The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

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.

Unrecognized History of Transient Atrial Fibrillation at the Time of Discharge from an Index Stroke Hospitalization Is Associated with Increased Recurrent Stroke Risk

Chia-Yu Hsu,Daniel E. Singer,Hooman Kamel,Yi-Ling Wu,Pei-Chun Chen,Jiann-Der Lee,Meng Lee,Bruce Ovbiagele 대한뇌졸중학회 2019 Journal of stroke Vol.21 No.2

Background and Purpose Preceding episodes of paroxysmal atrial fibrillation (AF) among stroke patients can be easily overlooked in routine clinical practice. We aim to determine whether an unrecognized history of paroxysmal AF is associated with an increased risk of recurrent stroke. Methods We retrospectively identified all adult patients hospitalized with a primary diagnosis of ischemic stroke who had no AF diagnosis on their discharge records, using the Taiwan National Health Insurance Research Database between January 2001 and December 2012. Patients were categorized into two groups: unrecognized AF history and no AF. Patients with unrecognized AF history were defined as having documented AF preceding the index ischemic stroke hospitalization, but not recording at the index ischemic stroke. Primary endpoint was recurrent stroke within 1 year after the index stroke. Results Among 203,489 hospitalized ischemic stroke patients without AF diagnosed at discharge, 6,731 patients (3.3%) had an unrecognized history of prior transient AF. Patients with an unrecognized AF history, comparing to those without AF, had higher adjusted risk of all recurrent stroke ([original cohort: hazard ratio (HR), 1.41; 95% confidence interval [CI], 1.30 to 1.53], [matched cohort: HR, 1.51; 95% CI, 1.37 to 1.68]) and recurrent ischemic stroke ([original cohort: HR, 1.42; 95% CI, 1.30 to 1.55], [matched cohort: HR, 1.56; 95% CI, 1.40 to 1.74]) during the 1-year follow-up period. Conclusions Unrecognized history of AF among patients discharged after an index ischemic stroke hospitalization is associated with higher recurrent stroke risk. Careful history review to uncover a paroxysmal AF history is important for ischemic stroke patients.

Factors Affecting In vitro True Digestibility of Napiergrass

Chen, Chia-Sheng,Wang, Su-Min,Hsu, Jih-Tay Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.4

Changes of in vitro true digestibility (IVTD) of Napiergrass (Pennisetum purpureum) were determined by a filter bag system, and their relationships to chemical composition, leaf to stem ratio, plant height, geographic location, climatic factors and harvest interval were studied and used to develop prediction models for the crude protein (CP), acid-detergent fiber (ADF), and neutral-detergent fiber (NDF) contents and IVTD. Partitioning the total variance of IVTD of Napiergrass showed that 80% was attributable to the effect of harvest interval. Days of growth, plant height, leaf/stem ratio, CP, ADF and NDF of Napiergrass had highly significant relationships (p<0.01) with IVTD. The highest coefficient of correlation between the ADF, NDF, and IVTD of Napiergrass and growth degree days was obtained when the base temperature was set at $0^{\circ}C$. Growth degree days could predict ADF, NDF, and IVTD of Napiergrass more accurately than plant height, and plant height is not suitable to predict IVTD.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes

Chia-Jung Hsieh,Chun-Yu Wu,Yen-Heng Lin,Yu-Cheng Huang,Wen-Chi Yang,Tom Wei-Wu Chen,Wei-Li Ma,Wei-Hsin Lin,Feng-Ming Hsu,Furen Xiao,Shih-Hung Yang,Dar-Ming Lai,Chang-Mu Chen,Shin-Yi Chao,Fon-Yih Tsuan 대한척추신경외과학회 2023 Neurospine Vol.20 No.4

Objective: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease

Chen Cheng-Hsu,Huang Shih-Chien,Yeh En-Ling,Lin Pei-Chih,Tsai Shang-Feng,Huang Yi-Chia 한국영양학회 2022 Nutrition Research and Practice Vol.16 No.4

BACKGROUND/OBJECTIVES Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.

Evaluation of a rotating packed bed equipped with blade packings for methanol and 1-butanol removal

Chia-Chang Lin,Yu-Chiao Lin,Shu-Ching Chen,Ling-Jung Hsu 한국공업화학회 2010 Journal of Industrial and Engineering Chemistry Vol.16 No.6

Absorption removal of methanol and 1-butanol from gaseous streams with water was investigated in the RPB equipped with blade packings. The removal efficiency (E) of methanol and 1-butanol was found to increase with the RPB speed and the liquid flow rate but decrease with the gas flow rate. Also, the overall volumetric gas-side mass transfer coefficient (KGa) for methanol and 1-butanol absorption was observed to increase with the RPB speed, the gas flow rate, and the liquid flow rate. According to the obtained dependence of KGa on the gas and liquid flow rates, the mass transfer in methanol and 1-butanol absorption was observed to be controlled primarily by the gas-side mass transfer. Furthermore, the height of a transfer unit (HTU) for methanol and 1-butanol absorption decreased with the RPB speed and the liquid flow rate but increased with the gas flow rate. The obtained results demonstrated that mass transfer efficiency of the RPB equipped with blade packing was comparable to that of a hollow fiber absorber. Consequently, the RPB equipped with blade packings has a great potential in the removal of alkanols from the exhausted gases. 2010 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

Predictive maintenance of abnormal wind turbine events by using machine learning based on condition monitoring for anomaly detection

Huan Chen,Jyh-Yih Hsu,Jia-You Hsieh,Hsin-Yao Hsu,Chia-Hao Chang,Yu-Ju Lin 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.12

The predictive maintenance of wind turbines has become a critical issue with the rapid development of wind power generation. The early detection of abnormal operation conditions can prevent failure status, which takes a long time to recover. Energy waste can also be reduced while maintenance efficiency can be improved by using a supervisory control and data acquisition (SCADA) system to monitor the operation status of wind turbines. Massive data are generated from different sensors during wind turbine operation, and SCADA can be used to gather reports about hundreds of possible abnormal conditions. The popular maintenance methods have been mostly designed on the basis of statistical analysis and data mining. However, such schemes need not only big data but also sophisticated processing techniques. This study addresses the aforementioned challenges by proposing a deep learning model with comprehensive data preprocessing and hyperparameter tuning on batch size to achieve abnormal early detection. The necessary data preprocessing is initially conducted besides the conventional data cleaning and normalization steps, and time-series data windowing and label settings are also performed. Then, the imbalanced classes in the records are addressed by adopting an augmentation scheme called the synthetic minority oversampling technique. Principal component analysis is also used to enhance the training. Finally, the proposed deep learning method with fine-tuning is compared with three machine learning models for early anomaly event detection. Experimental results show that the proposed scheme can identify potential faults 72 hours before they occur, and the precision rate exceeds 90 %.

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

WHO IS THE MORE INFLUENTIAL DECISION-MAKER? : SPA TRAVEL IN BALI AIMING AT TAIWANESE AND MAINLAND CHINESE COUPLE TOURISTS

Wen-Yu Chen,Chia-Yuan Hsu,Magdalena Samidjen 글로벌지식마케팅경영학회 2014 Global Marketing Conference Vol.2014 No.5

Spa tourism is part of wellness tourism, which has been prosperously booming over the past decade. In accordance to the aforesaid, the spa-tourism-oriented marketing strategy is exceedingly significant for businesses akin to hotel, resort and even governments which aim at appealing to more tourists. For the future success, spa tourism needs to appreciate the changing demands of the spa market while providing enough capacity to satisfy them (Henderson, 2004). The worldwide spa industry revenue is growing up from US 60 billion in 2007 to US 73 billion in 2012 (Global Spa & Wellness Summit, 2012). Spa market is one of the fastest growing leisure markets both on the supply and demand sides. Nevertheless, spa industry is utterly fragmented with each segment catering for different customer needs (Harmsworth, 2004). Bali is a popular tourist destination renown for its nature beauty, which attracts both domestic and international tourists. Over the years, it has been dubbed as “the morning of the world”, “the last paradise” and “island with a thousand temples”. According to Indonesian Central Bureau of Statistics (BPS, 2013), it was chosen as the most favorite tourist destination worldwide with a number of tourists totaled at 2,756,579. Among the foreign spa tourism patrons, Mainland Chinese tourists ranked the second while Taiwanese tourists being the fifth in ranking. CNN Travel (2012) reported that the Indonesian government estimated one million Mainland Chinese tourists would patronize the spa tourism in Bali by 2014. Regardless Mainland China and Taiwan are dual sovereignties which identically possess similar culture, there are still some aspects such as gender issue that distinguishes one from another. Furthermore, age, occupation, education, family structure, and life experience are some other aspects that differentiate Taiwanese and Mainland Chinese. In summation, the main objectives of this paper is threefold: (1) to compare the decision making process between Taiwanese and Chinese tourists, specifically, amid the wedded/unwedded couples; (2) to identify the most influential decision maker among the wedded-couple tourists/unwedded-couple tourists in Taiwan and Mainland China; (3) to assist travel agencies which aim at luring couple tourists to concoct the customized package tours. This research develops a quantitative survey for data collection, inference and the resulting data. The first part of questionnaire evaluates the influence regarding wedded / unwedded couples over how much influence each other have (problem recognition, information search, and a final decision) (Davis & Rigaux, 1974). The second part consists of fourteen sub-decisions: the destination (Bali), budget (how much money to spend), days (how much time to spend), accommodation (where to stay), and departure time (when to go) (Belch, Belch, & Ceresino, 1985; Szybillo & Sosanie, 1977); airline, restaurant, local transportation, shopping, travel agency, tour leader, tour guide, optional tour, and spa activities (Wang, Hsieh, & Huan, 2000; Heung & Chu, 2000) and the other kinds of activities (Jenkins, 1979) complete with five-point Likert scale, ranging from “no influence at all” to “all of the influence”. The third part provides some questions asking respondents regarding where they receive the information about Bali. The fourth part asking the respondents provide information such as frequency of visiting destination; how long have the couples been together and how the package tour was booked. Eventually, this questionnaire provides information related to socio-demographic variables, including gender, respondents’ age, occupation, monthly income, and the highest education level (Howard & Madrigal, 1990; Darley & Lim, 1986; Fodness, 1992). The ultimate version of the questionnaire items are refined through the purification process. Above all, this study invites three experts to examine the validity and reliability concerning the questionnaire. 350 valid questionnaires were collected (consists of 171 Taiwanese tourists and 179 Chinese tourists) which was adequate to questions only one spouse in summer period. There is merely one significant discrepancy exists between the wedded and unwedded couples in the decision-making stages, that is, “Information search” conducted under the joint decision making. The nature beauty and wellness services combined with evening entertainment are relatively satisfactory in Bali. During the check-in process, wellness tourists are supposed to be notified of all the spa-oriented services in the spa area. Overall, the satisfaction level of spa in Bali is exceedingly-high. With hindsight, customer service seems to be the greatest asset in Bali. The presented study is an unprecedented research focusing on the behavioral disparity between Taiwanese and Chinese spa tourists when it comes to decision-making stages. The results of this study unfurls the different decision making process between Taiwanese and Chinese couples; according to the research result, the unwedded couples possess more influence than the wedded couples in decision making stages. Moreover, the findings of this research do not entirely support earlier statement given by Tourism Queensland (2013), which mentioned considerable spa customers are female, married, and age approximately 34 to 52 year olds. According to our research, actually, men accounts for a quarter of spa users. The research result indicates the mini-tour is a niche business in the tourism industry that can both benefit Taiwan and Mainland China; mini-tour is a novel concept mentioned in a previous research, which focuses on seniors’ GPT (Wang et al., 2013). This study provides information concerning customer satisfaction level in Bali spa business and travel agency services. The sub-decisions regarding couple tourists are thoroughly researched. Therefore, this presented study can potentially bring benefits to all parties (spa prov