Tumor tissue-specific biomarkers of colorectal cancer by anatomic location and stage

The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p 0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670–0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens

Organoid Imaging Strategies for Accelerating Translational Research

View full abstracthttps://openworks.mdanderson.org/leading-edge/1063/thumbnail.jp

Sex differences in colon cancer metabolism reveal a novel subphenotype

Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients

Non-linear relationship between gender diversity in the partnership and profit performance in accounting firms

[[abstract]]Purpose This study aims to examine how gender diversity within the CPA partnership team impacts the firm’s profit performance. Design/methodology/approach The authors use the two-stage least squares method in analyzing the gender–diversity–performance relationship using the pooled sample obtained from the National Survey Reports on Taiwan CPA firms between 1992 and 2008. Findings The authors observe a non-linear relationship between gender diversity at the partner level and profit performance. The relationship curves vary according to firm size. After identifying the point of inflexion for these curves, the findings indicate that the average gender diversity is below the inflexion point for large CPA firms, but exceeds the inflexion point for medium size firms. Practical implications According to the critical mass theory, increasing gender diversity within the partnership team can have a positive influence on the value of the firm. Hence, the authors argue that for large CPA firms in Taiwan, the proportion of female partners leaves room for improvement. If the average number of female partners could be increased by 0.95 persons, the critical mass would be attained. Originality/value The study provides the empirical evidence that increasing a CPA firm’s proportion of female partners positively impacts the firm’s profit performance. The findings serve a practical value as reference source for any further studies.[[notice]]補正完畢[[journaltype]]國外[[conferencetype]]國際[[conferencedate]]20130803~20130807[[ispeerreviewed]]Y[[booktype]]電子版[[iscallforpapers]]Y[[conferencelocation]]Anaheim, USA[[countrycodes]]US

Analysis of Behavioral Strategies of Construction Safety Subjects Based on the Evolutionary Game Theory

In construction safety management practices, identifying key stakeholders and specifying their safety behavior patterns are critical to avoid unsafe practices, which are the major cause of construction accidents. This paper argues that the main contractor and construction workers are key safety stakeholders in the construction safety management in China. The purpose of this paper is to develop an evolutionary game model to explore the safety behavior strategies of the main contractor and construction workers. In this framework, we explored the effects of model parameter changes on the evolution of safety behavior strategies and verify the evolution paths under different initial values by numerical simulations. The findings of this paper are as follows: Firstly, the safety and stability of construction projects are related to the possible losses caused by accidents, the amount of work required by construction workers to comply with safety regulations, the gain of bravado, the probability of accidents, and cost savings from the main contractor’s lax supervision. Secondly, the role of restraining the unsafe behavior of construction workers through the form of fines is limited, and increasing the fines to the main contractor cannot effectively reduce the unsafe behaviors. Thirdly, strengthening safety education, creating a safe atmosphere, and optimizing operating procedures are effective measures to improve the effectiveness of safety behavior. This study further extends the application of evolutionary game theory to construction safety management, and the findings can provide clear guidance for the development of effective incentives and constraints on safety behavior