Abstract Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 ( P < 3.5 × 10 –9 ) and 3145 ( P < 1 × 10 –5 ) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3 . The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2 , KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
Our objective is to determine whether prolonged infusion (PI) of beta-lactam antibiotics yields superior outcomes compared to intermittent infusion (II) in patients with Gram-Negative Bacterial (GNB) infections.
Renal cell carcinoma (RCC) was the most common and lethal urological malignancy with the dismal outcome when distant metastasis. Melatonin was known as a potential oncostatic agent against several types of malignancy and sorafenib had been considered as an agent to treat RCC, but the synergistic effects of melatonin and sorafenib on human RCC have not been elucidated.Human renal cancer cell lines (Caki-1 and ACHN) were treated with melatonin combined with sorafenib were detected the cell growth and cell cycle by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and flow cytometry. The ability of cell migration/invasion was performed with in vitro migration and invasion assay. The proteins and mRNA expression of metastasis-associated protein 2 (MTA2) from the RCC cells were measured by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical significance of MTA2 in RCC tissues was analyzed from The Cancer Genome Atlas database by using TISIDB software.Our results showed that melatonin combined with sorafenib, sorafenib or melatonin-treated alone did not induce the cytotoxic effects or cell cycle arrest in human RCC cells and HK2 cells. Additionally, cotreatment with melatonin and sorafenib synergistically reduced migration and invasion in human Caki-1 and ACHN cells through synergistically suppression of MTA2 expression. Bioinformatics analysis showed that MTA2 expression significantly correlated with overall survival (P < 0.002), tumor grade (P < 0.001) and tumor stage (P < 0.001) in human RCC.Our results demonstrated that concomitantly used melatonin and sorafenib could significantly reduce the abilities of migration and invasion of RCC cells through inhibiting MTA2. We considered that this novel promising combination strategy towards the treatment of RCC, but further studies are warranted.
Making correct diagnoses is the foundation of clinical practice in traditional Chinese medicine (TCM). The diversity in making diagnoses is one of the leading handicaps for the proper use of TCM.This study explores the key components for the diagnosis of qi deficiency among TCM experts.A modified Delphi process was used to draw opinions from TCM experts. A total of five rounds of questionnaires were carried out over 2 years. Open-ended questions were used to uncover the detailed issues that the Chinese doctors experienced in diagnosing qi deficiency. Content analysis was used to explore qualitative data and generated new statements, which were incorporated into the next round of questionnaires as feedback for participants.The questionnaires were mailed to the participants who were from mainland China and from Taiwan. The participants administered questionnaires in their natural setting.Thirteen participants were from mainland China: three from Beijing, five from Sichuan, one from Shandong, two from Jiangsu, one from Hunan, and one from Shanghai. For the 17 Taiwanese experts, nine came from north Taiwan, seven from mid-south Taiwan, and one from east Taiwan. Participants included diagnostic professors, TCM theoretical experts, and specialists in TCM formulae and pharmacy.The selection rates for each item were calculated in the five questionnaires. Mean and standard deviation were used to identify the degree of the experts' agreement and disparity for each item. The trend of divergence for the items determined if a consensus was reached.Twenty-eight out of 30 experts completed all five rounds of the survey. In the first questionnaire, the research team identified 74 symptoms and signs and 39 risk factors as the preliminary elements in the diagnosis of qi deficiency. Analyses of the five rounds of questionnaires identified two definitions, 19 symptoms and signs, and 15 risk factors as the key components of qi deficiency in TCM.The results show that TCM doctors use a set of complicated methods to diagnose qi deficiency rather than simply relying on the enacted symptoms and disease characteristics.
AbstractCorporate social responsibility (CSR) refers to corporations exhibiting ethical behaviours towards societal members. This responsibility should be demonstrated towards all stakeholders rather than only stockholders. Corporations should be responsible for the effects that their actions have on stakeholders by assuming a fair and responsible attitude and valuing sustainable development. Corporations that affect their stakeholders must assume their responsibilities by focusing on sustainable development and exhibiting a fair attitude; for example, providing staff members with a positive work environment, introducing green products, sustaining environmental quality, offering satisfactory after-sales services and maintaining positive interaction with the community. Relevant studies that have integrated green production (GP) with CSR evaluation were scarce in the past. Moreover, previous studies regarding standard criteria for CSR evaluation have involved a major shortcoming, in that a majority of these studies have assumed mutual independence and no influencing and causal relationships among CSR criteria. The present study focused on GP and employed a novel decision-making trial and evaluation laboratory method to evaluate and investigate green corporate social responsibility (GCSR) indicators. In addition, the degrees of influence and the causal relationships among GCSR indicators were explored.Keywords: green productiongreen corporate social responsibilityDEMATELstrategic managementgreen industry lawsgreen environment performance Additional informationFundingFunding. This work was supported by Department of Social Sciences of the Ministry of Education of the People's Republic of China, [grant number 11JJD630002]; National Natural Science Foundation of China, [grant number 71372092].
// Dung-Tsa Chen 1 , Po-Yu Huang 2 , Hui-Yi Lin 3 , Alberto A. Chiappori 4 , Dmitry I. Gabrilovich 5 , Eric B. Haura 4 , Scott J. Antonia 4 and Jhanelle E. Gray 4 1 Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA 2 Computational Intelligence Technology Center, Industrial Technology Research Institute, Taichung, Taiwan 3 Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA 4 Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA 5 Translational Tumor Immunology, The Wistar Institute, Philadelphia, PA, USA Correspondence to: Dung-Tsa Chen, email: // Keywords : Bayesian posterior probability, Simon two-stage design, pick the winner design Received : April 19, 2017 Accepted : April 24, 2017 Published : July 07, 2017 Abstract Purpose: Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. Methods: We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian posterior probability, as the rule to pick the winner, is defined as probability of the response rate in one arm higher than in the other arm. The posterior probability aims to determine the winner when both arms pass the second stage of the Simon two-stage design. Results: When both arms are competitive (i.e., both passing the second stage), the Bayesian posterior probability performs better to correctly identify the winner compared with the Fisher exact test in the simulation study. In comparison to a standard two-arm randomized design, the Bayesian pick-the-winner design has a higher power to determine a clear winner. In application to two studies, the approach is able to perform statistical comparison of two treatment arms and provides a winner probability (Bayesian posterior probability) to statistically justify the winning arm. Conclusion: We developed an integrated design that utilizes Bayesian posterior probability, Simon two-stage design, and randomization into a unique setting. It gives objective comparisons between the arms to determine the winner.
First aid is a primary part in the medical system; however, large-scale medical centers are facing the dilemma of overcrowding. When the number of emergency patients increases over the allocation of manpower and equipment, emergency is likely to be overloaded. Such a dilemma might crowd out the resources for critical patients, seriously affect the emergency service quality, and reduce the morale of staff before the patients being safe.With system simulation, this study establishes an emergency simulation model aiming at the researched subjects to discuss the authenticity of present emergency room. Furthermore, National Emergency Department Overcrowding Scale (NEDOCS), the emergency compound standard, is utilized for evaluating the overcrowding degree in emergency rooms. Two strategies, proposed for improving the overcrowded emergency rooms receiving emergency patients, are also evaluated the effects on the overcrowding degree with NEDOCS. The outcomes show that the proposed strategies could actually improve the overcrowding in emergency rooms.
Childhood obstructive sleep apnea syndrome (OSA) affects not only the children's physical health, but also their mental development, behavioral problems and learning difficulties. Therefore, an early diagnosis is important. However, the assessment tools of polysomnography are demanding. The Obstructive Sleep Apnea Questionnaire-18 (OSA-18) is designed to screen OSA and has good reliability and validity. The goal of this study was to validate the Chinese version of the OSA-18, to analyze the frequency of symptoms and find the most common symptoms of OSA in Taiwanese children.We validated the OSA-18 in an ethnic Chinese group and compared the treatment outcomes to show the sensitivity of the questionnaire. The caregivers completed the questionnaire twice at an interval of 4 weeks to test reliability. In the validation study, we included 88 OSA children. The OSA-18 and follow-up polysomnography were performed before and 6 months after adenotonsillectomy.Results showed the excellent test-retest reliability (r = 0.84**) of the OSA-18. There was a statistically significant correlation between the OSA-18 and, respectively, the Apnea-Hypopnea Index (r = 0.29*), and the Hypopnea Index (r = 0.29*). Quality of life showed a significant correlation with the Apnea Index (r = 0.43**), central apnea count (r = 0.50***), and mixed apnea count (r = 0.36*). The cut-off point of the OSA-18 total scores for detecting pediatric OSA in children aged 6-12 years was 66. The common symptoms of pediatric OSA were poor attention span, loud snoring, caregiver worried about child's health, difficulty awakening, and mouth breathing.Our results show that the Chinese version of the OSA-18 is a reliable and valid instrument. The questionnaire also showed improvement in the quality of life of OSA children post-adenotonsillectomy.
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