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Chang Gung University is a private university in Guishan District, Taoyuan City, Taiwan. Wikipedia.


Tang H.H.,National Taiwan University of Science and Technology | Lee Y.Y.,Chang Gung University | Gero J.S.,George Mason University
Design Studies | Year: 2011

This study compares the design processes of designers in both digital and traditional sketching environments, where the digital environment emulates the traditional face-to-face, pen-and-paper environment. The design processes were empirically examined through protocol analysis using a coding scheme based on the function-behaviour-structure ontology. The distributions of the different types of segments, and their transitions in the two environments were quantitatively compared using Chi-Square tests and Paired-T tests. The results indicate that the design processes in the two environments were not statistically different in terms of their distributions and transitions. The higher-level cognitive activities were not affected by the change of medium. Some implications for design computing and design practice are discussed. © 2010 Elsevier Ltd. All rights reserved.


Chen T.-Y.,Chang Gung University
Information Sciences | Year: 2011

Interval-valued fuzzy sets have been developed and applied to multiple criteria analysis. However, the influence of optimism and pessimism on subjective judgments and the cognitive dissonance that accompanies the decision making process have not been studied thoroughly. This paper presents a new method to reduce cognitive dissonance and to relate optimism and pessimism in multiple criteria decision analysis in an interval-valued fuzzy decision environment. We utilized optimistic and pessimistic point operators to measure the effects of optimism and pessimism, respectively, and further determined a suitability function through weighted score functions. Considering the two objectives of maximal suitability and dissonance reduction, several optimization models were constructed to obtain the optimal weights for the criteria and to determine the corresponding degree of suitability for alternative rankings. Finally, an empirical study was conducted to validate the feasibility and applicability of the current method. We anticipate that the proposed method can provide insight on the influences of optimism, pessimism, and cognitive dissonance in decision analysis studies. © 2010 Elsevier Inc. All rights reserved.


Chang C.-J.,Chang Gung University
Laser Therapy | Year: 2011

Background and Objectives: Hemangiomas remain a challenge for patients and plastic surgeons. Promising results have been reported using intralesional photocoagulation (ILP) for treatment. The objective of our study is to review the long term results of a large series of hemangiomas in patients treated by ILP. Materials (Subjects) and Methods: A retrospective review of 684 hemangiomas in patients were treated by ILP with an Nd:YAG (neodymium-yttrium-aluminium-garnet) (1064 nm) laser over a period of 10 years (January 1996 - January 2005). Patients' ages ranged from one month to 11 years 5 months (mean, 1 year 10 months). The patient group consisted of 474 females and 210 males. Results: Patients were treated with an Nd:YAG laser delivered through a 600 m optical fiber. Laser power was set at 7 to 15 watts (W) and delivered with pulse duration of 7 to 15 seconds (s). The results showed 603 (88.6%) patients had more than 50% reduction of the volume in hemangiomas at 3 months after one treatment; and 663 (96.9%) patients had more than 50% reduction of the volume at 3 months after two treatments. Patients who had continuous ILP achieved excellent results. Conclusions: Postoperative complications have been related to photocoagulation that has been delivered too extensively or superficially, with resultant ulceration, infection, bleeding, and scarring. These complications can be avoided if this potential for harm is kept in mind. © 2011 JMLL, Tokyo, Japan.


Huang C.-H.,Industrial Technology Research Institute of Taiwan | Liu W.-R.,Chung Yuan Christian University | Chan T.-S.,National Synchrotron Radiation Research Center | Lai Y.-T.,Chang Gung University
Dalton Transactions | Year: 2014

A Eu2+-activated Ca3Si2O 7:Eu2+ orangish-yellow-emitting phosphor with strong luminescence was synthesized and its crystal structure was determined on the basis of XRD profiles using synchrotron radiation. The crystal structure was refined by the Rietveld refinement method. The excitation and emission spectra of the Ca3Si2O7:Eu2+ phosphor show broad excitation bands in the range of 240-550 nm and a broad yellow emission band centered at 603 nm, depending on the concentration of Eu2+. The optimized concentration of Eu2+ in the Ca3Si 2O7:Eu2+ phosphor was determined to be 0.015 mol. The critical distance and average decay time were found to be short and fast, respectively, ranging from 19.74 Å to 13.69 Å and from 2.56 μs to 2.34 μs on increasing the Eu2+ doping content. Warm-white light-emitting diodes (LEDs) fabricated using an InGaN-based blue LED chip combined with the Ca3Si2O7:0.015Eu2+ phosphor gave color rendering indices between 76.0 and 38.9, correlated color temperatures between 1924 K and 4992 K, and tuned CIE chromaticity coordinates in the range from orangish-yellow (0.543, 0.389) to reddish purple (0.333, 0.219). The color coordinates and emission intensity of a Ca3Si 2O7:0.015Eu2+-based white LED display were slightly yellow-shifted and the intensity increased on increasing the forward-bias current. These results indicate that orangish-yellow-emitting Ca3Si2O7:0.015Eu2+ can serve as a promising candidate for applications in warm-white LEDs. This journal is © the Partner Organisations 2014.


Wong C.-H.,Singapore General Hospital | Ong Y.S.,Singapore General Hospital | Wei F.-C.,Chang Gung University
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2012

Introduction: Complex and extensive lower limb defects remain difficult reconstructive problems. Conventional flaps may not be large enough or lack the versatility that allows precise tissue positioning to optimally cover the wound. The anterolateral thigh-vastus lateralis conjoint flap provides a superior reconstructive solution for these difficult wounds. Methods and materials: From Jan 2010 to June 2011, seven patients were reconstructed with the anterolateral thigh-vastus lateralis conjoint flap. Three cases were traumatic degloving injury of the lower limb, three were open fractures of the tibia with extensive soft-tissue loss and one was a large soft-tissue defect as a result of necrotising fasciitis. The skin island and muscle component were raised with independent pedicles to allow complete freedom in the inset of each flap based on a common pedicle. The descending and oblique branches of the lateral circumflex femoral artery were used as the pedicle of the conjoint flap in four and three cases, respectively. Results: The mean size of the skin flap was 355 cm 2 (range: 312-420 cm 2) and the volume of the muscle flap was 210 cm 3 (range: 42-360 cm 3). All flaps survived completely and no infective complications were noted in our patients. The skin and muscle component were widely separated to expand the area of coverage. In cases where specific areas of the wound were severely traumatised with significant tissue loss, the muscle component can be precisely positioned to obliterate the dead space and to optimise soft-tissue coverage of the wound. Conclusion: The anterolateral thigh-vastus lateralis conjoint flap is superior to conventional flaps available for coverage of extensive defects of the lower limb. It can cover far greater area as well as providing the versatility needed to optimise soft-tissue coverage. © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.


Liao J.-C.,Chang Gung University
International Journal of Molecular Sciences | Year: 2016

Degenerative discs can cause low back pain. Cell-based transplantation or growth factors therapy have been suggested as a strategy to stimulate disc regeneration. Bone marrow-derived mesenchymal stem cells (BMDMSC) containing bone morphogenetic protein-7 (BMP-7) gene were constructed. We evaluated the effectiveness of these BMP-7 overexpressing cells on degenerative discs in rat tails. In vitro and in vivo studies were designed. In the first stage, the rats were divided into two group according to discs punctured by different needle gauges (18 gauge and 22 gauge). In the second stage, the ideal size of needle was used to induce rat tail disc degeneration. These animals are divided into three groups according to timing of treatment (zero-week, two-week, four-week). Each group was divided into three treating subgroups: control group, BMDMSC group, and Baculo-BMP-7-BMDMSC group. Each rat undergoes radiography examination every two weeks. After eight weeks, the discs were histologically examined with hematoxylin and eosin stain and Alcian blue stain. The 18-gauge group exhibited significant decrease in disc height index (%) than 22-gauge group at eight weeks at both Co6-7 (58.1% ± 2.8% vs. 63.7% ± 1.0%, p = 0.020) and Co8-9 discs (62.7% ± 2.8% vs. 62.8% ± 1.5%, p = 0.010). Baculo-BMP-7-BMDMSCs group showed significant difference in disc height index compared to the BMDMSCs group at both Co6-7 (93.7% ± 1.5% vs. 84.8% ± 1.0%, p = 0.011) and Co8-9 (86.0% ± 2.1% vs. 81.8% ± 1.7%, p = 0.012). In Baculo-BMP-7-BMDMSCs group, the zero-week treatment subgroup showed significant better in disc height index compared to two-week treatment group (p = 0.044), and four-week treatment group (p = 0.011). The zero-week treatment subgroup in Baculo-BMP-7-BMDMSCs group also had significant lower histology score than two-week treatment (4.3 vs. 5.7, p = 0.045) and four-week treatment (4.3 vs. 6.0, p = 0.031). In conclusion, Baculo-BMP-7-BMDMSC can slow down the progression of disc degeneration, but could not provide evidence of regeneration. Early treatment might obtain more distinct results. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Lin S.-W.,Chang Gung University | Lee Z.-J.,Huafan University | Ying K.-C.,National Taipei University of Technology | Lu C.-C.,National Taipei University of Technology
Computers and Operations Research | Year: 2011

In this paper, we consider an identical parallel machine scheduling problem with sequence-dependent setup times and job release dates. An improved iterated greedy heuristic with a sinking temperature is presented to minimize the maximum lateness. To verify the developed heuristic, computational experiments are conducted on a well-known benchmark problem data set. The experimental results show that the proposed heuristic outperforms the basic iterated greedy heuristic and the state-of-art algorithms on the same benchmark problem data set. It is believed that this improved approach will also be helpful for other applications. © 2010 Elsevier Ltd.


Abstract The technique for order preference by similarity to ideal solutions (TOPSIS) is a well-known compromising method for addressing decision-making problems. In general, incomplete preference information and vague subjective judgments are realistic in practice. Accordingly, the theory of interval type-2 fuzzy sets has received increasing attention in the decision-making field because of its great ability to handle imprecise and ambiguous information in a convenient manner. The purpose of this paper is to develop a novel interval type-2 fuzzy TOPSIS method for multiple criteria decision analysis that is based on interval type-2 trapezoidal fuzzy numbers. This paper introduces the concept of approximate positive-ideal and negative-ideal solutions and presents a simple way to approach the evaluative ratings of ideal solutions using interval type-2 trapezoidal fuzzy numbers. Based on the likelihoods of interval type-2 trapezoidal fuzzy binary relations, this paper proposes certain likelihood-based comparison indices to establish a likelihood-based closeness coefficient of each alternative relative to the approximate ideals. Applying a likelihood-based comparison approach with the approximate ideals, this paper develops the interval type-2 fuzzy TOPSIS procedure to determine the priority ranking orders of the alternatives under consideration of the multiple criteria evaluation/selection. Three practical applications involving landfill site selection, supplier selection, and car evaluation are examined to show the effectiveness and practicability of the proposed method. Furthermore, this paper makes a comparison of the solution results yielded by other interval type-2 fuzzy decision-making methods. The comparative analyses demonstrate that the proposed interval type-2 fuzzy TOPSIS method is easy to implement and produces effective and valid results for solving multiple criteria decision-making problems. © 2015 Elsevier Ltd. All rights reserved.


Liao C.-H.,Far Eastern Memorial Hospital | Ko W.-C.,National Cheng Kung University | Lu J.-J.,Chang Gung University | Hsueh P.-R.,National Taiwan University Hospital
Antimicrobial Agents and Chemotherapy | Year: 2012

A total of 403 nonduplicate isolates of Clostridium difficile were collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC90 of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC90 of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (n = 81, 20.1%) was accompanied by single or multiple mutations in gyrA and gyrB genes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreported gyrB mutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains of C. difficile in the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potent in vitro activity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Binary and ternary poly(vinylidene fluoride) (PVDF) nanocomposites filled with organoclay (15A) and/or multi-walled carbon nanotubes (MWNTs) were successfully prepared. MWNTs were dispersed more homogeneously than 15A within PVDF matrix, and the presence of MWNTs facilitated the dispersibility of 15A. The 15A addition induced β-form PVDF crystal formation, but MWNTs hardly changed the α-form crystal development. Both nanofillers facilitated the nucleation of PVDF (up to 12.3 C increase), and the efficiency of enhancing PVDF crystallization followed the sequence MWNT > 15A/MWNT > 15A. The nanocomposites possess higher Tm than neat PVDF. In particular, adding 15A led to a Tm (β-form) increase of no less than 11 C. A rheological percolation threshold at 1 wt.% MWNT loading was determined. The electrical resistivity dropped by more than 13 orders of magnitude at 5 wt.% MWNT loading. The nanocomposites exhibited enhanced tensile modulus (up to 83% increase with MWNTs inclusion) compared with neat PVDF. © 2013 Elsevier B.V. All rights reserved.


Chuang Y.-Y.,St Marys Hospital | Huang Y.-C.,Chang Gung Memorial Hospital | Huang Y.-C.,Chang Gung University
The Lancet Infectious Diseases | Year: 2013

In Asia, most reports on the epidemiology of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) are from developed countries, with few data from resource-limited countries, not because of low actual prevalence, but probably because of scarce diagnostic facilities. The rate of MRSA in all community-associated S aureus infections in Asian countries ranges from 2·5% to 39%. Unlike the predominance of USA300-sequence type (ST) 8 staphylococcal cassette chromosome mec (SCC. mec) type IV in the USA, the molecular epidemiology of CA-MRSA in Asia is characterised by clonal heterogeneity, similar to that in Europe. The emergence of CA-MRSA is a threat in both community and hospital settings because such strains are now more prevalent than are health-care-associated MRSA (HA-MRSA) strains. Many epidemic clones are in circulation in Asia and with scarce data available, concern has arisen that CA-MRSA could have devastating results if it becomes epidemic in resource-poor regions. The epidemiology of CA-MRSA in Asia is closely linked with the health of both developing and developed countries. The present situation of CA-MRSA in Asia is important not only for local public health, but also to provide a better understanding of the successful epidemic clones of this global pathogen. © 2013 Elsevier Ltd.


The purpose of this paper was to conduct a comparative study of score functions in multiple criteria decision analysis based on intuitionistic fuzzy sets. The concept of score functions has been conceptualized and widely applied to multi-criteria decision-making problems. There are several types of score functions that can identify the mixed results of positive and negative parts in a bi-dimensional framework of intuitionistic fuzzy sets. Considering various perspectives on score functions, the present study adopts an order of preference based on similarity to the ideal solution as the main structure to estimate the importance of different criteria and compute optimal multi-criteria decisions in intuitionistic fuzzy evaluation settings. An experimental analysis is conducted to examine the relationship between the results yielded by different score functions, considering the average Spearman correlation coefficients and contradiction rates. Furthermore, additional discussions clarify the relative differences in the ranking orders obtained from different combinations of numbers of alternatives and criteria as well as different importance conditions. © 2011 Elsevier Inc. All rights reserved.


Chen T.-Y.,Chang Gung University
Expert Systems with Applications | Year: 2011

The frequently used methods of handling optimism and pessimism in multiple criteria decision analysis are Hurwicz's and Yager's approaches. Despite their wide usage, a critical issue has been raised about unidimensionality. Numerous psychological researches and empirical findings have convincingly supported that optimism and pessimism do not represent opposite poles on a single, bipolar dimension, but they are conceived as two partially independent dimensions instead. The focus of this paper is a two-dimensional approach by adequately employing the degrees of membership and non-membership based on Atanassov fuzzy sets. This study develops optimistic and pessimistic estimations with several fuzzy point operators to draw the influences of optimism and pessimism on multicriteria decision making for the sake of a better fit than the unidimensional model. Given a typology from empirical grounds, the appropriate point operators specific to each type are suggested to identify adaptational outcomes. Base upon a series of new score functions, a useful method for multiple criteria decision analysis is provided to efficiently facilitate decision analysis with a multimeasure approach. Feasibility and effectiveness of the proposed methods are illustrated by a practical example. © 2010 Elsevier Ltd. All rights reserved.


Wu A.M.,Chang Gung University
Advances in Experimental Medicine and Biology | Year: 2011

Lectins are an important class of proteins or glycoproteins of nonimmune origin that specifically or selectively bind carbohydrate moieties of complex carbohydrates. They play many critical roles in life processes, such as fertilization, embryogenesis, cell migration, organ formation, inflammation, immune defense, and microbial infection [8, 22, 40]. Specificity of lectins toward particular carbohydrate structures allows them to be used for characterization of unknown structures and identification and fractionation of glycoconjugates [23]. Moreover, this unique group of proteins has provided researchers with powerful tools to explore many biological processes in which lectins are involved. Considering the role of lectins in vivo, we have to realize that lectins in living organisms interact with multivalent macromolecules (glycoproteins) or clusters of oligosaccharide ligands on the cell surface. © 2011 Springer Science+Business Media, LLC.


Wu A.M.,Chang Gung University
Advances in Experimental Medicine and Biology | Year: 2011

"Biochemistry text books commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked" [1]. This statement from a recent review guides the readers to look at and fully appreciate the chemical/lectinochemical characteristics of carbohydrates that underlie the concept of the sugar code [2]. © 2011 Springer Science+Business Media, LLC.


Antigenic determinants (glycotopes) of human blood group ABH antigens are located on the complex glycoconjugates. These ABH glycotope-containing glycans are generally conjugated with polypeptides or ceramides to form glycoproteins and glycosphingolipids, respectively [15, 35]. © 2011 Springer Science+Business Media, LLC.


Yew K.C.,Tan Tock Seng Hospital | Chuah S.-K.,Chang Gung University
Gastroenterology Research and Practice | Year: 2013

The basic principle of antireflux procedures employing endoscopic intervention aims to create a mechanical barrier to prevent primary pathophysiology in gastroesophageal reflux disease (GERD). We review, highlight, and discuss the past and present status of endoluminal therapy. Currently, there are 3 commonly employed anti-reflux endoluminal procedures: fundoplication or suturing techniques (EndoCinch, NDO, and EsophyX), intramural injection or implant techniques (enhancing lower esophageal sphincter (LES) volume and/or strengthening compliance of the LES-Enteryx and Gatekeeper), and radiofrequency ablation of LES and cardia. EndoCinch plication requires further study and modification of technique before it can be recommended because of durability issues. Esophynx, the transoral incisionless fundoplication, may reduce hiatal hernias and increase LES length. Preliminary studies have shown promising reduction in symptoms and medication use but evidence concerning safety and long-term durability is still pending. The safety issue with injection technique is the main concern as evident from the incidences of implant withdrawals after reported major adverse events. Future research with cautious monitoring is required before any new implant material can be recommended for commercial application. Radiofrequency ablation therapy is regaining popularity in treating refractory symptoms despite PPI use due to improved efficacy, durability, and safety after years of refinement of protocol. © 2013 Kuo Chao Yew and Seng-Kee Chuah.


Lin S.-M.,Chang Gung University
Journal of Medical Ultrasound | Year: 2013

Radiofrequency ablation (RFA) is one of the curative treatment modalities for small (diameter, ≤3 cm) or early stage (single tumor ≤5 cm in diameter or up to three tumors of ≤3 cm diameter each) hepatocellular carcinoma (HCC). RFA is more commonly used than other local ablative modalities because the technique is highly effective, minimally invasive, and requires fewer sessions. RFA is advocated as the first-line curative therapy for unresectable or even resectable very early stage or early stage HCC based on a survival rate comparable to that seen with resection. Although RFA is highly effective for local ablation of small HCC tumors, current RFA procedures are less effective against tumors that are in high-risk or difficult-to-ablate locations, are poorly visualized on ultrasonography (US), are associated with major complications, and are large (>3 cm in diameter). Recent advances can overcome these issues by creation of artificial ascites or pleural effusion, application of real-time virtual US assistance, incorporation of contrast-enhanced US before or after RFA, use of combination therapy before RFA, or switching RF controller with multiple electrodes. This review article provides updates on the clinical outcomes and advances in RFA in the treatment of HCC, particularly the aforementioned issues. © 2013, Elsevier Taiwan LLC and the Chinese Taipei Society of Ultrasound in Medicine.


Lee C.-H.,Chang Gung University
Dermatologica Sinica | Year: 2016

Itch is an unpleasant perception that provokes one to desire to scratch. It results from the activation of free nerve endings by noxious stimuli in the skin. Atopic dermatitis (AD) is a prototypic inflammatory skin disease that always occurs with an intense itch. AD involves many components of skin-associated lymphoid tissue (SALT). As a disease with polarized T helper 2 cell activation, AD involves eosinophil infiltration and immunoglobulin E, interleukin (IL)-2, IL-4, IL-13, and IL-31 production. As a disease involving an impaired skin barrier, AD is characterized by the enhanced transepidermal entry of allergens and the production of thymic stromal lymphopoietin (TSLP) from epidermal keratinocytes, which worsen atopic March and disease progression. Both immune and epidermal events interact with cutaneous nerve components, including transient receptor potential (TRP) channels and opioid receptors, causing both the perception and propagation of itch from the skin to the brain. In addition to treating itch through TRP channels and opioid receptors, it might be possible to target the various cellular components of SALT, including keratinocytes, eosinophils, and soluble factors, such as IL-31, IL-4, IL-13, IL-31, and TSLP. © 2015, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC.


This paper presents a useful method of relating optimism and pessimism to multiple criteria decision analysis in the context of intuitionistic fuzzy sets based on the unipolar bivariate model. We use eight point operators to estimate the adaptational outcome expectations of optimism and/or pessimism and then determine the net predisposition, the aggregated effect of positive and negative evaluations. A series of new net predispositions for bivariate evaluations are proposed for neutrality; for complete, moderate, and rational optimism; for complete, moderate, and rational pessimism; and for complete and moderate optimism-pessimism. The suitability function, which measures the overall evaluation of each alternative, is then presented. Because positive or negative leniency may exist, such that most of the criteria may be assigned unduly high or low ratings, respectively, we introduce deviation variables to mitigate the effects of such ratings on the apparent importance of various criteria. Based on the two objectives of maximal weighted suitability and minimal deviation values, an integrated programming model is used to compute the optimal weights for the criteria and the corresponding degrees of suitability of the alternative rankings. We establish flexible algorithms that incorporate both objective and subjective information to compute the optimal optimistic and pessimistic decisions. The proposed methods are illustrated and discussed using a numerical example, a multi-criteria supplier selection problem. Finally, an empirical study of job choices is conducted to establish the feasibility and applicability of the current method. © 2011 Elsevier Inc. All rights reserved.


Chao C.C.-K.,Chang Gung University
Current Topics in Pharmacology | Year: 2010

The efficacy of cisplatin-based chemotherapy is often reduced by the emergence of cancer cells that become resistant to the treatment used. While biochemical and pharmacological mechanisms have been proposed to explain cisplatin resistance, the genes involved in this process have until recently become understood. To further understand the mechanisms underlying chemoresistance, we earlier used genome-wide DNA microarrays and quantitative RT-PCR to identify the genes that were upregulated in cisplatin-resistant HeLa cells. By using this approach, we identified nine genes, referred to as cisplatin resistance (CPR) genes, which were consistently upregulated in resistant cells. CPR genes were found to encode various extracellular (ADM), cytoplasmic (EHD1, MARK2, MVD, NAPA, and PTPN21), and nuclear proteins (CABIN1, CITED2, and HISTIHIA). The involvement of CPR proteins in chemoresistance was demonstrated by showing that reducing their expression by using short-hairpin RNA (shRNA) could sensitize various cell lines to cisplatin, but not to mitosis-disrupting agents. As such, knockdown of CPR genes partially or entirely reversed acquired chemoresistance. Conversely, ectopic expression of a single CPR gene was sufficient to enhance cisplatin resistance in the treated cells. The cisplatin-sensitization effects of shRNA-mediated CPR gene knockdowns (e.g., NAPA and CITED2) was shown to require the tumor suppressor p53. Importantly, combined cisplatin/shRNA treatments suppressed tumor growth in vivo in xenograph experiments performed in mice, thereby indicating that the newly identified CPR genes may represent potential candidates for novel target therapies.


Lou D.-C.,Chang Gung University | Huang H.-F.,National Taichung Institute of Technology
International Journal of Communication Systems | Year: 2011

In three-party password-based key exchange protocol, a client is allowed to share a human-memorable password with a trusted server such that two clients can negotiate a session key to communicate with each other secretly. Recently, many three-party password-based key exchange protocols have been developed. However, these proposed schemes cannot simultaneously achieve security and efficiency. Based on elliptic curve cryptography (ECC), this paper will propose a new simple three-party password-based authenticated key exchange scheme. The proposed method not only reduces computation cost for remote users and a trusted server but also is more efficient than previously proposed schemes. It is better suited for resource constrained devices, such as smart cards or mobile units. © 2010 John Wiley & Sons, Ltd. Recently, many three-party password-based key exchange protocols have been developed. However, these proposed schemes cannot simultaneously achieve security and efficiency. Based on elliptic curve cryptography (ECC), this paper, will propose a new simple three-party password-based authenticated key exchange protocol. The proposed method not only reduces computation cost for remote users and a trusted server but also is more efficient than previously proposed schemes. It is better suited for resource constrained devices, such as smart cards or mobile units. © 2010 John Wiley & Sons, Ltd.


Lin S.-W.,Chang Gung University | Lu C.-C.,National Taipei University of Technology | Ying K.-C.,National Taipei University of Technology
International Journal of Advanced Manufacturing Technology | Year: 2011

The unrelated parallel machine scheduling problem with sequence- and machine-dependent setup times in the presence of due date constraints represents an important but relatively less-studied scheduling problem in the literature. In this study, a simple iterated greedy (IG) heuristic is presented to minimize the total tardiness of this scheduling problem. The effectiveness and efficiency of the proposed IG heuristic are compared with existing algorithms on a benchmark problem dataset used in earlier studies. Extensive computational results indicate that the proposed IG heuristic is capable of obtaining significantly better solutions than the state-of-the-art algorithms on the same benchmark problem dataset with similar computational resources.


Yap F.G.H.,Chang Gung University | Yen H.-H.,Shih Hsin University
Sensors (Switzerland) | Year: 2014

Wireless Visual Sensor Networks (WVSNs) where camera-equipped sensor nodes can capture, process and transmit image/video information have become an important new research area. As compared to the traditional wireless sensor networks (WSNs) that can only transmit scalar information (e.g., temperature), the visual data in WVSNs enable much wider applications, such as visual security surveillance and visual wildlife monitoring. However, as compared to the scalar data in WSNs, visual data is much bigger and more complicated so intelligent schemes are required to capture/process/ transmit visual data in limited resources (hardware capability and bandwidth) WVSNs. WVSNs introduce new multi-disciplinary research opportunities of topics that include visual sensor hardware, image and multimedia capture and processing, wireless communication and networking. In this paper, we survey existing research efforts on the visual sensor hardware, visual sensor coverage/deployment, and visual data capture/ processing/transmission issues in WVSNs. We conclude that WVSN research is still in an early age and there are still many open issues that have not been fully addressed. More new novel multi-disciplinary, cross-layered, distributed and collaborative solutions should be devised to tackle these challenging issues in WVSNs. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Zelken J.,Chang Gung University
Annals of Plastic Surgery | Year: 2015

BACKGROUND: Donor site scarring after forehead flap nasal reconstruction is acceptable. However, as aesthetic outcomes standards for cosmetic and reconstructive surgery merge, we aim to enhance results. We recently demonstrated the cosmetic benefit of botulinum toxin type A (BTX-A) for cleft lip cheiloplasty outcomes. We hypothesize that similar mechanism(s) benefit forehead flap donor scars. METHODS: A single surgeon performed 26 forehead flap reconstructions. Indications were cancer (n = 17), trauma (n = 3), and congenital deformity (n = 6). In this split-scar study half the forehead was pretreated with BTX-A and half with normal saline after random assignment. Photographs were evaluated at most recent follow-up. Scar evaluation was based on photographs by 3 plastic surgeons using a composite subjective visual analogue score (VAS). RESULTS: Photographic follow-up was 27 months (range, 10–60 months). Botulinum toxin type A was assigned to the upper forehead in 16 cases and lower forehead in 10 cases. Intrarater reliability among 4 evaluators of 104 VAS scores was 78.1%. Upper forehead VAS (7.9 ± 1.2) was not different than lower forehead VAS (7.9 ± 1.2) regardless of treatment (P = 0.62). The VAS score of BTX-A–treated scars (8.5 ± 1.0) was significantly higher than the control (7.3 ± 1.1; P < 0.0001). Among 104 individual comparisons (26 patients × 4 observers), there were 73 instances (70.2%) where the experimental VAS score was higher than the control. CONCLUSIONS: Preoperative BTX-A injection is feasible and enhances donor site scar appearance after forehead flap nasal reconstruction in an Asian population. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Lai M.,Beth Israel Deaconess Medical Center | Liaw Y.-F.,Chang Gung University
Clinics in Liver Disease | Year: 2010

There have been major advances in the field of hepatitis B (HBV) over the last few decades. These advances have resulted in the understanding of the natural history of chronic HBV infection, effective vaccines against the virus, sensitive assays for screening and monitoring of treatment, and effective treatments for viral suppression, all leading to improved outcomes. Debates and controversies remain, however, over the ideal management strategies of patients with chronic hepatitis B. To eradicate HBV, the global community needs to improve current preventive, screening, and treatment strategies. © 2010 Elsevier Inc.


Chang C.-H.,Chang Gung University
International Health | Year: 2014

Background: Identification of cut-off values for key biomarkers of clinical risk is a useful clinical tool. The kappa coefficient is a popular descriptive statistical measure for summarising the cross classification of two nominal variables with identical classes. On the basis of this definition, I propose that the kappa coefficient can also be used to capture discrimination, in the same way that the receiver operating characteristic (ROC) curve is used in preventive epidemiology studies. Methods: The statistics were determined using Cohen's kappa statistics for a gold standard and a continuous biomarker. The proposed design is compared with the ROC curve by applying it to articles on the metabolic syndrome and a colon cancer clinical trial. Results: The two methods gave similar results. Moreover, Monte Carlo simulation results confirm that, from a power perspective, the proposed method is to be preferred. In general, the proposed method has higher power than the area under the ROC curve (AUC) for a study of positively correlative design. Conclusion: Overall, the power performance of the proposed method is better that that of the AUC. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.


Chen T.-Y.,Chang Gung University
International Journal of Systems Science | Year: 2012

The theory of Atanassov's intuitionistic fuzzy sets (A-IFSs) developed over the last several decades has found useful application in fields requiring multiple-criteria decision analysis. Since the membership-nonmembership pair in A-IFSs belongs to the bivariate unipolarity type, this article describes an approach that relates optimism and pessimism to multi-criteria decision analysis in an intuitionistic fuzzy-decision environment. First, several optimistic and pessimistic point operators were defined to alter the estimation of decision outcomes. Next, based on the core of the estimations, optimistic and pessimistic score functions were developed to evaluate each alternative with respect to each criterion. The suitability function was then established to determine the degree to which each an alternative satisfies the decision maker's requirement. Because the information on multiple criteria corresponding to decision importance is often incomplete, this study included suitability functions in the optimisation models to account for poorly known membership grades. Using a linear equal-weighted summation method, these models were transformed into a single objective optimisation model to generate the optimal weights for criteria. The feasibility and effectiveness of the proposed methods were illustrated through a practical example. Finally, computational experiments with enormous amounts of simulation data were designed to conduct a comparative analysis on the ranking orders yielded by different optimistic/pessimistic point operators. © 2012 Taylor & Francis.


Lee M.,University of California at Los Angeles | Lee M.,Chang Gung University | Hong K.-S.,University of California at Los Angeles | Hong K.-S.,Inje University | Saver J.L.,University of California at Los Angeles
Stroke | Year: 2010

BACKGROUND AND PURPOSE-: Although intra-arterial (IA) fibrinolysis for acute ischemic stroke has been clinically available for many years, it is not a therapy approved by the US Food and Drug Administration. Single, randomized, clinical trials (RCTs) have suggested beneficial effects, but no single RCT has demonstrated that IA fibrinolysis yields increases in both good (modified Rankin Scale score 0 to 2) and excellent (modified Rankin Scale score 0 to 1) outcomes when compared with the control group. Relatively few participants and inadequate statistical power in single RCTs may have contributed to this difficulty. METHOD-: We performed a systematic literature search to identified RCTs of IA fibrinolysis in acute ischemic stroke. Multiple outcomes were analyzed, with emphasis on good and excellent outcomes at 90 days or at trial end point. RESULTS-: The systematic search identified 5 RCTs with 395 participants comparing IA fibrinolysis and control. IA fibrinolysis was associated with increased good (odds ratio=2.05; 95% CI, 1.33 to 3.14; P=0.001) and excellent (odds ratio=2.14; 95% CI, 1.31 to 3.51; P=0.003) outcomes. For additional end points, IA fibrinolysis was associated with increased frequencies of minimal neurologic deficit (National Institutes of Health Stroke Scale score 0 to 1), minimal impairment of activities of daily living (Barthel Index 90 to 100 or 95 to 100), and recanalization. IA fibrinolysis was associated with increased radiological and symptomatic intracerebral hemorrhage. However, there was no difference in mortality between groups. CONCLUSIONS-: Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke. Increased hemorrhage frequencies are not associated with any increase in mortality. © 2010 American Heart Association, Inc.


Chen H.-H.,Chang Gung University
Annals of Plastic Surgery | Year: 2015

BACKGROUND: The osteoseptocutaneous fibula flap has been widely used for bone and soft tissue reconstruction from its first description in 1975. Nowadays, this flap has become the workhorse flap for head and neck reconstruction because of its suitability for mandible reconstruction. However, the reliability of the skin paddle is still controversial. We described a modified method for the harvesting of an osteoseptocutaneous flap to obtain a more reliable skin paddle while minimizing the donor site morbidity. METHODS: One hundred fifty-one consecutive patients were enrolled in the current study from January 2005 to December 2013. All of them underwent a free osteoseptocutaneous flaps for either head and neck (n = 135) or extremity (n = 16) reconstruction following the posterior approach harvest technique. Demographics data of all the patients were collected: age, sex, defect location, and etiology. The variables included for the statistical analysis were: size of the skin paddle, time of harvesting, reoperation, split skin paddle, and single or double barrel fashion for the inset. The outcomes measured were the flap success rate and the skin paddle survival. RESULTS: The flap success rate was 97.3%. The mean harvesting time was 45 minutes. The mean width and length of the skin paddle was 7.1 ± 2.6 and 17.41 ± 4.4 cm, respectively. The reexploration rate was 18.5%, and the salvage was achieved 85.7% of the cases. Partial skin paddle necrosis was found in 13.2% of the cases. The fact of having a reexploration in the postoperative period was the only variable significantly associated with the skin paddle necrosis (P = .001). CONCLUSIONS: According to our experience, the posterior approach for the harvest of the osteoseptocutaneous fibula flap is a safe technique and offers many advantages, such as a better visualization of the perforators, beneficial for chimeric flap elevation, preservation of the muscular fascia in the donor site, and an earlier diagnosis of any anatomical variation. Both the reliable and the versatility of the skin paddle can substantially improve with this approach. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


BACKGROUND:: Hematopoietic stem cell transplantation has prolonged life for children with life-threatening diseases. Quality of life is an essential outcome for evaluating the long-term effects of transplantation. OBJECTIVE:: The aims of this study were to compare the quality of life of children posttransplantation to that of healthy peers and explore the variables associated with the quality of life of posttransplant children. METHODS:: A cross-sectional study was conducted with 43 pediatric transplantation survivors and 43 age- and sex-matched healthy peers. RESULTS:: The mean age of the transplant group was 12.06 years. The mean time since transplant was 3.73 years. After covariate adjustment, there was no difference between posttransplant and healthy children in each domain and overall quality of life, except for physical functioning where the posttransplant children had lower scores than did the healthy group. Chronic graft-versus-host disease was found to be the primary factor associated with poor posttransplant overall quality of life and emotional and social functioning. Sociodemographic variables, symptom distress, and caregiver depression were not correlated with posttransplant quality of life. CONCLUSIONS:: The quality of life of pediatric transplantation survivors was comparable to that of healthy peers. IMPLICATIONS FOR PRACTICE:: The finding that children after transplant may achieve quality of life similar to their healthy peers is important information for parents to consider as they consider treatment options. For those sick children who cannot regularly attend school, their emotional and social functioning should be closely monitored. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved


Similar to the current trends in America that were recognized by the Association of American Medical College and the Howard Hughes Medical Institute in their 2009 report titled "Scientific Foundations for Future Physicians," Taiwanese medical students are lacking in their ability to apply their knowledge of basic sciences to real-life situations. The report recommended developing a competency-based approach to learning and also called for an increase in integrated and interdisciplinary courses in the education of medical students. Such a class, which would encourage students to look at biological concepts through chemical and physical principles, has been developed at Chang Gung University, and it strives to develop the medical student's ability to work in groups, think critically, and clearly and convincingly present ideas. The course requires students to present biological topics in groups after working closely with a teacher, and it trains the students to identify useful and trustworthy sources, to constructively criticize each other, and work together to present a cohesive and informative presentation for their peers. From my teaching experience, classes such as this have led me to conclude that the teacher's role does not simply encompass that of the informant, but also the facilitator of the academic success of the students, and this has led me to create certain class policies for teachers that help students of any field success in class. © 2011, Elsevier Taiwan LLC. All rights reserved.


The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216-256 and 18-125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm(2)/h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 μm to ∼140 μm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA.


Chen F.-P.,Keelung Chang Gung Memorial Hospital | Hu C.-H.,National Taiwan Ocean University | Wang K.-C.,Chang Gung University
Climacteric | Year: 2013

Objective To determine whether estrogen regulates mesenchymal stem cell (MSC) activity in bone marrow from osteoporotic postmenopausal women. Methods MSCs were collected from bone marrows which were aspirated simultaneously during iliac bone graft procedures in spine fusion surgery in osteoporotic postmenopausal women. We investigated proliferation, differentiation, osteogenic activity, and estrogen receptor (ER) α and β mRNA expression of primary culture MSCs isolated from four osteoporotic postmenopausal women, treated in vitro with or without 17β-estradiol. The expression of alkaline phosphatase (ALP), osteocalcin, interleukin-6, ERα and ERβ mRNA was evaluated. Results The expression of ALP and osteocalcin mRNA was detected during the cultures of MSCs and was observed to increase up to day 20. As compared with MSCs not treated with estradiol, a significant increase in DNA content, ERα mRNA, and ALP mRNA expression was observed in cultures with estradiol. The mRNA expression of osteocalcin and interleukin-6 was significantly lower in MSCs treated with estradiol than those without estradiol. There was no significant difference in the mRNA expression of ERβ between MSCs cultured with and without estradiol. Conclusions In the proper environment, MSCs from osteoporotic women can differentiate into osteoblasts and estrogen enhances the osteogenic activity possibly via ERα activity. © 2012 International Menopause Society.


Jha V.,Jawaharlal Institute of Postgraduate Medical Education & Research | Jha V.,George Institute of Global Health | Garcia-Garcia G.,University of Guadalajara | Iseki K.,University of Ryukyus | And 7 more authors.
The Lancet | Year: 2013

Summary Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases. © 2013 Elsevier Ltd.


Ober C.,University of Chicago | Yao T.-C.,Chang Gung University
Immunological Reviews | Year: 2011

Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits. © 2011 John Wiley & Sons A/S.


Liaw Y.-F.,Chang Gung University
Liver International | Year: 2011

Chronic hepatitis B virus (HBV) infection is a dynamic series of interactions between HBV, hepatocytes and the patient's immune system. HBV replication is the key motor of disease progression, including the development of cirrhosis and hepatocellular carcinoma (HCC). HBV elimination or suppression can reduce the risk of or slow the progression of liver disease. Studies have shown that a finite course of conventional interferon-α (IFN) therapy provides long-term benefit for achieving a cumulative response as well as reducing the progression of fibrosis and the development of cirrhosis and/or HCC. Long-term therapy with nucleos(t)ide analogues (NUCs) may also improve fibrosis or reverse advanced fibrosis as well as reduce disease progression and the development of HCC. The problems associated with drug resistance can be overcome by the timely use of rescue NUCs without cross-resistance. The outcome with pegylated IFN (PEG-IFN) and newer NUCs may be even better because of more effective treatment and/or a low risk of resistance. However, the treatment outcomes still need to be improved, and more effective, safe and affordable anti-HBV agents/strategies are needed. © 2011 John Wiley & Sons A/S.


Biodegradable poly(butylene succinate-co-adipate) (PBSA)-based nanocomposites were successfully prepared. A commercial halloysite nanotube (HNT) and an organo-montmorillonite (denoted as 15A) served as reinforcing fillers. Scanning electron microscopy and transmission electron microscopy results confirmed the nano-scale dispersion of HNT and 15A in the composites. Differential scanning calorimetry results showed that 15A served as nucleating agent for PBSA crystallization, but HNT hardly affected the nucleation of PBSA. Both nanofillers assisted the isothermal crystallization of PBSA, with 15A demonstrating superior efficiency. Melting behavior study suggests that the presence of HNT or 15A hampered the melting-recrystallization process of the originally less stable crystals during heating scans. Thermogravimetric analyses revealed that 15A enhanced the thermal stability of PBSA in air environment, but HNT caused a decline at high loadings. The rigidity of PBSA, including Young's/flexural moduli, evidently increased after the addition of HNT or 15A, with 15A showing higher enhancing efficiency than HNT at similar loadings. The flexural modulus increased up to 94% with 20 wt% in HNT and up to 48% with 5 wt% 15A loading. The rheological property measurements confirmed the achievement of pseudo-network structure at 5 wt% 15A loading, whereas the HNT-included system did not develop a network structure. © 2016 Elsevier Ltd


Wan G.-H.,Chang Gung University | Chung F.-F.,Chang Gung Institute of Technology | Tang C.-S.,Fu Jen Catholic University
American Journal of Infection Control | Year: 2011

Background: Maintenance of adequate indoor air quality (IAQ) in operating rooms (ORs) is critical to the prevention of nosocomial infection in hospitalized patients. This study evaluated the characteristics of IAQ in various ORs in a medical center. Methods: Air temperature, relative humidity, carbon dioxide (CO 2), particulate matter (PM), and bacterial concentrations were monitored in the ORs, and monthly variations were noted. Results: The mean CO 2 concentrations in the ORs were lower than the suggested level (600 ppm average over 8 hours) set by Taiwan's Environmental Protection Agency. Positive relationships were found among the number of persons, temperature (Spearman's rho coefficient [r s] = 0.19; P < .01), and CO 2 concentration (r s = 0.34; P < .01) in the OR. Bacterial concentration was significantly associated with PM level when adjusted for OR category and the number of persons in the room. Gram-positive bacteria (eg, Bacillus spp, Micrococcus spp, Staphylococcus spp) were frequently found in the monitored ORs. Conclusion: The IAQ in the ORs varied significantly from month to month. The number of persons in the OR affected IAQ, and a decreased PM level might indicate reduced microbial contamination in the OR. Copyright © 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.


High mobility group box 1 (HMGB1) is a nuclear protein that involves the binding with DNA and influences chromatin regulation and transcription. HMGB1 is also a cytokine that can activate monocytes and neutrophils involved in inflammation. In this study, we investigated the role of HMGB1 on cellular activation using human fibroblast cell line WI-38. After treatment with 1, 10, and 100 ng/mL of HMGB1 for 24 h, we did not find obviously cytotoxicity and cellular proliferation of WI-38 cells by MTT and BrdU incorporation assay, respectively. However, we found that treatment with 10 and 100 ng/mL of HMGB1 induced the differentiation of lung fibroblasts into myofibroblasts and myofibroblasts showed higher migration ability through activation of matrix metalloproteinase (MMP)-9 activation. To delineate the mechanism underlying HMGB1-induced cellular migration, we examined HMGB1-induced mitogen activated protein kinases (MAPKs), including extracellular signal related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen activated protein kinase (p38) phosphorylation, as well as nuclear factor (NF)-κB nuclear translocation. Using specific inhibitors and shRNAs of protein kinases, we observed that repression of ERK, JNK, p38, and NF-κB all inhibited HMGB1-induced cellular differentiation, migration and MMP-9 activation in WI-38 cells. In addition, knocking down of RAGE but not TLR2 and TLR4 by shRNAs attenuated HMGB1-induced myofibroblast differentiation and migration. In conclusion, our study demonstrated that HMGB1 induced lung fibroblasts' differentiation into myofibroblasts and enhanced cell migration through induction of MMP-9 activation and the RAGE-MAPK and NF-κB interaction signaling pathways. Targeting HMGB1 might be a potential therapeutic approach for alleviation of airway remodeling seen in chronic airway inflammatory diseases. © 2015 Lee et al.


Lin J.-D.,Chang Gung University
Journal of Medical Ultrasound | Year: 2010

Ultrasound and fine needle aspiration cytology are advocated as first-line examinations for the assessment of thyroid nodules. This review investigates the incidence of thyroid cancer in thyroid nodules after ultrasonographic examination. Furthermore, patient characteristics, histological patterns, and therapeutic results among patients who received thyroid ultrasound and fine needle aspiration cytology are discussed. The incidence of thyroid cancer in thyroid nodules, as detected by thyroid ultrasound, was found to range from 7.9% to 32.7% depending on the selected population. The incidence of thyroid cancer in thyroid nodules reported depends on the studied cohort, ethnic group, age, sex and iodine intake. Radiation exposure is also an important factor. Of the 6,330 patients with thyroid nodules who underwent surgical treatment, benign lesions were observed in 75.5% (4,782 cases) of the cases. Papillary thyroid carcinoma was observed in 79.8% (1,236 cases) of the 1,548 malignant cases. The percentage of malignancy was found to increase after the age of 50 in both men and women. A decrease in tumor size correlated with decreased cancer mortality; however, the beneficial effects of a small tumor size were not seen in older patients. Radiation-exposed populations and thyroid nodules or thyroid cancer were major problems from the atomic bomb in World War II and the Chernobyl nuclear accident. However, most occupational radiation exposure studies have not illustrated this harmful effect of radiation. In summary, over the time course in the diagnosis of thyroid cancer in nodules, there is a trend of decrease in tumor size and increase in the patient's age. The diagnosis and treatment of non-well-differentiated thyroid cancer in ageing patients is a major obstacle that needs to be overcome in the future. © 2010 Chinese Taipei Society of Ultrasound in Medicine & Elsevier.


Cheng C.Y.,Chang Gung University | Pickler R.H.,Cincinnati Childrens Hospital Medical Center
The Scientific World Journal | Year: 2014

Stress and fatigue are common complaints of pregnant and postpartum women as is depression. These symptoms may be related to immunomodulation. However, few studies have examined these relationships. The aim of this study was to examine the relationships among stress, fatigue, depression, and cytokines as markers of immune modulation in prenatal and postpartum women. Women completed questionnaires and gave blood samples during late pregnancy and again at 4-6 weeks postpartum. Blood was analyzed for cytokines as measures of immune modulation. Stress, fatigue, and depression were experienced at moderately high levels, with higher levels of fatigue and depression in the postpartum but higher stress in the prenatal period. Levels of several cytokines were increased in the postpartum over the prenatal period. Stress and depression were related in the prenatal period and stress, depression, and fatigue were related in the postpartum. While various cytokines were related to each other in both periods, only stress was related to MIP-1β, a cytokine that may be important for childbirth processes. More studies, especially longitudinal and interventional studies, are needed to increase our knowledge about etiology, patterns, symptoms, factors, and management of maternal distress. The search for reliable biomarkers for at-risk mothers remains a priority. © 2014 C. Y. Cheng and R. H. Pickler.


Chen H.-C.,R and ular Surface Center | Chen H.-C.,Chang Gung University | Zhu Y.-T.,R and ular Surface Center | Chen S.-Y.,R and ular Surface Center | Tseng S.C.,R and ular Surface Center
Laboratory Investigation | Year: 2012

Proliferation and epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy. This study aims at clarifying the role of growth factors, such as epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor-Β1 (TGF-Β1), in controlling how RPE proliferates while undergoing EMT. When contact inhibition of post-confluent ARPE-19 cells was disrupted by EGTA, an increase of BrdU labeling was noted only in the presence of EGF and/or FGF-2, and was accompanied by EMT as evidenced by the loss of a normal RPE phenotype (altered cytolocalization of RPE65, N-cadherin, ZO-1, and Na,K-ATPase) and the gain of a mesenchymal phenotype (increased expression of vimentin, S100A4, and α-smooth muscle actin). EMT with proliferation by EGTA+EGF+FGF-2 was accompanied by activation of canonical Wnt signaling (judged by the TCF/LEF promoter activity, increased nuclear levels of and interaction between Β-catenin and LEF1 proteins, and the replication by overexpression of Β-catenin), abolished by concomitant addition of XAV939, a Wnt inhibitor, but not associated with suppression of Hippo signaling (negative expression of nuclear TAZ or YAP and cytoplasmic p-TAZ or p-YAP). The causative role of Wnt signaling on EMT with proliferation was confirmed by overexpression of stable S33Y Β-catenin with EGTA treatment. In addition, contact inhibition disrupted by EGTA in the presence of TGF-Β1 also led to EMT, but suppressed proliferation and Wnt signaling. The Wnt signaling triggered by EGFFGF-2 was sufficient and synergized with TGF-Β1 in activating the Smad/ZEB1/2 signaling responsible for EMT. These findings establish a framework for further dissecting how RPE might partake in a number of proliferative vitreoretinopathies characterized by EMT. © 2012 USCAP, Inc All rights reserved.


Liang K.-H.,Liver Research Center | Yeh C.-T.,Liver Research Center | Yeh C.-T.,Chang Gung University
BMC Genomics | Year: 2013

Background: Alus are primate-specific retrotransposons which account for 10.6% of the human genome. A large number of protein-coding mRNAs are encoded with sense or antisense Alus in the un-translated regions.Results: We postulated that mRNAs carrying Alus in the two opposite directions can generate double stranded RNAs, capable of regulating the levels of other Alu-carrying mRNAs post-transcriptionally. A gene expression profiling assay showed that the levels of antisense and sense Alus-carrying mRNAs were suppressed in a reversible manner by over-expression of exogenous sense and antisense Alus derived from mRNAs (Family-wise error rate P= 0.0483 and P < 0.0001 respectively). Screening through human mRNAs on the NCBI-RefSeq database, it was found that sense and antisense Alu-carrying transcripts were enriched in distinct cellular functions. Antisense Alu-carrying genes were particularly enriched in neurological and developmental processes, while sense Alu-carrying genes were enriched in immunological functions.Conclusions: Taken together, we proposed a novel Alu-mediated regulation network capable of stabilizing Alu-carrying mRNA levels in different cell types and restricting the activated expression levels of protein-coding, Alu-carrying mRNAs. © 2013 Liang and Yeh; licensee BioMed Central Ltd.


Wu C.-C.,Chang Gung University
Orthopaedics and Traumatology: Surgery and Research | Year: 2015

Introduction: Pelvic width has been believed to affect patellar tracking by influencing the quadriceps angle (Q-angle). Anatomically, the upper arm of the Q-angle does not closely match the orientation of the quadriceps femoris. The pelvis is often considered wider and the Q-angle larger in female than in male individuals. The purpose of this retrospective study was to investigate the accuracy of such an assumption by using a radiologic comparison, which might be more objective. Materials and methods: One hundred consecutive adult patients (50 men and 50 women) aged 18-30 years with unilateral injury to the lower extremity were studied. Full-length standing X-rays of these patients was used to analyze the relationship between the pelvis and the uninjured lower extremity and compare it between the sexes. The pelvic width was defined as the distance between the centers of the bilateral femoral heads. Results: The pelvic width did not differ statistically between male and female (P = 0.74). The femur length and sum of the lengths of the femur and tibia differed between the sexes (both P< 0.001). Normalization of the pelvic width to the femur length or sum of the lengths of the femur and tibia resulted in a significant difference between male and female (P < 0.001). The angle formed by the femoral and tibial mechanical axes correlated strongly with the angle formed by the femoral anatomic and tibial mechanical axes (Pearson correlation coefficient = 0.89). Discussion: Pelvic width does not differ with respect to gender. The pelvis may appear relatively wider in women due to the difference in body height. However, this difference may not increase Q-angle. Patellar mal-tracking may stem from other, more critical predisposing factors. Level of evidence: Level IV. Anatomic study. © 2015 Elsevier Masson SAS.


Chen Y.-J.,Chang Gung University
Case Reports in Ophthalmology | Year: 2011

An 8-year-old active boy suffered a penetrating injury to his right eye. A temporal retinal perforation with an adherent blood clot about 4-disc diameter from the fovea was noted. Six weeks after the initial primary repair, a macular hole (MH) and retinal folds radiating from the penetrating site of the retina were found. Two months after the injury, the patient underwent a standard pars plana vitrectomy. Intraoperatively, the retinal folds still existed after creating a posterior hyaloid detachment and disappeared concurrently within the area of the internal limiting membrane peeling. Occlusion therapy was carried out after absorption of the intraocular gas. One year after the vitrectomy surgery, the MH remained closed with a visual acuity improving from 20/60 to 20/25 in his right eye. Our results suggest that vitrectomy with internal limiting membrane peeling and sequential occlusion therapy can achieve both anatomical and functional improvement in a child suffering a penetrating injury with a MH and retinal folds. Copyright © 2011 S. Karger AG, Basel.


Yang C.-H.,National Taipei University of Nursing and Health Sciences | Huang Y.-T.A.,Chang Gung University | Hsueh Y.-S.A.,University of Melbourne
International Journal for Equity in Health | Year: 2013

Background: Previous studies have evaluated the effects of various health manpower policies but did not include full consideration of the effect of universal health insurance on physician re-distribution. This study examines the effects of implementing National Health Insurance (NHI) on the problem of geographic mal-distribution of health providers in Taiwan. Methods. Data on health providers and population between 1971 and 2001 are obtained from relevant governmental publications in Taiwan. Gini coefficients derived from the Lorenz curve are used under a spline regression model to examine the impact of the NHI on the geographic distribution of health providers. Results: The geographic distribution equality of the three key health providers has improved significantly after the implementation of NHI program. After accounting for the influences of other confounding factors, Gini coefficients of the three key providers have a net reduction of 1.248% for dentists, 0.365% for western medicine physicians, and 0.311% for Chinese medicine physicians. Overall, the absolute values of the three key providers' Gini coefficients also become close to one another. Conclusions: This study found that NHI's offering universal health coverage to all citizens and with proper financial incentives have resulted in more equal geographic distributions among the key health care providers in Taiwan. © 2013 Yang et al.


Liu K.-S.,Biomaterials Laboratory | Wang Y.-C.,Chang Gung University | Liu S.-J.,Biomaterials Laboratory
Chest | Year: 2013

Background: Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems. Methods: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed. Results: The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for > 4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for > 5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area. Conclusions: Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for > 5 weeks, which showed great potential in the treatment of malignant airway obstruction. © 2013 American College of Chest Physicians.


Chen T.-Y.,Chang Gung University
Neural Computing and Applications | Year: 2016

The purpose of this paper was to develop a likelihood-based assignment method based on interval type-2 fuzzy sets and apply it to decision-making problems involving multiple criteria evaluation and the ranking/selection of alternatives. The linear assignment method is a well-known outranking method in the field of multiple criteria decision analysis. The theory of interval type-2 fuzzy sets is useful for addressing the uncertainty and imprecision associated with a subjective environment. In this paper, the key feature of the proposed method is the incorporation of the extended concept of likelihoods of fuzzy preference relations between interval type-2 trapezoidal fuzzy numbers into the main structure of the linear assignment methodology. An effective ranking procedure using the optimal membership degree determination method is proposed to determine criterion-wise preference rankings of the alternatives. The proposed method establishes the novel concepts of an (adjusted) rank frequency matrix and an (adjusted) rank contribution matrix to combine the relative performances of the alternatives in terms of each criterion. Based on a signed distance comparison approach, this paper constructs a likelihood-based assignment model to obtain an aggregate ranking of the alternatives that is in the closest agreement with the criterion-wise preferences of the alternatives. The feasibility and applicability of the proposed method are illustrated with two practical multiple criteria decision-making applications concerning the selection of landfill sites and the selection of treatment options. Finally, a comparative analysis with other relevant methods is conducted to validate the effectiveness and advantages of the current methods in decision aiding. © 2016 The Natural Computing Applications Forum


Purpose: To perform a validation test of the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines against quality of life (QoL) questionnaire datasets collected prospectively from patients with head and neck (HN) cancers, including HN squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC). Methods and materials: QoL questionnaire datasets from 95 patients with NPC and 142 with HNSCC were analyzed separately. The European Organization for Research and Treatment of Cancer H&N35 QoL questionnaire was used as the endpoint evaluation. The primary endpoint (grade 3+ xerostomia) was defined as moderate to severe xerostomia 3 and 12 months after the completion of RT, and excluded patients with grade 3 + xerostomia at the baseline. The Lyman-Kutcher-Burman normal tissue complication probability (NTCP) model was used to describe the incidence of xerostomia. Negative predictive values (NPVs) were used to determine the rate of correctly predicting the lack of complications. Results: NTCP fitted parameters were TD50 = 37.8 Gy (CI: 29.1-46.9 Gy), m = 0.59 (CI: 0.48-0.80) and TD50 = 43.9 Gy (CI: 33.2-52.8 Gy), m = 0.48 (CI: 0.37-0.76) at the 3-month and 12-month time points, respectively. For QUANTEC validation, HN and HNSCC data validation gave similar results at 3 months; at mean doses to the spared parotid of ≤20 and ≤25 Gy, the QoL dataset showed approximately 22% and 28% rates of xerostomia, respectively. At 12 months, the rates of xerostomia were approximately 13% and 19%, respectively. For NPC cases, the dataset showed approximately 0% and 33% (∼67% NPV) rates of xerostomia at 3 months. At 12 months, both rates of xerostomia were approximately 0% (∼100% NPV), which differed significantly from the results for the HNSCC cohort. Conclusion: The QoL datasets validated the QUANTEC guidelines and suggested that the modified QUANTEC 20/20-Gy spared-gland guideline is suitable for clinical use in HNSCC cohorts to effectively avoid xerostomia, and the QUANTEC 25-Gy guideline is justified for NPC cohorts. © 2013 Elsevier Ireland Ltd. All rights reserved.


Background Hypertrophic scars (HScs) are inelastic scars that can cause functional loss and disfigurement. Decorin regulates collagen fibrillogenesis, and its expression is lower in HScs than in normal skin and during wound healing. Objective To evaluate the efficacy of combined verapamil and triamcinolone in treating HScs. Methods Excised human HSc fragments from surgically treated burned patients were divided into three groups: A (normal saline), B (verapamil), and C (verapamil and triamcinolone). The specimens were bilaterally implanted in the back of nude mice, treated using intralesional injections, and observed for 4 weeks. We compared the fibroblast viability and proliferation, decorin staining, and scar weights to evaluate treatment efficacy. Results Viability and proliferation of HSc fibroblasts from groups B and C were significantly lower at all time intervals after transplantation (p<.001). Treatment (Groups B and C) stimulated strong decorin staining by 4 weeks. Nonsignificant differences in changes in scar weight were observed between groups. Conclusions We present the first evidence of verapamil-augmented decorin expression spatially correlated with collagen bundles in HScs. Combination therapy can reduce the dosage of each drug but achieve equal or better efficacy than monotherapy, reducing the side effects of a single drug. © 2010 by the American Society for Dermatologic Surgery, Inc.


Chen S.-C.,Chang Gung University
Scandinavian Journal of Caring Sciences | Year: 2012

The incidence of oral cancer has rapidly increased in Taiwan. Oral cancer and its surgical treatment may also cause physical and psychological problems for patients. During the postoperative period, patients face adjustments in their disease, treatment and lives. However, research on these relevant issues is scant. A qualitative study was conducted with the purpose of exploring the life experiences of surgically treated Taiwanese oral cancer patients during the postoperative period. Thirteen patients with oral cancer were recruited from the otolaryngology head and neck surgery wards of a medical centre in northern Taiwan. Semi-structured interviews were conducted and tape recorded after informed consent had been obtained. Data were analysed using the content analysis method. Results show that the life experiences of the patients with oral cancer were related to the impact of threatening symptoms, concerns about survival, restriction of interpersonal relationships, self-restructuring and constructing a support network. The results of this study can provide healthcare professionals with a reference for implementing care plans to address the unique needs of patients with oral cancer. © 2011 The Author. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.


Cheng M.-H.,Chang Gung University | Cheng M.-H.,Seton Institute of Reconstructive Plastic Surgery | Chen S.-C.,Seton Institute of Reconstructive Plastic Surgery | Henry S.L.,Seton Institute of Reconstructive Plastic Surgery | And 3 more authors.
Plastic and Reconstructive Surgery | Year: 2013

BACKGROUND: Vascularized groin lymph node flap transfer is an emerging approach to the treatment of postmastectomy upper limb lymphedema. The authors describe the pertinent flap anatomy, surgical technique including different recipient sites, and outcome of this technique. METHODS: Ten cadaveric dissections were performed to clarify the vascular supply of the superficial groin lymph nodes. Ten patients underwent vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema using the wrist (n = 8) or elbow (n = 2) as a recipient site. Ten patients who chose to undergo physical therapy were used as controls. Intraoperatively, indocyanine green was injected subcutaneously on the flap margin to observe the lymph drainage. Outcomes were assessed using improvement of circumferential differentiation, reduction rate, and decreased number of episodes of cellulitis. RESULTS: A mean 6.2 ± 1.3 groin lymph nodes with consistent pedicles were identified in the cadaveric dissections. After indocyanine injection, the fluorescence was drained from the flap edge into the donor vein, followed by the recipient vein. At a mean follow-up of 39.1 ± 15.7 months, the mean improvement of circumferential differentiation was 7.3 ± 2.7 percent and the reduction rate was 40.4 ± 16.1 percent in the vascularized groin lymph node group, which were statistically greater than those of the physical therapy group (1.7 ± 4.6 percent and 8.3 ± 34.7 percent, respectively; p < 0.01 and p = 0.02, respectively). CONCLUSIONS: The superficial groin lymph nodes were confirmed as vascularized with reliable arterial perfusion. Vascularized groin lymph node flap transfer using the wrist or elbow as a recipient site is an efficacious approach to treating postmastectomy upper limb lymphedema. Copyright © 2013 by the American Society of Plastic Surgeons.


Chien R.-N.,Chang Gung University
Journal of Gastroenterology and Hepatology (Australia) | Year: 2010

Chronic infection with hepatitis B virus (HBV) is a major global health problem and an important cause of morbidity and mortality from sequelae of liver cirrhosis and hepatocellular carcinoma. In the past decades, better understanding of the natural history and immunopathogenesis of chronic HBV infection and of the development of many powerful antiviral agents has allowed us to improve therapeutic efficacy. Among these agents, nucleos(t)ide analogs are important and potent viral suppressors. However, when administered alone, they are not able to permanently eradicate HBV, and long-term maintenance therapy is required for therapeutic efficacy. Additionally, prolonged treatment is frequently associated with the emergence of drug-resistant HBV mutants. Before an 'ideal' drug(s), or drug combination, with optimal antiviral efficacy and negligible rates of drug resistance becomes available, the on-treatment monitoring approach using serum HBV DNA level as a predictor for therapeutic efficacy and drug resistance is useful. However, most countries in the Asia-Pacific region have low income economies, insufficient medical care systems, and low awareness of the disease among the general population and government officers. The easy approach of the road-map concept using an affordable drug to treat chronic HBV infection is more important in this region. There is already evidence that the long-term outcomes of chronic HBV infection can be improved under well-managed antiviral therapy. Profound and long-lasting suppression of HBV replication, either maintained on-therapy or sustained after stopping therapy, has been identified as the key determinant for achieving the goals of therapy, for reducing liver damage, and for preventing development of cirrhosis and/ or hepatocellular carcinoma. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.


Prolonged glucocorticoid treatment increases the risk of osteopenic disorders. Bone loss and marrow fat accumulation are prominent features of glucocorticoid-induced skeletal destruction. Cannabinoid receptor 1 (CB(1) ) has been found to regulate energy expenditure and adipose tissue lipogenesis. We undertook this study to investigate whether CB(1) signaling regulates glucocorticoid-induced bone loss. Rats were administered glucocorticoid, CB(1) antisense oligonucleotide, CB(1) sense oligonucleotide, or the CB(1) antagonist AM251. Bone mineral density, microstructure, biomechanical strength, and signaling transduction were assessed by dual x-ray absorptiometry, micro-computed tomography, material testing, and immunoblotting, respectively. Primary bone marrow stromal cells were isolated for assessment of ex vivo osteoblast and adipocyte differentiation. Glucocorticoid administration accelerated bone deterioration and fatty marrow formation in association with up-regulation of CB(1) expression. Genetic and pharmacologic blockade of CB(1) by CB(1) antisense oligonucleotide and AM251 attenuated the deleterious effects of glucocorticoid treatment on bone mineral density, trabecular microarchitecture, and mechanical properties. CB(1) antagonism improved osteoblast survival, osteoblast surface, and bone mineral acquisition, but abrogated marrow adiposity. Knockdown of CB(1) restored osteogenic differentiation capacity and attenuated the promoting effects of glucocorticoid on adipogenic differentiation in primary bone marrow mesenchymal cells. CB(1) signaling modulated ERK, JNK, and Akt activation as well as runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ2 signaling. Adiponectin signaling was activated by CB(1) regulation of bone formation and fatty marrow. CB(1) mediates glucocorticoid-induced suppression of bone formation and marrow fat homeostasis. CB(1) antagonism reduces adipogenic and apoptotic reactions in bone microenvironments, thereby abrogating the deleterious effects of glucocorticoid treatment on bone integrity. Modulation of CB(1) signaling has therapeutic potential for preventing glucocorticoid-induced osteopenic disorders. Copyright © 2012 by the American College of Rheumatology.


Yazar S.,Acibadem University | Lin C.-H.,Chang Gung University
Journal of Reconstructive Microsurgery | Year: 2012

The main focus of this paper is the selection of proper vessels for successful free tissue transfer in lower extremities which have suffered extensive trauma. The selection of proper recipient vessels for traumatized lower extremities still presents difficulties for surgeons. This review will provide a general guideline for the selection of proper recipient vessels in traumatic lower extremity reconstruction and describe the possible reasons why some recipient vessels present more problems than others. Copyright © 2012 by Thieme Medical Publishers, Inc.


Chen S.-H.,Chang Gung University
Pediatrics and Neonatology | Year: 2015

Asparaginase is one of the most important chemotherapeutic agents against pediatric acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. The therapeutic efficacy (e.g., chemoresistance) and adverse effects of asparaginase (e.g., hypersensivity and pancreatitis) have been investigated over the past four decades. It was suggested early on that leukemic cells are resistant to asparaginase because of their increased asparagine synthetase activity. Afterward, other mechanisms associated with asparaginase resistance were reported. Not only leukemic cells but also patients themselves may play a role in causing asparaginase resistance, which has been associated with unfavorable outcome in children with ALL. This article will briefly review asparaginase therapy in children with ALL and comprehensively analyze recent reports on the potential mechanisms of asparaginase resistance. Copyright © 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.


Objective: The aim of this study was to assess the results of tibial lengthening with ankle arthrodesis in poliomyelitic patients with unilateral dysfunction of both knee extension and ankle dorsiflexion. Methods: Twenty-five consecutive adult patients with poliomyelitic sequelae of unilateral dysfunction of both knee extension and ankle dorsiflexion were treated. Patients had an average shorthening of 5.4 cm (range: 4.5-6.5 cm) on the affected side. The tibia was osteotomized and lengthened with external fixators, which were then replaced with plates supplemented with bone grafting. Ankle arthrodesis was performed concomitantly. Protected weight bearing was advised until bony union was achieved. Gait function was evaluated with Functional Mobility Scale and modified Mazur Scoring System. Results: Twenty-one patients were followed up for an average of 4.3 years (range: 2.0-8.2 years). External fixation was applied for an average of 6.2 weeks (range: 5-8 weeks). Complete bone healing was achieved in all patients and the average union time was 4 months (range: 3.5-4.5 months) after plating. At final follow-up, gait function significantly improved according to Functional Mobility Scale and modified Mazur Scoring System scores (p< 0.001 for both). Conclusion: The tibial lengthening with ankle arthrodesis appears to be an efficient alternative for treating poliomyelitic patients with unilateral dysfunction of both knee extension and ankle dorsiflexion. © 2016 Turkish Association of Orthopaedics and Traumatology.


Wu C.-C.,Chang Gung University
Archives of Orthopaedic and Trauma Surgery | Year: 2011

Introduction: Using antegrade exchange locked nailing to treat femoral supracondylar aseptic nonunion may sometimes have some limitations. Using retrograde locked nailing to treat such situations may achieve great advantages. The feasibility of such a technique was investigated. Materials and methods: Fifteen consecutive adult patients were treated. Indications for this technique were an aseptic nonunion of the femoral supracondyle, an antegradely inserted locked nail, shortening of the femur less than 1.5 cm, and a dilapidated cortex of the distal fragment unsuitable for performing antegrade exchange locked nailing. The technique included the closed removal of all previous implants, insertion of a retrograde dynamic locked nail, cancellous bone grafting from the lateral tibial condyle, and with or without plate augmentation. Early ambulation with protected weight bearing was allowed postoperatively, and knee range of motion exercise was encouraged. Results: Thirteen patients were followed up for a median of 2.5 years (range 1.1-4.5 years). All fractures were healed with a median union period of 4.5 months (range 3.5-5.5 months). There were no wound infections, non-unions or malunions. The knee function satisfactorily improved from none to 11 out of 13 patients (p<0.001). Conclusion: Retrograde dynamic locked nailing is an excellent alternative treatment for the treatment of aseptic nonunions of femoral supracondyles after antegrade locked nailing. However, this technique may only be used when antegrade exchange locked nailing is unsuitable for use. The technique is not complex and its success rate is high. © Springer-Verlag 2010.


Chang L.-K.,National Taiwan University of Science and Technology | Chuang J.-Y.,National Taiwan University of Science and Technology | Nakao M.,Kumamoto University | Liu S.-T.,Chang Gung University
Nucleic Acids Research | Year: 2010

Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle. The two proteins often collaborate to activate the transcription of EBV lytic genes synergistically. This study demonstrates that Rta and Zta form a complex via an intermediary protein, MCAF1, on Zta response element (ZRE) in vitro. The interaction among these three proteins in P3HR1 cells is also verified via coimmunoprecipitation, CHIP analysis and confocal microscopy. The interaction between Rta and Zta in vitro depends on the region between amino acid 562 and 816 in MCAF1. In addition, overexpressing MCAF1 enhances and introducing MCAF1 siRNA into the cells markedly reduces the level of the synergistic activation in 293T cells. Moreover, the fact that the synergistic activation depends on ZRE but not on Rta response element (RRE) originates from the fact that Rta and Zta are capable of activating the BMRF1 promoter synergistically after an RRE but not ZREs in the promoter are mutated. The binding of Rta-MCAF1-Zta complex to ZRE but not RRE also explains why Rta and Zta do not use RRE to activate transcription synergistically. Importantly, this study elucidates the mechanism underlying synergistic activation, which is important to the lytic development of EBV. © The Author(s) 2010. Published by Oxford University Press.


Jeng M.-J.,Chang Gung University
International Journal of Photoenergy | Year: 2012

It is well known that nitride-based devices suffer the polarization effects. A promising way to overcome the polarization effects is growth in a direction perpendicular to the c-axis (nonpolar direction). Nonpolar devices do not suffer polarization charge, and then they have a chance to achieve the high solar efficiency. The understanding of the solar performance of non-polar InGaN-based solar cells will be interesting. For a pin non-polar solar cell with GaN p- and n-cladding layers, the conduction band offset (or barrier height, E) between an intrinsic layer and n-GaN layer is an important issue correlating to the efficiency and fill factor. The efficiency and fill factor will be seriously degraded due to sufficiently high barrier height. To reduce a high barrier height, some graded layers with an energy bandgap between the energy bandgap of n-GaN and InxGa1xN intrinsic layer can be inserted to the interface of n-GaN and In xGa 1-xN layers. From simulation, it indicates that the insertion of graded layer is an effective method to lower energy barrier when there exists a high energy band offset in non-polar nitride devices. © Copyright 2012 Ming-Jer Jeng.


Tseng S.-Y.,Chang Gung University | Tsai C.-T.,National Chin - Yi University of Technology
International Journal of Photoenergy | Year: 2012

This paper proposes a photovoltaic (PV) power system for battery charger applications. The charger uses an interleaving boost converter with a single-capacitor turn-off snubber to reduce voltage stresses of active switches at turn-off transition. Therefore, active switches of the charger can be operated with zero-voltage transition (ZVT) to decrease switching losses and increase conversion efficiency. In order to draw the maximum power from PV arrays and obtain the optimal power control of the battery charger, a perturbation-and-observation method and microchip are incorporated to implement maximum power point tracking (MPPT) algorithm and power management. Finally, a prototype battery charger is built and implemented. Experimental results have verified the performance and feasibility of the proposed PV power system for battery charger applications. © 2012 Sheng-Yu Tseng and Cheng-Tao Tsai.


Alison M.R.,Center for Tumour Biology | Lin W.-R.,Chang Gung University
Journal of Pathology | Year: 2016

The liver's ability to regenerate is indisputable; for example, after a two-thirds partial hepatectomy in rats all residual hepatocytes can divide, questioning the need for a specific stem cell population. On the other hand, there is a potential stem cell compartment in the canals of Hering, giving rise to ductular reactions composed of hepatic progenitor cells (HPCs) when the liver's ability to regenerate is hindered by replicative senescence, but the functional relevance of this response has been questioned. Several papers have now clarified regenerative mechanisms operative in the mouse liver, suggesting that the liver is possibly unrivalled in its versatility to replace lost tissue. Under homeostatic conditions a perivenous population of clonogenic hepatocytes operates, whereas during chronic damage a minor population of periportal clonogenic hepatocytes come to the fore, while the ability of HPCs to completely replace the liver parenchyma has now been shown. © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Kang H.-Y.,Chang Gung University
Stem Cell Research and Therapy | Year: 2013

MicroRNA-21 (miR-21) functions have been linked to cancer progression and chemo- or radiotherapy resistance. While an increasing number of studies have reported a potential role of miR-21 expression in promoting growth of a small population of stem/progenitor cells, knowledge on its role as a regulator of stemness in cancers remains limited. In a previous issue of Stem Cell Research & Therapy, Chung and colleagues provide evidence that miR-21 is highly expressed in stem/progenitor populations of ovarian teratocarcinoma cells and has the potential to mediate growth and self-renewal in cancer stem/progenitor cells. Here we summarize current knowledge on miR-21 functions in human cancers and discuss how this finding provides insight into the role of miR-21 as an oncogenic regulator in stem/progenitor cell populations of human cancers. © 2013 Bio Med Central Ltd.


Hsiao C.-Y.,Chung Shan Medical University | Tsai Y.-F.,Chang Gung University
Nursing Research | Year: 2014

Background: Caring for relatives with schizophrenia is complicated and has been associated with burden. Caregivers may also experience satisfaction, but these outcomes have not been simultaneously studied in family caregivers of relatives with schizophrenia. Objectives: The aim was to investigate the attributes of caregiver burden and satisfaction among individuals and families as well as the association of caregiver burden on caregiver satisfaction in the care of Taiwanese individuals with schizophrenia. Methods: A cross-sectional, descriptive, correlational design was used. A convenience sample of 140 families (243 individual family caregivers) was recruited from two psychiatric hospitals in Taiwan. Participants were interviewed individually to complete questionnaires regarding pileup of demands, sense of coherence, mutuality, caregiver burden, and caregiver satisfaction. Linear mixed modeling was used. Results: Female caregivers, greater family demands, decreased sense of coherence, and lower mutuality were associated with higher levels of caregiver burden, whereas being siblings or close relatives and being friends of the affected individuals were associated with lesser self-reported burden. Satisfaction was positively associated with caregiver age, sense of coherence, and mutuality. Burden and satisfaction were not significantly related. Discussion: Caring for family members with schizophrenia is burdensome but can also be a source of satisfaction. Correlates of caregiver burden appeared to be somewhat distinct from those of caregiver satisfaction. Further research on negative and positive aspects of caregiving is warranted to broaden the understanding of caregiving experiences and design therapeutic interventions to mitigate caregiver burden and enhance the sense of satisfaction with caregiving. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Yu V.F.,National Taiwan University of Science and Technology | Lin S.-W.,Chang Gung University
Applied Soft Computing Journal | Year: 2014

The location routing problem with simultaneous pickup and delivery (LRPSPD) is a new variant of the location routing problem (LRP). The objective of LRPSPD is to minimize the total cost of a distribution system including vehicle traveling cost, depot opening cost, and vehicle fixed cost by locating the depots and determining the vehicle routes to simultaneously satisfy the pickup and the delivery demands of each customer. LRPSPD is NP-hard since its special case, LRP, is NP-hard. Thus, this study proposes a multi-start simulated annealing (MSA) algorithm for solving LRPSPD which incorporates multi-start hill climbing strategy into simulated annealing framework. The MSA algorithm is tested on 360 benchmark instances to verify its performance. Results indicate that the multi-start strategy can significantly enhance the performance of traditional single-start simulated annealing algorithm. Our MSA algorithm is very effective in solving LRPSPD compared to existing solution approaches. It obtained 206 best solutions out of the 360 benchmark instances, including 126 new best solutions. © 2014 Elsevier B.V.


Wu B.-R.,Chang Gung University
Applied Physics Letters | Year: 2011

Bandgaps play a central role in modern device physics, and a tunable bandgap can provide great flexibility in device design. Herein, an investigation of trilayer graphene modulated using an external electric field is presented. The calculations for trilayer graphene with hexagonal, Bernal, and rhombohedral stacking have been carried out. It was found that the bandgap of rhombohedral trilayer graphene can be tuned using an electric field. Symmetry plays a crucial role in the modulation the bandgap of trilayer graphene through an electric field. © 2011 American Institute of Physics.


Lin H.-H.,Chang Gung University
Advances in Experimental Medicine and Biology | Year: 2010

Asamacrophage-restrictedreagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 isnotrequired for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8 + regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR. © 2010 Landes Bioscience and Springer Science+Business Media, LLC.


Chen T.W.,Chang Gung University
BMC genomics | Year: 2012

Recent developments in high-throughput sequencing (HTS) technologies have made it feasible to sequence the complete transcriptomes of non-model organisms or metatranscriptomes from environmental samples. The challenge after generating hundreds of millions of sequences is to annotate these transcripts and classify the transcripts based on their putative functions. Because many biological scientists lack the knowledge to install Linux-based software packages or maintain databases used for transcript annotation, we developed an automatic annotation tool with an easy-to-use interface. To elucidate the potential functions of gene transcripts, we integrated well-established annotation tools: Blast2GO, PRIAM and RPS BLAST in a web-based service, FastAnnotator, which can assign Gene Ontology (GO) terms, Enzyme Commission numbers (EC numbers) and functional domains to query sequences. Using six transcriptome sequence datasets as examples, we demonstrated the ability of FastAnnotator to assign functional annotations. FastAnnotator annotated 88.1% and 81.3% of the transcripts from the well-studied organisms Caenorhabditis elegans and Streptococcus parasanguinis, respectively. Furthermore, FastAnnotator annotated 62.9%, 20.4%, 53.1% and 42.0% of the sequences from the transcriptomes of sweet potato, clam, amoeba, and Trichomonas vaginalis, respectively, which lack reference genomes. We demonstrated that FastAnnotator can complete the annotation process in a reasonable amount of time and is suitable for the annotation of transcriptomes from model organisms or organisms for which annotated reference genomes are not avaiable. The sequencing process no longer represents the bottleneck in the study of genomics, and automatic annotation tools have become invaluable as the annotation procedure has become the limiting step. We present FastAnnotator, which was an automated annotation web tool designed to efficiently annotate sequences with their gene functions, enzyme functions or domains. FastAnnotator is useful in transcriptome studies and especially for those focusing on non-model organisms or metatranscriptomes. FastAnnotator does not require local installation and is freely available at http://fastannotator.cgu.edu.tw.


Chan Y.-S.,Chang Gung University
Chang Gung Medical Journal | Year: 2011

Like other intra-articular fractures, the tibial plateau fracture is challenging for orthopedic surgeons because of its severity of trauma, associated soft tissue injuries. Open reduction incurs serious complications, especially wound healing after traditional dissections. Unsatisfactory results often occur in complex or bicondylar tibial plateau fractures. Traditional surgical methods achieved satisfactory results in 70-80% of cases. However, these methods have a high incidence of complications including loss of reduction, infection, and septic arthritis. The advantages of arthroscopy-assisted reduction and internal fixation include direct visualization of intra-articular fracture, accurate fracture reduction, and reduced morbidity. It is straightforward in the diagnosis and treatment of meniscal and ligamentous injuries, and removal of loose fragments. Good early to medium-term results of arthroscopically assisted osteosynthesis of tibial plateau fractures have been reported. The author reviews the current surgical principles, pitfalls, approaches, clinical results, and complications of arthroscopyassisted surgery for tibial plateau fractures.


Liaw Y.-F.,Chang Gung University
Digestive and Liver Disease | Year: 2010

Studies have shown that hepatitis B virus (HBV) replication is the key driver of disease progression, including development of cirrhosis and hepatocellular carcinoma (HCC), in patients with chronic HBV infection. Among the currently available anti-HBV drugs, the most extensive and longest experience has been gained with conventional interferon α (IFN) and lamivudine. Both controlled studies and meta-analyses have shown that a finite course of IFN therapy has long-term benefit in achieving cumulative response and corresponding reduction of cirrhosis and/or HCC. Maintained virological response to lamivudine therapy has similar long-term benefits in reducing disease progression. Although emergence of lamivudine drug resistance may negate therapeutic effect, rescue drugs are now available to overcome the adverse effect of drug resistance. Pegylated IFN and newer nucleos(t)ide analogs may have even better long-term outcomes because of better therapeutic efficacy and/or much lower risk of drug resistances. However, the treatment outcomes are still far from satisfactory. The development of safe and affordable anti-HBV agents/strategies is needed to further improve outcomes. © 2010 Editrice Gastroenterologica Italiana S.r.l.


Jana D.,University of Calcutta | Sun C.-L.,Chang Gung University | Chen L.-C.,National Taiwan University | Chen K.-H.,National Taiwan University | Chen K.-H.,Academia Sinica, Taiwan
Progress in Materials Science | Year: 2013

This review covers the electronic, optical and electrochemical properties along with electronic behaviors of boron (B) and nitrogen (N) substituted Single Wall Carbon Nanotubes (SWCNTs) underlying density functional theory (DFT) simulations. It is intended to be of interest for both experimentalists and theorists to expand application in the fields of SWCNTs. In particular, this article will focus on the electronically driven optical properties of C xNy nanotubes as a function of N concentration and B xCy nanotubes as a function of B under the action of a uniform electric field with various polarization directions through relaxed C-C bond length ab initio DFT. The link between the electronic band structure and the peak of the loss function will be highlighted. Within the formalism of DFT, we also consider the aspects of vacancy-defected SWCNTs. The effect of nitrogen incorporation is quite pronounced in enhancing the electrochemical properties of CNTs. In fact, this is a growing field due to the need of developing next-generation H-based energies. Finally, an attempt will be made for a comparative study of these theoretical results with experimental ones. Although there are ample experimental reports of N incorporation, at least less than 10%, in the nanostructured carbon, the experimental results on B-alloyed and N-alloyed SWCNTs are scarce. The review concludes with an outlook on the technological potential of these nano-composite systems as optical devices and nano-sensors. © 2013 Elsevier Ltd. All rights reserved.


Liu Y.-M.,University of Toronto | Wang H.-S.,Chang Gung University
Biomedical Journal | Year: 2013

The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.


This paper presents an interval-valued intuitionistic fuzzy permutation method with likelihood-based preference functions for managing multiple criteria decision analysis based on interval-valued intuitionistic fuzzy sets. First, certain likelihood-based preference functions are proposed using the likelihoods of interval-valued intuitionistic fuzzy preference relationships. Next, selected practical indices of concordance/discordance are established to evaluate all possible permutations of the alternatives. The optimal priority order of the alternatives is determined by comparing all comprehensive concordance/discordance values based on score functions. Furthermore, this paper considers various preference types and develops another interval-valued intuitionistic fuzzy permutation method using programming models to address multiple criteria decision-making problems with incomplete preference information. The feasibility and applicability of the proposed methods are illustrated in the problem of selecting a suitable bridge construction method. Moreover, certain comparative analyses are conducted to verify the advantages of the proposed methods compared with those of other decision-making methods. Finally, the practical effectiveness of the proposed methods is validated with a risk assessment problem in new product development. © 2016 Elsevier B.V. All rights reserved.


Lei K.F.,Chang Gung University
Micromachines | Year: 2014

In general, cell culture-based assays, investigations of cell number, viability, and metabolic activities during culture periods, are commonly performed to study the cellular responses under various culture conditions explored. Quantification of cell numbers can provide the information of cell proliferation. Cell viability study can understand the percentage of cell death under a specific tested substance. Monitoring of the metabolic activities is an important index for the study of cell physiology. Based on the development of microfluidic technology, microfluidic systems incorporated with impedance measurement technique, have been reported as a new analytical approach for cell culture-based assays. The aim of this article is to review recent developments on the impedance detection of cellular responses in micro/nano environment. These techniques provide an effective and efficient technique for cell culture-based assays. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Hung C.-I.,Chang Gung University
Current Opinion in Psychiatry | Year: 2014

PURPOSE OF REVIEW: Poor adherence and discontinuation of treatment are the major challenges of pharmacotherapy among patients with depression. This article reviews the factors predicting adherence to and persistence of antidepressant treatment identified in recent years. RECENT FINDINGS: Study populations have been extended to subgroups of patients with depression or depressive patients with comorbid medical conditions. Some studies have investigated the issues by analysing medical claims databases. Socio-demographic variables, clinical features of depression, comorbidities, pharmacological factors, attitudes towards antidepressants, previous experiences of antidepressant treatment, patient-professional relationship and genes were found to be common factors. An older age, positive attitudes to antidepressants and previous experiences and vicarious experiences of depression or treatment were found to be factors predicting better adherence or persistence. Conversely, patients in minority groups, those with a low family income, pregnancy, experience of side effects, dissatisfaction with treatment and a poor patient-professional relationship were found to be associated with poorer adherence or persistence. SUMMARY: The factors predicting adherence and persistence are complex and interactive. Different methods of studies have limitations in terms of exploring all these factors. Future studies should integrate these factors simultaneously and explore specific factors predicting adherence and persistence among subgroups of patients with depression. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Salmonellosis or Salmonella, one of the most common food-borne diseases, remains a major public health problem worldwide. Intestinal epithelial cells (IECs) play an essential role in the mucosal innate immunity of the host to defend against the invasion of Salmonella by interleukin (IL)−8 and human β-defensin-2 (hBD-2). Accumulated research has unravelled important roles of vitamin D in the regulation of innate immunity. Therefore, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25D3) on Salmonella-induced innate immunity in IECs. We demonstrate that pretreatment of 1,25D3 results in suppression of Salmonella-induced IL-8 but enhancement of hBD-2, either protein secretion and mRNA expression, in IECs. Furthermore, 1,25D3 enhanced Salmonella-induced membranous recruitment of nucleotide oligomerization domain (NOD2) and its mRNA expression and activation of protein kinase B (Akt), a downstream effector of phosphoinositide 3-kinase (PI3K). Inhibition of the PI3K/Akt signal counteracted the suppressive effect of 1,25D3 on Salmonella-induced IL-8 expression, while knock-down of NOD2 by siRNA diminished the enhanced hBD-2 expression. These data suggest differential regulation of 1,25D3 on Salmonella-induced IL-8 and hBD-2 expression in IECs via PI3K/Akt signal and NOD2 protein expression, respectively. Active vitamin D-enhanced anti-microbial peptide in Salmonella-infected IECs protected the host against infection, while modulation of proinflammatory responses by active vitamin D prevented the host from the detrimental effects of overwhelming inflammation. Thus, active vitamin D-induced innate immunity in IECs enhances the host's protective mechanism, which may provide an alternative therapy for invasive Salmonella infection. © 2016 British Society for Immunology.


Lin C.C.,Chang Gung University | Tseng L.C.,Shih Kun Company
Expert Systems with Applications | Year: 2010

The growth of the Internet has led to many studies on adaptive websites based on web usage mining. Most studies focus on providing assistance to users rather than optimizing the website structure itself. A recent work pioneered the use of 0-1 programming models to optimally reorganize websites based on the cohesion among web pages obtained by web usage mining. The proposed models reduce the information overload and search depth for users surfing the web. A heuristic approach has also been proposed to reduce the required computation time. However, the heuristic approach involving two successive 0-1 programming models still requires a very long computation time to find the optimal solution, especially when the website contains many hyperlinks. To resolve the efficiency problem, this study proposes an ant colony system to reorganize website structures. The proposed algorithm is tested extensively with numerical examples. Additionally, an empirical study with a real-world website is conducted to verify the algorithm applicability. © 2010 Elsevier Ltd. All rights reserved.


Tsai M.Y.,Chang Gung University | Morton J.,University of Oxford
International Journal of Solids and Structures | Year: 2010

The mechanics of double-lap joints with unidirectional ([016]) and quasi-isotropic ([0/90/-45/45]2S) composite adherends under tensile loading are investigated experimentally using moiré interferometry, numerically with a finite element method and analytically through a one-dimensional closed-form solution. Full-field moiré interferometry was employed to determine in-plane deformations of the edge surface of the joint overlaps. A linear-elastic two-dimensional finite element model was developed for comparison with the experimental results and to provide deformation and stress distributions for the joints. Shear-lag solutions, with and without the inclusion of shear deformations of the adherend, were applied to the prediction of the adhesive shear stress distributions. These stress distributions and mechanics of the joints are discussed in detail using the results obtained from experimental, numerical and theoretical analyses. © 2010 Elsevier Ltd. All rights reserved.


Chang C.-T.,Chang Gung University
IEEE Transactions on Fuzzy Systems | Year: 2010

In general, to formulate a fuzzy-linear-programming problem with n S-shaped utility (membership) functions, traditional methods require n or more extra binary variables because S-shaped curves are neither convex nor concave in all places. Adding binary variables does not improve the bound of the linear-programming relaxation. On the contrary, added binary variables increase the computational burden in the solution process if problems get large. Therefore, a formulation without binary variables should be more efficient. Accordingly, this study proposes a piecewise-linear approach to formulate an S-shaped membership function (MF) without adding any extra binary variables, which improves the efficiency of fuzzy-linear programming in solving decision/management problems with S-shaped MFs. Finally, a computational experiment is provided to demonstrate the superiority of the proposed models. An illustrative example is also provided to show the usefulness of the proposed method. © 2010 IEEE.


Lin T.-S.,Chang Gung University
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2016

Aim The aim of this study is to evaluate the use of one-stage debulking procedure to separate the fingers after flap reconstruction for degloving injury of the hand. Patients and methods From January 2009 to June 2014, 15 patients with degloving injuries of the hand were treated at the Kaohsiung Chang Gung Memorial Hospital. Among the 15 patients, 11 sustained degloving injury of the fingers; free flap reconstruction was performed in three patients, and a pedicle flap was used in eight. Four patients sustained complete degloving injuries of the hand; reconstruction was performed with an anterolateral thigh pocketing procedure. One-stage debulking procedure was performed for debulking of the flap and interdigitation from the flap envelope. Results After the 12-month follow-up and rehabilitation, the fingers could move independently and perform in opposition with the thumb. Protective sensation was also regained. The patients with degloving injury of the fingers could return to daily activity and work after 1-year follow-up, while those with complete degloving injury of the hand could return to daily activities and work after 18-month follow-up. Conclusion The use of ALT pocketing procedure is simple for salvage of complete degloving injury of the hand. One-stage debulking procedure provides thin and durable skin coverage for hand after reconstruction. The fingers can also be separated from the envelope of a bulky flap for independent movement to fulfill functional and aesthetic requirements. © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons.


Kolios G.,Chang Gung University
Plastic and Reconstructive Surgery | Year: 2016

Background: Many strategies exist to reconstruct composite nasal defects, but free flaps are necessary for extensive defects. The workhorse radial forearm flap is hair-bearing and donor-site cosmesis is unfavorable. The ulnar forearm flap is overlooked despite important aesthetic benefits. The authors describe their experience with the ulnar forearm flap, with a novel folding technique in staged nasal reconstruction. Methods: Between December of 2010 and April of 2015, 10 nasal reconstructions in five men and five women were performed. Average patient age was 47.6 years (range, 31 to 76 years). The ulnar forearm flap was designed as a narrow contiguous flap along the ulnar vascular axis. Inset began with the nasal floor; the flap was then tubularized twice to create nasal passages before it was folded on itself for coverage. Caudal edges were sewn together to create alae and a columella. Follow-up time, complications, number of operations, and reconstructive duration were documented. Results: Average follow-up was 25.2 months (range, 18 to 44 months). Patients had satisfactory aesthetic and functional outcomes after 6.4 operations (range, five to eight) over 11.1 months (range, 8 to 18 months). Partial necrosis of the alar lining in one case was salvaged with the covering flap. Two cases of chondritis were managed with conservative débridement and antibiotics. One case of severe chondritis necessitated removal and de novo reconstruction. Conclusions: The ulnar forearm flap is safe and reliable in nasal reconstruction, with superior donor-site cosmesis. The tubular folding method creates a vascular envelope amenable to same-stage framework construction. With thoughtful planning and sufficient refinement, excellent aesthetic and functional results are achievable. Clinical Question/Level of Evidence: Therapeutic, V. © 2016 by the American Society of Plastic Surgeons.


Wu C.-C.,Chang Gung University
European Journal of Orthopaedic Surgery and Traumatology | Year: 2016

Objective: Supracondylar femoral nonunions after dynamic condylar screw (DCS) treatment are uncommon, and few studies have addressed an optimal treatment technique for this disorder. Re-insertion of a new plate may not be secure because of bony defects in the distal fragment, created by the lag screw of the DCS. Materials and methods: Forty-two consecutive adult patients with 42 supracondylar femoral nonunions were treated with removal of the DCS, re-alignment of the knee axis, and insertion of a retrograde dynamic traditional femoral locked nail. When necessary, a humeral plate was augmented to reinforce rotational stability. Results: A final group of 36 patients with 36 nonunions were followed for an average of 2.8 years (range 1.1–6.2 years). All nonunions healed with a union rate of 100 %, and the average time to union was 4.2 months (range 2.5–5.5 months). Complications included two malunions. There were no instances of nonunion or deep infection. Satisfactory knee function among 36 patients improved from 8.2 % preoperatively to 86.1 % at the last follow-up (p < 0.001). All 36 patients could walk without aids. Conclusion: The described technique may be an excellent alternative treatment for an aseptic supracondylar femoral nonunion after DCS treatment. The technique is not difficult, and the union rate and satisfactory rate are high. © 2016, Springer-Verlag France.


Wang C.-H.,National Central University | Cheng K.-W.,Chang Gung University | Tseng C.-J.,National Central University
Solar Energy Materials and Solar Cells | Year: 2011

Ternary silverindiumsulfide samples were deposited on fluorine-doped tin oxide (FTO) coated glass substrates using a one-step electrodeposition method. A new procedure for the deposition of AgInS2 samples is reported. The effect of the [Ag]/[In] molar ratio in solution bath on the structural, morphological, and photoelectrochemical properties of samples was examined. X-ray diffraction patterns of samples show that the films are the AgInS 2 phase. The thickness, direct band gap, and indirect band gap of the films were in the ranges 2091021 nm, 1.821.85 eV, and 1.441.51 eV, respectively. The carrier densities and flat-band potentials of films obtained from Mott-Schottky and open-circuit potential measurements were in the ranges of 4.2×10199.5×1019 cm-3 and -0.736 to -0.946 V vs. the normal hydrogen electrode (NHE), respectively. It was found that the samples with molar ratio [Ag]/[In]=0.8 in solution bath had a maximum photocurrent density of 9.28 mA/cm2 with an applied bias of 1.0 V vs. an Ag/AgCl electrode in contact with electrolyte containing 0.25 M K 2SO3 and 0.35 M Na2S. The results show that high-quality AgInS2 films can be deposited on FTO-coated glass substrates for photoelectrochemical (PEC) applications. © 2010 Elsevier B.V. All rights reserved.


Nguyen M.L.,Yuan Ze University | Juang R.-S.,Chang Gung University
Journal of the Taiwan Institute of Chemical Engineers | Year: 2015

Glutaraldehyde-crosslinked chitosan beads modified with histidine and Saccharomyces cerevisiae (SC-HIS-CCBs) were applied as new biosorbents for enhanced adsorption of Ni(II) from aqueous solutions. The SC-HIS-CCBs were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analysis. The effects of various parameters, such as pH, contact time, and amount of biosorbent, on Ni(II) biosorption were investigated. The optimal pH was found to be 6.0. Isotherm data fit the Freundlich equation well, although they could be described by the Langmuir equation. The pseudo-second-order kinetic model could better follow the biosorption process in contrast to the pseudo-first-order kinetic model. The thermodynamic parameters of Ni(II) biosorption, including Gibbs free energy change (δ. G), enthalpy change (δ. H), and entropy change (δ. S), were calculated. The negative δ. G value indicated the spontaneous nature of Ni(II) biosorption on the SC-HIS-CCBs. © 2015 Taiwan Institute of Chemical Engineers.


Background: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. Methods: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. Results: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). Conclusion: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.


Poly(vinyl alcohol)/poly(2-acrylamido-2-methyl-1-propanesulfonic acid (PAMPS)/3-glycidyloxypropyl)trimethoxysilane (PVA/PAMPS/GPTMS) organic/inorganic proton-conducting polymer membranes are prepared by a solution casting method. PAMPS is a polymeric acid commonly used as a primary proton donor, while 3-(glycidyloxypropyl)trimethoxysilane (GPTMS) is an inorganic precursor forming a semi-interpenetrating network (SIPN). Varying amounts of sulfosuccinic acid (SSA) are used as the cross-linker and secondary proton source. The characteristic properties of PVA/PAMPS/GPTMS composite membranes are investigated by thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), micro-Raman spectroscopy and the AC impedance method. Direct methanol fuel cells (DMFCs) made of PVA/PAMPS/GPTMS composite membranes are assembled and examined. Experimental results indicate that DMFCs employing an inexpensive, non-perfluorinated, organic/inorganic SIPN membrane achieve good electrochemical performance. The highest peak power density of a DMFC using PVA/PAMPS/GPTMS composite membrane with 2 M CH3OH solution fuel at ambient temperature is 23.63 mW cm-2. The proposed organic/inorganic proton-conducting membrane based on PVA/PAMPS/GPTMS appears to be a viable candidate for future DMFC applications. © 2011 Elsevier B.V. All rights reserved.


Chang M.Y.,Chang Gung University
Contributions to nephrology | Year: 2011

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease in man and is caused by germline mutations in PKD1 or PKD2. Affected patients develop progressively enlarged kidneys due to the growth of multiple renal epithelial cysts. Several studies have demonstrated marked intrafamilial phenotypic variability in PKD1 or PKD2 pedigrees, indicating the importance of nonallelic factors such as genetic modifying loci in determining individual phenotype. Endothelin (ET)-1 exerts multiple and often opposing effects on different aspects of renal physiology through its major ET receptor subtypes, ET(A) and ET(B). Recent studies have reported that EDN1 and EDNRA polymorphisms can influence the age of onset of end-stage renal disease in ADPKD. Both circulating and local ET-1 systems are abnormally activated in human disease and experimental models, and ET(A) receptor expression is specifically upregulated in human ADPKD kidneys. Overexpression of ET-1 in transgenic mice is sufficient to trigger cyst initiation. However, studies utilizing selective ET(A) and ET(B) receptor antagonists to delay cystic disease progression in rodent PKD models have proved disappointing and do not support further extension into clinical trials. A critical balance between ET(A) and ET(B) action in the cystic kidney appears to be necessary to maintain kidney structure and function. Current evidence suggests that ET-1 and its receptors act as major modifying genes for renal disease progression in ADPKD. The future challenge will be to translate these findings to modify disease severity or for predicting prognosis in man. Copyright © 2011 S. Karger AG, Basel.


Cheng C.-Y.,Chang Gung University
Journal of Orthopaedic Surgery and Research | Year: 2010

The natural course of untreated posterior lateral rotatory instability of the elbow is unclear. A case of elbow arthrosis with progressing deformity and flexion contracture after an episode of elbow dislocation about 20 years ago presented the possibility the long term outcome of untreated posterior lateral rotatory instability of the elbow. © 2010 Cheng; licensee BioMed Central Ltd.


Teng C.-I.,Chang Gung University
Computers in Human Behavior | Year: 2010

Software designers often attempt to increase the customizability of their products to facilitate human-computer interaction and improve user response. However, exactly how customizability affects online gaming is unclear. This study posits that customization enhances gamer immersion satisfaction and loyalty. The study sample consists of 865 online gamers who provided valid responses to an online survey. Three models are compared using structural equation modeling: a partial mediator model, in which customization increases gamer loyalty directly and indirectly via enhanced immersion satisfaction; a full mediator model, in which immersion satisfaction fully mediates how customization influences loyalty; and an independent variable model, in which customization and immersion satisfaction are independent variables impacting gamer loyalty. The results of this study demonstrate that the partial mediator model significantly outperforms the other two models, suggesting that online game providers that increase customization and satisfy gamer needs regarding immersion can better foster gamer loyalty. © 2010 Elsevier Ltd. All rights reserved.


Liao H.-T.,University of Pittsburgh | Liao H.-T.,Chang Gung University | Marra K.G.,University of Pittsburgh | Marra K.G.,McGowan Institute for Regenerative Medicine | And 2 more authors.
Tissue Engineering - Part B: Reviews | Year: 2014

Due to the natural properties of fat, fat grafting remains a popular procedure for soft tissue volume augmentation and reconstruction. However, clinical outcome varies and is technique dependent. Platelet-rich plasma (PRP) contains α-granules, from which multiple growth factors such as platelet-derived growth factor, transforming growth factor-β, vascular endothelial growth factor, and epidermal growth factor can be released after activation. In recent years, the scope of PRP therapies has extended from bone regeneration, wound healing, and healing of musculoskeletal injuries, to enhancement of fat graft survival. In this review, we focus on the definition of PRP, the different PRP preparation and activation methods, and growth factor concentrations. In addition, we discuss possible mechanisms for the role of PRP in fat grafting by reviewing in vitro studies with adipose-derived stem cells, preadipocytes, and adipocytes, and preclinical and clinical research. We also review platelet-rich fibrin, a so-called second generation PRP, and its slow-releasing biology and effects on fat grafts compared to PRP in both animal and clinical research. Finally, we provide a general foundation on which to critically evaluate earlier studies, discuss the limitations of previous research, and direct plans for future experiments to improve the optimal effects of PRP in fat grafting. © Mary Ann Liebert, Inc.


Wu C.-J.,National Taiwan Normal University | Liao J.-J.,National Taiwan Normal University | Chang T.-W.,Chang Gung University
Journal of Electromagnetic Waves and Applications | Year: 2010

Using electro-optical defect layer, lithium niobate (LiNbO3), in a one-dimensional quarter-wave photonic crystal, a theoretical analysis of the tunable resonance in near infrared region for a multilayer Fabry-Perot resonator (FPR) is given. With the fact that the refractive index of LiNbO3 is voltage-dependent, tunable optical resonant properties have been investigated based on the calculated wavelength-dependent transmittance spectrum. The resonant peak wavelength as a function of applied voltage is numerically illustrated. Additionally, the angle-dependent resonant peak positions for both TE and TM waves are also examined. © 2010 VSP.


Huang S.-B.,National Cheng Kung University | Wu M.-H.,Chang Gung University | Lee G.-B.,National Cheng Kung University
Sensors and Actuators, B: Chemical | Year: 2010

This study reports a new microfluidic device for continuous generation of alginate microbeads. The working mechanism is based on the use of a pneumatically driven micro-vibrator to continuously generate tiny alginate microdroplets into a thin oil layer. The temporarily formed alginate microdroplets soon sink into a sterile calcium chloride solution to form jelled microbeads. By regulating the flow rate of the alginate suspension and the pulsing frequency of the micro-vibrator, the size of the alginate microbeads can be controlled. Experimental results showed that alginate microbeads with sizes ranging from 73 to 302 μm in diameter can be generated at suspension flow rates and vibration frequency ranges of 1.48-9.35 μl/min and 2-16 Hz, respectively. For the aforementioned parameter ranges, the alginate microbeads had reasonable size uniformity with coefficients of variation from 3.8% to 7.8%. Moreover, its application for the microencapsulation of chondrocytes in alginate microbeads has also been demonstrated with high cell viability (94 ± 2%). As a whole, the proposed device has opened up a route to generate alginate microbeads or microencapsulation of cells in a simple, continuous, controllable, uniform, and cell-friendly manner with less contamination. © 2010 Elsevier B.V. All rights reserved.


Chen W.,Chang Gung University
International Journal of Technology and Design Education | Year: 2015

Design is a powerful weapon for modern companies so it is important to have excellent designers in the industry. The purpose of this study is to explore the learning problems and the resources that students use to overcome problems in undergraduate industrial design studio courses. A survey with open-type questions was conducted to collect data. Participants in this study were 189 undergraduate industrial design students from three universities, and two coding schema were formulated for analysing the data. The results demonstrated that the most difficult design tasks included concept generation, design presentation, and design research. The learning resources used to solve the learning problems included four categories: people, object, method, and environment. This information will increase the understanding of the learning process of students and provide a reference for teaching and the setting of learning resources in industrial design education. © 2015 Springer Science+Business Media Dordrecht


Hsieh C.-H.,Chang Gung University
Translational Research in Biomedicine | Year: 2016

MicroRNAs (miRNAs) are small noncoding RNAs that function as fundamental regulators of gene and protein expression by RNA interference. Currently, miRNAs are being investigated as diagnostic and prognostic markers as well as potential therapeutic targets in transplantation. Their characteristics prompted their evaluation as candidate molecular markers and therapeutic agents to monitor or treat patients with vascularized composite allotransplantation (VCA): their specific circulating expression profile that could serve as noninvasive predictive tools or surrogate end points for rejection might help clinicians individualize immunosuppression and allow for early intervention, ideally prior to clinically evident allograft dysfunction. Furthermore, a specific suppression of miRNAs by antisense oligonucleotides has the potential to reduce the rejection rate of transplanted allografts and decrease the use of immunosuppressive drugs. In this review, the general characteristics of miRNAs as biomarkers and surrogate end points of VCA, potential biomarkers according current information from organ allotransplantation, and the prominent barriers to the translation of miRNAs research into clinical practice are discussed. © 2016 S. Karger AG, Basel.


Chang K.-H.,Imperial College London | Chang K.-H.,Chang Gung University | Li M.,Imperial College London
Stem Cells | Year: 2013

Pluripotent stem cells of different embryonic origin respond to distinct signaling pathways. Embryonic stem cells (ESCs), which are derived from the inner cell mass of preimplantation embryos, are dependent on LIF-Stat3 signaling, while epiblast stem cells (EpiSCs), which are established from postimplantation embryos, require acti-vin-Smad2/3 signaling. Recent studies have revealed heterogeneity of ESCs and the presence of intermediate pluripotent stem cell populations, whose responsiveness to growth factors, gene expression patterns, and associated chromatic signatures are compatible to a state in between ESCs and EpiSCs. However, it remains unknown whether such cell populations represent a stable entity at single-cell level. Here, we describe the identification of clonal stem cells from mouse ESCs with global gene expression profiles representing such a state. These pluripotent stem cells display dual responsiveness to LIF-Stat3 and activin-Smad2/3 at single-cell level and thus named as intermediate epiblast stem cells (IESCs). Furthermore, these cells show accelerated temporal gene expression kinetics during embryoid body differentiation in vitro consistent with a more advanced differentiation stage than that of ESCs. The successful isolation of IESCs supports the notion that traverse from naïve ground state toward lineage commitment occurs gradually in which transition milestones can be captured as clonogenic entity. Our finding provides a new model to better understand the multiple pluripotent states. © AlphaMed Press.


Chuah S.-K.,Chang Gung University | Tsay F.-W.,National Yang Ming University | Hsu P.-I.,Taipei Medical University | Wu D.-C.,Kaohsiung Medical University
World Journal of Gastroenterology | Year: 2011

With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e., 80% or less) in most countries. Therefore, several treatment regimens have emerged to cure Helicobacter pylori (H. pylori) infection. Novel first-line anti-H. pylorii therapies in 2011 include sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy. After the failure of standard triple therapy, a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI), bismuth, tetracycline and metronidazole can be employed as rescue treatment. Recently, triple therapy combining a PPI, levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy. This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects. The best second-line therapy for patients who fail to eradicate H. pylori with first-line therapies containing clarithromycin, amoxicillin and metronidazole is unclear. However, a levofloxacin-based triple therapy is an accepted rescue treatment. Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test. Nonetheless, an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H. pylorii infection if antimicrobial sensitivity data are unavailable. © 2011 Baishideng. All rights reserved.


Ohno-Matsui K.,Tokyo Medical and Dental University | Lai T.Y.Y.,Chinese University of Hong Kong | Lai C.-C.,Chang Gung University | Cheung C.M.G.,Singapore National Eye Center
Progress in Retinal and Eye Research | Year: 2016

Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve.Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy.In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. © 2016 Elsevier Ltd.


Lin P.-Y.,Chang Gung University | Lin P.-Y.,Center for Translational Research in Biomedical science | Tseng P.-T.,Tsyr Huey Mental Hospital
Journal of Psychiatric Research | Year: 2015

Glial cell-line derived neurotrophic factor (GDNF) has been shown to promote development, differentiation, and protection of CNS neurons and was thought to play an important role in various neuropsychiatric disorders. Several studies have examined the GDNF levels in patients with depression but shown inconsistent results. In this study, we compared blood GDNF levels between depressive patients and control subjects through meta-analytic method. The effect sizes (ESs) from all eligible studies were synthesized by using a random effect model. In this meta-analysis, we included 526 patients and 502 control subjects from 12 original articles. Compared to control subjects, blood GDNF levels are significantly decreased in patients with depression (ES=-0.62, p=0.0011). However, significant heterogeneity was found among included studies. Through subgroup analysis, we found that GDNF was still decreased in studies with major depressive disorder (ES=-0.73, p=0.0001); in studies with non-old-age depression (ES=-1.25, p=0.0001), but not with old-age depression; and in studies using serum samples (ES=-0.86, p<0.0001), but not in studies using plasma sample. Meta-regression did not show moderating effects of mean age of subjects, gender distribution, and age of onset of depression. Our findings support blood GDNF levels as a biomarker of depression as a whole, but the results were modulated by psychiatric diagnosis, age of included subjects, and sampling sources. With these results, future studies are required to examine whether effective antidepressant treatment is associated with an increase in serum GDNF levels. © 2015 Elsevier Ltd.


Wu C.-C.,Chang Gung University
International Orthopaedics | Year: 2012

Purpose: Traditionally, valgus knee deformity is predominately corrected by stabilisation with a plate inserted via the medial approach to the supracondylar region of the femur. However, this technique is unfavourable from both a biomechanical and a biological point of view. A revised retrograde dynamic locked nailing was developed to improve correction of this defect. Method: Forty-one knees with valgus deformity (average tibiofemoral angle, 22° ; range, 16-29° ) in 25 adult patients were treated by oblique femoral supracondylar varus osteotomy and stabilised with retrograde dynamic locked nails. Postoperatively, early ambulation with protected weight bearing and range of motion knee exercises were encouraged. Result: Thirty-five knees of 21 patients were followed-up for an average of 2.6 years (range, 1.1-4.5 years). All osteotomy sites healed with an average union period of 3.4 months (range, 2.5-5.0 months). There were no significant complications. At the latest follow-up, the average tibiofemoral angle was 7.1° valgus (range, 4-10° valgus). For all of the knees, the outcomes were satisfactory (p<0.001). Conclusion: The technique described here may be a feasible alternative for correction of valgus knee deformity. The advantages of this technique include the use of a biomechanically more appropriate method, a minimal complication rate and a high rate of satisfactory outcomes. © Springer-Verlag 2012.


Sahoo P.K.,Chang Gung University
Sensors (Switzerland) | Year: 2012

Recent technological advances in wireless communications and physiological sensing allow miniature, lightweight, ultra-low power, intelligent monitoring devices, which can be integrated into a Wireless Body Sensor Network (WBSN) for health monitoring. Physiological signals of humans such as heartbeats, temperature and pulse can be monitored from a distant location using tiny biomedical wireless sensors. Hence, it is highly essential to combine the ubiquitous computing with mobile health technology using wireless sensors and smart phones to monitor the well-being of chronic patients such as cardiac, Parkinson and epilepsy patients. Since physiological data of a patient are highly sensitive, maintaining its confidentiality is highly essential. Hence, security is a vital research issue in mobile health (mHealth) applications, especially if a patient has an embarrassing disease. In this paper a three tier security architecture for the mHealth application is proposed, in which light weight data confidentiality and authentication protocols are proposed to maintain the privacy of a patient. Moreover, considering the energy and hardware constraints of the wireless body sensors, low complexity data confidential and authentication schemes are designed. Performance evaluation of the proposed architecture shows that they can satisfy the energy and hardware limitations of the sensors and still can maintain the secure fabrics of the wireless body sensor networks. Besides, the proposed schemes can outperform in terms of energy consumption, memory usage and computation time over standard key establishment security scheme. © 2012 by the author; licensee MDPI, Basel, Switzerland.


Liang W.Z.,National Sun Yat - sen University | Lu C.H.,National Sun Yat - sen University | Lu C.H.,Chang Gung University
Life Sciences | Year: 2012

Aims: This study examined whether the essential oil component carvacrol altered cytosolic free Ca 2+ level ([Ca 2+] i) and viability in human glioblastoma cells. Main methods: The Ca 2+- sensitive fluorescent dye fura-2 was applied to measure [Ca 2+] i. Cell viability was measured by detecting reagent WST-1. Apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. Key findings: Carvacrol at concentrations of 400-1000 μM induced a [Ca 2+] i rise in a concentration-dependent fashion. The response was decreased partially by removal of extracellular Ca 2+. Carvacrol-induced Ca 2+ signal was not altered by nifedipine, econazole, SK&F96365, and protein kinase C activator phorbol myristate acetate (PMA), but was inhibited by the protein kinase C inhibitor GF109203X. When extracellular Ca 2+ was removed, incubation with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin or 2,5-di-tert- butylhydroquinone (BHQ) abolished carvacrol-induced [Ca 2+] i rise. Incubation with carvacrol also abolished thapsigargin or BHQ-induced [Ca 2+] i rise. Inhibition of phospholipase C with U73122 abolished carvacrol-induced [Ca 2+] i rise. At concentrations of 200-800 μM, carvacrol killed cells in a concentration-dependent manner. This cytotoxic effect was not changed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N, N′,N - tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that carvacrol (200, 400 and 600 μM) induced apoptosis in a concentration-dependent manner. At concentrations of 200, 400 and 600 μM, carvacrol induced production of ROS. Significance: In human glioblastoma cells, carvacrol induced a [Ca 2+] i rise by inducing phospholipase C-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via protein kinase C-sensitive, non store-operated Ca 2+ channels. Carvacrol induced cell death that might involve ROS-mediated apoptosis. © 2012 Elsevier Inc.


Lin S.-W.,Chang Gung University | Yu V.F.,National Taiwan University of Science and Technology | Chou S.-Y.,National Taiwan University of Science and Technology
Expert Systems with Applications | Year: 2010

This study considers the relaxed truck and trailer routing problem (RTTRP), a relaxation of the truck and trailer routing problem (TTRP). TTRP is a variant of the well studied vehicle routing problem (VRP). In TTRP, a fleet of trucks and trailers are used to service a set of customers with known demands. Some customers may be serviced by a truck pulling a trailer, while the others may only be serviced by a single truck. This is the main difference between TTRP and VRP. The number of available trucks and available trailers is limited in the original TTRP but there are no fixed costs associated with the use of trucks or trailers. Therefore, it is reasonable to relax this fleet size constraint to see if it is possible to further reduce the total routing cost (distance). In addition, the resulting RTTRP can also be used to determine a better fleet mix. We developed a simulated annealing heuristic for solving RTTRP and tested it on 21 existing TTRP benchmark problems and 36 newly generated TTRP instances. Computational results indicate that the solutions for RTTRP are generally better than the best solutions in the literature for TTRP. The proposed SA heuristic is able to find better solutions to 18 of the 21 existing benchmark TTRP instances. The solutions for the remaining three problems are tied with the best so far solutions in the literature. For the 36 newly generated problems, the average percentage improvement of RTTRP solutions over TTRP solutions is about 5%. Considering the ever rising crude oil price, even small reduction in the route length is significant. © 2009 Elsevier Ltd. All rights reserved.


OBJECTIVE: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant-negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking. MATERIALS AND METHODS: To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated. RESULTS: The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5–6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes. CONCLUSION: Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Nguyen P.A.T.,Simon Fraser University | Liou W.,Chang Gung University | Hall D.H.,Yeshiva University | Leroux M.R.,Simon Fraser University
Journal of Cell Science | Year: 2014

How signaling domains form is an important, yet largely unexplored question. Here, we show that ciliary proteins help establish two contiguous, yet distinct cyclic GMP (cGMP) signaling compartments in Caenorhabditis elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by proteins associated with Bardet-Biedl syndrome (BBS), Meckel syndrome and nephronophthisis at its base, and requires NPHP-2 (known as inversin in mammals) to anchor a cGMP-gated ion channel within the proximal ciliary region. The other, a subcompartment with profuse microvilli and a different lipid environment, is separated from the dendrite by a cellular junction and requires BBS-8 and DAF-25 (known as Ankmy2 in mammals) for correct localization of guanylyl cyclases needed for thermosensation. Consistent with a requirement for a membrane diffusion barrier at the subcompartment base, we reveal the unexpected presence of ciliary transition zone proteins where no canonical transition zone ultrastructure exists. We propose that differential compartmentalization of signal transduction components by ciliary proteins is important for the functions of ciliated sensory neurons. © 2014.


Lai J.-Y.,Chang Gung University
Journal of Mechanics in Medicine and Biology | Year: 2011

To overcome the drawbacks posed by surgical manipulation of bioengineered corneal endothelial cell (CEC) sheets, a simple stirring process combined with freeze-drying method was recently developed for the production of cross-linked porous gelatin hydrogels that can provide the support structure and improve the aqueous humor circulation. In this study, we further evaluated the influence of cross-linking time (048 h) on the delivery performance of carbodiimide modified gelatin carriers. It was found that smaller pore size, lower porosity, and larger superficial area were associated with increasing extent of cross-linking of the carrier discs. Although the hydrogels treated for short reaction time (i.e., below 6 h) had low resistance to initial nutrient permeation, these materials exhibited rapid swelling, implying a potential anterior segment tissue squeezing effect for use as intraocular implants. In addition, the delivery carriers with limited extent of cross-linking degraded too fast to be effective for retention of cell sheet grafts at the site of injury. By contrast, the gelatin samples with cross-linking degrees greater than 50% showed slower degradation rates and smaller porous structure, thereby possibly causing a significant inhibition of CEC proliferation. Cell sheet transfer studies demonstrated that the carrier discs with a high cross-linking degree (59.4 ± 1.3%) were more difficult to achieve stable cell attachment than their counterparts with a low cross-linking degree (48.3 ± 1.5%). Our findings suggest that among the cross-linked porous samples studied, 12 h is the best cross-linking reaction time for preparation of cell sheet carriers with suitable delivery performance. © 2011 World Scientific Publishing Company.


Wu J.-J.,Chang Gung University
Journal of Adhesion Science and Technology | Year: 2012

In this work, the adhesive contact between a slightly wavy surface and a half-space has been investigated numerically. The surface traction was described by the Lennard-Jones potential with the Derjaguin's approximation. The deformation was first obtained by using the formula for the line contact and then, using the arc-length continuation algorithm, the relation between the contact half-width and the total force per asperity was obtained. The pull-off forces were then determined. The numerical simulation presented in this paper can be used to simulate all adhesive contacts ranging from the JKR contact to a rigid contact. © 2012 Copyright Taylor and Francis Group, LLC.


Wu J.-J.,Chang Gung University
Journal of Adhesion Science and Technology | Year: 2012

This paper investigates the interaction between two rigid spheres and between a rigid sphere and a rigid half-space, based on the Lennard-Jones potential. By using the divergence theorem and integrating the Lennard-Jones potential over the surfaces, the analytical forms of the surface tractions were obtained, and by integrating the Lennard-Jones potential over the volumes, the analytical form of the total force between two rigid spheres was obtained. The results are compared to those with the Derjaguin approximations and with the parabolic approximation for the sphere profile. The accuracy of the Derjaguin approximation and the parabolic approximation were estimated. The analytical surface traction can be used for the adhesive contact between an elastic body and a rigid one. © 2012 Copyright Taylor and Francis Group, LLC.


Hwang T.-L.,Chang Gung University
Nutrients | Year: 2012

Females with sepsis have a better prognosis than males, while those of both genders with cirrhosis have a high mortality. Impaired immunity accompanies liver cirrhosis. The potential association between sex and immunologic response of cirrhotic rats in sepsis following immunonutrition was investigated. One hundred and forty-three rats were randomly divided into groups. Liver cirrhosis was produced by weekly feeding of CCl4 for 8 weeks. Among them, 24 male and 19 female underwent castration one month before studying. The rats were fed with either immune enhancing diet or control diet for five days, then sepsis was induced with cecalligation and two holes puncture. Main outcomes included mortality and serum cytokines (IL-1β, 6, and 10). Comparisons were made both within and between genders. Cirrhotic non-castrated male rats showed a significant decrease in mortality (64.1% vs. 32.1%, p = 0.032) with better survival than control diet following immune enhancing diet. Lower mortality of cirrhotic non-castrated female rats was found after immune enhancing diet (69.6% vs. 52.1%, p = 0.365). Cirrhotic castrated male rats showed a lower mortality (44.4%) following immune enhancing diet, and cirrhotic castrated female rats also showed significantly lower mortality and better survival than control diet after immune enhancing diet (87.5% vs. 33.3%, p = 0.004). Plasma concentrations of IL-1β were higher in non- oophorectomized female rats fed with control diet compared to immune enhancing diet. Non-orchidectomized males and non-oophorectomized females exhibited similar increases in IL-10 after immune enhancing diet. Our results demonstrated that immunonutrition was more beneficial for male than female cirrhotic rats following sepsis. Though orchidectomy was not found to be more advantageous for the normal male rats in sepsis, immunonutrition seemed to be as important as sex hormone for female rats in sepsis. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


The theory of interval type-2 fuzzy sets provides an intuitive and computationally feasible way of addressing uncertain and ambiguous information in decision-making fields. The aim of this paper is to develop an interactive method for handling multiple criteria group decision-making problems, in which information about criterion weights is incompletely (imprecisely or partially) known and the criterion values are expressed as interval type-2 trapezoidal fuzzy numbers. With respect to the relative importance of multiple decision-makers and group consensus of fuzzy opinions, a hybrid averaging approach combining weighted averages and ordered weighted averages was employed to construct the collective decision matrix. An integrated programming model was then established based on the concept of signed distance-based closeness coefficients to determine the importance weights of criteria and the priority ranking of alternatives. Subsequently, an interactive procedure was proposed to modify the model according to the decision-makers' feedback on the degree of satisfaction toward undesirable solution results for the sake of gradually improving the integrated model. The feasibility and applicability of the proposed methods are illustrated with a medical decision-making problem of patient-centered medicine concerning basilar artery occlusion. A comparative analysis with other approaches was performed to validate the effectiveness of the proposed methodology. © 2013 Springer Science+Business Media New York.


Liao W.C.,Chang Gung University | Lin Y.-H.,China University of Science and Technology | Chang T.-M.,Hungkuang University | Huang W.-Y.,Hungkuang University
Food Chemistry | Year: 2012

The purpose of this study was to identify two licorice species, Glycyrrhiza uralensis and Glycyrrhiza glabra. A simple method including HPLC and LC/MS was developed to simultaneously separate, identify, and quantify 15 bioactive components of Glycyrrhiza species. G. uralensis was found to contain quercetin but G. glabra did not. G. glabra provided by Brion Research Institute of Taiwan contained uralsaponin B, but G. glabra brought from herbal shops did not. The DPPH radical scavenging activity of G. uralensis and G. glabra achieved approximately 72-75% if 10 mg/mL or more licorice extract was used. G. uralensis had slightly better radical scavenging activity than G. glabra. G. uralensis also showed higher reducing ability than G. glabra. © 2011 Elsevier Ltd. All rights reserved.


Alison M.R.,Queen Mary, University of London | Lin W.-R.,Chang Gung University
Hepatology | Year: 2011

The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status. © 2011 American Association for the Study of Liver Diseases.


Lin S.-W.,Chang Gung University | Ying K.-C.,National Taipei University of Technology | Huang C.-Y.,National Taipei University of Technology
Computers and Operations Research | Year: 2013

In this paper, the problem of scheduling multistage hybrid flowshops with multiprocessor tasks is contemplated. This is a strongly NP-hard problem for which a hybrid artificial bee colony (HABC) algorithm with bi-directional planning is developed to minimize makespan. To validate the effectiveness of the proposed algorithm, computational experiments were tested on two well-known benchmark problem sets. The computational evaluations manifestly support the high performance of the proposed HABC against the best-so-far algorithms applied in the literature for the same benchmark problem sets. © 2012 Elsevier Ltd.


Chiou S.-Y.,Chang Gung University
International Journal of Security and its Applications | Year: 2016

In the paper, we propose a new digital signature scheme based on factoring and discrete logarithms. Specially, we prove that the security of the proposed signature scheme is based on both the security of the ElGamal signature scheme and the security of the modified OSS signature scheme. This is the first scheme which can be proved that its security is based on two hard problems. Like Meta-ElGamal signature schemes, the proposed signature scheme can be extended to many kinds of scheme. The corresponding computations for our proposed scheme are also discussed. © 2016 SERSC.


Huang T.-T.,Chang Gung University | Yeh C.-Y.,Health Station of Taoyuan City | Tsai Y.-C.,Tainan Municipal Hospital
Midwifery | Year: 2011

Objective: to examine the effect of individual counselling on diet and physical activity from pregnancy to six months post partum, or from birth to six months post partum, on weight retention among Taiwanese women. Design: a randomised controlled trial assigned participants to two experimental groups [from pregnancy to six months post partum (EP) and from birth to six months post partum (EPP)] and one comparison group. Setting: a 3900-bed medical centre in northern Taiwan with around 3000 births annually. Participants: a sample of 189 women who had regular check-ups during pregnancy and gave birth at the medical centre. Interventions: the comparison group received the routine outpatient department obstetric educational programme. The EP group attended regularly scheduled clinic visits with individualised dietary and physical activity education plans from 16 gestational weeks to six months post partum, and received on brochure. The EPP group received the same educational intervention as the EP group from 24-48 hours after birth to six months post partum. Measurements: body weight, body mass index, health-promoting behaviour and psycho-social variables (self-efficacy, body image, depression and social support). Findings: average gestational weight gain was 14.02, 15.27 and 16.22. kg in the three EP, EPP and comparison groups respectively, and average weight retention at six months post partum was 2.34, 4.06 and 5.08. kg in the three groups, respectively. Key conclusions: a diet and physical activity intervention from pregnancy is effective for reducing post-pregnancy weight retention. Implications for practice: the findings of the present study should be taken into consideration when incorporating significant others and weight-loss maintenance strategies with interventions for a healthier family lifestyle. © 2009 Elsevier Ltd.


Chen C.-H.,National Chiayi University | Chang Y.-J.,Taipei Medical University | Ku M.S.B.,National Chiayi University | Chung K.-T.,University of Memphis | Yang J.-T.,Chang Gung University
Journal of Molecular Medicine | Year: 2011

Temozolomide (TMZ) is an oral alkylating agent that has been widely used in the treatment of refractory glioma, although inherent and acquired resistance to this drug is common. The clinical use of valproic acid (VPA) as an anticonvulsant and moodstabilizing drug has been reported primarily for the treatment of epilepsy and bipolar disorder and less commonly for major depression. VPA is also used in the treatment of glioma-associated seizures with or without intracranial operation. In this study, we evaluated the potential synergistic effect of TMZ and VPA in human glioma cell lines. Compared with the use of TMZ or VPA alone, concurrent treatment with both drugs synergistically induced apoptosis in U87MG cells as evidenced by p53 and Bax expression, mitochondrial transmembrane potential loss, reactive oxygen species production, and glutathione depletion. This synergistic effect correlated with a decrease in nuclear translocation of the nuclear factor-erythroid 2 p45-related factor and corresponded with reduced heme oxygenase-1 and γ-glutamylcysteine synthetase expression. Pretreatment with N-acetylcysteine partially recovered the apoptotic effect of the TMZ/VPA combination treatment. The same degree of synergism is also seen in p53-mutant Hs683 cells, which indicates that p53 may not play a major role in the increased proapoptotic effect of the TMZ/VPA combination. In conclusion, VPA enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism. The TMZ/VPA combination may be effective for treating glioma cancer and may be a powerful agent against malignant glioma. This drug combination should be further explored in the clinical setting. © Springer-Verlag 2011.


Lam W.-L.,Chang Gung Memorial Hospital | Wei F.-C.,Chang Gung University
Clinics in Plastic Surgery | Year: 2011

Microsurgical toe-to-hand transplantation remains a valuable reconstructive option for severe, mutilated hand injuries ever since its inception in the 1960s, allowing composite replacement of amputated digits through a single-stage procedure with minimal donor morbidity. Increased experience over the past 40 years has allowed establishment of certain principles that yield consistent results with optimal functional and esthetic outcomes. This article critically examines the latest innovations and refinements in the continual pursuit of excellence for microsurgical toe-to-hand transplantation. © 2011.


Chuang D.C.-C.,Chang Gung University
Seminars in Plastic Surgery | Year: 2010

Adult brachial plexus injury remains a dilemma to a reconstructive microsurgeon, especially when attempting to reconstruct cases of total root avulsion. Different degrees and different levels of injury require different strategies of reconstruction. The purpose of this article is to illustrate the author's reconstructive strategy in correlation with the injury level of classification. Nerve transfer, functioning free muscle transplantation, and other palliative surgery are reconstructive options for level 1 injuries. Neurolysis, nerve repair, nerve grafts (free nerve graft or vascularized ulnar nerve graft), nerve transfer if associated with level 1 lesion in other spinal nerves, and palliative reconstruction are chosen options for level 2, 3, and 4 lesions. A clavicle osteotomy is often required in level 3 lesions. Nerve grafts are frequently applied in level 4 lesions, which result in less aberrant reinnervation and a better prognosis. Copyright © 2010 by Thieme Medical Publishers, Inc.


Chen Y.C.,Chang Gung University
The Cochrane database of systematic reviews | Year: 2013

The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications. We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation. Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion. Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 ± 18.7 x 10(9)/L, postoperative 194.3 ± 26.5 x 10(9)/L; P < 0.05) but not in the LMWH group (preoperative 260.8 ± 32.5 x 10(9)/L, postoperative 252.4 ± 29.1 x 10(9)/L; P > 0.05). Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.


Chi C.C.,Chang Gung University
Cochrane database of systematic reviews (Online) | Year: 2011

Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers. To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials. We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies. Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus. Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion. We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups. The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.


Lin S.-M.,Liver Research Unit | Lin S.-M.,Chang Gung University
Oncology | Year: 2010

Objectives: To illustrate the situation of radiofrequency ablation (RFA) and percutaneous ethanol injection for early-stage hepatocellular carcinoma (HCC) in Taiwan. Methods: LeVeen, RITA, Medsphere and internally cooled electrodes are currently available in Taiwan. Only LeVeen and Medsphere impedance-control RF electrodes are reimbursed. Results: When using the LeVeen electrode, we experienced that an interactive algorithm could enhance necrosis better than in those treated by standard algorithm. We reported that RFA was superior to ethanol or acetic acid injection in terms of lower local tumor progression and higher overall survival for HCC no larger than 3 or 4 cm. For high-risk located HCC, we found that combined ethanol injection and RFA tended to have a higher rate of complete ablation than RFA monotherapy. Since 2006, we have also employed a creation of artificial ascites or pleural effusion for HCC contiguous with vital structure. We found a lower major complication and higher survival rate compared to the era without artificial ascites or pleural effusion creation. Conclusions: RFA is the first option of local ablation for HCC in Taiwan due to its effective result. Refined algorithms of RFA could improve its effect. Copyright © 2010 S. Karger AG.


Lin C.-H.,Chang Gung University | Lin C.-H.,China Medical University at Taichung | Lane H.-Y.,China Medical University at Taichung | Tsai G.E.,University of California at Los Angeles
Pharmacology Biochemistry and Behavior | Year: 2012

Glutamatergic neurotransmission, particularly through the N-methyl-d-aspartate (NMDA) receptor, has drawn attention for its role in the pathophysiology of schizophrenia. This paper reviews the neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to NMDA neurotransmission, and discusses the relationship between NMDA hypofunction and different domains of symptom in schizophrenia as well as putative treatment modality for the disorder. A series of clinical trials and a meta-analysis which compared currently available NMDA-enhancing agents suggests that glycine, d-serine, and sarcosine are more efficacious than d-cycloserine in improving the overall psychopathology of schizophrenia without side effect or safety concern. In addition, enhancing glutamatergic neurotransmission via activating the AMPA receptor, metabotropic glutamate receptor or inhibition of d-amino acid oxidase (DAO) is also reviewed. More studies are needed to determine the NMDA vulnerability in schizophrenia and to confirm the long-term efficacy, functional outcome, and safety of these NMDA-enhancing agents in schizophrenic patients, particularly those with refractory negative and cognitive symptoms, or serious adverse effects while taking the existing antipsychotic agents. © 2011 Elsevier Inc. All rights reserved.


Wang C.-J.,Chang Gung University
Journal of Orthopaedic Surgery and Research | Year: 2012

The sources of shockwave generation include electrohydraulic, electromagnetic and piezoelectric principles. Electrohydraulic shockwaves are high-energy acoustic waves generated under water explosion with high voltage electrode. Shockwave in urology (lithotripsy) is primarily used to disintegrate urolithiasis, whereas shockwave in orthopedics (orthotripsy) is not used to disintegrate tissues, rather to induce tissue repair and regeneration. The application of extracorporeal shockwave therapy (ESWT) in musculoskeletal disorders has been around for more than a decade and is primarily used in the treatment of sports related over-use tendinopathies such as proximal plantar fasciitis of the heel, lateral epicondylitis of the elbow, calcific or non-calcific tendonitis of the shoulder and patellar tendinopathy etc. The success rate ranged from 65% to 91%, and the complications were low and negligible. ESWT is also utilized in the treatment of non-union of long bone fracture, avascular necrosis of femoral head, chronic diabetic and non-diabetic ulcers and ischemic heart disease. The vast majority of the published papers showed positive and beneficial effects. FDA (USA) first approved ESWT for the treatment of proximal plantar fasciitis in 2000 and lateral epicondylitis in 2002. ESWT is a novel non-invasive therapeutic modality without surgery or surgical risks, and the clinical application of ESWT steadily increases over the years. This article reviews the current status of ESWT in musculoskeletal disorders. © 2012 Wang; licensee BioMed Central Ltd.


Huang J.-L.,Chang Gung University
Chang Gung Medical Journal | Year: 2012

Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders of chronic arthritis in childhood with no apparent etiology. Juvenile idiopathic arthritis is the most common pediatric rheumatic disease and is associated with significant long-term morbidity and mortality. There have been major advances in recent years in our understanding of the pathogenesis of JIA, the definition of disease control, and biological treatments for JIA. Multiple environmental and genetic factors have been linked with the onset and / or the exacerbation of JIA, including perinatal factors, viral and bacterial infections, epigenetic factors, and malnutrition. However, no single causative factor has been identified to date. As our understanding of the complex network of immune cells and inflammatory cytokines has improved, biologics have been developed to modulate the inflammatory processes. Indeed, a number of such biologics have been demonstrated effective for the treatment of JIA. Although biologic agents may alleviate the inflammation associated with JIA and prevent disability caused by joint destruction, continued and comprehensive observation is required to determine the long-term outcomes associated with such treatment.


Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.


OBJECTIVE: To investigate the effects of radial extracorporeal shock wave therapy (rESWT) and to determine the posttreatment common extensor tendon stiffness among patients with lateral epicondylosis. DESIGN: Thirty patients with lateral epicondylosis were randomly divided into experimental and control groups. Participants in the experimental group received rESWT plus physical therapy, and those in the control group received sham shock wave plus physical therapy for 3 weeks. Visual analog scale; grip strength dynamometer; Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; and ultrasonography in 2-dimensional image, and real-time sonoelastography were used in the assessments at baseline and after 6, 12, and 24 weeks (T3). RESULTS: The experimental group had more significant pain reduction at T3 than the control group. Compared with the control group, the experimental group had significantly higher maximal grip strength at 12 and 24 weeks, with significant increases. Compared to baseline, the experimental group had significantly lower Taiwan version DASH disability/symptom scores and work module scores at all posttreatment follow-up points. Five participants in the experimental group had partial tear within common extensor tendon at their involved elbow, and all the tears totally healed at T3. However, the inter-rater reliabilities for real-time sonoelastography were poor to fair. CONCLUSIONS: Patients with lateral epicondylosis had better and faster pain reduction, grip strength increase, and functional improvement after receiving rESWT in addition to physical therapy than those who received physical therapy only. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Lloyd-Lavery A.,University of Oxford | Chi C.-C.,Chang Gung University | Wojnarowska F.,University of Oxford | Taghipour K.,Kings College London
JAMA Dermatology | Year: 2013

Objective: To explore associations between bullous pemphigoid (BP) and previous drug use in the United Kingdom. Design: A case-control study comparing the drug history of consecutive patients with BP and control subjects. Setting: Tertiary care center for immunobullous diseases and skin tumor clinics at Oxford University Hospitals. Patients or Other Participants: Eighty-six consecutive BP patients and 134 consecutive controls from the same region and similar in age and sex who presented with other dermatological diagnoses. Main Outcome Measures: Crude and adjusted odds ratios and 95% confidence interval of BP in relation to each drug. Results: Loop diuretics were used significantly more frequently by the BP patients (crude odds ratio, 2.4 [95% CI, 1.2-5.0; P=.02]; adjusted odds ratio, 3.8 [1.5-9.7; P=.006]). No significant differences were found between groups for use of other diuretics, aspirin, antidepressants, antiepileptics, antihypertensives, or central nervous system agents (eg, antipsychotics). Patients with BP used calcium or vitamin D supplements, antibiotics, antihistamines, and prednisolone significantly more often on multivariate analysis. Conclusions: The findings of our study demonstrate increased use of loop diuretics in patients with BP before the development of BP. The mechanism behind such an association clearly warrants further investigation. © 2013 American Medical Association.


Wang C.-W.,National Yang Ming University | Chung W.-H.,Chang Gung University | Cheng Y.-F.,Academia Sinica, Taiwan | Ying N.-W.,Academia Sinica, Taiwan | And 3 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and graft-versus-host disease (GVHD) are distinct immune reactions elicited by drugs or allogeneic antigens; however, they share a pathomechanism with the activation of cytotoxic T lymphocytes (CTLs). CTLs produce cytotoxic proteins, cytokines, chemokines, or immune alarmins, such as granulysin (GNLY), leading to the extensive tissue damage and systemic inflammation seen in patients with SJS/TEN or GVHD. Currently, there is no effective therapeutic agent specific for CTL-mediated immune disorders. Objectives: By targeting GNLY+ CTLs, we aimed to develop a nucleic acid-based agent consisting of an anti-CD8 aptamer with GNLY small interfering RNA (siRNA). Methods: We performed systematic evolution of ligands using exponential enrichment to select and identify effective anti-CD8 aptamers. We developed an aptamer-siRNA chimera using a "sticky bridge" method by conjugating the aptamer with siRNA. We analyzed the inhibitory effects of the aptamer-siRNA chimera on CTL responses in patients with SJS/TEN or GVHD. Results: We identified a novel DNA aptamer (CD8AP17s) targeting CTLs. This aptamer could be specifically internalized into human CTLs. We generated the CD8AP17s aptamer-GNLY siRNA chimera, which showed a greater than 79% inhibitory effect on the production of GNLY by drug/alloantigen-activated T cells. The CD8AP17s aptamer-GNLY siRNA chimera decreased cytotoxicity in in vitro models of both SJS/TEN (elicited by drug-specific antigen) and GVHD (elicited by allogeneic antigens). Conclusions: Our results identified a new nucleic acid-based agent (CD8 aptamer-GNLY siRNA chimera) that can significantly inhibit CTL-mediated drug hypersensitivity, such as that seen in patients with SJS/TEN, as well as the alloreactivity seen in patients with GVHD. This study provides a novel therapeutic strategy for CTL-mediated immune disorders. © 2013 American Academy of Allergy, Asthma & Immunology.


Hung T.-H.,Chang Gung Memorial Hospital at Taipei | Hung T.-H.,Chang Gung University | Hsieh T.-T.,Chang Gung Memorial Hospital at Taipei
PLoS ONE | Year: 2015

Background In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommended a new strategy for the screening and diagnosis of gestational diabetes mellitus (GDM). However, no study has indicated that adopting the IADPSG recommendations improves perinatal outcomes. The objective of this study was to evaluate the effects of implementing the IADPSG criteria for diagnosing GDM on maternal and neonatal outcomes. Methodology/Principal Findings Previously, we used a two-step approach (a 1-h, 50-g glucose challenge test followed by a 3-h, 100-g glucose tolerance test when indicated) to screen for and diagnose GDM. In July 2011, we adopted the IADPSG recommendations in our routine obstetric care. In this study, we retrospectively compared the rates of various maternal and neonatal outcomes in all women who delivered after 24 weeks of gestation during the periods before (P1, between January 1, 2009 and December 31, 2010) and after (P2, between January 1, 2012 and December 31, 2013) the IADPSG criteria were implemented. Pregnancies complicated by multiple gestations, fetal chromosomal or structural anomalies, and pre-pregnancy diabetes mellitus were excluded. Our results showed that the incidence of GDM increased from 4.6% using the two-step method to 12.4%using the IADPSG criteria. Compared to the women in P1, the women in P2 experienced less weight gain during pregnancy, lower birth weights, shorter labor courses, and lower rates of macrosomia (<4000 g) and large-for-gestational age (LGA) infants. P2 was a significant independent factor against macrosomia (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43-0.90) and LGA (adjusted OR 0.74, 95% CI 0.61-0.89) after multivariable logistic regression analysis. Conclusions/Significance The adoption of the IADPSG criteria for diagnosis of GDM was associated with significant reductions in maternal weight gain during pregnancy, birth weights, and the rates of macrosomia and LGA. © 2015 Hung Hsieh.


Chen S.-C.,National Taiwan University of Science and Technology | Lin S.-W.,Chang Gung University | Chou S.-Y.,National Taiwan University of Science and Technology
Applied Soft Computing Journal | Year: 2011

Data-mining algorithms have been used in many classification problems. Among them, the decision tree (DT), back-propagation network (BPN), and support vector machine (SVM) are popular and can be applied to various areas. Nevertheless, different problems may require different parameter values when applying DT, BPN or SVM. If parameter values are not set well, results may turn out to be unsatisfactory. Further, a dataset may contain many features; however, not all features are beneficial for classifications. Therefore, a scatter search (SS) approach is proposed to obtain the better parameters and select the beneficial subset of features to attain better classification results. The above classification algorithms have their respective advantages and disadvantages, and suitability is influenced by the characteristics of the problem. If the algorithms can function together in a so-called ensemble, it is expected that better results can be obtained. Therefore, this study adapts ensemble to further enhance the classification accuracy rate. In order to evaluate the performance of the proposed approach, datasets in UCI (University of California, Irvine) were applied as the test problem set. The corresponding results were compared to several well-known, published approaches. The comparative study shows that the proposed approach improved the classification accuracy rate in most datasets. Thus, the proposed approach can be useful to both practitioners and researchers. © 2010 Elsevier B.V. All rights reserved.


Chen T.-Y.,Chang Gung University
Applied Soft Computing Journal | Year: 2011

The purpose of this paper is to present a new TOPSIS (the technique for order preference by similarity to ideal solution) for estimating the importance of criteria and reducing the leniency bias in multiple-criteria decision analysis based on interval-valued fuzzy sets. Several types of net predispositions are defined to represent an aggregated effect of interval-valued evaluations. The relative closeness of each alternative to the ideal solution is then determined by net predispositions. Because positive or negative leniency may exist when most criteria are assigned unduly high or low ratings, respectively, some deviation variables are introduced to mitigate the effects of overestimated and underestimated ratings on criterion importance. Considering the two objectives of maximal closeness coefficient and minimal deviation values, an integrated programming model is proposed to compute optimal weights for the criteria and corresponding closeness coefficients for alternative rankings. A flexible algorithm using interval-valued fuzzy TOPSIS methods is established by considering both objective and subjective information to compute optimal multiple-criteria decisions. The feasibility and effectiveness of the proposed methods are illustrated by a numerical example. Finally, an experimental analysis of interval-valued fuzzy rankings given different conditions for the criterion weights is conducted with discussions on average Spearman correlation coefficients and contradiction rates. © 2011 Elsevier B.V. All rights reserved.


Lee M.,Chang Gung University | Saver J.L.,University of California at Los Angeles | Hong K.-S.,Inje University | Ovbiagele B.,Medical University of South Carolina
Stroke | Year: 2012

Background and Purpose: Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage. Our objective was to investigate the qualitative and quantitative risks of intracranial hemorrhage in patients receiving PAR-1 antagonist therapy. Methods: Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from 1966 to May 2012, were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo and in which the total number of patients and intracranial hemorrhage events were reported separately for active treatment and control groups. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the I2 statistic. Results: In 9 PAR-1 antagonist trials with 42 000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of intracranial hemorrhage (0.59% vs 0.30%; relative risk, 1.98; 95% CI, 1.46-2.68; P<0.00001; number needed to harm, 345). There was no heterogeneity across trials (P=0.84; I2=0%), PAR-1 antagonist agent (P=0.52), treatment duration (P=0.38), or trial-qualifying event (P=0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups. Conclusion: In a pooled analysis of data from 9 trials, PAR-1 antagonist therapy was associated with an increased risk for intracranial hemorrhage. © 2012 American Heart Association, Inc.


Schreiber M.P.,University of Nevada, Las Vegas | Colantuoni E.,Johns Hopkins University | Bienvenu O.J.,Johns Hopkins University | Neufeld K.J.,Johns Hopkins University | And 4 more authors.
Critical Care Medicine | Year: 2014

OBJECTIVE: Delirium is common in mechanically ventilated patients in the ICU and associated with short-and long-term morbidity and mortality. The use of systemic corticosteroids is also common in the ICU. Outside the ICU setting, corticosteroids are a recognized risk factor for delirium, but their relationship with delirium in critically ill patients has not been fully evaluated. We hypothesized that systemic corticosteroid administration would be associated with a transition to delirium in mechanically ventilated patients with acute lung injury. DESIGN: Prospective cohort study. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: Five hundred twenty mechanically ventilated adult patients with acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delirium evaluation was performed by trained research staff using the validated Confusion Assessment Method for the ICU screening tool. A total of 330 of the 520 patients (64%) had at least two consecutive ICU days of observation in which delirium was assessable (e.g., patient was noncomatose), with a total of 2,286 days of observation and a median (interquartile range) of 15 (9, 28) observation days per patient. These 330 patients had 99 transitions into delirium from a prior nondelirious, noncomatose state. The probability of transitioning into delirium on any given day was 14%. Using multivariable Markov models with robust variance estimates, the following factors (adjusted odds ratio; 95% CI) were independently associated with transition to delirium: older age (compared to < 40 years old, 40-60 yr [1.81; 1.26-2.62], and ≥ 60 yr [2.52; 1.65-3.87]) and administration of any systemic corticosteroid in the prior 24 hours (1.52; 1.05-2.21). CONCLUSIONS: After adjusting for other risk factors, systemic corticosteroid administration is significantly associated with transitioning to delirium from a nondelirious state. The risk of delirium should be considered when deciding about the use of systemic corticosteroids in critically ill patients with acute lung injury. © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Lin S.-W.,Chang Gung University | Ying K.-C.,National Taipei University of Technology
Computers and Operations Research | Year: 2013

In this study, a bi-objective multi-start simulated-annealing algorithm (BMSA) is presented for permutation flowshop scheduling problems with the objectives of minimizing the makespan and total flowtime of jobs. To evaluate the performance of the BMSA, computational experiments were conducted on the well-known benchmark problem set provided by Taillard. The non-dominated sets obtained from each of the existing benchmark algorithms and the BMSA were compared, and then combined to form a net non-dominated front. The computational results show that more than 64% of the solutions in the net non-dominated front are contributed by the proposed BMSA. It is believed that these solutions can serve as new benchmarks for future research. © 2011 Elsevier Ltd.


Lee M.,Chang Gung University | Saver J.L.,University of California at Los Angeles | Hong K.-S.,Inje University | Hao Q.,University of California at Los Angeles | Ovbiagele B.,University of California at San Diego
Annals of Neurology | Year: 2012

Objective: The purpose of this study was to compare the impact of achieving tight versus usual systolic blood pressure (SBP) control on stroke prevention through meta-analysis of randomized controlled trials. Methods: We searched PubMed and bibliographies of recent review articles. Relative risk with 95% confidence interval was used as a measure of the association between an active treatment group with achieved SBP <130mmHg versus a comparator group with achieved SBP 130 to 139mmHg, and risk of stroke after pooling data across trials. Results: The search identified 11 studies with 42,572 participants and 794 stroke events. The final SBPs, weighted for trial size, were a mean of 126.5mmHg in the intensive treatment arms and 132.6mmHg in the conventional arms (mean SBP reduction, 6.1mmHg). Achieving a tight SBP level was associated with a lower stroke risk (relative risk, 0.80; 95% confidence interval, 0.70-0.92; p < 0.01) and a lower risk of major vascular events (0.91; 0.86-0.96; p < 0.001). In subgroup analyses, subjects with risk factors but no established cardiovascular disease showed substantial reduction of future stroke risk with tight control (0.49; 0.34-0.69), but those with established cardiovascular disease at entry did not experience stroke risk reduction with tight control (0.92; 0.83-1.03). Interpretation: Achieving an SBP <130mmHg compared to 130 to 139mmHg appears to provide additional stroke protection only among people with risk factors but no established cardiovascular disease. Copyright © 2011 American Neurological Association.


Chiou Y.-C.,University of California at San Diego | Kuo J.-T.,Chang Gung University
Progress in Electromagnetics Research | Year: 2011

Planar multiband bandpass filters are implemented based on the versatile multimode stepped-impedance resonators (SIRs). The resonant spectrum of a SIR can be calculated as functions of the length ratios for various impedance ratios of the high- and low-impedance sections. Thus, by properly selecting the geometric parameters and designing the input/output coupling structure, the SIRs are feasible to realize multiband multimode filters. Using a single SIR, a dual-mode dual-band, a dual-mode triple-band or a hybrid dual-/triple-mode dual-band bandpass filter can be realized. Emphasis is also placed on designing specified ratios of center frequencies and fractional bandwidths of the passbands. To extend the design °exibility, extra shunt open stubs are used to adjust the ratio of the passband frequencies. In addition, sharpness of the transition bands is improved by designing the input/output stages. Simulation results are validated by the measured responses of experimental circuits.


Lee M.,University of California at Los Angeles | Saver J.L.,University of California at Los Angeles | Chang K.-H.,Chang Gung University | Chang S.-C.,University of California at Los Angeles | Ovbiagele B.,University of California at Los Angeles
Stroke | Year: 2010

Background and Purpose: Microalbuminuria, a marker of both kidney disease and endothelial dysfunction, may be associated with global vascular risk, but the nature and magnitude of the link between microalbuminuria and incident stroke has not been clearly defined. The purpose of this study was to assess the consistency and strength of the association of microalbuminuria with risk of stroke in prospective studies using meta-analysis. Methods: We conducted a systematic search of electronic databases and bibliographies for studies reporting a multivariate-adjusted estimate, represented as relative risk with 95% CI, of the association between microalbuminuria and stroke risk. Studies were excluded if a majority of study participants had established kidney disease or pre-eclampsia. Estimates were combined using a random-effect model. Results: We identified 12 studies, with a total of 48 596 participants and 1263 stroke events. Overall, presence of microalbuminuria was associated with greater stroke risk (relative risk, 1.92; 95% CI, 1.61 to 2.28; P<0.001) after adjustment for established cardiovascular risk factors. There was evidence of significant heterogeneity in the magnitude of the association across studies (P for heterogeneity <0.001, I=68%), which was partially explained by differences in study population, microalbuminuria definition, and different microalbuminuria-related risk among stroke subtypes. However, in stratified analyses, microalbuminuria was associated with increased risk of subsequent stroke in all subgroups (general population, diabetics, those with known stroke). Conclusions: Microalbuminuria is strongly and independently associated with incident stroke risk. Future studies should explore whether microalbuminuria is just a risk marker or a modifiable risk factor for stroke. © 2010 American Heart Association, Inc.


Hsu C.-L.,Chang Gung University
ICIC Express Letters | Year: 2010

Hwang et al. recently proposed an efficient user identification schemebased on identity-based, (ID-based) cryptosystem, for wireless environments. InHwang et al.'s scheme, the mobile device can prove his legitimacy to a, basestation for gaining the access privilege. The mobile device and, the basestation check the legitimacy of their identities. This paper, however, will showthat Hwang et al. 's scheme is vulnerable to the impersonation attack. That is,the adversary can successfully use the intercepted, message to masquerade as a,legal mobile device to cheat the intended, base station. We further propose asecure ID-based user identification scheme against the pointed impersonationattack for wireless environments. Performance of the proposed scheme is moreefficient than that of Hwang et al. 's scheme. ICIC International © 2010.


Wu M.-H.,National Cheng Kung University | Chuang P.-C.,Chang Gung University | Lin Y.-J.,Chung Hwa University of Medical Technology | Tsai S.-J.,National Cheng Kung University
Human Reproduction | Year: 2013

STUDY QUESTION: Is annexin A2 involved in the reduced phagocytic ability of macrophages in endometriosis?SUMMARY ANSWERData from women with endometriosis and a murine model of the disease show that expression of annexin A2 in peritoneal macrophages is inhibited by prostaglandin E2 (PGE 2) and this impairs the phagocytic ability of macrophages.WHAT IS ALREADY KNOWNEndometriosis is a chronic inflammatory disease that recruits many immune cells, especially macrophages, to the peritoneal cavity. The phagocytic ability of peritoneal macrophages isolated from women with endometriosis is reduced.STUDY DESIGN, SIZE, DURATIONA laboratory study. Thirty-five patients (20 with and 15 without endometriosis) of reproductive age with normal menstrual cycles were recruited.PARTICIPANTS/MATERIALS, SETTING, METHODSPeritoneal macrophages isolated from women with or without endometriosis were cultured and treated with vehicle, PGE2 and different EP receptor agonists, and the expression of annexin A2 was quantified by RT-PCR and western blotting. Annexin A2 was knocked down (by small interfering RNA) in normal macrophages or overexpressed (by treatment with recombinant protein) in endometriotic macrophages and their phagocytic ability was measured by flow cytometry. Peritoneal macrophages were isolated from a mouse model of endometriosis and treated with PGE2 or cyclo-oxygenase (COX) inhibitors, and annexin A2 mRNA was quantified. MAIN RESULTS AND THE ROLE OF CHANCE: Levels of annexin A2 were markedly reduced in peritoneal macrophages from women with endometriosis versus controls (mRNA: P < 0.01). The level of annexin A2 mRNA in the macrophages was reduced by PGE2 (P < 0.01/P < 0.05 in women without/with endometriosis versus control) via the EP2/EP4 receptor-dependent signaling pathway. Treatment with PGE2 or knockdown of annexin A2 inhibited the phagocytic ability of macrophages (P < 0.05 versus control), while treatment with annexin A2 recombinant protein enhanced phagocytosis. Autologous transplantation animal studies further confirmed that levels of annexin A2 in peritoneal macrophages were markedly reduced in mice treated with PGE2 (P < 0.01 versus control). In contrast, treatment with COX inhibitors to inhibit PGE2 production enhanced annexin A2 expression in peritoneal macrophages (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: We have provided no direct demonstration that phagocytic activity is indeed decreased in peritoneal cells from patients with endometriosis or that their endometriotic fluid contains increased amounts of PGE2 when compared with control subjects. WIDER IMPLICATIONS OF THE FINDINGS: Inhibiting PGE2 signaling, in order to restore or enhance the phagocytic capability of macrophages, may represent a new direction of thinking in developing novel strategies against endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from National Science Council of Taiwan, Republic of China (NSC97-2314-B-006-020-MY3) to M.-H.W. and (NSC98-2320-B-006-026-MY3) to S.-J.T., and grants from the Chang Gung Memorial Hospital, Taiwan, Republic of China (CMRPG891432 and CMRPG8A0531) to P.-C.C. None of the authors have any conflicts of interest. © 2013 The Author.


Badreddine Assouar M.,CNRS Jean Lamour Institute | Sun J.-H.,Chang Gung University | Lin F.-S.,National Yunlin University of Science and Technology | Hsu J.-C.,National Yunlin University of Science and Technology
Ultrasonics | Year: 2014

We propose hybrid phononic-crystal plates which are composed of periodic stepped pillars and periodic holes to lower and widen acoustic band gaps. The acoustic waves scattered simultaneously by the pillars and holes in a relevant frequency range can generate low and wide acoustic forbidden bands. We introduce an alternative double-sided arrangement of the periodic stepped pillars for an enlarged pillars' head diameter in the hybrid structure and optimize the hole diameter to further lower and widen the acoustic band gaps. The lowering and widening effects are simultaneously achieved by reducing the frequencies of locally resonant pillar modes and prohibiting suitable frequency bands of propagating plate modes. © 2014 Elsevier B.V. All rights reserved.


Pan K.-K.,Chang Gung University
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2010

Sixth-order series expansions for the free energy and the staggered susceptibility of a spin-1 Heisenberg antiferromagnet with easy-plane single-ion anisotropy on three-dimensional bipartite lattices have been calculated from the linked-cluster series expansion. We obtain accurate estimate of TN vs D phase diagram separating paramagnetic and planar antiferromagnetic phases. The critical point and critical exponent of the quantum phase transition occurring at T=0 are also determined. The results are compared with related works. © 2010 Elsevier B.V. All rights reserved.


Chang S.-L.,National Cheng Kung University | Wu B.-R.,Chang Gung University | Wong J.-H.,National Cheng Kung University | Lin M.-F.,National Cheng Kung University
Carbon | Year: 2014

Configuration-dependent geometric and electronic structures of bilayer zigzag graphene nanoribbons are investigated by first-principles calculations. These properties are dominated by the stacking configurations, interlayer edge-edge interactions, spin arrangements, and ribbon widths. The optimal configuration exists between the AA and ABα ( AA′ and ABβ) stackings, mainly owing to the competition of the stacking and quantum confinement effects. The interlayer edge-edge interactions lead to the destruction or creation of magnetism and cause the AA-stacked system to exhibit a pair of metallic linear bands. However, other stacked nanoribbons are exclusively indirect- or direct-gap semiconductors. The splitting of spin-up and spin-down states could be induced by different magnetic environments. The band-edge states, with a high density of states, are sensitive to changes in the relative displacement. © 2014 Elsevier Ltd. All rights reserved.


Li L.-C.,Chang Gung University | Liu R.-S.,Yuan Ze University
IEEE Transactions on Wireless Communications | Year: 2010

In this paper, we address key management in cluster-based mobile ad hoc networks (MANETs). Ensuring secure communication in an ad hoc network is extremely challenging because of the dynamic nature of the network and the lack of centralized management. For this reason, key management is particularly difficult to implement in such networks. We present a fully-distributed ID-based multiple secrets key management scheme (IMKM). This scheme is implemented via a combination of ID-based multiple secrets and threshold cryptography. It eliminates the need for certificate-based authenticated public-key distribution and provides an efficient mechanism for key update and key revocation schemes, which leads to more suitable, economic, adaptable, scalable, and autonomous key management for mobile ad hoc networks. © 2010 IEEE.


BACKGROUND: Deferasirox (DFRA) is a new approved oral iron chelator. Its advantages are that it is convenient and better tolerated and adhered to due to "once-daily" oral dosage. However, its use in the field is limited and it is yet to be subjected to postmarketing surveillance. CASE REPORT: A 18.75-year-old male with β-thalassemia major received oral DFRA therapy due to transfusional iron overload for 27 months. He had received iron chelation therapy with deferoxamine injection together with oral deferiprone. However, his compliance was poor (very high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25 months of DFRA therapy, the serum ferritin level declined from 4097 to 1343 ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome, hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator. After we discontinued DFRA, he recovered fully without hepatic dysfunction, thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia. CONCLUSIONS: Our case illustrates the potential risks of DFRA-induced renal toxicity, hepatic dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and hematopoietic function is mandatory for patients undergoing treatment with DFRA. Further investigation of the potential risk and adverse effects of long-term DFRA use is necessary. © 2010 American Association of Blood Banks.


Lei K.F.,Chang Gung University
Journal of Laboratory Automation | Year: 2012

Because of intensive developments in recent years, the microfluidic system has become a powerful tool for biological analysis. Entire analytic protocols including sample pretreatment, sample/reagent manipulation, separation, reaction, and detection can be integrated into a single chip platform. A lot of demonstrations on the diagnostic applications related to genes, proteins, and cells have been reported because of their advantages associated with miniaturization, automation, sensitivity, and specificity. The aim of this article is to review recent developments in microfluidic systems for diagnostic applications. Based on the categories of various fluid-manipulating mechanisms and biological detection approaches, in-depth discussion of the microfluidic-based diagnostic systems is provided. Moreover, a brief discussion on materials and manufacturing techniques will be included. The current excellent integration of microfluidic systems and diagnostic applications suggests a solid foundation for the development of practical point-of-care devices. © 2012 Society for Laboratory Automation and Screening.


Chang C.-T.,Chang Gung University
Renewable and Sustainable Energy Reviews | Year: 2015

This paper proposes a multi-choice goal programming model for dealing with the capacity expansion planning problem of the renewable energy industry. This model involves decisions regarding the optimal mix of different plant types, location selection and other criteria. Different types of plants should be located in appropriate places so as to minimize the total deviations from predefined goals concerning power generated, investment cost, emission avoided, jobs created, operation and maintenance costs, distance security, and social acceptance. The proposed method is superior to the goal programming model proposed by Ramón and Cristóbal, in that it can avoid underestimation of aspiration level, expand the potential feasible region, and achieve findings more closely approach actual conditions. In addition, the social acceptance of the renewable energy planning problem in Taiwan is modeled by the MCGP to demonstrate its usefulness. © 2014 Elsevier Ltd.


Chen C.M.,Chang Gung University
The international journal of cardiovascular imaging | Year: 2012

A 320-row multidetector CT provides the capability for prospective electrocardiogram (ECG)-gated coronary CT angiography (CTA) and tube current modulated cardiac function assessment (CFA). We assessed and compared the effective radiation dose of these two modes. On a prospective basis, we performed ECG-gated cardiac CT on 119 patients (87 were males). For heart rates (HRs) /=80 bpm were scanned with either two or three heartbeats acquisitions, respectively. We used two types of scans. One type was based on a prospective ECG-gated CTA mode and the other using a tube current modulated CFA mode covering an entire R-R interval. The mean BMI of patients was 25.4 (range 18.8-49.3). Fifty-one patients (42.9 %) underwent CFA scanning, while the remaining 68 (57.1 %) had CTA. The majority of patients completed the scan in a single heartbeat (59.7 %). The mean dose of CTA mode at 65-85 % phase window for one and two heartbeats was 3.68 mSv (2.40-7.23) and 8.61 mSv (6.76-10.60), respectively. The mean dose of CFA mode for a single heartbeat measurement with dose modulation (25 % dose for CFA, and 100 % dose during 65-85 % phase window for CTA) was 6.32 mSv (4.69-8.89). CTA with prospective ECG-gating allows for acceptable image quality and radiation dose. HR reduction is mandatory to minimize radiation exposure. Global left ventricle function can be assessed with a single heartbeat within an acceptable radiation dose.


Hsieh S.-I.,Chang Gung University | Hsu L.-L.,National Taipei University of Nursing and Health Sciences
Nurse Education Today | Year: 2013

Limited literature is available for demographic and learning factors related to performance of baccalaureate nursing students. The study aimed at examining mean differences in nursing competency between the first week and the sixth week of a nursing clinical practicum as well as evaluating mean differences in nursing competency by demographic and learning factors at the sixth week of a nursing clinical practicum controlling for baseline scores of nursing competency. A comparative study design was conducted using the competency inventory for baccalaureate senior nursing students based on learning outcomes. Participants were surveyed at the first week and the sixth week of a nursing practicum with 95% mean response rate. Paired t test was used to compare within-subjects differences in mean nursing competency. ANCOVA and Kruskal-Wallis test, and Mann-Whitney U test were conducted to compare between-subjects differences in mean nursing competency. There are significant mean differences in nursing competency in general clinical skills, lifelong learning, clinical biomedical science, caring, and critical thinking and reasoning between the 1st week and the 6th week of nursing practicum. Likewise, type of nursing program, prior schooling, type of nursing license, interest in nursing, and extracurricular activity experience were significantly related to mean total nursing competency. Similarly, demographic attributes (location of school, type of nursing program, prior schooling, type of nursing license, a family member working as a medical practitioner or a nurse, interest in nursing, attributes of preferred workplace after college) and learning factors (extracurricular activity experience, played an active role in classroom discussions and asked questions, academic class rank, and English grade, clinical biomedical science, nursing science, and nursing practicum) were significantly related to six-subscale scores of nursing competency. There are mean differences in nursing competency across several demographic and learning factors. These factors should be given greater emphasis by nurse educators in planning the academic and clinical phases of professional education. © 2013.


Chang H.,Chang Gung University
Diagnostic Cytopathology | Year: 2013

Acute myeloid leukemia (AML) may be associated with extramedullary tumor growth, which is commonly known as myeloid sarcoma. Although AML with leukemic pleural effusion is considered rare, the true incidence is not clear. We report three cases of AML involving pleural effusion in this study. The cases were encountered in a single institute within two years, suggesting that leukemic effusion is more common than previously reported. Leukemic cells showed evidence of monocytic differentiation in all cases. Two patients presented with advanced AML. Both had concurrent myeloid sarcoma. Both were ineligible for intensive treatment and died soon after diagnosis of myeloid sarcoma. The third patient had pleural effusion upon diagnosis of AML. Remission was achieved and the effusion disappeared after treatment. We conclude leukemic effusion may become more common in an era of improved care and prolonged survival for AML patients. The prognostic impact is unclear and patients should be given standard AML treatment whenever possible. © 2012 Wiley Periodicals, Inc.


Huang F.-C.,Chang Gung University
International Journal of Molecular Sciences | Year: 2014

It was previously observed that plasma membrane cholesterol plays a critical role in the Salmonella-induced phosphatidylinositol 3-kinase-dependent (PI3K)-dependent anti-inflammatory response in intestinal epithelial cells (IECs). The PI3K/Akt pathway is associated with autophagy which has emerged as a critical mechanism of host defense against several intracellular bacterial pathogens. Plasma membrane contributes directly to the formation of early Atg16L1-positive autophagosome precursors. Therefore, this study aimed to investigate the role of plasma membrane cholesterol on the Salmonella-induced autophagy in IECs. By using methyl-beta-cyclodextrin (MBCD), it was demonstrated that disruption of membrane cholesterol by MBCD enhanced NOD2 and Atg16L1 proteins expression in membrane, and autophagic LC3II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells, which was counteracted by Atg16L1 siRNA. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) siRNA enhanced the Salmonella-induced activation of Akt in Caco-2 cells. However, inhibitors of Akt or extracellular signal-regulated kinases (ERK) had no significant effect on Salmonella-induced autophagy Beclin 1 or LC3 proteins expression. In conclusion, our study suggests that cholesterol accumulation in the plasma membrane at the entry site of Salmonella results in the formation of Salmonella-containing vacuole (SCV) and decreased autophagy. Our results offer mechanistic insights on the critical role of membrane cholesterol in the pathogenesis of Salmonella infection in intestinal epithelial cells and the therapeutic potential of its antagonists. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Chen J.-Y.,Chang Gung University | Hsu C.-T.,Cheng Hsin General Hospital | Liu J.-H.,National Yang Ming University | Tung T.-H.,Fu Jen Catholic University
BMC Gastroenterology | Year: 2014

Background: Gallstone disease (GSD) is a common gastrointestinal disorder throughout the world. The authors explored the incidence of GSD in Taiwan and its condition-associated predictive factors.Methods: The initial study cohort comprised 2386 healthy adult participants, who were voluntarily admitted to a teaching hospital for a physical check-up in 2002 in Taipei, Taiwan. After excluding 126 patients who exhibited prevalent GSD, 2260 non-GSD participants received annual follow-up screenings for GSD until 31 December, 2007. Of those, 1296 (57.3%) patients were re-examined to collect blood samples and conduct ultrasound sonography.Results: Among the 1296 participants who exhibited no GSD at the first screening, 23 patients developed GSD during 3640 person-years of follow-up. The incidence was 0.632% per year (95% CI: 0.292%-2.009%). After conducting a Cox regression, increased age (50-59 years versus < 40 years, RR = 2.16 [95% CI: 1.09-5.97], 60+ years versus < 40 years, RR = 3.81 [95% CI: 2.77-8.63]), high body mass index (≥27 kg/m2 versus < 24 kg/m2, RR = 1.64 [95% CI: 1.07-2.98]), high fasting plasma glucose levels (≥126 mg/dL versus < 110 mg/dL, RR = 1.68, 95% CI: 1.10-3.87), and nonalcoholic fatty liver disease (yes versus no, RR = 1.44, 95% CI: 1.21-1.90) appeared to be significantly related to developing GSD.Conclusion: Increased age is a well-established risk factor for developing GSD. The current findings indicated that high body mass index, elevated fasting plasma glucose levels, and nonalcoholic fatty liver disease were also associated with GSD. © 2014 Chen et al.; licensee BioMed Central Ltd.


Lin S.-W.,Chang Gung University | Ying K.-C.,National Taipei University of Technology
European Journal of Industrial Engineering | Year: 2012

Flowshop manufacturing cell scheduling problems (FMCSPs) with sequence-dependent family setup times (SDFSTs) have become a key area in the field of scheduling. Though the need to consider multiple criteria in real-world scheduling is widely recognised, most of the currently available algorithms for FMCSPs with SDFSTs only deal with the optimisation of a single performance criterion. In this study, a two-level multi-start simulated annealing (TLMSA) heuristic was presented for this problem with the objectives of simultaneously minimising makespan and total flow time (or total tardiness). To validate the performance of the proposed approach, the obtained sets of non-dominated solutions were evaluated by seven multi-objective performance indicators. The computational results showed that the proposed TLMSA significantly outperforms the benchmark algorithm in terms of the seven performance indicators. It is believed that it can serve as a new benchmark approach for future research on the two FMCSPs with SDFSTs addressed in this study. Copyright © 2012 Inderscience Enterprises Ltd.


Chen F.-P.,Chang Gung University
Taiwanese Journal of Obstetrics and Gynecology | Year: 2013

Objective: To assess the clinical response to imiquimod 5% cream in patients with persistent human papillomavirus (HPV) infection after treatment of genital intraepithelial neoplasia. Materials and Methods: Imiquimod 5% cream was applied to treat 76 women with persistent HPV after surgical therapy for cervical or vaginal intraepithelial neoplasia (CIN or VAIN). One sachet of cream was placed in the cervical os and vagina with an applicator twice weekly for 8 weeks. Repeated HPV evaluation and Papanicolaou (Pap) smear and/or biopsy were performed 3 months following treatment completion. Results: In total, 58 of the 76 patients (76.3%) were clear of HPV infection and had normal Pap smears after administration of imiquimod cream. Although atypia or mild dysplasia was noted in 15 of the 18 patients (83.3%) with persistent HPV infection after imiquimod cream treatment, the degree of severity was noticeably less than the initial diagnosis in most of these patients. Persistent HPV positivity was observed in 12 of the 64 patients (18.8%) with CIN and 6 of the 12 patients (50.0%) with VAIN. Conclusion: Topical imiquimod 5% cream may be beneficial in most cases of genital intraepithelial neoplasia, especially CIN, with persistent HPV following surgical treatment. © 2013.


Lin T.-Y.,McGill University | Lin T.-Y.,Chang Gung University | Poon A.H.,McGill University | Hamid Q.,McGill University
Current Opinion in Pulmonary Medicine | Year: 2013

PURPOSE OF REVIEW: It is increasingly clear that asthma is not a single disease, but a disorder with vast heterogeneity in pathogenesis, severity, and treatment response. In this review, we discuss the present understanding of different asthma phenotypes and endotypes, and the prospects of personalized medicine for asthma. RECENT FINDINGS: The recognition of diverse biological backgrounds in which asthma, and particularly severe asthma, can manifest has prompted the search for refined phenotypes and endotypes in asthma. Such appreciation of the heterogeneity in asthma is also prompting clinical trials to focus on specific subgroups of asthma, as demonstrated by the clinical trial of lebrikizumab. SUMMARY: Patients with severe asthma have asthma symptoms that are difficult to control, require high dosages of medication, and continue to experience persistent symptoms, asthma exacerbations or airflow obstruction even with aggressive therapy. Although asthma is traditionally viewed as an eosinophilic inflammatory disorder associated with a T-helper cell type 2 (Th2) immune response, recent studies have identified involvement of other effector cells, nonclassical Th2 cytokines and non-Th2 cytokines in severe asthma pathogenesis. Results of several clinical trials of anticytokine antibodies demonstrated the effectiveness of tailoring asthma treatment on the basis of an individual's biology. Copyright © 2012 Lippincott Williams &Wilkins.


Shaw S.W.S.,University College London | Shaw S.W.S.,Chang Gung University | David A.L.,University College London | De Coppi P.,University College London
Current Opinion in Obstetrics and Gynecology | Year: 2011

PURPOSE OF REVIEW: To review the potential of stem cells derived from amniotic fluid and applications in prenatal and postnatal therapy. RECENT FINDINGS: We have recently described that pluripotent stem cells can be isolated from amniotic fluid defined as amniotic fluid stem (AFS) cells by selection for expression of the membrane stem cell factor receptor c-Kit. AFS cells maintained for over 250 population doublings retained long telomeres and normal karyotype. Clonal human lines verified by retroviral marking were induced to differentiate into cell types representing each embryonic germ layer, including adipogenic, osteogenic, myogenic, endothelial, neuronal, and hepatic lineages. Rat AFS cells have been able to improve the repair of damaged smooth muscle in cryoinjury bladders. Furthermore, AFS cells could be differentiated toward cardiomyogenic lineages, when co-cultured with neonatal cardiomyocytes and have potential to generate hematopoietic lineages both in vitro and in vivo. These cells have been applied into fetal therapy, and widely used for tissue repair in animal models. Finally, we demonstrated a feasible way to do in-utero autologous AFS transplantation in sheep. SUMMARY: Stem cells derived from amniotic fluid are a relatively new source of cells that could have a therapeutic value in various diseases prenatally and/or postnatally. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Chung C.-Y.,National Chung Cheng University | Yang J.-T.,Chang Gung Memorial Hospital | Yang J.-T.,Chang Gung University | Kuo Y.-C.,National Chung Cheng University
Biomaterials | Year: 2013

Hypertensive intracerebral hemorrhage (ICH) is a rapidly evolutional pathology, inducing necrotic cell death followed by apoptosis, and alters gene expression levels in surrounding tissue of an injured brain. For ICH therapy by controlled gene release, the development of intravenously administrable delivery vectors to promote the penetration across the blood-brain barrier (BBB) is a critical challenge. Toenhance transfer efficiency of genetic materials under hypoxic conditions, polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were used to mediate the intracellular transport of plasmid neurotrophin-3 (NT-3) containing hormone response element (HRE) with a cytomegalovirus (cmv) promoter and to differentiate induced pluripotent stem cells (iPSCs). The differentiation ability of iPSCs to neurons was justified by various immunological stains for protein fluorescence. The effect of PBCA NP/cmvNT-3-HRE complexes on treating ICH rats was studied by immunostaining, western blotting and Nissl staining. Wefound that the treatments with PBCA NP/cmvNT-3-HRE complexes increased the capability of differentiating iPSCs to express NT-3, TrkC and MAP-2. Moreover, PBCA NPs could protect cmvNT-3-HRE against degradation with EcoRI/PstI and DNase I invitro and raise the delivery across the BBB invivo. Theadministration of PBCA NP/cmvNT-3-HRE complexes increased the expression of NT-3, inhibited the expression of apoptosis-inducing factor, cleaved caspase-3 and DNA fragmentation, and reduced the cell death rate after ICH invivo. PBCA NPs are demonstrated as an appropriate delivery system for carrying cmvNT-3-HRE to the brain for ICH therapy. © 2013 Elsevier Ltd.


Lin K.-Y.,Chang Gung University | Liu S.-J.,en Hwa 1st Road
Macromolecular Materials and Engineering | Year: 2010

This study has examined the morphological development in fluid assisted injection molded HDPE/PC blends. Samples for microscopic observation were prepared by an 80-ton injection-molding machine equipped with a tube cavity and with both gas and water injection units. It was observed that the shape and size of the dispersed phase depended onthe position both across the part thickness and along theflowdirection. Water molded parts with a smaller PC particle distribution than gas. Additionally, high fluid pressures were found to mold parts with smaller PC particle distribution. For both gas and water assisted injection molding, small and large particles coexisted in the skin and subskin layers, indicating that both coalescence and breakup of the dispersed phase occurred in that layer. These findings are expected to help foster understanding of the mechanism of morphology evolution during the melt filling, fluid injection,andcooling stages of the fluid assisted injection molding process. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


This article presents a useful method for relating anchor dependency and accuracy functions to multiple attribute decision-making (MADM) problems in the context of Atanassov intuitionistic fuzzy sets (A-IFSs). Considering anchored judgement with displaced ideals and solution precision with minimal hesitation, several auxiliary optimisation models have proposed to obtain the optimal weights of the attributes and to acquire the corresponding TOPSIS (the technique for order preference by similarity to the ideal solution) index for alternative rankings. Aside from the TOPSIS index, as a decision-maker's personal characteristics and own perception of self may also influence the direction in the axiom of choice, the evaluation of alternatives is conducted based on distances of each alternative from the positive and negative ideal alternatives, respectively. This article originates from Li's [Li, D.-F. (2005), Multiattribute Decision Making Models and Methods Using Intuitionistic Fuzzy Sets, Journal of Computer and System Sciences, 70, 73-85] work, which is a seminal study of intuitionistic fuzzy decision analysis using deduced auxiliary programming models, and deems it a benchmark method for comparative studies on anchor dependency and accuracy functions. The feasibility and effectiveness of the proposed methods are illustrated by a numerical example. Finally, a comparative analysis is illustrated with computational experiments on averaging accuracy functions, TOPSIS indices, separation measures from positive and negative ideal alternatives, consistency rates of ranking orders, contradiction rates of the top alternative and average Spearman correlation coefficients. © 2012 Taylor and Francis Group, LLC.


Lee H.-Y.,Dermatology Unit | Chung W.-H.,Drug Hypersensivity Clinical and Research Center | Chung W.-H.,Chang Gung University
Current Opinion in Allergy and Clinical Immunology | Year: 2013

PURPOSE OF REVIEW: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe adverse drug reactions. Once thought to be idiosyncratic and unpredictable, there has been significant progress made in the understanding of the pathomechanism and pharmacogenetics of such reactions. These advances together with their clinical implications will be elaborated in this review. RECENT FINDINGS: It is now known that the human leukocyte antigen (HLA) association in SJS/TEN is more than just a genetic marker and has a functional role as well. This reaction is mediated by cytotoxic T lymphocytes (CTLs) in an HLA-restricted fashion. Certain drugs may bind directly to the HLA complex and facilitate the development of self-reactivity due to drug-modified HLA-peptide repertoire. The role of the drug-specific T cells and their T-cell receptors has also been clarified. Downstream cytotoxic signals have been elucidated with granulysin, a cytotoxic protein produced by CTLs or natural killer cells deemed to be the key mediator in the reaction. SUMMARY: Pharmacogenetic screening of HLA alleles prior to drug initiation has already been shown useful in the prevention of such reactions. The other advances in the disease mechanism will form the basis for better preventive and therapeutic strategies. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Kuo Y.-C.,National Chung Cheng University | Shih K.-H.,National Chung Cheng University | Yang J.-T.,Chang Gung University
Electrophoresis | Year: 2010

This study analyzes the varying electrophoretic mobility and zeta potential of bone marrow stromal cells (BMSCs) during their differentiation towards neurons. Electrophoresis of primary BMSCs and neuron growth factor (NGF)-induced neuron-like cells with the uptake of heparin-functionalized poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are also investigated. Immunofluorescent images revealed that a high concentration of NGF accelerated the differentiation of BMSCs into neurons. When the concentration of NGF increased, the absolute values of electrophoretic mobility and zeta potential of the differentiating BMSCs increased. In addition, a longer inductive period yielded higher charge of the differentiating BMSCs and a smaller uptake amount of heparin-functionalized PLGA NPs. However, an increase in the loading efficiency of heparin on PLGA NPs enhanced the uptake and reduced the electrical characteristics of the primary and differentiating BMSCs. Hence, a general rule is drawn that an increase in the uptake of heparin-functionalized PLGA NPs decreased the electrophoretic mobility and zeta potential of BMSCs during differentiation towards neurons. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Chung C.-Y.,National Chung Cheng University | Yang J.-T.,Chang Gung Memorial Hospital | Yang J.-T.,Chang Gung University | Kuo Y.-C.,National Chung Cheng University
Biomaterials | Year: 2013

Guided neuronal differentiation of induced pluripotent stem cells (iPSCs) with genetic regulation is an important issue in biomedical research and in clinical practice for nervous regeneration and repair. To enhance the intracellular delivery of plasmid DNA (. pDNA), polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were employed to mediate the transport of neurotrophin-3 (NT-3) into iPSCs. The ability of iPSCs to differentiate into neuronal lineages was shown by immunofluorescent staining, western blotting, and flow cytometry. By transmission electron microscopy, we found that PBCA NPs could efficiently grasp pDNA, thereby increasing the particle size and conferring a negative surface charge. In addition, the treatments with PBCA NP/NT-3 complexes enhanced the expression of NT-3, TrkC, NH-H, NSE, and PSD95 by differentiating iPSCs. Neurons produced from iPSCs were incapable of returning to pluripotency, demonstrating with a series of differentiation scheme for adipogenesis and osteogenesis. The pretreatment with PBCA NP/NT-3 complexes can be one of critical biotechnologies and effective delivery systems in gene transfection to accelerate the differentiation of iPSCs into neurons. © 2013 Elsevier Ltd.


Reduced health related quality of life (HRQOL) has been associated with increased mortality in individuals with diabetes. In contrast, increased leisure time physical activity (LTPA) has been associated with reduced mortality. The aim of this study was to investigate the combined relationship of HRQOL and LTPA on mortality and whether high levels of LTPA are associated with reduced risk of mortality in adults with diabetes and inferior HRQOL. We analyzed data from a national sample of adults (18 years or older) with self-reported physician-diagnosed diabetes, who participated in the 2001 National Health Interview Survey in Taiwan (N = 797). A total of 701 participants had complete Short Form 36 (SF-36) and LTPA data and were followed from 2002 to 2008. Participants were divided into 3 groups based on their LTPA: (1) a regularly active group who reported 150 or more min/week of moderate-intensity activity; (2) an intermediately active group who reported engaging in LTPA but did not meet the criterion for the "regular" category; and (3) an inactive group who reported no LTPA. The physical component summary (PCS) and mental component summary (MCS) scores were dichotomised at the median (high vs. low) (PCS = 45.11; MCS = 47.91). Cox proportional-hazards models were used to investigate associations between baseline characteristics and mortality. After 4,570 person-years of follow-up, 121 deaths were recorded and the crude mortality rate was 26.5 per 1,000 person-years. Both PCS scores and LTPA were significant predictors of mortality, whereas no significant relationship was observed between MCS and mortality. After adjustment for other factors, participants with low PCS who reported no LTPA had a hazard ratio (HR) for mortality of 4.49 (95% CI = [2.15-9.36]). However, participants with low PCS who were active (including intermediate and regular LTPA) had a HR for mortality of 1.36 (95% CI = [0.64-2.92]). Our results show a significantly increased mortality risk of diabetes associated with reduced HRQOL in individuals who report no LTPA. Engaging in LTPA may be associated with improved survival in participants with diabetes with poor self-rated physical health status.


In this paper, we deal with the existence and multiplicity of positive solutions for the quasilinear elliptic problem-δpu-∑i=1kμi|u|p-2|x-ai|Pu=|u|p*-2u+λ|u|q-2u,x∈Ω, where Ω⊂ℝN (N ≥ 3) is a smooth bounded domain such that the different points ai ∈ Ω, i = 1,2,. .,k, 0 ≤ μi < μ-=(N-pp)p,λ>0,1≤q


Lin K.-T.,Academia Sinica, Taiwan | Wang Y.-W.,Academia Sinica, Taiwan | Chen C.-T.,National Health Research Institute | Ho C.-M.,Academia Sinica, Taiwan | And 3 more authors.
Clinical Cancer Research | Year: 2012

Purpose: Histone deacetylase inhibitors (HDACi) are actively explored as new-generation epigenetic drugs but have low efficacy in cancer monotherapy. To reveal new mechanism for combination therapy, we show that HDACi induce cell death but simultaneously activate tumor-progressive genes to ruin therapeutic efficacy. Combined treatments to target tumorigenesis and HDACi-activated metastasis with low toxic modalities could develop new strategies for long-term cancer therapy. Experimental Design: Because metastasis is the major cause of cancer mortality, we measured cell migration activity and profiled metastasis-related gene expressions in HDACi-treated cancer cells. We developed low toxic combination modalities targeting tumorigenesis and HDACi-activated metastasis for preclinical therapies in mice. Results: We showed that cell migration activity was dramatically and dose dependently enhanced by various classes of HDACi treatments in 13 of 30 examined human breast, gastric, liver, and lung cancer cell lines. Tumor metastasis was also enhanced in HDACi-treated mice. HDACi treatments activated multiple PKCs and downstream substrates along with upregulated proapoptotic p21. For targeting tumorigenesis and metastasis with immediate clinical impact, we showed that new modalities of HDACi combined drugs with PKC inhibitory agent, curcumin or tamoxifen, not only suppressed HDACi-activated tumor progressive proteins and cell migration in vitro but also inhibited tumor growth and metastasis in vivo. Conclusion: Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease. ©2012 AACR.


Wang L.,University of Michigan | Yang R.T.,University of Michigan | Sun C.-L.,Chang Gung University
AIChE Journal | Year: 2013

Significance: Four types of carbons (activated carbon, Maxsorb superactivated carbon, mesoporous templated carbon CMK-3, and graphene) were investigated as selective sorbents for adsorption of thiophene from its solution in n-octane. Graphene showed clearly the highest sulfur capacity. The relative sulfur capacities correlated well with the relative heats of adsorption. The carbene-type zigzag edge sites and the carbyne-type armchair edge sites on graphene are among the possible sites for strong interactions with thiophene. © 2012 American Institute of Chemical Engineers (AIChE).


Nyamoradi N.,Razi University | Hsu T.-S.,Chang Gung University
Acta Mathematica Scientia | Year: 2014

In this article, we consider a class of degenerate quasilinear elliptic problems with weights and nonlinearity involving the critical Hardy-Sobolev exponent and one sign-changing function. The existence and multiplicity results of positive solutions are obtained by variational methods. © 2014 Wuhan Institute of Physics and Mathematics.


Chiou S.-Y.,Chang Gung University
BioMed Research International | Year: 2013

Biometric systems refer to biometric technologies which can be used to achieve authentication. Unlike cryptography-based technologies, the ratio for certification in biometric systems needs not to achieve 100% accuracy. However, biometric data can only be directly compared through proximal access to the scanning device and cannot be combined with cryptographic techniques. Moreover, repeated use, improper storage, or transmission leaks may compromise security. Prior studies have attempted to combine cryptography and biometrics, but these methods require the synchronization of internal systems and are vulnerable to power analysis attacks, fault-based cryptanalysis, and replay attacks. This paper presents a new secure cryptographic authentication method using biometric features. The proposed system combines the advantages of biometric identification and cryptographic techniques. By adding a subsystem to existing biometric recognition systems, we can simultaneously achieve the security of cryptographic technology and the error tolerance of biometric recognition. This method can be used for biometric data encryption, signatures, and other types of cryptographic computation. The method offers a high degree of security with protection against power analysis attacks, fault-based cryptanalysis, and replay attacks. Moreover, it can be used to improve the confidentiality of biological data storage and biodata identification processes. Remote biometric authentication can also be safely applied. © 2013 Shin-Yan Chiou.


Lin H.-H.,Chang Gung University
Chang Gung Medical Journal | Year: 2012

The adhesion-class G protein-coupled receptors (adhesion- GPCRs) constitute the second largest GPCR sub-family in humans. Adhesion-GPCRs are defined by the chimeric structure of an unusually large extracellular cell-adhesion domain and a GPCR-like seven-pass transmembrane domain. Adhesion-GPCRs are hence expected to display both cellular adhesion and signaling functions in many biological systems. Adhesion-GPCRs are normally expressed in the central nervous, immune, and reproductive systems in a cell type- or tissue- restricted fashion. However, aberrant expression of distinct adhesion-GPCR molecules has been identified in various human cancers with some of the receptors closely associated with cancer development. Tumor-associated adhesion-GPCRs are thought to involve in tumorigenesis by affecting the growth of tumor cells, angiogenesis, tumor cell migration, invasion and metastasis either positively or negatively. Furthermore, some adhesion-GPCRs are considered potential biomarkers for specific types of cancers. In this review article, the expressional characteristics and functional role of cancer-associated adhesion-GPCRs are discussed in depth.


Wu R.-C.,Johns Hopkins University | Wu R.-C.,Chang Gung University | Wang T.-L.,Johns Hopkins University | Shih I.-M.,Johns Hopkins University
Cancer Biology and Therapy | Year: 2014

ARID1A has emerged as a tumor suppressor gene, which is mutated in a broad spectrum of cancers, especially in those arising from ectopic or eutopic endometrium. As a subunit of SWI/SNF chromatin remodeler, ARID1A facilitates target-specific binding of SWI/SNF complexes to chromatin, thereby altering the accessibility of chromatin to a variety of nuclear factors. In human cancer, ARID1A possesses not only features of a gatekeeper, regulating cell cycle progression, but also features of a caretaker, preventing genomic instability. An increasing body of evidence suggests crosstalk between ARID1A and PI3K/Akt pathways, and between ARID1A and p53. In this review, we discuss the spectrum of ARID1A alterations in cancers, tumor suppression mechanisms of ARID1A, oncogenic pathways cooperating with ARID1A, and clinical implications of ARID1A mutation. © 2014 Landes Bioscience.


Lin P.-Y.,Chang Gung University | Huang S.-Y.,Taipei Medical University | Su K.-P.,Taipei Medical University | Su K.-P.,China Medical University at Taichung
Biological Psychiatry | Year: 2010

Background: On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. Methods: Weconducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Results: Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. Conclusions: The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted. © 2010 Society of Biological Psychiatry.


This paper develops new methods based on the preference ranking organization method for enrichment evaluations (PROMETHEE) that use a signed distance-based approach within the environment of interval type-2 fuzzy sets for multiple criteria decision analysis. The theory of interval type-2 fuzzy sets provides an intuitive and computationally feasible way of addressing uncertain and ambiguous information in decision-making fields. Many studies have developed multiple criteria decision analysis methods in the context of interval type-2 fuzzy sets; most of these methods can be characterized as scoring or compromising models. Nevertheless, the extended versions of outranking methods have not been thoroughly investigated. This paper establishes interval type-2 fuzzy PROMETHEE methods for ranking alternative actions among multiple criteria based on the concepts of signed distance-based generalized criteria and comprehensive preference indices. We develop interval type-2 fuzzy PROMETHEE I and interval type-2 fuzzy PROMETHEE II procedures for partial and complete ranking, respectively, of the alternatives. Finally, the feasibility and applicability of the proposed methods are illustrated by a practical problem of landfill site selection. A comparative analysis is also performed with ordinary fuzzy PROMETHEE methods to validate the effectiveness of the proposed methodology. © 2013 Springer-Verlag Berlin Heidelberg.


Epicutaneous sensitization with protein allergen that induces predominant Th2 responses is an important sensitization route in atopic dermatitis. Fungal components have been shown to modulate Th cell differentiation. However, the effects of fungal components on epicutaneous sensitization are unclear. In this study, we showed that co-administration of curdlan, a dectin-1 agonist, during epicutaneous ovalbumin sensitization of BALB/c mice decreased the IL-5 and IL-13 levels in supernatants of lymph node cell ovalbumin reactivation cultures. Mechanistically, curdlan co-administration decreased IL-4 and IL-1β expressions in draining lymph nodes. Curdlan co-administration also lower the migration of langerin+ CD103- epidermal Langerhans cells into draining lymph nodes at 96 hours post-sensitization which might be attributed to decreased expressions of IL-18 and IL-1β in patched skin. Moreover, adoptive transfer of CFSE-labeled transgenic CD4 T cells confirmed that curdlan co-administration decreased the proliferation and IL-4-production of ovalbumin -specific T cells primed by epidermal Langerhans cells. These results indicated that concurrent exposure to a dectin-1 agonist suppresses the epicutaneously induced Th2 response by modulating the cytokine expression profiles in draining LNs and the migration of epidermal Langerhans cells. These results highlight the effects of fungal components on epicutaneous allergen sensitization in atopic diseases.


Kossoff E.,Johns Hopkins University | Wang H.-S.,Chang Gung University
Biomedical Journal | Year: 2013

Since their introduction in 1921, high-fat, low-carbohydrate "ketogenic" diets have been used worldwide for refractory childhood epilepsy. Approximately half of the children have at least half their seizures reduced, including 15% who are seizure free. The mechanisms of action of dietary therapies are under active investigation and appear to involve mitochondria. Once perceived as a last resort, modifications to initiation and maintenance, as well as the widespread use of pre-made ketogenic formulas have allowed dietary treatment to be used earlier in the course of epilepsy. For infantile spasms (West syndrome) specifically, the ketogenic diet is successful about 50% of the time as a first-line treatment. New "alternative" diets such as the modified Atkins diet were created in 2003 and can be started more easily and are less restrictive. They may have particular value for countries in Asia. Side effects include constipation, dyslipidemia, growth slowing, acidosis, and kidney stones. Additionally, neurologists are studying ketogenic diets for conditions other than epilepsy, including Alzheimer′s disease, autism, and brain tumors.


Lin S.-W.,Chang Gung University | Ying K.-C.,National Taipei University of Technology
Computers and Operations Research | Year: 2014

To date, the topic of unrelated parallel machine scheduling problems with machine-dependent and job sequence-dependent setup times has received relatively little research attention. In this study, a hybrid artificial bee colony (HABC) algorithm is presented to solve this problem with the objective of minimizing the makespan. The performance of the proposed HABC algorithm was evaluated by comparing its solutions to state-of-the-art metaheuristic algorithms and a high performing artificial bee colony (ABC)-based algorithm. Extensive computational results indicate that the proposed HABC algorithm significantly outperforms these best-so-far algorithms. Since the problem addressed in this study is a core topic for numerous industrial applications, this article may help to reduce the gap between theoretical progress and industrial practice. © 2014 Elsevier Ltd.


Liao J.-C.,Chang Gung University
International Journal of Molecular Sciences | Year: 2016

Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs) genetically modified with baculoviral bone morphogenetic protein-2 (Bac-BMP-2) vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs) were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6) was implanted with collagen-β-tricalcium phosphate (TCP)-hydroxyapatite (HA), Group II (n = 6) was implanted with collagen-β-TCP-HA plus BMDMSCs, and Group III (n = 6) was implanted with collagen-β-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme-linked immunosorbent assay (ELISA). Spinal fusion was examined using computed tomography (CT), manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12), 8 in Group II (67%, 8/12), and 12 in Group III (100%, 12/12). The fusion rate, determined by manual palpation, was 0% (0/6) in Group I, 0% (0/6) in Group II, and 83% (5/6) in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-β-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits. © 2016 by the author; licensee MDPI, Basel, Switzerland.


Horng S.-C.,Chaoyang University of Technology | Lin S.-Y.,Chang Gung University
Information Sciences | Year: 2013

This work proposes an evolutionary algorithm (EA) that is assisted by a surrogate model in the framework of ordinal optimization (OO) and optimal computing budget allocation (OCBA) for use in solving the real-time combinatorial stochastic simulation optimization problem with a huge discrete solution space. For real-time applications, an off-line trained artificial neural network (ANN) is utilized as the surrogate model. EA, assisted by the trained ANN, is applied to the problem of interest to obtain a subset of good enough solutions, S. Also for real-time application, the OCBA technique is used to find the best solution in S, and this is the obtained good enough solution. Most importantly, a systematic procedure is provided for evaluating the performance of the proposed algorithm by estimating the distance of the obtained good enough solution from the optimal solution. The proposed algorithm is applied to a hotel booking limit (HBL) problem, which is a combinatorial stochastic simulation optimization problem. Extensive simulations are performed to demonstrate the computational efficiency of the proposed algorithm and the systematic performance evaluation procedure is applied to the HBL problem to quantify the goodness of the obtained good enough solution. © 2013 Elsevier Inc. All rights reserved.


White K.D.,Vanderbilt University | Chung W.-H.,Chang Gung Memorial Hospital | Chung W.-H.,Drug Hypersensitivity Clinical and Research Center | Chung W.-H.,Chang Gung University | And 5 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Immune-mediated (IM) adverse drug reactions (ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B cell-mediated and primary T cell-mediated IM-ADRs. In this review we summarize the role of host genetics, microbes, and drugs in IM-ADR development; expand on the existing models of IM-ADR pathogenesis to address multiple unexplained observations; discuss the implications of this work in clinical practice today; and describe future applications for preclinical drug toxicity screening, drug design, and development. © 2015 American Academy of Allergy, Asthma & Immunology.


Lin C.-E.,National Central University | Yu C.-J.,Chang Gung University | Chen C.-C.,National Central University
Optics Express | Year: 2013

In this article, we propose an optical heterodyne common-path gyroscope which has common-path configuration and full-dynamic range. Different from traditional non-common-path optical heterodyne technique such as Mach-Zehnder or Michelson interferometers, we use a twofrequency laser light source (TFLS) which can generate two orthogonally polarized light with a beat frequency has a common-path configuration. By use of phase measurement, this optical heterodyne gyroscope not only has the capability to overcome the drawback of the traditional interferometric fiber optic gyro: lack for full-dynamic range, but also eliminate the total polarization rotation caused by SMFs. Moreover, we also demonstrate the potential of miniaturizing this gyroscope as a chip device. Theoretically, if we assume that the wavelength of the laser light is 1550nm, the SMFs are 250m in length, and the radius of the fiber ring is 3.5cm, the bias stability is 0.872 deg/hr. © 2013 Optical Society of America.


Chen H.-K.,National Taiwan University | Wang T.,Chang Gung University | Lu S.-S.,National Taiwan University
IEEE Transactions on Microwave Theory and Techniques | Year: 2011

A millimeter-wave multiband phase-locked loop (PLL) is presented for the first time, which covers 40-, 60-, and 80-GHz bands. Three voltage-controlled oscillators corresponding to different frequencies are input to a multiband injection-locked frequency divider and switched on one at a time by a multiplexer as a band selector. The feedback loop embraces the following components: a chain of dividers with a fixed division-modulus of 256, a phase-frequency detector, a charge-pump, and a second-order loop filter. The PLL is clocked by a reference frequency of 78 MHz and its output power is higher than -9.5 dBm. The phase noise is -103 dBc/Hz at an offset frequency of 10 MHz. With a supply voltage of 1.5 V, the entire PLL consumes 114 mW. The chip is implemented in a 90-nm CMOS technology and measures 1.12 mm 2. © 2011 IEEE.


An interval-valued intuitionistic fuzzy set contains membership and non-membership values that are crisp intervals and represent an extension of the ordinary fuzzy sets that are widely used because of their usefulness in handling imprecise or uncertain information. The linear programming technique for multidimensional analysis of preference (LINMAP) is a representative decision-making method with respect to preference information for given alternatives. In this paper, we present a new linear programming technique with weight assessment, an extended LINMAP method, for addressing multiple criteria group decision-making problems in the interval-valued intuitionistic fuzzy framework. With consideration given to the degrees of relative agreement and the importance weights of multiple decision makers, this paper presents an inclusion-based hybrid averaging operation with an inclusion comparison approach for forming a collective decision environment. The concept of inclusion-based indices that relate to anchor dependency with multiple points of reference is developed as the core of the extended LINMAP method. We also establish a linear programming model to handle the incomplete preference information for alternatives. The optimal weights of the criteria can be determined, and the priority order of the alternatives can be obtained according to the resulting comprehensive inclusion-based indices. The feasibility and applicability of the proposed methods are illustrated with an example addressing graduate admission, and a comparative analysis is performed with another interval-valued intuitionistic fuzzy LINMAP approach to validate the effectiveness of the proposed methodology. © 2013 Elsevier B.V. All rights reserved.


Steven Shaw S.-W.,Chang Gung University
Gynecology and Minimally Invasive Therapy | Year: 2014

Amniotic fluid stem cells can be expanded without feeder layers and can differentiate into mesenchymal and hematopoietic lineages. Long-term engraftment has been difficult to achieve after prenatal stem cell transplantation, mainly because of allogeneic rejection. Autologous cells can be obtained from amniotic fluid with minimal risk. This review aims to define the potential of human amniotic fluid stem cells as an autologous stem cell source for minimal invasive prenatal cell or cell-based gene therapy. We conclude that amniotic fluid-derived stem cells are an important source of autologous cells that may have prenatal therapeutic value in cell or cell-based gene therapy in the near future. © 2014.


Wu P.-C.,Kaohsiung Medical Center | Tsai C.-L.,Chang Gung University | Hu C.-H.,Kaohsiung Medical Center | Yang Y.-H.,Kaohsiung Medical University
Ophthalmic Epidemiology | Year: 2010

Purpose:The aim was to identify the prevalence and risk factors of myopia among elementary school students in a rural area of Taiwan. Methods:A cross-sectional study was conducted. Elementary school students aged 712 years were recruited from the two schools located on Chimei Island. Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction. Results:One hundred and forty five students were recruited for this study. Myopia prevalence was 31%. In univariate analysis, myopia was significantly associated with school year, myopic parent, and watching television (TV) (P < .0001,0.007 and0.029, respectively). Multiple logistic regression analysis revealed that myopia was significantly associated with school year and myopic parent. However, the effect of watching TV was not statistically significant (P0.059). Outdoor activity showed significance and was inversely associated with myopia (Odds Ratio [OR]0.3, 95% Confidence Interval [CI]0.10.9, P0.025). Conclusion:This study suggests that outdoor activities might be an important protecting factor for myopia in rural school children. © 2010 Informa Healthcare USA, Inc.


Chang P.-C.,Chang Gung University | Chen P.-S.,Indiana University
Trends in Cardiovascular Medicine | Year: 2015

Small-conductance Ca2+-activated K+ (SK) currents are important in the repolarization of normal atrial (but not ventricular) cardiomyocytes. However, recent studies showed that the SK currents are upregulated in failing ventricular cardiomyocytes, along with increased SK channel protein expression and enhanced sensitivity to intracellular Ca2+. The SK channel activation may be either anti-arrhythmic or pro-arrhythmic, depending on the underlying clinical situations. While the SK channel is a new target of anti-arrhythmic therapy, drug safety is still one of the major concerns. © 2015 Elsevier Inc..


Lin T.-S.,Chang Gung University
Plastic and Reconstructive Surgery | Year: 2016

BACKGROUND:: Free or local flaps that are used to reconstruct the foot are often associated with a multitude of problems, most in regard to poor aesthetic and functional outcomes. This is the result of the bulkiness of the flap as well as its difference from the native glabrous skin of the weight-bearing region of the foot. Although these can be improved using various debulking procedures, the results are not satisfactory. PATIENTS AND METHODS:: From January 2002 to July 2014, one-stage debulking procedures were performed for 42 feet after flap reconstructions. Twelve patients (28.6%) had bulky flaps over the weight-bearing area of the foot compared to 30 (71.4%) on the non-weight-bearing area. The functional and cosmetic outcomes were reviewed after 12 months follow up. RESULTS:: The overall mean follow-up time was 20 months. All the grafted skin took well except for partial superficial skin necrosis which healed by secondary intention and one skin loss which needed further skin graft. The patients were able to dress in their preinjury shoes without any difficulty and with ease of ambulation due to improvement in skin stability. The skin sensation and texture of the reconstructed feet matched the normal sides well. No long-term ulceration was noted. All of the patients were satisfied with the results. CONCLUSIONS:: One-stage debulking procedure can provide long-term constant, reliable, thin skin coverage for the feet after free flap or local flap reconstruction. ©2016American Society of Plastic Surgeons


Huang L.-T.,Chang Gung University
Pediatric Research | Year: 2011

The perinatal period is particularly sensitive to a variety of insults during which stress-regulating systems can be permanently altered and psychopathologies ensue. The programming of physiological, endocrinological, and behavioral functions by perinatal adversities is mediated by altered levels of glucocorticoids or the hypothalamic-pituitary-adrenal axis activity in either the mother or offspring. In this article, I review the integrated data from human studies and from animal models that suggest the programming effects of perinatal glucocorticoids exposure. Finally, the concept of developmental origins of psychiatric disorders is discussed. Copyright © 2011 International Pediatric Research Foundation, Inc.


Liaw Y.-F.,Chang Gung University
Liver International | Year: 2013

Chronic hepatitis B virus (HBV) infection is a dynamic state in which HBV replication is the key driving force of disease progression, resulting in the development of hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC). The primary aim of therapy is to eliminate or suppress HBV to reduce the activity of hepatitis thus reducing the risk of or slowing the progression of liver disease. Treatment with nucleos(t)ide analogues (Nuc) may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function thus increasing survival in patients with hepatic decompensation. The long-term benefits of a finite course of interferon α (IFN) therapy include a sustained and cumulative response, as well as a reduction in the progression of fibrosis and in the development of cirrhosis and/or HCC. Long-term Nuc therapy may also result in histological improvement or reversal of advanced fibrosis and reduction in disease progression including the development of HCC. Hepatitis B surface antigen (HBsAg) seroclearance, a status close to a "cure", may also occur in patients with a sustained or maintained viral response, especially in those with IFN-based therapy. Pegylated IFN (PEG-IFN) and newer Nucs may have even better long-term outcomes because of improved efficacy and/or a low risk of drug resistance. However, treatment outcomes are still far from satisfactory. The development of more effective and safe but affordable anti-HBV agents/strategies is needed to further improve outcomes. © 2012 John Wiley & Sons A/S.


Liu H.-L.,Chang Gung University | Fan C.-H.,National Tsing Hua University | Ting C.-Y.,National Tsing Hua University | Yeh C.-K.,National Tsing Hua University
Theranostics | Year: 2014

Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality. Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival. Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery. MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors. Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment. In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy. © Ivyspring International Publisher.


Huang Y.,Chang Gung University | De Leval L.,University of Lausanne | Gaulard P.,French Institute of Health and Medical Research | Gaulard P.,University Paris Est Creteil
Best Practice and Research: Clinical Haematology | Year: 2013

Peripheral NK/T-cell lymphoma (PTCL) is a heterogeneous group of uncommon hematologic malignancies with aggressive clinical course and unfavorable prognosis. Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is the most common extranodal entity worldwide, with heterogeneous geographic distribution, and it is characterized by its association with EBV, a nasal or less often extranasal presentation and aggressive behavior. Recent works using array-based technologies have provided novel insights into the pathogenesis and discovered new biomarkers with diagnostic and therapeutic implications in NKTCL. Gene expression profiling identified that most of the NKTCL are derived from activated natural killer cells with distinctively high expression of granzyme H compared to other PTCLs, which might serve as a new diagnostic biomarker. Frequent deletions and promoter methylations in PRDM1, ATG5, AIM1, FOXO3, HACE1 mapping to 6q21-q25, suggest their roles as potential tumor suppressors. The deregulation of oncogenic pathways (PDGF, JAK-STAT, AKT) provides a rationale for developing targeted therapies in the future. © 2013 Elsevier Ltd. All rights reserved.


Background: Sphingolipids are important for innate immune response to eliminate infected pathogens and involved in autophagy. On the other hand, nucleotide-binding oligomerization domain-containing protein 2 (NOD2) served as an intracellular pattern recognition receptor to enhance host defense by inducing autophagy and the production of antimicrobial peptides, such as human beta-defensin-2 (hBD-2). However, the role of sphingolipids in Salmonella-induced autophagy and hBD-2 response in intestinal epithelial cells has not been previously elucidated. Methods: Salmonella typhimurium wild-type strain SL1344 was used to infect SW480, an intestinal epithelial cell. hBD-2 and interleukin-8 (IL-8) mRNA expressions were assessed in SW480 cells using RT-PCR, and intracellular signaling pathways and autophagy protein expression were analyzed by Western blot in SW480 cells in the presence or absence of inhibitors or transfected with siRNA. Results: We demonstrated that inhibition of de novo sphingolipid synthesis repressed the membrane recruitment of NOD2 and autophagy-related protein 16-like 1 (Atg16L1), suppressed Salmonella-induced autophagic protein LC3-II expression, and reduced NOD2-mediated hBD-2 response in Salmonella-infected SW480 cells. Contrasting to the utilization of membrane cholesterol on maintenance of Salmonella-containing vacuoles and anti-inflammation by Salmonella, sphingolipids act on epithelial defense against the invasive pathogen. Conclusions: Our results offer mechanistic insights on the role of de novo sphingolipid synthesis in the innate immunity of intestinal epithelial cells to Salmonella infection. The pharmaceuticals enhancing or diet enriched with sphingolipids may induce the dual anti-bacterial mechanisms. The role of de novo sphingolipid synthesis on inflammatory bowel disease is deserved to be further investigated. © 2016 Huang.


The serum-free medium from Japanese encephalitis virus (JEV) infected Baby Hamster Kidney-21 (BHK-21) cell cultures was analyzed by liquid chromatography tandem mass spectrometry (LC-MS) to identify host proteins that were secreted upon viral infection. Five proteins were identified, including the molecular chaperones Hsp90, GRP78, and Hsp70. The functional role of GRP78 in the JEV life cycle was then investigated. Co-migration of GRP78 with JEV particles in sucrose density gradients was observed and co-localization of viral E protein with GRP78 was detected by immunofluorescence analysis in vivo. Knockdown of GRP78 expression by siRNA did not effect viral RNA replication, but did impair mature viral production. Mature viruses that do not co-fractionate with GPR78 displayed a significant decrease in viral infectivity. Our results support the hypothesis that JEV co-opts host cell GPR78 for use in viral maturation and in subsequent cellular infections.


Interval type-2 fuzzy sets (T2FSs) with interval membership grades are suitable for dealing with imprecision or uncertainties in many real-world problems. In the Interval type-2 fuzzy context, the aim of this paper is to develop an interactive signed distance-based simple additive weighting (SAW) method for solving multiple criteria group decision-making problems with linguistic ratings and incomplete preference information. This paper first formulates a group decision-making problem with uncertain linguistic variables and their transformation to interval type-2 trapezoidal fuzzy numbers. Concerning the relative importance of multiple decision-makers and group consensus of fuzzy opinions, a procedure using hybrid averages is then employed to construct a collective decision matrix. By an appropriate extension of the classical SAW approach, this paper utilizes the concept of signed distances and establishes an integrated programming model to manage multi-criteria group decisions under the incomplete and inconsistent preference structure. Further, an interactive procedure is established for group decision making. Finally, the feasibility and effectiveness of the proposed methods are illustrated by a collaborative decision-making problem of patient-centered care (PCC). © 2014 World Scientific Publishing Company.


Lee M.,Chang Gung University | Markovic D.,University of California at Los Angeles | Ovbiagele B.,Medical University of South Carolina
American Journal of Kidney Diseases | Year: 2013

Background: Low estimated glomerular filtration rate (eGFR) has been linked to higher risk of primary stroke, but little is known about the relation of low eGFR to recurrent vascular risk after stroke. B Vitamin therapy has been used to lower homocysteine levels, but its interaction with kidney function on future major vascular events has not been assessed. The objective of this study was to conduct a secondary analysis based on the Vitamin Intervention for Stroke Prevention (VISP) trial to clarify these issues. Study Design: In the VISP trial, patients with a prior ischemic stroke were randomly assigned to receive the high- or low-dose B vitamin therapy. The trial did not find a difference between randomly assigned groups. The present study is a secondary analysis of the VISP trial. Setting & Participants: We analyzed the database of a multicenter trial comprising 3,673 patients with recent ischemic stroke who were followed up for 2 years. Predictor: We subdivided the cohort based on eGFR into 6 groups (≥105, 90-104, 75-89, 60-74, 45-59, and <45 mL/min/1.73 m 2) for the analyses and used eGFR of 60-74 mL/min/1.73 m2 as the reference category. Low eGFR was defined as <45 mL/min/1.73 m 2. Outcomes: The primary end point for this analysis was major vascular events, defined as the composite of nonfatal ischemic stroke, nonfatal myocardial infarction, and vascular death (whichever event came first). The secondary end point was recurrent ischemic stroke. Also, the effects of high-dose B vitamin treatment on future major vascular events according to baseline eGFR categories were analyzed and reported separately. Results: Mean baseline eGFR was 73.9 ± 21.8 (SD) mL/min/1.73 m2. 471 major vascular events during an average of 20 months of follow-up, including 300 recurrent strokes, were recorded. Baseline low eGFR was associated with increased risk of major vascular events (HR, 1.83; 95% CI, 1.32-2.52; P < 0.001) and recurrent stroke (HR, 1.53; 95% CI, 1.01-2.32; P = 0.04) after adjustment for traditional vascular risk factors and homocysteine level. At baseline eGFR <45 mL/min/1.73 m2, high-dose B vitamin therapy compared to low dose showed a trend of higher risk of future major vascular events (HR, 1.49; 95% CI, 0.95-2.34; P = 0.08). The overall P value for interaction between B vitamin dose and eGFR was not significant (P = 0.6). Limitations: No data for albuminuria. Conclusions: Low eGFR is associated with higher risk of future major vascular events and recurrent stroke after a recent ischemic stroke. © 2013 National Kidney Foundation, Inc.


Chen K.-J.,National Tsing Hua University | Liang H.-F.,Industrial Technology Research Institute of Taiwan | Chen H.-L.,National Tsing Hua University | Wang Y.,Georgia Institute of Technology | And 4 more authors.
ACS Nano | Year: 2013

The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drug delivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 °C), decomposition of ABC generates CO2 bubbles, creating permeable defects in the lipid bilayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO2 bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor a temperature-controlled drug delivery process. © 2012 American Chemical Society.


This study aimed to consider the effect of dispositional optimism and pessimism to provide simple and useful decision models and methods for multiple criteria decision analysis within an interval-valued fuzzy environment. Uncertain and imprecise assessment information is usually present in many practical decision-making situations. Interval-valued fuzzy sets are useful for modeling impressions and quantifying the ambiguous nature of subjective judgments in a convenient way. Based on measurement tool estimations defined on interval-valued fuzzy sets, dual optimistic and pessimistic point operators were utilized in this study, and this paper discusses several important properties of optimistic/pessimistic averaging operations. Two algorithmic procedures were developed to address the effects of optimism and pessimism, involving changes in overall judgments and in the separate evaluations of alternatives with respect to each criterion. Furthermore, this study explored the practical problem of medical decision making to demonstrate the feasibility and applicability of the proposed method and to make a comparison with other existing methods. Finally, computational experiments were designed using enormous amounts of simulation data, and a comparative analysis of rank orders yielded by dual optimistic and pessimistic averaging operations was conducted. © 2014 Elsevier B.V. All rights reserved.


Carr B.I.,Tel Aviv Sourasky Medical Center | Guerra V.,National Institute for Digestive Diseases | Steel J.L.,University of Pittsburgh | Lu S.-N.,Chang Gung University
Seminars in Oncology | Year: 2015

Hepatocellular carcinoma (HCC) is a leading cause of cancer death and has characteristic causes, epidemiology and clinical features. The leading causes include hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, and aflatoxin B1 dietary exposure, as well as combinations of these factors. Few cancers offer the opportunity to study the clinical and cancer phenotype that results from different causes, quite like HCC. Advantage was taken of a large cohort of advanced, unresectable and untransplantable HCCs to compare the phenotypes resulting from HBV-based compared with HCV-based HCC. The main findings were that HBV-based HCC patients were statistically significantly younger, had a higher percent of males, had larger maximum tumor sizes, and had higher blood alpha-fetoprotein (AFP) and albumin levels and platelet counts than HCV-based HCC patients. These differences partly reflect an earlier age of HBV infection and a lesser degree of cirrhosis-associated liver damage, as a result of the different biological consequences of chronic HBV compared with chronic HCV infection. © 2015 Elsevier Inc. All rights reserved.


Huang L.-T.,Chang Gung University
New Review of Hypermedia and Multimedia | Year: 2016

Research indicated that in order for properly utilizing recommendation agents (RAs), customers must rationally evaluate capability and suggestions of RAs during the interaction process. However, enjoying interactive processes and interface is also important. Methods for increasing user enjoyment of RAs are yet unknown. This study investigated the influences of utilitarian and hedonic factors on intention to adopt RAs suggestions and their antecedents. Involvement influences relative importance of utilitarian and hedonic factors. Contrary to common assumptions, customers may make unplanned purchases, rather than rational purchase. A field experiment with 2 x 2 x 2 factorial design reveals main findings. First, information diagnosticity and enjoyment enhance adoption intention simultaneously. Information diagnosticity is more important than enjoyment. Diagnosticity was determined by outcome similarity, and enjoyment was determined by both outcome similarity and atmospherics. The context of interacting with RAs is important. Outcome similarity even directly affects adoption intention. Second, highly involved users considered enjoyment and diagnosticity when forming adoption intentions, while users with low involvement only considered enjoyment. Third, information cascades altered the relationship between adoption intention and unplanned purchases. Most customers change selection after seeing ratings from other customers, even if they originally strongly want to adoption suggestion from RAs. Theoretical and managerial implications are proposed. © 2015 Taylor & Francis.


Lu C.-C.,National Taipei University of Technology | Lin S.-W.,Chang Gung University | Ying K.-C.,National Taipei University of Technology
Applied Soft Computing Journal | Year: 2014

This research addresses a single machine scheduling problem with uncertain processing times and sequence-dependent setup times represented by intervals. Our objective is to obtain a robust schedule with the minimum absolute deviation from the optimal makespan in the worst-case scenario. The problem is reformulated as a robust traveling salesman problem (RTSP), whereby a property is utilized to efficiently identify worst-case scenarios. A local search-based heuristic that incorporates this property is proposed to solve the RTSP, along with a simulated annealing-based implementation. The effectiveness and efficiency of the proposed heuristic are compared to those of an exact solution method in the literature. © 2014 Elsevier B.V. © 2014 Elsevier B.V. All rights reserved.


BACKGROUND: F-18 fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is related to tumor biology and has predictive value for tumor recurrence after liver transplantation. This retrospective study assessed whether the degree of FDG uptake in positron emission tomography (PET) can be used to predict HCC recurrence after living donor liver transplantation (LDLT). METHODS: One hundred forty-seven patients with HCC underwent FDG-PET studies before LDLT. The semiquantification of FDG uptake in FDG-positive HCC was done with maximum standardized uptake value (SUVmax) and tumor to nontumor ratio (TNR). Recurrence-free survivals (RFS) were calculated using the Kaplan-Meier method. RESULTS: In univariable analysis, T stage, presence of microvascular invasion, being FDG-positive, SUVmax, and TNR were significant predictors for worse RFS. The optimal cutoff values of SUVmax and TNR were 4.8 and 2.0, respectively. The high FDG uptake HCC (TNR ≥ 2) was a strong predictor for worse RFS (hazard ratio, 13.52; 95% confidence interval, 4.77-38.29; P < 0.001). Using a combination of FDG-PET and University of California San Francisco (UCSF) criteria, the patients can be divided into low-risk (within UCSF criteria and FDG-negative), intermediate-risk (beyond UCSF criteria and FDG-negative; FDG-positive and TNR < 2), and high-risk (FDG-positive and TNR ≥ 2) groups. The estimated 5-year RFS in these groups were 85.5%, 83.9%, and 29.6% according to the combination of FDG-PET and clinical UCSF criteria, and 94.0%, 75.8%, and 29.6% according to the combination of FDG-PET and pathologic UCSF criteria, respectively. CONCLUSIONS: Combination of FDG-PET and UCSF criteria can be used to predict the risk of HCC recurrence after LDLT. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Peng J.,University of Alberta | Chen Y.-T.,Chang Gung University | Chen C.-L.,Chang Gung Memorial Hospital | Li L.,University of Alberta
Analytical Chemistry | Year: 2014

Large-scale metabolomics study requires a quantitative method to generate metabolome data over an extended period with high technical reproducibility. We report a universal metabolome-standard (UMS) method, in conjunction with chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS), to provide long-term analytical reproducibility and facilitate metabolome comparison among different data sets. In this method, UMS of a specific type of sample labeled by an isotope reagent is prepared a priori. The UMS is spiked into any individual samples labeled by another form of the isotope reagent in a metabolomics study. The resultant mixture is analyzed by LC-MS to provide relative quantification of the individual sample metabolome to UMS. UMS is independent of a study undertaking as well as the time of analysis and useful for profiling the same type of samples in multiple studies. In this work, the UMS method was developed and applied for a urine metabolomics study of bladder cancer. UMS of human urine was prepared by 13C2-dansyl labeling of a pooled sample from 20 healthy individuals. This method was first used to profile the discovery samples to generate a list of putative biomarkers potentially useful for bladder cancer detection and then used to analyze the verification samples about one year later. Within the discovery sample set, three-month technical reproducibility was examined using a quality control sample and found a mean CV of 13.9% and median CV of 9.4% for all the quantified metabolites. Statistical analysis of the urine metabolome data showed a clear separation between the bladder cancer group and the control group from the discovery samples, which was confirmed by the verification samples. Receiver operating characteristic (ROC) test showed that the area under the curve (AUC) was 0.956 in the discovery data set and 0.935 in the verification data set. These results demonstrated the utility of the UMS method for long-term metabolomics and discovering potential metabolite biomarkers for diagnosis of bladder cancer. © 2014 American Chemical Society.


Mani V.,National Taipei University of Technology | Chen S.-M.,National Taipei University of Technology | Lou B.-S.,Chang Gung University
International Journal of Electrochemical Science | Year: 2013

Graphene and carbon nanotubes (CNT) are two important nanomaterials having exceptional physicochemical properties, revolutionized the entire research world and enjoyed widespread applications. Recently several efforts were made to assemble these two nanomaterials to prepare 3D hierarchical graphene-CNT hybrid with synergic properties of CNTs and graphene. The combination of 2D graphene of high charge density and 1D CNTs of large surface area generates a versatile 3D graphene-CNT hybrid network with synergic properties. Herein, we review the recent progress in the various preparation methodologies of graphene oxide (GO) -CNT and graphene-CNT hybrid nanomaterials (GO/graphene-CNT) and their characterization studies. In addition, we discussed the outstanding applications of the hybrid material in diverse fields of research including supercapacitors, dye sensitized solar cells (DSSCs), sensors, biosensors and batteries. © 2013 by ESG.


Huang T.L.,Chang Gung University
Current Medicinal Chemistry | Year: 2013

Brain-derived neurotropic factor (BDNF) is involved in the development of the brain, and likely influences the neuroplasticity in schizophrenia. BDNF is also believed to interact with other neurotransmitter systems implicated in schizophrenia, such as dopamine, glutamate, serotonin and GABA. Therefore, BDNF is a candidate gene for schizophrenia. In past decades, the blood (serum or plasma) BDNF protein levels and BDNF gene alleles and genotypes to the clinical features of schizophrenia, such as age of onset, clinical subtypes, symptom severity, and drug response, have been evaluated among different populations. However, the results are still inconsistent. Further, different drugs have been reported to have different effects on BDNF protein levels. A cross-sectional survey revealed that serum BDNF levels in chronic schizophrenic patients treated with clozapine exceeded those of patients treated with risperidone or with typical antipsychotics. In recent times, BDNF epigenetic studies have also been conducted in clinical studies of schizophrenia to address the question of why patients with the same gene genotype and alleles have different clinical presentations. In addition, the effects of different antipsychotic drugs on gene methylation and protein acetylation have also been reported. In conclusion, more data are needed regarding BDNF in the brain and in peripheral blood, including protein levels, single nucleotide polymorphisms, epigenetic regulation, and clinical data in order to understand the role of BDNF in schizophrenia. © 2013 Bentham Science Publishers.


Chang T.-W.,Chang Gung University | Wu C.-J.,National Taiwan Normal University
Journal of Superconductivity and Novel Magnetism | Year: 2011

The microwave reflection and transmission for a type-II superconducting superlattice in the mixed state are theoretically calculated based on the vortex dynamical model together with the transfer matrix method in a layered medium. The superlattice is made of alternating layers of high-temperature superconductors and dielectric materials. We analyze the microwave reflection and transmission as functions of the static magnetic field, the number of periods, and the thickness of the dielectric layer. It is shown that the reflection decreases as the static field increases. In addition, the reflection will be enhanced by increasing the number of periods. © 2010 Springer Science+Business Media, LLC.


Ke P.-Y.,Academia Sinica, Taiwan | Ke P.-Y.,Chang Gung University | Chen S.S.-L.,Academia Sinica, Taiwan
PLoS ONE | Year: 2013

So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81. © 2013 Ke, Chen.


Lei K.F.,Chang Gung University
Recent Patents on Nanotechnology | Year: 2013

Microfluidic systems provide a total solution of biological and chemical analysis from the sample application to the display of the analysis results. A lot of developments on the point-of-care diagnostic applications have been reported and the commercial possibility is shown. To achieve sensitive and specific biological sensing, nanoparticles may provide a promising tool because they have similar length scale with the biomolecules. The nano-sensing technology suggests a molecular level detection of the biomolecules to pursue higher performance. In this review, recent developments and patents on the biological sensing using nanoparticles in microfluidic systems are discussed. An updated, systematic and rapid reference in the field of nano-biological sensing is provided. © 2013 Bentham Science Publishers.


Tzaan W.-C.,Chang Gung Memorial Hospital | Tzaan W.-C.,Chang Gung University
Journal of Spinal Disorders and Techniques | Year: 2011

Study Design: Clinical study of percutaneous endoscopic surgery for cervical intervertebral disc herniation (CHIVD). Objectives: Our aim was to evaluate the efficacy of anterior percutaneous endoscopic cervical discectomy (APECD), previously known as percutaneous endoscopic cervical discectomy, for CHIVD. In addition, the ways to avoid major complications, including case selection and surgical techniques, are highlighted. Summary of Background Data: CHIVD is a common disease and can cause cervical radiculopathy, namely, radiating arm pain, numbness or weakness of the upper extremity, or myelopathy. If conservative treatment failed, most patients were treated by anterior cervical discectomy and fusion. Methods: From October 2002 to July 2008, a total of 107 consecutive patients with clinically symptomatic CHIVD who underwent APECD were enrolled. The clinical outcomes were evaluated using the visual analog scale, Neck Disability Index, and modified MacNab criteria. Radiographic follow-up included static and dynamic plain cervical radiographs and magnetic resonance imaging. Results: Eighty-six patients (80%) could be followed up for at least 12 months (range: 12 to 60 mo; mean, 22.4 mo) for outcome evaluation. The visual analog scale and Neck Disability Index improved significantly (P<0.001) after the operation. According to the modified MacNab criteria, excellent and good outcome were achieved in 29 (34%) and 49 (57%) patients, respectively. Two patients (2 of 107, 2%) experienced operation-related complications: 1 patient sustained carotid artery injury and was treated with angiographic stenting, whereas the other patient had postoperative headache and recovered after conservative treatment. Conclusions: APECD is not only minimally invasive but can also avoid the morbidities of conventional open cervical discectomy. Patients have a more rapid postoperative recuperation. Nevertheless, it carries the risk of major complications. With careful patient selection and use of meticulous surgical techniques, it is still a safe and effective alternative to open surgical modalities for CHIVD. Copyright © 2011 by Lippincott Williams & Wilkins.


Chen Y.-Z.,University of Colorado at Boulder | Chen Y.-Z.,Chang Gung University | Mapes J.,University of Colorado at Boulder | Lee E.-S.,University of Colorado at Boulder | And 2 more authors.
Nature Communications | Year: 2013

During apoptosis, phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and serves as an 'eat-me' signal to trigger phagocytosis. It is poorly understood how PS exposure is activated in apoptotic cells. Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. Cleavage of CED-8 by CED-3 activates its proapoptotic function and generates a carboxyl-terminal cleavage product, acCED-8, that promotes PS externalization in apoptotic cells and can induce ectopic PS exposure in living cells. Consistent with its role in promoting PS externalization in apoptotic cells, ced-8 is important for cell corpse engulfment in C. elegans. Our finding identifies a crucial link between caspase activation and PS externalization, which triggers phagocytosis of apoptotic cells. © 2013 Macmillan Publishers Limited. All rights reserved.


Pan K.-K.,Chang Gung University
Physica A: Statistical Mechanics and its Applications | Year: 2012

The staggered susceptibility of spin-1 and spin-3/2 Heisenberg antiferromagnet with easy-axis single-ion anisotropy on the cubic lattice films consisting of n=2, 3, 4, 5 and 6 interacting square lattice layers is studied by high-temperature series expansions. Sixth order series in J kBT have been obtained for free-surface boundary conditions. The dependence of the Néel temperature on film thickness n and easy-axis anisotropy D has been investigated. The shifts of the Néel temperature from the bulk value can be described by a power law n- λ with a shift exponent λ, where λ is the inverse of the bulk correlation length exponent. The effect of easy-axis single-ion anisotropy on shift exponent of antiferromagnetic films has been studied. A comparison is made with related works. The results obtained are qualitatively consistent with the predictions of finite-size scaling theory. © 2011 Elsevier B.V. All rights reserved.


Chen L.-S.,Taipei Medical University | Yen A.M.F.,Taipei Medical University | Chiu S.Y.H.,Chang Gung University | Liao C.-S.,Shin Kong Wu Ho Su Memorial Hospital | Chen H.-H.,National Taiwan University
The Lancet Oncology | Year: 2011

Background: Despite widespread use of the immunochemical faecal occult blood test (iFOBT), little is known about the subsequent risk of developing colorectal neoplasia for participants with negative iFOBT results. We investigated whether the concentration of faecal haemoglobin at the first screen is predictive of the subsequent incidence of colorectal neoplasia in those with a negative screening result. Methods: Between 2001 and 2007, we did a prospective cohort study within the Keelung community-based iFOBT screening programme for residents aged 40-69 years, using a cutoff faecal haemoglobin concentration of 100 ng/mL to classify attendees as negative and positive groups for further clinical investigations. 44 324 participants with negative findings and 1668 with a positive result at the first screen (854 non-referrals who refused colonoscopy and 814 with a false-positive result as assessed by colonoscopy) were followed up to ascertain cases of colorectal neoplasia. We investigated the association between baseline faecal haemoglobin concentration and risk of incident colorectal neoplasia, after adjusting for possible confounders. Findings: Median follow-up was 4·39 years (IQR 2·53-6·12) for all 45 992 participants, during which the incidence of colorectal neoplasia increased from 1·74 per 1000 person-years for those with baseline faecal haemoglobin concentration 1-19 ng/mL, to 7·08 per 1000 person-years for those with a baseline concentration of 80-99 ng/mL. The adjusted hazard ratios (HRs) increased from 1·43 (95% CI 1·08-1·88) for baseline faecal haemoglobin concentration of 20-39 ng/mL, to 3·41 (2·02-5·75) for a baseline concentration of 80-99 ng/mL (trend test p<0·0001), relative to 1-19 ng/mL. These results did not change when we included repeated iFOBT measurements. Non-referrals had the highest risk of incident colorectal neoplasia (adjusted HR 8·46 [6·08-11·76]). Interpretation: Quantitative faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia. During follow-up, risk stratification based on faecal haemoglobin could help clinicians, with particular attention being paid to those with higher initial faecal haemoglobin concentrations, especially those just under the threshold taken to indicate presence of colorectal neoplasia. Funding: None. © 2011 Elsevier Ltd.


Wang Y.-Y.,Chang Gung University
Digital Signal Processing: A Review Journal | Year: 2014

This study presents an efficient carrier-frequency-offset (CFO) and symbol-timing-offset (STO) estimation algorithm for time-dispersive orthogonal frequency division multiplexing (OFDM) system using a general inter-carrier interference (ICI) self-cancellation scheme. This study takes advantage of the time shift invariant property in the precoded signal to estimate the CFO. The proposed algorithm first stacks the receive time samples spaced by a pre-determined time interval into sample vectors, which can be expressed in a form having a CFO-directed response vector. This CFO-directed structure enables the proposed approach to estimate the CFO by using the multiple signal classification (MUSIC) algorithm in the time domain. Equalization is required before the MUSIC algorithm to remove the scaling factor generated in the signal stacking. Using the CFO estimate, the proposed approach compensates for the frequency error in the receive signal and then estimates the STO by invoking the MUSIC algorithm in the frequency domain. Unlike conventional algorithms, in addition to having a larger CFO estimation range linearly proportional to the precoding order, the proposed approach can easily handle the case of fractional STO. This study presents some statistical analysis of the undesired equalization residues and the mean square error of the perturbed MUSIC algorithm to provide further insights into the proposed approach. © 2014 Elsevier Inc.


Lu C.-C.,National Taipei University of Technology | Ying K.-C.,National Taipei University of Technology | Lin S.-W.,Chang Gung University
Computers and Industrial Engineering | Year: 2014

This research deals with the single machine scheduling problem (SMSP) with uncertain job processing times. The single machine robust scheduling problem (SMRSP) aims to obtain robust job sequences with minimum worst-case total flow time. We describe uncertain processing times using intervals, and adopt an uncertainty set that incorporates a budget parameter to control the degree of conservatism. A revision of the uncertainty set is also proposed to address correlated uncertain processing times due to a number of common sources of uncertainty. A mixed integer linear program is developed for the SMRSP, where a linear program for determining the worst-case total flow time is integrated within the conventional integer program of the SMSP. To efficiently solve the SMRSP, a simple iterative improvement (SII) heuristic and a simulated annealing (SA) heuristic are developed. Experimental results demonstrate that the proposed SII and SA heuristics are effective and efficient in solving SMRSP with practical problem sizes. © 2014 Elsevier Ltd. All rights reserved.


Lin T.-W.,National Chiao Tung University | Kuo J.-T.,Chang Gung University | Chung S.-J.,National Chiao Tung University
IEEE Transactions on Microwave Theory and Techniques | Year: 2012

Dual-mode ring resonator filters are implemented with asymmetric inductive perturbation for creating transmission zeros on both sides of the passband. In analysis, dependence of the resonance modes and the zeros on positions and sizes of both the inductive and capacitive perturbations is investigated. Under certain conditions, the even-and odd-mode frequencies for a capacitively perturbed ring are the same as the odd and even ones, respectively, for a ring with inductive perturbation. Theoretical background is clearly explained how the two transmission zeros are split up from the center frequency. Two dual-mode ring resonator filters are fabricated and measured for demonstration. To obtain a miniaturized circuit area, the 1-\lambda ring trace is folded into a double-ring or spiral configuration. The inductive perturbation is chosen as the crossover and implemented by a short high-impedance coplanar waveguide interconnection in the ground plane of the microstrip. Measurement results show good agreement with the simulation responses. © 1963-2012 IEEE.


Chung W.-H.,Chang Gung University | Hung S.-I.,National Yang Ming University
Journal of Dermatological Science | Year: 2012

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions (SCARs), which are majorly (65-75%) induced by a variety of drugs. SJS/TEN could be recognized as SCARs or drug immune reactions, if the reactions are elicited by drugs. The recent studies suggested that SJS/TEN is a specific immune reaction initiated by the cytotoxic T lymphocytes (CTLs) via human leukocyte antigens (HLAs)-restricted pathway. The patho-mechanism involving HLA-restricted presentation of a drug or its metabolites for T-cell activation is supported by the findings of strong genetic associations with HLA alleles (e.g. HLA-B*15:02 and carbamazepine-SJS/TEN, and HLA-B*58:01 and allopurinol-SJS/TEN). However, the genetic associations of SJS/TEN or drug induced cutaneous immune reactions are complex, which are drug specific and ethnicity specific. The genetic polymorphisms and diversity of HLA alleles may provide different binding affinities for drug antigens to launch the activation of specific CTLs responses, further leading to the unique clinical manifestations in SJS/TEN. Fas-FasL and perforin/granzyme B have been advocated mediating the epidermal necrosis in SJS/TEN. Our recent study showed that granulysin, a cytotoxic protein produced by CTLs or natural killer (NK) cells, is the key mediator for disseminated keratinocyte death in SJS/TEN. From the point of view of a physician, the profounder understanding of the genetic predisposition and patho-mechanism we discover, the better strategies for prevention, clinical management, and therapeutic methods of SJS/TEN we can develop in the near future. © 2012 Japanese Society for Investigative Dermatology.


Wu C.-T.,Chang Gung University
Journal of Pediatric Hematology/Oncology | Year: 2016

Oligodendrogliomas occurring rarely in children are incompletely characterized. The purpose of this study was to identify prognostic factors affecting the local control and survival in the management of children with oligodendrogliomas. We retrospectively analyzed clinical data on 20 pediatric patients with oligodendrogliomas treated at Chang Gung Children’s Hospital between 1994 and 2014. There were 12 males and 8 females with a median age of 9.2 years at diagnosis (range, 3 mo to 18 y). Eighteen (90%) tumors were located in the cerebral hemispheres, 10 cases were located on the right, 8 on th