Search results for: Janet H. Hsiao

Authors: Liu Wei-Hsien, Chuang Hsiao-Li, Huang Yen-Te, Wu Chien-Chen, Chou Geng-Ting, Tsai Ying-Chieh

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Intestinal microflora play an important role in communication along the gut-brain axis. Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host. Here we administered Lactobacillus plantarum PS128 (PS128) to the germ-free (GF) mouse to investigate the impact of the gut-brain axis on emotional behavior. Administration of live PS128 significantly increased the total distance traveled in the open field test; it decreased the time spent in the closed arm and increased the time spent and total entries into the open arm in the elevated plus maze. In contrast, heat-killed PS128 caused no significant changes in the GF mice. Treatment with live PS128 significantly increased levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. However, live PS128 did not alter pro- or anti-inflammatory cytokine production by mitogen-stimulated splenocytes. The above data indicate that the normalization of emotional behavior correlated with monoamine neurotransmission, but not with immune activity. Our findings suggest that daily intake of the probiotic PS128 could ameliorate neuropsychiatric disorders such as anxiety and excessive psychological stress.

Keywords: dopamine, hypothalamic-pituitary-adrenal axis, intestinal microflora, serotonin

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Authors: Maria Janet, Anita David, P. Vijayasamundeeswarimaria

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Introduction: The main purpose of this study is to compare the effectiveness of web-based and blended learning on Paediatric Basic Life Support on competency among undergraduate nursing students in selected nursing colleges in Chennai. Materials and methods: A descriptive pre-test and post-test study design were used for this study. Samples of 100 Fourth year B.Sc., nursing students at Sri Ramachandra Faculty of Nursing SRIHER, Chennai, 100 Fourth year B.Sc., nursing students at Apollo College of Nursing, Chennai, were selected by purposive sampling technique. The instrument used for data collection was Knowledge Questionnaire on Paediatric Basic Life Support (PBLS). It consists of 29 questions on the general expansion of Basic Life Support and Cardiopulmonary Resuscitation, Prerequisites of Basic Life Support, and Knowledge on Paediatric Basic Life Support in which each question has four multiple choices answers, each right answer carrying one mark and no negative scoring. This questionnaire was formed with reference to AHA 2020 (American Heart Association) revised guidelines. Results: After the post-test, in the web-based learning group, 58.8% of the students had an inadequate level of objective performance score, while 41.1% of them had an adequate level of objective performance score. In the blended learning group, 26.5% of the students had an inadequate level of an objective performance score, and 73.4% of the students had an adequate level of an objective performance score. There was an association between the post-test level of knowledge and the demographic variables of undergraduate nursing students undergoing blended learning. The age was significant at a p-value of 0.01, and the performance of BLS before was significant at a p-value of 0.05. The results show that there was a significant positive correlation between knowledge and objective performance score of undergraduate nursing students undergoing web-based learning on paediatric basic life support.

Keywords: basic life support, paediatric basic life support, web-based learning, blended learning

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Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

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Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

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Authors: Szu Mei Hsiao

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This study explores the spiritual needs of inpatients with advanced cancer and their family caregivers in one southern regional teaching hospital in Taiwan and elucidates the differences and similarities of spiritual needs between them. Little research reports the different phases of spiritual needs and the potential impact of Chinese cultural values on the spiritual needs. Qualitative inquiry was used. Twenty-one patients with advanced cancer and twenty-two family caregivers were recruited. During hospitalization, all participants identified spiritual needs both the palliative phase and the dying phase: (a) the need to foster faith/confidence and hope for medicine and/or God; (b) to understand the meaning and values of life; (c) to experience more reciprocal human love and forgiveness; and (d) to obey God’s/Heaven will. Furthermore, the differences of spiritual needs between patients with advanced cancer and their family caregivers are as follows: (a) family caregivers emphasized the need to inform relatives and say goodbye in order to die peacefully; (b) patients highlighted a need to maintain a certain physical appearance in order to preserve their dignity; nurture one’s willpower; learn about the experiences of cancer survivors; and identify one’s own life experience for understanding the meaning and values of life. Moreover, the dissimilarity of spiritual needs is that the patients pointed out the need to understand God’s will during the palliative treatment phase. However, the family caregivers identified the need to forgive each other, and inform relatives and say goodbye to patients in the dying phase. This research has shown that the needs of meaning/values of life and facing death peacefully are different between two groups. Health professionals will be encouraged to detect and to develop individualized care strategies to meet spiritual needs.

Keywords: advanced cancer, Chinese culture, family caregivers, qualitative research, spiritual needs

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Authors: Chi-Yuan Huang, Mei-Chuan Kuo, Ching-Yi Hsiao

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In this study, acids with various chain lengths (C₆, C₈, C₁₀ and C₁₂) modified by methane sulfonic acid (MSA) and temperature were used to modify tapioca starch (TPS), then the glycerol (GA) were added into modified starch, to prepare new blends. The mechanical properties, thermal properties and physical properties of blends were studied. This investigation was divided into two parts.  First, the biodegradable materials were used such as starch and glycerol with hexanedioic acid (HA), suberic acid (SBA), sebacic acid (SA), decanedicarboxylic acid (DA) manufacturing with different temperatures (90, 110 and 130 °C). And then, the solution was added into modified starch to prepare the blends by using single-screw extruder. The FT-IR patterns indicated that the characteristic peak of C=O in ester was observed at 1730 cm^-1. It is proved that different chain length acids (C₆, C₈, C₁₀ and C₁₂) reacted with glycerol by esterification and these are used to plasticize blends during extrusion. In addition, the blends would improve the hydrolysis and thermal stability. The water contact angle increased from 43.0° to 64.0°.  Second, the HA (110 °C), SBA (110 °C), SA (110 °C), and DA blends (130 °C) were used in study, because they possessed good mechanical properties, water resistances and thermal stability. On the other hand, the various contents (0, 0.005, 0.010, 0.020 g) of MSA were also used to modify the mechanical properties of blends. We observed that the blends were added to MSA, and then the FT-IR patterns indicated that the C=O ester appeared at 1730 cm^-1. For this reason, the hydrophobic blends were produced. The water contact angle of the MSA blends increased from 55.0° to 71.0°. Although break elongation of the MSA blends reduced from the original 220% to 128%, the stress increased from 2.5 MPa to 5.1 MPa. Therefore, the optimal composition of blends was the DA blend (130 °C) with adding of MSA (0.005 g).

Keywords: chain length acids, methane sulfonic acid, Tapioca starch (TPS), tensile stress

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Authors: Shih-Wen Hsiao, Rong-Qi Chen

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In the field of fashion design, 3D Mannequin is a kind of assisting tool which could rapidly realize the design concepts. While the concept of 3D Mannequin is applied to the computer added fashion design, it will connect with the development and the application of design platform and system. Thus, the situation mentioned above revealed a truth that it is very critical to develop a module of 3D Mannequin which would correspond with the necessity of fashion design. This research proposes a concrete plan that developing and constructing a system of 3D Mannequin with Kinect. In the content, ergonomic measurements of objective human features could be attained real-time through the implement with depth camera of Kinect, and then the mesh morphing can be implemented through transformed the locations of the control-points on the model by inputting those ergonomic data to get an exclusive 3D mannequin model. In the proposed methodology, after the scanned points from the Kinect are revised for accuracy and smoothening, a complete human feature would be reconstructed by the ICP algorithm with the method of image processing. Also, the objective human feature could be recognized to analyze and get real measurements. Furthermore, the data of ergonomic measurements could be applied to shape morphing for the division of 3D Mannequin reconstructed by feature curves. Due to a standardized and customer-oriented 3D Mannequin would be generated by the implement of subdivision, the research could be applied to the fashion design or the presentation and display of 3D virtual clothes. In order to examine the practicality of research structure, a system of 3D Mannequin would be constructed with JAVA program in this study. Through the revision of experiments the practicability-contained research result would come out.

Keywords: 3D mannequin, kinect scanner, interactive closest point, shape morphing, subdivision

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Authors: Chiung-Yun Chang, Po-Chou Chen, Jiun-Shiang Tzeng, Ka-Wai Mac, Chia-Chi Hsiao, Jo-Chi Jao

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This study aimed to measure R2* relaxation rates in the liver of New Zealand White (NZW) rabbits. R2* relaxation rate has been widely used in various hepatic diseases for iron overload by quantifying iron contents in liver. R2* relaxation rate is defined as the reciprocal of T2* relaxation time and mainly depends on the composition of tissue. Different tissues would have different R2* relaxation rates. The signal intensity decay in Magnetic resonance imaging (MRI) may be characterized by R2* relaxation rates. In this study, a 1.5T GE Signa HDxt whole body MR scanner equipped with an 8-channel high resolution knee coil was used to observe R2* values in NZW rabbit’s liver and muscle. Eight healthy NZW rabbits weighted 2 ~ 2.5 kg were recruited. After anesthesia using Zoletil 50 and Rompun 2% mixture, the abdomen of rabbit was landmarked at the center of knee coil to perform 3-plane localizer scan using fast spoiled gradient echo (FSPGR) pulse sequence. Afterward, multi-planar fast gradient echo (MFGR) scans were performed with 8 various echo times (TEs) (2/4/6/8/10/12/14/16 ms) to acquire images for R2* calculations. Regions of interest (ROIs) at liver and muscle were measured using Advantage workstation. Finally, the R2* was obtained by a linear regression of ln(SI) on TE. The results showed that the longer the echo time, the smaller the signal intensity. The R2* values of liver and muscle were 44.8  10.9 s-1 and 37.4  9.5 s-1, respectively. It implies that the iron concentration of liver is higher than that of muscle. In conclusion, R2* is correlated with iron contents in tissue. The correlations between R2* and iron content in NZW rabbit might be valuable for further exploration.

Keywords: liver, magnetic resonance imaging, muscle, R2* relaxation rate

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Authors: Darn H. Hsiao, Zhu-Yun Zheng

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Since Taiwan is located between the Eurasian and Filipino plates and earthquakes often thus occur. The coastal plains in western Taiwan are alluvial plains, and the soils of the alluvium are mostly from the Lao-Shan belt in the central mountainous area of ​​southern Taiwan. It could come mostly from sand/shale and slate. The previous investigation found that the soils in the Kaohsiung area of ​​southern Taiwan are mainly composed of slate, shale, quartz, low-plastic clay, silt, silty sand and so on. It can also be found from the past earthquakes that the soil in Kaohsiung is highly susceptible to soil subsidence due to liquefaction. Insufficient bearing capacity of building will cause soil liquefaction disasters. In this study, the boring drilling data from nine districts among the Love River Basin in the city center, and some factors affecting liquefaction include the content of fines (FC), standard penetration test N value (SPT N), the thickness of clay layer near ground-surface, and the thickness of possible liquefied soil were further discussed for liquefaction potential as well as groundwater level. The results show that the liquefaction potential is higher in the areas near the riverside, the backfill area, and the west area of ​​the study area. This paper also uses the old paleo-geological map, soil particle distribution curve, compared with LPI map calculated from the analysis results. After all the parameters finally were studied for five sub zones in the Love River Basin by maximum-minimum method, it is found that both of standard penetration test N value and the thickness of the clay layer will be most influential.

Keywords: liquefaction, western Taiwan, liquefaction potential map, high liquefaction potential areas

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Authors: Fernando Valerio-Holguin

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Over the recent three decades, the tourism industry in the Dominican Republic has had an enormous impact on the country’s culture. The arrival of tourists from Germany, France, Italy, Russia and the United States has rewritten Dominican cultural identity and created a cultural palimpsest in the areas of language, gastronomy, habits, fashion, values, and gender relations. As a consequence of tourism, a prostitution network has flourished across the country. In the film Sand Dollars (2015) directed by Laura Amelia Guzmán and Israel Cárdenas, Noelí (Janet Mojica), a young mulatto woman, altogether with her boyfriend (Ricardo Ariel Toribio), strips tourists of dollars and euro through prostitution. One of her frequent clients is Anne, a mature French woman (Geraldine Chaplin). While Noeli’s goal is to get all the euros she can, Anne falls in love with her and tries to bring her to France. Both the content of the film and its cinematographic languages are analyzed in light of theory of coloniality. This concept shows how European and American tourism, through the power of money, perpetuates colonial discourse, i. e., how race and ethnocentrism permeate cultural activities in their former colonies. Moreover, in the content analysis of the film the concepts of exchange value and fetishism are crucial to understanding how the colonial body becomes sexual commodity. They facilitate grasping the film’s inequity in terms of power in the relationship between the two women: the white old European woman and the young, poor, third-world mulatta. Even though the film attempts to break away from compulsory heterosexuality, the power relation between the two women persists due to the presence of the axis of race, ethnicity, age and gender. Both the novel Les dollars des sables written by Jean-Noel Pancrazi, and the film Sand Dollars offer an interesting insight into sex tourism and coloniality and shed additional light on the power relations between the former colonizers and its colonies.

Keywords: coloniality, ethnocentrism, exchange value, Europe, fetishism, money, power, prostitution, sex tourism, United States of America

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Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

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Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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Authors: Bernice Boafoaa Gyapong, Anne Jones, Sam Bassett, Janet Anderson

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Background: Maternal mortality and morbidity are global concerns, especially in sub-Saharan Africa (SSA). Most maternal mortalities occur at the time of birth. Quality intrapartum care is essential for improving maternal and newborn health outcomes. This scoping review aimed to assess and describe the quality of care during childbirth in SSA to provide an overview of the regional trend of the quality of intrapartum care, the challenges to quality care provision, and identify research gaps. Methods: A scoping review based on Arksey and O’Malley’s scoping review framework was conducted. Medline, CINAHL, PsycINFO, and maternal-infant databases were searched to identify the relevant studies for this review. A narrative summary was presented using themes based on the Donabedian structure, process, and outcome quality of care model. Results: A total of five hundred and forty-seven (547) publications were identified. Fifty-six (56) studies conducted in twenty (20) countries were included in the review. Thirty-four (34) were quantitative, sixteen (16) were qualitative, and six (6) were mixed methods. Most of the studies were related to the process component of quality of care. The provision of emergency obstetric care services, infrastructure, and availability of essential staff and equipment for perinatal care was inadequate in many facilities, particularly rural and peripheral health facilities. Many women experienced disrespectful care during childbirth. Routine care during labour and delivery was observed to be sub-optimal, yet some women reported high satisfaction with care. The use of health facilities for delivery was lower in health centres compared to hospitals. Conclusion: There are variations in the quality of maternity care provided in SSA. Intrapartum care quality is generally deficient in SSA, particularly in peripheral health facilities, health centres, and community clinics. Many of the quality-of-care issues identified are related to the structure component. Stakeholders must develop interventions that comprehensively address these interrelated issues to improve maternal healthcare quality, especially in primary healthcare facilities.

Keywords: quality of care, maternity health, Sub-Saharan Africa, intrapartum

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Authors: Chia-Chen Hsieh, Fei-Hsiu Hsiao

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Objective: To examine the effects of supportive care interventions on depressive symptoms in patients with lung cancer. Methods: The databases of Cochrane Central Register of Controlled Trials (CENTRAL), Ovid EMBASE, PubMed, and Chinese Electronic Periodical Services (CEPS) were searched from their inception until September 2015. We included the studies with randomized controlled trial design that compared standard care with supportive care interventions using psychotherapeutic or exercises approach. The standardized mean differences (SMD) (Cohen’s d) were calculated to estimate the treatment effects. The Cochrane Risk of Bias Tool was used for quality assessment and subgroup analysis was conducted to identify possible sources of heterogeneity. Results: A total of 1472 patients with lung cancer were identified. Compared with standard care, the overall effects of all supportive care interventions significantly reduced depressive symptoms (SMD = -0.74 with 95% CI = -1.07 to -0.41), and the effect was maintained at the 4th, 8th, and 12th weeks of follow-up. Either psychotherapy combined with psychoeducation or exercise alone produced significant improvements in depressive symptoms, while psychoeducation alone did not. The greater improvements in depressive symptoms occurred in lung cancer patients with severe depressive symptoms at baseline, total duration of interventions of less than ten weeks, and intervention provided through face-to-face delivery. Conclusions: Psychotherapy combined with psychoeducation can help patients manage the causes of depressive symptoms, including both symptom distress and psychological trauma due to lung cancer. Exercise can target the impaired respiratory function that is a cause of depressive symptoms in lung cancer patients.

Keywords: supportive care intervention, depressive symptoms, lung cancer, meta-analysis

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Authors: Dixon, Lieh-Chi Su, Hsiao-Ling Yu, Ren-Yi Huang, Yung-Tan Lee

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The present paper analyzed the major, trace elements, rare earth elements of these Cenozoic basalts and combined with Sr-Nd isotopic compositions to discuss the petrogenesis of these basalts and the tectonic setting of the study area. Based on major, trace elements and fractional crystallization model we suggest that the basaltic magma has experienced olivine, clinopyroxene, and plagioclase fractionation during its evolution. Spidergrams and REE patterns reveal that Cenozoic basalts found in the Jiashan County, Anhui Province have geochemical characteristics similar to those of ocean island basalts(OIB) suggesting a derivation related to OIB-like mantle source. The slight positive Nb and Ti anomalies found in basaltic rocks of this study suggest the presence of Ti-bearing minerals in the mantle source and these Ti-bearing minerals had contributed to basaltic magma during partial melting, indicating a metasomatic event might have occurred before the partial melting. Based on 143Nd/144Nd vs. 87Sr/86Sr diagram we suggest that basalts of this study can be produced by MORB and EM-I components mixing and small degree of partial melting may be the major controlling factor during generation of basaltic magma. Some basaltic magma may be derived from partial melting of EM-Ⅰ heated by the upwelling asthenospheric mantle. The basalts fall within the WPB field in the discriminant plot of 2Nb-Zr/4-Y indicate that the volcanic activities in this region may be closely related to deep continental rifting process.

Keywords: geochemistry, cenozoic basalts, Anhui Province, Nushan Geopark, tectonic setting, fractionation

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Authors: Hsiao-Tien Pao, Yi-Ying Li, Hsin-Chia Fu

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This paper addressed the impacts of energy consumption, economic growth, financial development, and population size on environmental degradation using grey relational analysis (GRA) for China, where foreign direct investment (FDI) inflows is the proxy variable for financial development. The more recent historical data during the period 2004–2011 are used, because the use of very old data for data analysis may not be suitable for rapidly developing countries. The results of the GRA indicate that the linkage effects of energy consumption–emissions and GDP–emissions are ranked first and second, respectively. These reveal that energy consumption and economic growth are strongly correlated with emissions. Higher economic growth requires more energy consumption and increasing environmental pollution. Likewise, more efficient energy use needs a higher level of economic development. Therefore, policies to improve energy efficiency and create a low-carbon economy can reduce emissions without hurting economic growth. The finding of FDI–emissions linkage is ranked third. This indicates that China do not apply weak environmental regulations to attract inward FDI. Furthermore, China’s government in attracting inward FDI should strengthen environmental policy. The finding of population–emissions linkage effect is ranked fourth, implying that population size does not directly affect CO₂ emissions, even though China has the world’s largest population, and Chinese people are very economical use of energy-related products. Overall, the energy conservation, improving efficiency, managing demand, and financial development, which aim at curtailing waste of energy, reducing both energy consumption and emissions, and without loss of the country’s competitiveness, can be adopted for developing economies. The GRA is one of the best way to use a lower data to build a dynamic analysis model.

Keywords: China, CO₂ emissions, foreign direct investment, grey relational analysis

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Authors: Janet Modu, Jean-Francois Georgin, Laurent Briancon, Eric Antoinet

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The current practice during the repowering phase of wind turbines is deconstruction of existing foundations and construction of new foundations to accept larger wind loads or once the foundations have reached the end of their service lives. The ongoing research project FUI25 FEDRE (Fondations d’Eoliennes Durables et REpowering) therefore serves to propose scalable wind turbine foundation designs to allow reuse of the existing foundations. To undertake this research, numerical models and laboratory-scale models are currently being utilized and implemented in the GEOMAS laboratory at INSA Lyon following instrumentation of a reference wind turbine situated in the Northern part of France. Sensors placed within both the foundation and the underlying soil monitor the evolution of stresses from the foundation’s early age to stresses during service. The results from the instrumentation form the basis of validation for both the laboratory and numerical works conducted throughout the project duration. The study currently focuses on the effect of coupled mechanisms (Thermal-Hydro-Mechanical-Chemical) that induce stress during the early age of the reinforced concrete foundation, and scale factor considerations in the replication of the reference wind turbine foundation at laboratory-scale. Using THMC 3D models on COMSOL Multi-physics software, the numerical analysis performed on both the laboratory-scale and the full-scale foundations simulate the thermal deformation, hydration, shrinkage (desiccation and autogenous) and creep so as to predict the initial damage caused by internal processes during concrete setting and hardening. Results show a prominent effect of early age properties on the damage potential in full-scale wind turbine foundations. However, a prediction of the damage potential at laboratory scale shows significant differences in early age stresses in comparison to the full-scale model depending on the spatial position in the foundation. In addition to the well-known size effect phenomenon, these differences may contribute to inaccuracies encountered when predicting ultimate deformations of the on-site foundation using laboratory scale models.

Keywords: cement hydration, early age behavior, reinforced concrete, shrinkage, THMC 3D models, wind turbines

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Meng-Jie Hsiao, Cam Nguyen

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Wide-band devices in Ku band (12-18 GHz) and K band (18-27 GHz) have received significant attention for high-data-rate communications and high-resolution sensing. Especially, devices operating around 24 GHz is attractive due to the 24-GHz unlicensed applications. One of the most important components in RF systems is power amplifier (PA). Various PAs have been developed in the Ku and K bands on GaAs, InP, and silicon (Si) processes. Although the PAs using GaAs or InP process could have better power handling and efficiency than those realized on Si, it is very hard to integrate the entire system on the same substrate for GaAs or InP. Si, on the other hand, facilitates single-chip systems. Hence, good PAs on Si substrate are desirable. Especially, Si-based PA having good linearity is necessary for next generation communication protocols implemented on Si. We report a 16.5 to 25.5 GHz Si-based PA having flat saturated power of 19.5 ± 1.5 dBm, output 1-dB power compression (OP1dB) of 16.5 ± 1.5 dBm, and 15-23 % power added efficiency (PAE). The PA consists of a drive amplifier, two main amplifiers, and lump-element Wilkinson power divider and combiner designed and fabricated in TowerJazz 0.18µm SiGe BiCMOS process having unity power gain frequency (fMAX) of more than 250 GHz. The PA is realized as a cascode amplifier implementing both heterojunction bipolar transistor (HBT) and n-channel metal–oxide–semiconductor field-effect transistor (NMOS) devices for gain, frequency response, and linearity consideration. Particularly, a body-floating technique is utilized for the NMOS devices to improve the voltage swing and eliminate parasitic capacitances. The developed PA has measured flat gain of 20 ± 1.5 dB across 16.5-25.5 GHz. At 24 GHz, the saturated power, OP1dB, and maximum PAE are 20.8 dBm, 18.1 dBm, and 23%, respectively. Its high performance makes it attractive for use in Ku/K-band, especially 24 GHz, communication and radar systems. This paper was made possible by NPRP grant # 6-241-2-102 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.

Keywords: power amplifiers, amplifiers, communication systems, radar systems

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Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen

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High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Keywords: cardiac output, heart failure, obesity, transcriptomics

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Authors: Ying-Hsiang Ho, Hsiao-Tseng Lin

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Mudan Township is a remote mountainous area in Taiwan. In recent years, due to the migration of the population, inconvenient transportation, digital divide, and low production, agricultural products marketing have become a major issue. This research aims to develop the marketing strategy suitable for the agricultural products of the rural areas. The main objective of this work is to conduct in-depth interviews with scholars and experts in the marketing field, combined with the marketing 4P combination, to analyze and summarize the possible marketing strategies for agricultural products for remote districts. The interviews consist of seven experts from industry who have practical experience in producing, marketing, and selling agricultural products and three professors that have experience in teaching marketing management. The in-depth interviews are conducted for about an hour using a pre-drafted interview outline. The results of the interviews are summarized by semantic analysis and presented in a marketing 4P combination. The results indicate that in terms of products, high-quality products with original characteristics can be added through the implementation of production history, organic certification, and cultural packaging. In the place part, we found that the use of emerging communities, the emphasis on cross-industry alliances, the improvement of information application capabilities of rural households, production and marketing group, and contractual farming system are the development priorities. In terms of promotion, it should be an emphasis on the management of internet social media and word-of-mouth marketing. Mudan Township may consider promoting agricultural products through special festivals such as farmer's market, wild ginger flower season and hot spring season. This research also proposes relevant recommendations for the government's public sector and related industry reference for the promotion of agricultural products for remote area.

Keywords: marketing strategy, remote districts, agricultural products, in-depth interviews

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Authors: Ruth Nalugya, Claire Nimusiima, Elizabeth Kawesa, Harriet Nambejja, Geert van Hove, Janet Seeley, Femke Bannink Mbazzi

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Background: ‘Obuntu bulamu’, an intervention for children, parents, and teachers to improve the participation and inclusion of children with disabilities (CwD) through peer-to-peer support, was developed and tested in central Uganda between 2017 and 2019. The intervention consisted of children, parents, and teachers' training sessions and peer to peer support activities directed at disability inclusion using an African disability framework. In this paper, we discuss parent participation in and parent evaluation of the ‘Obuntu bulamu’ intervention. Methods: This qualitative Afrocentric intervention study was implemented in 10 communities in the Wakiso district in Central Uganda. We purposely selected children aged 8 to 14 years with different impairments, their peers, and parents, with different levels of household income and familial support, who were enrolled in primary schools in the ten communities with on average three children with disabilities per community. Sixty four parents (33 parents of CwDs and 31 peers) participating in the ‘Obuntu bulamu’ study were interviewed at baseline and endline. Two focus group discussions were held with parents at the midline. Parents also participated in a consultative meeting about the intervention design at baseline, and two evaluation workshops held at midline and endline. Thematic data analysis of the interview and focus group data was conducted. Results: Findings showed parents found the group-based activities inspiring and said they built hope and confidence. Parents felt the intervention was acceptable, culturally appropriate, and supportive as it built on values and practices from their own traditions. Parents reported the intervention enhanced a sense of togetherness and belonging through the group meetings and follow-up activities. Parents also mentioned that the training helped them develop more positive attitudes towards CwD and disability inclusion. Parents felt that the invention increased a child’s participation and inclusion at home, school, and in communities. Conclusion: The Obuntu bulamu peer to peer support intervention is an acceptable, culturally appropriate intervention that has the potential to improve the inclusion of CwD. A larger randomized control trial is needed to evaluate the impact of the intervention model.

Keywords: inclusion, participation, inclusive education, peer support, belonging, Ubuntu, ‘Obuntu bulamu’

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Authors: Szu-Mei Hsiao

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Many nurses have concerns about the difficulties of providing spiritual care for ethnic-Chinese patients and family members within their cultural context. This is due to a lack of knowledge and training. Most family caregivers are female. There has been little research exploring the potential impact of Chinese cultural values on the spiritual distress of couple dyadic participants in Taiwan. This study explores the spiritual issues of Taiwanese women coping with their husband’s advanced cancer during palliative care to death. Qualitative multiple case studies were used. Data was collected through participant observation and in-depth face-to-face interviews. Transcribed interview data was analyzed by using qualitative content analysis. Three couples were recruited from a community-based rural hospital in Taiwan where the husbands were hospitalized in a medical ward. Four spiritual distress themes emerged from the analysis: (1) A personal conflict in trying to come to terms with love and forgiveness; the inability to forgive their husband’s mistakes; and, lack of their family’s love and support. (2) A feeling of hopelessness due to advanced cancer, such as a feeling of disappointment in their destiny and karma, including expressing doubt on survival. (3) A feeling of uncertainty in facing death peacefully, such as fear of facing the unknown world; and, (4) A feeling of doubt causing them to question the meaning and values in their lives. This research has shown that caregivers needed family support, friends, social welfare, and the help of their religion to meet their spiritual needs in coping within the final stages of life and death. The findings of this study could assist health professionals to detect the spiritual distress of ethnic-Chinese patients and caregivers in the context of their cultural or religious background as early as possible.

Keywords: advanced cancer, Buddhism, Confucianism, Taoism, qualitative research, spiritual distress

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Authors: Yi Shan Cheng, Ya Hui Yeh, Hsiao Wen Hsu

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Delirium is an acute state of confusion, which is mainly the result of the interaction of many factors, including: age>65 years, comorbidity, cognitive function and visual/auditory impairment, dehydration, pain, sleep disorder, pipeline retention, general anesthesia and major surgery… etc. Researches show the prevalence of delirium in hospitalized elderly patients over 50%. If it doesn't improve in time, may cause cognitive decline or impairment, not only prolong the length of hospital stay but also increase mortality. Some studies have shown that multiple nonpharmacological interventions are the most effective and common strategies, which are reorientation, early mobility, promoting sleep and nutritional support (including water intake), could improve or prevent delirium in the hospitalized elderly. In Taiwan, only one research to compare the delirium incidence of the older patients who have received orthopedic surgery between multi-nonpharmacological interventions and general routine care. Therefore, the purpose of this study is to address the prevention or improvement of delirium incidence density in medical hospitalized elderly, provide clinical nurses as a reference for clinical implementation, and develop follow-up related research. This study is a quasi-experimental design using purposive sampling. Samples are from two wards: the geriatric ward and the general medicine ward at a medical center in central Taiwan. The sample size estimated at least 100, and then the data will be collected through a self-administered structured questionnaire, including: demographic and professional evaluation items. Case recruiting from 5/13/2023. The research results will be analyzed by SPSS for Windows 22.0 software, including descriptive statistics and inferential statistics: logistic regression、Generalized Estimating Equation(GEE)、multivariate analysis of variance(MANOVA).

Keywords: multiple nonpharmacological interventions, hospitalized elderly, delirium incidence, delirium

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Authors: Yichen Lin, Hsiao-Han Chen, Chi-Chen Jan

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Since 1990, the research area of Integrated Marketing Communications (IMC) has been presented from a different perspective. With advances in information technology and the rise of consumer consciousness, businesses are in a competitive environment. There is an urgent need to adopt more profitable and effective integrated marketing strategies to increase core competitiveness. The goal of the company's sustainable management is to increase consumers' willingness to purchase and to maximize profits. This research uses six aspects of IMC, which includes awareness integration, unified image, database integration, customer-based integration, stakeholders-based integration, and evaluation integration to examine the role of marketing strategies in the strengths and weaknesses of the six components of integrated marketing communications, their effectiveness, the most important components and the most important components that need improvement. At the same time, social media such as FaceBook, Instagram, Youtube, Line, or even TikTok have become marketing tools which firms adopt them more and more frequently in the marketing strategy. In the end of 2019, the outbreak of COVID-19 did really affect the global industries. Lockdown policies also accelerated closure of brick-mentor stores worldwide. Online purchases rose dramatically. Hence, the effectiveness of online marketing will be essential to maintain the business. This study uses multiple-case studies to extend the effects of social media and IMC. Moreover, the study would also explore the differences of social media and IMC during COVID-19. Through literature review and multiple-case studies, it is found that using social media combined with IMC did really help companies expand their business and make good connections with stakeholders. One of previous studies also used system theory to explore the interrelationship among Integrated Marketing Communication, collaborative marketing, and global brand building. Even during pandemic, firms could still maintain the operation and connect with their customers more tightly.

Keywords: integration marketing communications, multiple-case studies, social media, system theory

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Authors: Hsiao-ting Lin

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This paper analyzes the history of Taiwan’s secret program to develop its nuclear weapons during the Cold War. In July 1971, US President Richard Nixon shocked the world when he announced that his national security adviser Henry Kissinger had made a secret trip to China and that he himself had accepted an invitation to travel to Beijing. This huge breakthrough in the US-PRC relationship was followed by Taipei’s loss of political legitimacy and international credibility as a result of its UN debacle in the fall that year. Confronted with the Nixon White House’s opening to the PRC, leaders in Taiwan felt being betrayed and abandoned, and they were obliged to take countermeasures for the sake of national interest and regime survival. Taipei’s endeavor to create an effective nuclear program, including the possible development of nuclear weapons capabilities, fully demonstrates the government’s resolution to pursue its own national policy, even if such a policy was guaranteed to undermine its relations with the United States. With hindsight, Taiwan’s attempt to develop its own nuclear weapons did not succeed in sabotaging the warming of US-PRC relations. Worse, it was forced to come to a full stop when, in early 1988, the US government pressured Taipei to close related facilities and programs on the island. However, Taiwan’s abortive attempt to develop its nuclear capability did influence Washington’s and Beijing’s handling of their new relationship. There did develop recognition of a common American and PRC interest in avoiding a nuclearized Taiwan. From this perspective, Beijing’s interests would best be served by allowing the island to remain under loose and relatively benign American influence. As for the top leaders on Taiwan, such a policy choice demonstrated how they perceived the shifting dynamics of international politics in the 1960s and 1970s and how they struggled to break free and pursue their own independent national policy within the rigid framework of the US-Taiwan alliance during the Cold War.

Keywords: taiwan, richard nixon, nuclear program, chiang Kai-shek, chiang ching-kuo

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Hsiao-Yung Wang

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This essay aims to examine how the transgender imagery has been constructed in the Taiwanese news media and its evolution from 1953 to 2016. It also explores the discourse patterns and rhetorical strategies in the transgender-related issues which contributed to levels of evaluation in forming ‘social deviance.’ Samples for analysis were selected from mainstream newspapers, including China Times, United Daily and Apple Daily. The time frame for sample selection is from August 1953 (when the first transgender case was reported in Taiwan) to June 2016. To enhance understanding of media representation as nominalistic-based, the author refers to the representative of critical rhetoric Raymie McKerrow for his study on remembrance and forgetfulness in public discourse (especially in his model of ‘critique of domination’); thereby categorizing the 64 years of transgender discourse into five periods: (1) transgender as ‘intersex’ of surgical-reparative medical treatment; (2) transgender as ‘freak gender-bender’ with criminal behaviors; (3) transgender as ‘ladyboy’ (‘katoey in a Thai term) of bar girls or sex workers; (4) transgender as ‘cross dresser’ of transvestite performance; and (5) transgender as ‘life-style or human right’ of spontaneous gender identification. Based on the research findings, this essay argues that the characterization of transgender reporting as a site for the production of compulsory sexism and gender stereotype by the specific forms of name-calling. Besides, the evolution of word-image addressing to transgender issues also pinpoints media as a reflection of fashion of the day. While the transgender imagery might be crystallized as ‘still social problems’ or ‘gender transgression’ in insidious rhetoric; and while the so-called ‘phobia’ persistently embodies in media discourse to exercise name-calling in an ambiguous (rather than in a bullying) way or under the cover of humanist-liberalist rationales, these emergent rhetorical dilemma should be resolved without any delay.

Keywords: critical rhetoric, media representation, McKerrow, nominalistic, social deviance, transgender

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Authors: Shih-Wen Hsiao, Yi-Cheng Tsao

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In the field of reverse engineering and creative industries, applying 3D scanning process to obtain geometric forms of the objects is a mature and common technique. For instance, organic objects such as faces and nonorganic objects such as products could be scanned to acquire the geometric information for further application. However, although the data resolution of 3D scanning device is increasing and there are more and more abundant complementary applications, the penetration rate of 3D scanning for the public is still limited by the relative high price of the devices. On the other hand, Kinect, released by Microsoft, is known for its powerful functions, considerably low price, and complete technology and database support. Therefore, related studies can be done with the applying of Kinect under acceptable cost and data precision. Due to the fact that Kinect utilizes optical mechanism to extracting depth information, limitations are found due to the reason of the straight path of the light. Thus, various angles are required sequentially to obtain the complete 3D information of the object when applying a single Kinect for 3D scanning. The integration process which combines the 3D data from different angles by certain algorithms is also required. This sequential scanning process costs much time and the complex integration process often encounter some technical problems. Therefore, this paper aimed to apply multiple Kinects simultaneously on the field of developing a rapid 3D mannequin scan platform and proposed suggestions on the number and angles of Kinects. In the content, a method of establishing the coordination based on the relation between mannequin and the specifications of Kinect is proposed, and a suggestion of angles and number of Kinects is also described. An experiment of applying multiple Kinect on the scanning of 3D mannequin is constructed by Microsoft API, and the results show that the time required for scanning and technical threshold can be reduced in the industries of fashion and garment design.

Keywords: 3D scan, depth sensor, fashion and garment design, mannequin, multiple Kinect sensor

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

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Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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