Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Thiophene‐ and silarylene‐containing polyesters. Resonance effect on conductivity after polarization in an external electric field

Polyesters were synthesized by direct polycondensation of thiophene‐2,5‐dicarboxylic acid and five different silarylene‐containing diphenols using a tosyl chloride/pyridine/N,N‐dimethylformamide system as a condensing agent. Polymers were obtained in good yields and were characterized using Fourier transform infrared and NMR (¹H, ¹³C, 135‐DEPT and ²⁹Si) spectroscopy and elemental analysis. All polymers were completely soluble in aprotic organic polar solvents such as dimethylformamide, dimethylsulfoxide and N‐methyl‐2‐pyrrolidone. The range of effective mass of the polymers (m/z) was 1 × 10⁵–2 × 10⁵, determined using electrospray ionization mass spectrometry. Asymmetry and steric hindrance prevented dense packing of the polymeric chains, showing glass transition temperatures between ? 78 and ? 51 °C and loss of thermal stability at 177–199 °C (10% weight loss). Additionally, the melting points of the polyesters were found to be in the range 62–67 °C. Because of this, the samples were semi‐solid at room temperature. The optical band gaps of the polymers were observed between 4.54 and 4.48 eV, corresponding in all cases to insulator behavior. The molecular structure of the samples was studied using X‐ray diffraction, showing a degree of order that was associated with two monoclinic lattices. Additionally, the conductivity was studied using a two‐point method with contacts on top of polymer films. Prior to the electrical measurement, the samples were polarized in an external electric field of 0.8 to 6.4 V cm^?1, and the alignment of the dipoles increased the electrical conductivity. Copyright © 2012 Society of Chemical Industry     

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.     

Formal Metatheory of Programming Languages in the Matita Interactive Theorem Prover

This paper is a report about the use of Matita, an interactive theorem prover under development at the University of Bologna, for the solution of the POPLmark Challenge, part 1a. We provide three different formalizations, including two direct solutions using pure de Bruijn and locally nameless encodings of bound variables, and a formalization using named variables, obtained by means of a sound translation to the locally nameless encoding. According to this experience, we also discuss some of the proof principles used in our solutions, which have led to the development of a generalized inversion tactic for Matita.     

Revisiting the weighting function for lightness in the CIEDE2000 colour-difference formula

We have used 13 experimental datasets (7420 colour pairs) to study the performance of the weighting function for lightness proposed by the CIEDE2000 colour-difference formula, because it has been suggested that this function can be improved by using the weighting function for lightness S_L = 1 adopted by the CIE94 colour-difference formula. Using the standardised residual sum of squares (STRESS) index, it was found that: (i) replacing the S_L in CIEDE2000 with S_L = 1 improved the results for 7/13 datasets considered, but the improvement was statistically significant only for 1/13 datasets; (ii) a Whittle-type lightness-difference formula can be used to replace the term ∆L*/S_L in CIEDE2000, which led to a new colour-difference formula with no statistically significant difference with respect to CIEDE2000 for any of the 13 experimental datasets. A modification of the CIEDE2000 formula using a Whittle-type lightness formula is proposed.     

Mesomorphic form of isotactic polypropylene in stereodefective polypropylene: Solid mesophase or liquid-crystal like structure

A study of the crystallization of the mesomorphic form of isotactic polypropylene (iPP) in samples of different stereoregularity prepared with metallocene catalysts is presented. Contrary to what claimed in the literature, we have found that the mesomorphic form can be obtained by quenching of the melt at 0 °C also in the case of low stereoregular samples, provided that the samples are kept at 0 °C for long time. The key is the formation of mesomorphic bundles with chains in ordered 3/1 helical conformation of size large enough to be stable and inhibit the crystallization of the α form at room temperature. For stereoirregular samples the concentration of long ordered helical stretches is low and this requires long residence time at 0 °C for the formation of mesomorphic aggregates of size larger than the critical size. This result provides evidence that the mesomorphic aggregates are not formed as a result of a cooperative process driven by entropy, as in the case of liquid crystals, but rather they form via a nucleation and growth mechanism, as in the normal crystallization processes, according to the idea that the mesophase of iPP is a highly defective crystalline form.     

Analysis of bibliometric indicators for individual scholars in a large data set

Citation numbers and other quantities derived from bibliographic databases are becoming standard tools for the assessment of productivity and impact of research activities. Though widely used, still their statistical properties have not been well established so far. This is especially true in the case of bibliometric indicators aimed at the evaluation of individual scholars, because large-scale data sets are typically difficult to be retrieved. Here, we take advantage of a recently introduced large bibliographic data set, Google Scholar Citations, which collects the entire publication record of individual scholars. We analyze the scientific profile of more than 30,000 researchers, and study the relation between the h-index, the number of publications and the number of citations of individual scientists. While the number of publications of a scientist has a rather weak relation with his/her h-index, we find that the h-index of a scientist is strongly correlated with the number of citations that she/he has received so that the number of citations can be effectively be used as a proxy of the h-index. Allowing for the h-index to depend on both the number of citations and the number of publications, we find only a minor improvement.     

Improving the performance of fuzzy rules-based forecasters through application of FCM algorithm

Prediction models based on artificial intelligence techniques have been widely used in Time Series Forecasting in several areas. They are often fuzzy models or neural networks. This paper describes the development of neural and fuzzy models for forecasting time series of practical examples, and shows the comparisons of results between models, including the results of statistical modeling. The use of data clustering algorithms like Fuzzy C-Means is considered in fuzzy models.