age distribution of case control subjects were similar. Late menarche age $\geq$ 17 in premenopausal women was related to the lower risk of breast cancer OR = 0.41, 95% CI = 0.28-0.91. Family history of breast cancer was related to the higher risk of breast cancer only in premenopausal women (OR = 2.07, 95% CI = 1.35-2.71). Higher body mass index mass index (> 30) were associated with higher risk of breast cancer in postmenopausal women. For premenopausal women, women who had lactated $\geq$ 12 months to the first child had a significantly lower risk (OR = 0.53, 95% CI = 0.24-0.97) than the women had no breast feeding experience. However, results from postmenopausal women did not show an association with decreased breast cancer risk. These findings suggest that lactation may be a protective factor of breast cancer in Korean women.

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Comparison of plan dosimetry on multi-targeted lung radiotherapy: A phantom-based computational study using IMRT and VMAT

  • Khan, Muhammad Isa;Rehman, Jalil ur;Afzal, Muhammad;Chow, James C.L.
    • Nuclear Engineering and Technology
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    • v.54 no.10
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    • pp.3816-3823
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    • 2022
  • This work analyzed the dosimetric difference between the intensity modulated radiotherapy (IMRT), partial/single/double-arc volumetric modulated arc therapy (PA/SA/DA-VMAT) techniques in treatment planning for treating more than one target of lung cancer at different isocenters. IMRT and VMAT plans at different isocenters were created systematically using a Harold heterogeneous lung phantom. The conformity index (CI), homogeneity index (HI), gradient index (GI), dose-volume histogram and mean and maximum dose of the PTV were calculated and analyzed. Furthermore, the dose-volume histogram and mean and maximum doses of the OARs such as right lung, contralateral lung and non GTV were determined from the plans. The IMRT plans showed the superior target dose coverage, higher mean and maximum values than other VMAT techniques. PA-VMAT technique shows more lung sparing and DA-VMAT increases the V5/10/20 values of contralateral lung than other VMAT and IMRT techniques. The IMRT technique achieves highly conformal dose distribution to the target than other VMAT techniques. Comparing to the IMRT plans, the higher V5/10/20 and mean lung dose were observed in the contralateral lung in the DA-VMAT.

Non-alcoholic Fatty Liver Disease (NAFLD) and Significant Hepatic Fibrosis Defined by Non-invasive Assessment in Patients with Type 2 Diabetes

  • Sobhonslidsuk, Abhasnee;Pulsombat, Akharawit;Kaewdoung, Piyaporn;Petraksa, Supanna
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1789-1794
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    • 2015
  • Background: Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. Objectives: To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. Materials and Methods: One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ${\geq}7$ kPa was used to define significant hepatic fibrosis. Results: Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Conclusions: Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.

Pharmacopuncture for Acute peripheral facial paralysis: A systematic review and meta-analysis of randomized controlled trials

  • Choi, Min-Sun;Kim, Dong Il;Jang, Su Hee
    • The Journal of Korean Medicine
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    • v.36 no.2
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    • pp.8-20
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    • 2015
  • Objectives: This study aims to evaluate the efficacy of pharmacopuncture in the treatment of acute peripheral facial paralysis (APFP) through a meta-analysis of randomized controlled trials to assess the clinical evidence for pharmacopuncture as a treatment for PFP. Methods: Literature was searched using databases. The search terms used were "pharmacopuncture," "sweet BV," "apipuncture," "apitoxin," "injection acupuncture," and "herbal acupuncture" in English and "bongchim," "bongyakchim," and "yakchim" in Korean. The RevMan 5.2 program was used for meta-analysis. Results: In all, 1902 studies were screened and the full texts of 219 articles were reviewed. Of these, nine studies were included in the systematic review and nine studies were included in the meta-analysis. Treatments utilizing bee venom, sweet bee venom (SBV), Soyeom, Calculus Bovis Fel Ursi Moschus (BUM), Hominis Placenta, and Suseunghwagang (SSHG) were observed in nine RCTs. In the forest plot, the diamond favors the PA treatment against the control treatment. (95% CI: 0.34 [0.08, 0.60], Z = 2.57, P = 0.01), which Our meta-analysis in RevMan 5.2 confirmed the significant efficacy of PA in treating APFP. Conclusion: Our systematic review and meta-analysis suggest that treatments using Soyeom, bee venom, and BUM are effective in APFP and they reduce the duration of postauricular pain occurring at the acute stage of APFP. However, due to small effect size, further investigation is needed.

Human Papillomavirus Infection and Prognostic Predictors in Patients with Oropharyngeal Squamous Cell Carcinoma

  • Huang, Hui;Zhang, Bin;Chen, Wen;Zhou, Shuang-Mei;Zhang, Yong-Xia;Gao, Li;Xu, Zhen-Gang;Qiao, You-Lin;Tang, Ping-Zhang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.891-896
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    • 2012
  • This study focused on infection rates and subtypes of human papillomavirus (HPV) in patients with oropharyngeal squamous cell carcinoma (OSCC), and the relationship between HPV status and prognosis of the disease. We evaluated sixty-six OSCC patients who met the enrollment criteria during the period from January 1999 to December 2009. The presence or absence of oncogenic HPV types in tumors was determined using the SPF10 LiPA25 assay. Overall survival (OS) and disease specific survival (DSS) for HPV positive and HPV negative patients were estimated using Kaplan-Meier analysis. The Cox regression model was applied for multivariate analysis. HPV-DNA was detected in 11(16.7%) of all specimens. Among them, 7 were type HPV-16, while other types were HPV-16/11, HPV-35, HPV-58/52, and HPV-33/52/54. Patients with HPV positive tumors were more likely to be female, non-smokers and non-drinkers (p=0.002, 0.001 and 0.001, respectively). After a median follow-up of 24.5 months, patients with HPV positive tumors had significantly better overall survival (HR=0.106[95%CI=0.014-0.787], p=0.016,) and disease specific survival (HR=0.121[95%CI=0.016-0.906], p=0.030). Patients with HPV positive OSCC have significantly better prognosis than patients with HPV negative tumors. HPV infection is an independent prognostic factor.

Factors Related to Exertional Oxygen Desaturation in Patients with COPD (만성 폐쇄성 폐질환(COPD) 환자에서 운동 시 발생하는 산소 불포화 반응과 관련된 인자)

  • Shim, Sang-Woo;Jo, Jun-Yeon;Kwon, Yong-Sik;Chae, Jin-Nyeong;Park, Jie-Hae;Lee, Mi-Young;Rho, Byung-Hak;Choi, Won-Il
    • Tuberculosis and Respiratory Diseases
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    • v.70 no.6
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    • pp.498-503
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    • 2011
  • Background: The causes of exertional desaturation in patients with COPD can be multifactorial. We aimed to investigate factors predict exertional desaturation in patients with moderate to severe COPD. Methods: We tested 51 consecutive patients with stable COPD (FEV1/FVC, $40{\pm}13%$ predicted). Patients performed a six minute walk test (6MWT). Pulse oxymetric saturation (SpO2) and pulse rate were recorded. Results: Oxygen desaturation was found in 15 subjects after 6MWT, while 36 subjects were not desaturated. Lung diffusing capacity was significantly lower in desaturation (DS) group ($62{\pm}18%$ predicted) compared with not desaturated (ND) group ($84{\pm}20$, p<0.01). However there was no statistical difference of FEV1/FVC ratio or residual volume between two groups. The pulse rate change was significantly higher in the desaturated compared with the not desaturated group. Six minute walking distance, subjective dyspnea scale, airflow obstruction, and residual volume did not predict exertional oxygen desaturation. Independent factors assessed by multiple logistic regression revealed that a pulse rate increment (odd ratio [OR], 1.19; 95% confidence interval [CI], 1.01~1.40; p=0.02), a decrease in baseline PaO2 (OR, 1.105; 95% CI, 1.003~1.218; p=0.04) and a decrease in lung diffusing capacity (OR, 1.10; 95% CI, 1.01~1.19; p=0.01) were significantly associated with oxygen desaturation. Receiver operator characteristic (ROC) analysis showed that an absolute increment in pulse rate of 16/min gave optimal discrimination between desaturated and not desaturated patients after 6MWT. Conclusion: Pulse rate increment and diffusion capacity can predict exertional oxygen desaturation in stable COPD patients with moderate to severe airflow obstruction.

Alteration of Phospholipase D Activity in the Rat Tissues by Irradiation (방사선 조사에 의한 쥐 조직의 포스포리파제 D의 활성 변화)

  • Choi Myung Sun;Cho Yang Ja;Choi Myung-Un
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.197-206
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    • 1997
  • Purpose : Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer Process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. Materials and Methods : The reaction mixture for the PLD assay contained $0.1\;\muCi\;1,2-di[1-^{14}C]palmitoyl$ phosphatidylcholine 0.5mM phosphatidylcholine, 5mM sodium oleate, $0.2\%$ taurodeoxycholate, 50mM HEPES buffer(pH 6.5), 10mM $CaCl_2$, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cmx loom and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. Results : Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward $\gamma-rar$ with more than two times amplification in their activities In contrast, the PLD activity of bone marrow appears to be reduced to nearly $30\%$. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. Conclusion : The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation s1ron91y indicates that the PLD is closely related to the physiological function of these organs, Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell Proliferation to cell death on these organs.

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Photosynthetic Characteristics of Korean Endemic Plant, Aster koraiensis Nakai According to Growth and Development Conditions (생육환경에 따른 한국특산식물 벌개미취의 광합성 특성)

  • Nam, Hyo-Hoon;Son, Chang-Ki;Lee, Joong-Hwan;Kwon, Jung-Bae
    • Korean Journal of Plant Resources
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    • v.29 no.4
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    • pp.393-399
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    • 2016
  • This study was conducted to elucidate the photosynthetic response to the environment and establish optimum cultivation conditions for the Korean endemic plant, Aster koraiensis. Photosynthetic characteristics according to growth stage, light, CO2, and soil water potential were investigated. During the first year of transplanting, photosynthetic rates were drastically increased until June, after which they slowly declined, During the second year, photosynthetic rates declined throughout the entire growth period. The highest level of light compensation point was shown the early growth stage. Photosynthetic rates affected by intercellular CO2 concentration were maintained or decreased over the CO2 saturation point. The lowest CO2 compensation point was 16.1 μmol·mol−1 during March. The morphological changes of leaves were observed due to shading with chlorophyll contents increasing. Photosynthetic rates were higher at 0% and 50% shading treatments than at 75%. There were rarely any morphological changes of leaves due to soil moisture, however, changes to leaf compactness were observed. Photosynthetic rate, apparent quantum yield, and respiration rate increased, whereas water use efficiency decreased over −25 kPa of soil moisture.