Effective Antiviral Activity of the Tyrosine Kinase Inhibitor Sunitinib Malate against Zika Virus

Lin Chen-Sheng,Huang Su-Hua,Yan Bo-Yu,Lai Hsueh-Chou,Lin Cheng-Wen 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.4

Introduction: Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broadspectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. Materials and Methods: This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. Results: Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC50) value of 0.015 μM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 μM, and a substantial decrease in the titer of intracellular infectious particles by 1 μM. Conclusion: The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

Minimal Information Loss for Privacy-Preserved eHealth Applications

Ya-Ling Chen,Bo-Chao Cheng,Hsueh-lin Chen,Chia-I Lin,Guo-Tan Liao,Bo-Yu Hou,Shih-Chun Hsu 보안공학연구지원센터 2012 International Journal of Security and Its Applicat Vol.6 No.2

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

Possible Effect of Implementing a National Query Program on Site-Specific Cancer Mortality Rates in Taiwan

Lin, Ching-Yih,Cheng, Tain-Junn,Peng, Hua-Chun,Chen, Lea-Hua,Huang, Shiuh-Ming,Lu, Tsung-Hsueh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Background: This study aimed to examine possible effects of implementing a national query program on site-specific cancer mortality rates. Materials and Methods: A total of 2,874 query letters were sent out by the Department of Statistics, Ministry of Health and Welfare of Taiwan between January 2009 and December 2011 to medical certifiers who reported "neoplasm with uncertain nature" on the death certificate asking for more detailed information for coding. Results: Of the 2,571 responses, in 1,398 cases (54%) medical certifiers were still unable to determine the nature of the neoplasm. There were four neoplasm sites for which more than 50% of the responses changed the category to malignant, the gastrointestinal system (73%), urinary system (60%), stomach (55%) and rectum (53%). The liver was the cancer site that showed the largest absolute increase in the number of deaths after the query; however, the brain showed the largest relative increase, at 12%. Conclusions: Different neoplasm sites showed different magnitudes of change in nature after the query. Brain cancer mortality rates exhibited the largest increase.

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Kai-Chung Hsueh,Ying-Ju Lin,Jeng-Sheng Chang,Lei Wan,Yu-Hsin Tsai,Chang-Hai Tsai,Chih-Ping Chen,Fuu-Jen Tsai 대한의학회 2009 Journal of Korean medical science Vol.24 No.3

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10 -592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.

Direct Adaptive Fuzzy Sliding Mode Control for Under-actuated Uncertain Systems

Su, Shun-Feng,Hsueh, Yao-Chu,Tseng, Cio-Ping,Chen, Song-Shyong,Lin, Yu-San Korean Institute of Intelligent Systems 2015 INTERNATIONAL JOURNAL of FUZZY LOGIC and INTELLIGE Vol.15 No.4

The development of the control algorithms for under-actuated systems is important. Decoupled sliding mode control has been successfully employed to control under-actuated systems in a decoupling manner with the use of sliding mode control. However, in such a control scheme, the system functions must be known. If there are uncertainties in those functions, the control performance may not be satisfactory.In this paper, the direct adaptive fuzzy sliding mode control is employed to control a class of under-actuated uncertain systems which can be regarded as a combination of several subsystems with one same control input. By using the hierarchical sliding control approach, a sliding control law is derived so as to make every subsystem stabilized at the same time. But, since the system considered is assumed to be uncertain, the sliding control law cannot be readily facilitated. Therefore, in the study, based on Lyapunov stable theory a fuzzy compensator is proposed to approximate the uncertain part of the sliding control law. From those simulations, it can be concluded that the proposed compensator can indeed cope with system uncertainties. Besides, it can be found that the proposed compensator also provide good robustness properties.

Which is more influential on teaching practice, classroom management efficacy or instruction efficacy? Evidence from TALIS 2018

Robin Jung-Cheng Chen,Hsin-Chih Lin,Yi-Lung Hsueh,Chuan-Chung Hsieh 서울대학교 교육연구소 2020 Asia Pacific Education Review Vol.21 No.4

This study aims to explore relationship between teacher self-efficacy and teacher teaching practice in junior high schools at Taiwan. TALIS (2018) survey database is adopted, and 3106 teachers were analyzed in this research. Through literature review and exploratory factor analysis (EFA), the research model is assumed to include two constructs (classroom management efficacy and instruction efficacy) in teacher self-efficacy, and three constructs (clarity of instruction practice, cognitive activation practice, and classroom management practice) in teacher teaching practice. Through the analysis of Structural Equation Modeling (SEM), the main findings are as follows. (1) For clarity of instruction practice, instruction efficacy has more positive influences than classroom management efficacy. (2) For classroom management practice, classroom management efficacy as more positive influences than instruction efficacy. (3) For cognitive activation practice, instruction efficacy has positive influences but classroom management efficacy has negative influences.

Cervical Vagal Nerve Stimulation Activates the Stellate Ganglion in Ambulatory Dogs

이경석,Chia-Hsiang Hsueh,Jessica A. Hellyer,박형욱,이영수,Jason Garlie,Patrick Onkka,Anisiia T. Doytchinova,John B. Garner,Jheel Patel,Lan S. Chen,Michael C. Fishbein,Thomas Everett 4th,Shien-Fong Lin,Peng-She 대한심장학회 2015 Korean Circulation Journal Vol.45 No.2

Background and Objectives: Recent studies showed that, in addition to parasympathetic nerves, cervical vagal nerves contained significantsympathetic nerves. We hypothesized that cervical vagal nerve stimulation (VNS) may capture the sympathetic nerves within the vagalnerve and activate the stellate ganglion. Materials and Methods: We recorded left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA), and subcutaneouselectrocardiogram in seven dogs during left cervical VNS with 30 seconds on-time and 30 seconds off time. We then compared theSGNA between VNS on and off times. Results: Cervical VNS at moderate (0.75 mA) output induced large SGNA, elevated heart rate (HR), and reduced HR variability, suggestingsympathetic activation. Further increase of the VNS output to >1.5 mA increased SGNA but did not significantly increase the HR, suggestingsimultaneous sympathetic and parasympathetic activation. The differences of integrated SGNA and integrated VNA between VNSon and off times (ΔSGNA) increased progressively from 5.2 mV-s {95% confidence interval (CI): 1.25–9.06, p=0.018, n=7} at 1.0 mA to13.7 mV-s (CI: 5.97–21.43, p=0.005, n=7) at 1.5 mA. The difference in HR (ΔHR, bpm) between on and off times was 5.8 bpm (CI: 0.28–11.29, p=0.042, n=7) at 1.0 mA and 5.3 bpm (CI 1.92 to 12.61, p=0.122, n=7) at 1.5 mA. Conclusion: Intermittent cervical VNS may selectively capture the sympathetic components of the vagal nerve and excite the stellateganglion at moderate output. Increasing the output may result in simultaneously sympathetic and parasympathetic capture.

Value of CT in the Discrimination of Fatal from Non-Fatal Stercoral Colitis

Cheng-Hsien Wu,Chen-Chih Huang,Li-Jen Wang,Yon-Cheong Wong,Chao-Jan Wang,Wan-Chak Lo,Being-Chuan Lin,Yung-Liang Wan,Chuen Hsueh 대한영상의학회 2012 Korean Journal of Radiology Vol.13 No.3

Objective: Clinical presentation and physical signs may be unreliable in the diagnosis of stercoral colitis (SC). This study evaluates the value of computed tomography (CT) in distinguishing fatal from non-fatal SC. Materials and Methods: Ten patients diagnosed as SC were obtained from inter-specialist conferences. Additional 13 patients with suspected SC were identified via the Radiology Information System (RIS). These patients were divided into two groups; fatal and non-fatal SCs. Their CT images are reviewed by two board-certified radiologists blinded to the clinical data and radiographic reports. Results: SC occurred in older patients and displayed no gender predisposition. There was significant correlation between fatal SC and CT findings of dense mucosa (p = 0.017), perfusion defects (p = 0.026), ascites (p = 0.023), or abnormal gas (p = 0.033). The sensitivity, specificity, and accuracy of dense mucosa were 71%, 86%, and 81%, respectively. These figures were 75%, 79%, and 77% for perfusion defects; 75%, 80%, and 78% for ascites; and 50%, 93%, and 78% for abnormal gas, respectively. Each CT sign of mucosal sloughing and pericolonic abscess displayed high specificity of 100% and 93% for diagnosing fatal SC, respectively. However, this did not reach statistical significance in diagnosing fatal SC. Conclusion: CT appears to be valuable in discriminating fatal from non-fatal SC. Objective: Clinical presentation and physical signs may be unreliable in the diagnosis of stercoral colitis (SC). This study evaluates the value of computed tomography (CT) in distinguishing fatal from non-fatal SC. Materials and Methods: Ten patients diagnosed as SC were obtained from inter-specialist conferences. Additional 13 patients with suspected SC were identified via the Radiology Information System (RIS). These patients were divided into two groups; fatal and non-fatal SCs. Their CT images are reviewed by two board-certified radiologists blinded to the clinical data and radiographic reports. Results: SC occurred in older patients and displayed no gender predisposition. There was significant correlation between fatal SC and CT findings of dense mucosa (p = 0.017), perfusion defects (p = 0.026), ascites (p = 0.023), or abnormal gas (p = 0.033). The sensitivity, specificity, and accuracy of dense mucosa were 71%, 86%, and 81%, respectively. These figures were 75%, 79%, and 77% for perfusion defects; 75%, 80%, and 78% for ascites; and 50%, 93%, and 78% for abnormal gas, respectively. Each CT sign of mucosal sloughing and pericolonic abscess displayed high specificity of 100% and 93% for diagnosing fatal SC, respectively. However, this did not reach statistical significance in diagnosing fatal SC. Conclusion: CT appears to be valuable in discriminating fatal from non-fatal SC.

Direct Adaptive Fuzzy Sliding Mode Control for Under-actuated Uncertain Systems

Shun-Feng Su,Yao-Chu Hsueh,Cio-Ping Tseng,Song-Shyong Chen,Yu-San Lin 한국지능시스템학회 2015 INTERNATIONAL JOURNAL of FUZZY LOGIC and INTELLIGE Vol.15 No.4

The development of the control algorithms for under-actuated systems is important. Decoupled sliding mode control has been successfully employed to control under-actuated systems in a decoupling manner with the use of sliding mode control. However, in such a control scheme, the system functions must be known. If there are uncertainties in those functions, the control performance may not be satisfactory. In this paper, the direct adaptive fuzzy sliding mode control is employed to control a class of under-actuated uncertain systems which can be regarded as a combination of several subsystems with one same control input. By using the hierarchical sliding control approach, a sliding control law is derived so as to make every subsystem stabilized at the same time. But, since the system considered is assumed to be uncertain, the sliding control law cannot be readily facilitated. Therefore, in the study, based on Lyapunov stable theory a fuzzy compensator is proposed to approximate the uncertain part of the sliding control law. From those simulations, it can be concluded that the proposed compensator can indeed cope with system uncertainties. Besides, it can be found that the proposed compensator also provide good robustness properties.