Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance

Evidence from observational and in vitro studies suggests that insulin growth-factor-binding protein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased. However, the physiological pathways have not been explored yet, and the relevance of IGFBP2 as an important pathway integrator of metabolic disorders is still unknown. Here, we review and discuss the molecular structure of IGFBP2 as the first element of regulating the expression of IGFBP2. We highlight an update of the association between low serum IGFBP2 and an increased risk of obesity, type 2 diabetes, metabolic syndrome, and low insulin sensitivity. We hypothesize mechanisms of IGFBP2 on the development of obesity and insulin resistance in an insulin-independent manner, which meant that could be evaluated as a therapeutic target. Finally, we cover the most interesting lifestyle modifications that regulate IGFBP2, since lifestyle factors (diet and/or physical activity) are associated with important variations in serum IGFBP2

A study on using genetic niching for query optimisation in document retrieval

International audienceThis paper presents a new genetic approach for query optimisation in document retrieval. The main contribution of the paper is to show the effectiveness of the genetic niching technique to reach multiple relevant regions of the document space. Moreover, suitable merging procedures have been proposed in order to improve the retrieval evaluation. Experimental results obtained using a TREC sub-collection indicate that the proposed approach is promising for applications

Circulating vitamin D levels and colorectal cancer risk: a meta-analysis and systematic review of case-control and prospective cohort studies

The associations between circulating vitamin D concentrations and total and site-specific colorectal cancer (CRC) incidence have been examined in several epidemiological studies with overall inconclusive findings. The aim of this systematic review and meta-analysis of both case-control and prospective cohort studies was to evaluate the association between CRC and circulating levels of vitamin D. The main exposure and outcome were circulating total 25(OH)D and CRC, respectively, in the overall population (i.e., all subjects). Two reviewers, working independently, screened all the literature available to identify studies that met the inclusion criteria (e.g., case-control or prospective cohort studies, published in English, and excluding non-original papers). Data were pooled by the generic inverse variance method using a random or fixed effect model, as approriate. Heterogeneity was identified using the Cochran's Q-test and quantified by the I2 statistic. Results were stratified by study design, sex, and metabolite of vitamin D. Sensitivity and subgroup analyses were also performed. A total of 28 original studies were included for the quantitative meta-analysis. Meta-analyses comparing the highest vs lowest categories, showed a 39% lower risk between levels of total 25(OH)D and CRC risk (OR (95% CI): 0.61 (0.52; 0.71); 11 studies) in case-control studies; whereas a 20% reduced CRC risk in prospective cohort studies (HR (95% CI): 0.80 (0.66; 0.97); 6 studies). Results in women mirrored main results, whereas results in men were non-significant in both analyses. Our findings support an inverse association between circulating vitamin D levels and CRC risk

Impact of Tumor LINE-1 Methylation Level and Neoadjuvant Treatment and Its Association with Colorectal Cancer Survival

Recent studies suggest that long-interspersed nucleotide element-1 (LINE-1) hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of LINE-1 methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect LINE-1 methylation. Thus, the aim of this study was to assess the prognostic value of tumor LINE-1 methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor LINE-1 methylation, as well as pathological and oncological variables. We also studied the association between LINE-1 methylation and pathological features, and finally, we assessed the overall and disease-free survival of LINE1 methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. LINE-1 was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area (p < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, LINE-1 methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated LINE-1 tumors than those with normal LINE-1 methylation (p = 0.004 and 0.0049, respectively). Indeed, LINE-1 was hypermethylated more in the treated patients than in the non-treated patients (p < 0.05). The present study showed that tumor LINE-1 hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor LINE-1 methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC

Genetically predicted circulating B vitamins in relation to digestive system cancers

Funder: United Kingdom Research and Innovation Future Leaders Fellowship (MR/T043202/1)Funder: EC‐Innovative Medicines Initiative (BigData@Heart)Funder: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z)Abstract: Background: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer

Mercure At Trec7

Introduction The tests we performed for TREC-7 were focused on automatic ad hoc and filtering tasks. With regard to the automatic ad hoc task we assessed two query modification strategies. Both were based on blind relevance feedback processes. The first one carried on with the TREC6 tests: new parameter values of the relevance backpropagation formulas have been tuned. On the other hand, we proposed a new query modification strategy that uses a text mining approach. Three runs were sent. We sent two runs for the relevance backpropagation strategy: one used long topics (titles, descriptions and narratives) and the other one used titles and descriptions. We sent one run for the text mining strategy using long topics. With regard to the filtering task, we sent runs in batch filtering and routing using both relevance backpropagation and gradient neural backpropagation. 2 Mercure model Mercure is an information retrieval system based on a connectionist approach an

Mercure and MercureFiltre applied for Web and Filtering tasks at TREC-10

1 Summary The tests performed for TREC-10 focus on the Filtering (adaptive, batch and routing) tracks and web tracks. The runs are based on Mercure system for web, routing and batch tracks, and MercureFiltre for adaptive track. 2 Mercure model Mercure is an information retrieval system based on a connexionist approach and modeled by a multi-layered network. The network is composed of a query layer (set of query terms), a term layer (representing the indexing terms) and a document layer [2] [3]. Mercure includes the implementation of a retrieval process based on spreading activation forward and backward through the weighted links. Queries and documents can be used either as inputs or outputs. The links between two layers are symmetric and their weights are based on the tf \Gamma idf measure inspired from the OKAPI [5] and SMART term weightings.- the query-term (at stage s) links are weighted as follows: q(s)ui = ( nqu\Lambda qtfui nqu\Gamma qtfui if (nqu? qtfui) qtfui otherwise (1