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Multiclass prediction remains an obstacle for high-throughput data analysis such as microarray gene expression profiles. Despite recent advancements in machine learning and bioinformatics, most classification tools were limited to the applications of binary responses. Our aim was to apply partial least square (PLS) regression for breast cancer intrinsic taxonomy, of which five distinct molecular subtypes were identified. The PAM50 signature genes were used as predictive variables in PLS analysis, and the latent gene component scores were used in binary logistic regression for each molecular subtype. The 139 prototypical arrays for PAM50 development were used as training dataset, and three independent microarray studies with Han Chinese origin were used for independent validation (n = 535). The agreement between PAM50 centroid-based single sample prediction (SSP) and PLSregression was excellent (weighted Kappa: 0.988) within the training samples, but deteriorated substantially in independent samples, which could attribute to much more unclassified samples by PLS-regression. If these unclassified samples were removed, the agreement between PAM50 SSP and PLS-regression improved enormously (weighted Kappa: 0.829 as opposed to 0.541 when unclassified samples were analyzed). Our study ascertained the feasibility of PLS-regression in multi-class prediction, and distinct clinical presentations and prognostic discrepancies were observed across breast cancer molecular subtypes. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods: In all, 169 breast cancer samples (44 from Taiwan and 125 from China) of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) were retrieved for molecular subtype prediction. Results: For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD) remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ERpostive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions: We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective study with longer survival data is needed. [ABSTRACT FROM AUTHOR]

Technology development programs have proven to be useful strategies for governments to encourage private firms to undertake R&D projects. Due to limited budgets, a government must select proper R&D projects for funding. R&D project selection is full of uncertainty and can be viewed as a multiple-criteria decision that is normally made by a review committee. In this study, we propose a fuzzy analytic network process method to handle interdependency among evaluation criteria and integrate the divergent judgements of experts in a R&D project selection committee. Our findings suggest that 'scientific and technological merit' and 'project execution' are the most important criteria and, moreover, indicate that the relative importance of evaluation criteria changes in different degrees of uncertainty. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the association of quality-of-life status with baseline laboratory findings among Taiwanese adults having symptomatic gallstone disease. A prospective quality-of-life survey was administered at a tertiary referral medical center among 102 consecutive adults with symptomatic gallstone disease. Patients underwent regular laboratory testing at admission and were evaluated using the 36-Item Short-Form Health Survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Correlation and regression models were used to investigate quality-of-life predictors. Compared with the general Taiwanese adult population, patients having symptomatic gallstone disease had significantly poorer performance on all eight SF-36 subscales ( P < 0.001). Total GIQLI showed moderate to strong correlation with all eight SF-36 subscale scores (γ = 0.29 ~ 0.62, P < 0.05). In multivariate analysis, serum levels of direct bilirubin (β = −32.6, P = 0.001) and alkaline phosphatase (β = −13.6, P = 0.032) were predictive of worse total GIQLI (adjusted R2 = 0.183). Symptomatic gallstone disease may considerably affect patient quality of life in terms of general health status and gastrointestinal-specific measures. Before gallstone surgery, serum levels of direct bilirubin and alkaline phosphatase significantly correlated with quality-of-life measures and can be used to evaluate patient well-being at admission. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate changes in quality-of-life following laparoscopic cholecystectomy (LC) in adults with cholelithiasis.Methods: Patients were evaluated with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI) preoperatively and 12 months after LC. Outcome predictors were analyzed using correlation and regression statistics.Results: Ninety-nine patients were enrolled (male/female, 32:67, age 49.8 +/- 13.7 years old). At baseline, patients performed inferiorly to general population in all SF-36 general health dimensions (p < 0.0001). Postoperatively, the "role-physical", "role-emotional", and "bodily pain" dimensions of health significantly improved. There were significant improvements in GIQLI "total", "physical well-being", "mental well-being", "gastrointestinal digestion", and "defecation" subscales scores. Serum direct bilirubin level and drainage tube indwelling were significant predictors for quality-of-life improvement following LC.Conclusions: LC can greatly reduce gastrointestinal symptoms to improve quality-of-life for patients with cholelithiasis. Patients with severe baseline conditions may benefit from greater quality-of-life improvement following LC. [ABSTRACT FROM AUTHOR]

The relatively high incidence of gastric cancer in Taiwan warranted the need of a disease-specific quality of life (QOL) instrument. We translated the EORTC QLQ-C30 and QLQ-STO22 according to the guidelines from the EORTC. A total of 100 patients were interviewed. Convergent and discriminant validity, Cronbach's alpha coefficient and known-groups comparisons were used to examine the reliability and validity. We found good reliability for multi-item subscales of the QLQ-C30 and QLQ-STO22 (Cronbach's alpha coefficient: 0.70–0.94) except cognitive functioning of the QLQ-C30 and eating restriction of the QLQ-STO22. Patients in the active treatment group experienced compromised functional status and worse treatment-associated symptoms than those in the follow-up group. Similar results were found in comparisons based on Eastern Cooperative Oncology Group (ECOG) Performance Status and dysphagia grades. The study has ascertained the cross-cultural validity, reliability and clinical applicability of the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-STO22. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Symptomatic gallstone is one of the most common diseases in Taiwan. The aim of this study was to develop a Mandarin Chinese outcomes measure for the assessment on quality of life among gallstone patients. Materials and Methods: The Gastrointestinal Quality of Life Index (GIQLI) is a valid, disease-specific measure for the evaluation of health status and treatment effectiveness for adults with chronic gastrointestinal condition. The GIQLI was translated into Mandarin Chinese using a parallel model. The Chinese (Taiwan) version of the GIQLI (CGIQLI) was administered to 102 patients with symptomatic gallstone disease in a prospective manner; the CGIQLI then was validated according to established criteria for reliability, validity, and longitudinal sensitivity. Results: The CGIQLI demonstrates good test-retest reliability ( r = 0.92, P = 0.001) and internal consistency (Cronbach's α = 0.92). The CGIQLI significantly correlates with the Mandarin Chinese (Taiwan) version of the generic 36-Item Short-Form Health Survey (SF-36). The standardized response mean for the CGIQLI total score is 0.96, indicating excellent sensitivity to clinical change in the study group. Conclusion: This validation study demonstrated that the performance characteristics of the CGIQLI are equivalent to the English version, the GIQLI. This study demonstrates that the CGIQLI is a valid tool to evaluate adults with chronic gastrointestinal problems among the Chinese-speaking population. [ABSTRACT FROM AUTHOR]

A novel microstrip BPF designed using triangular open-loop resonators and a folded-line-shaped defected ground structure (DGS) is proposed. By appropriately choosing the tapping positions of the resonator's feed lines, the created transmission zeros can be properly located so as to improve the skirt rejection. Also, with the addition of the newly designed folded-line DGS, the skirt rejection at the upper passband edge can be increased. The results demonstrate that such a filter design can achieve a compact circuit size and a sharp passband skirt, while retaining the insertion loss at a relatively lower level. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 43–47, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21255 [ABSTRACT FROM AUTHOR]

Although laparoscopic cholecystectomy (LC) has become the gold standard for the management of gallstone disease, the application of laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis has been slower. The aim of this study is to determine the feasibility and effectiveness of LCBDE. A retrospective cohort study was conducted to compare LCBDE ( n = 82) with conventional common bile duct exploration (CCBDE) ( n = 75) and endoscopic sphincterotomy (EST) ( n = 80) in the management of choledocholithiasis. All our LCBDEs were performed through choledochotomy with T-tube placement. The mean operative time of the LCBDE group (124 ±48 minutes) was not significantly longer then the CCBDE group (118 ±35 minutes), while the postoperative hospitalization was shorter in both the LCBDE (8 ±5 days) and EST (9 ±4 days) groups than in the CCBDE (13 ±6 days) group. In the LCBDE group, 14 patients (17.1%) required postoperative choledochoscopy to clear residual stones through the T-tube tract. The only mortality occurred in the CCBDE group. The morbidity rate was 3.7% (3/82) in the LCBDE group, including bile leakage in 1 case and bile peritonitis in 2 cases; 6.7% (5/75) in the CCBDE group, including atlectasis in 2 cases, sepsis in 1, and wound infection in 2. There were 2 cases of postoperative pancreatitis (2.5%; 2/80) in the EST group. The difference in the average number of sessions needed for complete clearance of choledocholithiasis in each group was statistically significant (EST, 1.46 ±0.67; LCBDE, 1.23 ±0.42; and CCBDE, 1.09 ±0.28; P < 0.0001). Our results suggested that EST and LCBDE tended to require more therapeutic sessions then CCBDE, although these sessions were less invasive. The benefits of LCBDE include minimal invasiveness, concurrent treatment of gallbladder stone and CBD stones in a single session, and a shorter postoperative hospital stay. However a longer learning curve is needed. Selection of the most suitable therapeutic option for individual patients by an experienced surgeon gives the most benefits to patients. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Training Young Pediatricians as Leaders for the 21st Century," by L.K. Leslie, M.B. Miotto, G.C. Liu et al., in the March 2005 issue.

Breast cancer intrinsic subtypes have been identified based on the transcription of a predefined gene expression (GE) profiles and algorithm (prediction analysis of microarray 50 gene set, PAM50). The present study compared molecular subtyping with oligonucleotide microarray and NanoString nCounter assay. A total of 109 Taiwanese breast cancers (24 with adjacent normal breast tissues) were assayed with Affymetrix Human Genome U133 plus 2.0 microarrays and 144 were assayed with the NanoString nCounter while 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction (SSP)) was performed, and 16 out of 24 (67%) matched normal breasts were categorized as the normal breast-like subtype. For 64 breast cancers assayed for both platforms, 41 (65%, one unclassified by microarray) were predicted with an identical subtype, resulting in a fair κ statistic of 0.60. Taking nCounter subtyping as the gold standard, prediction accuracy was 43% (3/7), 81% (13/16), 25% (5/20), and 100% (20/20) for basal-like, human epidermal growth factor receptor II (HER2)-enriched, luminal A and luminal B subtypes predicted from microarray GE profiles. Microarray identified more luminal B cases from luminal A subtype predicted by nCounter. It is not uncommon to use microarray for breast cancer molecular subtyping for research. Our study showed that fundamental discrepancy existed between distinct GE assays, and cross-platform equivalence should be carefully appraised when molecular subtyping was conducted with oligonucleotide microarray. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. Markers of CRC may serve to provide the basis for decision-making, and may assist in cancer prevention, detection and prognostic prediction. DNA and messenger (m)RNA molecules that are present in human feces faithfully represent CRC manifestations. In the present study, exogenous mouse cells verified the feasibility of total fecal RNA as a marker of CRC. Furthermore, five significant genes encoding solute carrier family 15, member 4 (SLC15A4), cluster of differentiation (CD)44, 3-oxoacid CoA-transferase 1 (OXCT1), placenta-specific 8 (PLAC8) and growth arrest-specific 2 (GAS2), which are differentially expressed in the feces of CRC patients, were verified in different CRC cell lines using quantitative polymerase chain reaction. The present study demonstrated that the mRNA level of SLC15A4 was increased in the majority of CRC cell lines evaluated (SW1116, LS123, Caco-2 and T84). An increased level of CD44 mRNA was only detected in an early-stage CRC cell line, SW1116, whereas OXCT1 was expressed at higher levels in the metastatic CRC cell line CC-M3. In addition, two genes, PLAC8 and GAS2, were highly expressed in the recurrent CRC cell line SW620. Genes identified in the feces of CRC patients differed according to their clinical characteristics, and this differential expression was also detected in the corresponding CRC cell lines. In conclusion, feces represent a good marker of CRC and can be interpreted through the appropriate CRC cell lines. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2/neu). TNBC has worse clinical outcomes than other breast cancer subtypes. However, the key molecules and mechanisms of TNBC migration remain unclear. In this study, we compared two normalized microarray datasets from GEO database between Asian (GSE33926) and non-Asian populations (GSE46581) to determine the molecules and common pathways in TNBC migration. We demonstrated that 16 genes in non-Asian samples and 9 genes in Asian samples are related to TNBC migration. In addition, our analytic results showed that 4 genes, PIK3R3, ITGB1, ITGAL, and ITGA6, were involved in the regulation of actin cytoskeleton. Our results indicated potential genes that link to TNBC migration. This study may help identify novel therapeutic targets for drug development in cancer therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Our goal was to describe current resident interest, participation, curricula, resources, and obstacles related to global health training within pediatric residency programs. METHODS. We conducted a cross-sectional survey of the 201 accredited pediatric residency programs in the United States, Puerto Rico, and the Caribbean from October 2006 to January 2007. Survey topics included resident interest and participation in electives, training opportunities, program support, and educational curricular content related to global health. RESULTS. Of the 201 surveyed pediatric residency programs, 106 (53%) responded. Fifteen percent of responding programs reported that a majority of their residents were interested in global health. Fifty-two percent offered a global health elective within the previous year, and 47% had formally incorporated global health into their training curricula. Six percent of the programs reported a formalized track or certificate in global health. The median number of residents per program participating in global health electives within the previous year was 0 during postgraduate year 1, 1 during postgraduate year 2, and 2 during postgraduate year 3. The median number of all residents per program participating in a global health elective in the previous year was 3 (7.4% of program size). Among programs that offered a global health elective, support to participating residents included prerequisite clinical training (36%), cultural orientation (36%), language training (15%), faculty mentorship (82%), and postelective debriefing (77%). Fourteen percent of the programs provided full funding for resident electives. Characteristics of pediatric residency programs that were significantly associated with higher resident participation in a global health elective were larger program size, university affiliation, greater reported resident interest, and faculty involvement in global health. CONCLUSIONS. More than half of the pediatric residency programs surveyed offered a global health elective in the previous year. An American Academy of Pediatrics survey 10 years earlier had shown 1 of 4 programs with global health electives. Observance of American Academy of Pediatrics consensus guidelines for global health electives varied widely among programs, and additional efforts should focus on resident preparation, mentorship, and funding. [ABSTRACT FROM AUTHOR]