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In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis. (Cancer Res 2006; 66(13): 6871-6)

Supplementary Table 1 from TP53 and KRAS2 Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study

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Pascale Auraix-Jonchière (CELIS) et France Marchal-Ninosque (Centre Jacques-Petit) recueillent dans ce volume les actes d’un colloque qui s’est tenu au printemps 2008 à la MSH de Clermont-Ferrand. Ce colloque, « Barbey et l’esthétique », avait pour objectif d’envisager les rapports, souvent polémiques, que Barbey entretient avec les discours sur l’esthétique, avant de faire retour sur les principales caractéristiques de son écriture. Durant ces journées, s’est dégagée une ligne de force : qu’il s’agisse de critique, d’écriture intime ou de création romanesque, la pensée de Barbey s’articule autour de la notion féconde de paradoxe. Cet ouvrage met en regard les réflexions de l’écrivain et certaines des données d’une « esthétique en acte » et d’une authentique poétique.

Si l’œuvre poétique de Jules Barbey d’Aurevilly reste méconnue et réduite, limitée dans le temps du point de vue de son écriture (mais témoignant de persévérance pour ce qui est de sa publication), son activité de traducteur l’est plus encore. Il a pourtant publié quelques traductions de poèmes de William Wordsworth : « Nous sommes sept », « L’Enfant aveugle des montagnes », « Lucy Gray ou la solitude ». Il a aussi eu recours à la traduction en tant qu’image pour désigner sa propre création p...

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Wood dust is one of the most common occupational exposures, with about 3.6 million of workers in the wood industry in Europe. Wood particles can deposit in the nose and the respiratory tract and cause adverse health effects. Occupational exposure to wood dust has been associated with malignant tumors of the nasal cavity and paranasal sinuses. The induction of oxidative stress and the generation of reactive oxygen species through activation of inflammatory cells could have a role in the carcinogenicity of respirable wood dust. Therefore, we conducted a cross-sectional study to evaluate the prevalence of urinary 15-F2t isoprostane (15-F2t-IsoP), a biomarker of oxidative stress and peroxidation of lipids, in 123 wood workers compared to 57 unexposed controls living in Tuscany region, Italy. 15-F2t-IsoP generation was measured by ELISA. The main result of the present study showed that a statistically significant excess of this biomarker occurred in the workers exposed to 1.48 mg/m3 of airborne wood dust with respect to the unexposed controls. The overall mean ratio (MR) between the workers exposed to wood dust and the controls was 1.36, 95% Confidence Interval (C.I.) 1.18–1.57, after correction for age and smoking habits. A significant increment of 15-F2t-IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F2t-IsoP was significantly associated with co-exposure to organic solvents, i.e., MR of 1.41, 95% C.I. 1.17–1.70, after adjustment for age and smoking habits. A 41% excess was observed in long-term wood workers, 95% C.I. 1.14–1.75. Multivariate regression analysis showed that the level of 15-F2t-IsoP was linearly correlated to the length of exposure, regression coefficient (β) = 0.244 ± 0.002 (SE). The overall increment by exposure group persisted after stratification for smoking habits. For instance, in smokers, a 53% excess was detected in the wood workers as compared to the controls, 95% C.I. 1.23–1.91. Our data support the hypothesis that oxidative stress and lipid peroxidation can have a role in the toxicity of wood dust F2-IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens.

Tailored treatments for metastatic colorectal cancer (mCRC) have not yet completely evolved due to the variety in response to drugs. Therefore, artificial intelligence has been recently used to develop prognostic and predictive models of treatment response (either activity/efficacy or toxicity) to aid in clinical decision making. In this systematic review, we have examined the ability of learning methods to predict response to chemotherapy alone or combined with targeted therapy in mCRC patients by targeting specific narrative publications in Medline up to April 2022 to identify appropriate original scientific articles. After the literature search, 26 original articles met inclusion and exclusion criteria and were included in the study. Our results show that all investigations conducted on this field have provided generally promising results in predicting the response to therapy or toxic side-effects. By a meta-analytic approach we found that the overall weighted means of the area under the receiver operating characteristic (ROC) curve (AUC) were 0.90, 95% C.I. 0.80–0.95 and 0.83, 95% C.I. 0.74–0.89 in training and validation sets, respectively, indicating a good classification performance in discriminating response vs. non-response. The calculation of overall HR indicates that learning models have strong ability to predict improved survival. Lastly, the delta-radiomics and the 74 gene signatures were able to discriminate response vs. non-response by correctly identifying up to 99% of mCRC patients who were responders and up to 100% of patients who were non-responders. Specifically, when we evaluated the predictive models with tests reaching 80% sensitivity (SE) and 90% specificity (SP), the delta radiomics showed an SE of 99% and an SP of 94% in the training set and an SE of 85% and SP of 92 in the test set, whereas for the 74 gene signatures the SE was 97.6% and the SP 100% in the training set.

Facing the SARS-CoV-2 epidemic requires intensive testing on the population to early identify and isolate infected subjects. During the first emergency phase of the epidemic, RT-qPCR on nasopharyngeal (NP) swabs, which is the most reliable technique to detect ongoing infections, exhibited limitations due to availability of reagents and budget constraints. This stressed the need to develop screening procedures that require fewer resources and are suitable to be extended to larger portions of the population. RT-qPCR on pooled samples from individual NP swabs seems to be a promising technique to improve surveillance. We performed preliminary experimental analyses aimed to investigate the performance of pool testing on samples with low viral load and we evaluated through Monte Carlo (MC) simulations alternative screening protocols based on sample pooling, tailored to contexts characterized by different infection prevalence. We focused on the role of pool size and the opportunity to develop strategies that take advantage of natural clustering structures in the population, e.g. families, school classes, hospital rooms. Despite the use of a limited number of specimens, our results suggest that, while high viral load samples seem to be detectable even in a pool with 29 negative samples, positive specimens with low viral load may be masked by the negative samples, unless smaller pools are used. The results of MC simulations confirm that pool testing is useful in contexts where the infection prevalence is low. The gain of pool testing in saving resources can be very high, and can be optimized by selecting appropriate group sizes. Exploiting natural groups makes the definition of larger pools convenient and potentially overcomes the issue of low viral load samples by increasing the probability of identifying more than one positive in the same pool.

Le documentaire Asile ! [Histoire(s) du campement Gergovia] évoque les étapes et aboutissements du projet Réfugier qui, pour contribuer à penser et habiter le monde, croise recherche en littérature, sciences humaines et sociales, et création (littérature, arts visuels, arts de la scène, musique), s’inscrivant dans le champ de la recherche-création.

Molecular mechanisms underlying Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) pathogenesis are still unclear. Therefore, we analyzed the levels of 8-oxo-7,8-dihydro-2&prime, deoxyguanosine (8-oxodG) and other oxidative lesions at codon 176 of the p53 gene, as well as the generation of 3-(2-deoxy-&beta, d-erythro-pentafuranosyl)pyrimido[1,2-&alpha, ]purin-10(3H)-one deoxyguanosine (M1dG), in a cohort of HCV-related HCC patients from Italy. Detection of 8-oxodG and 5-hydroxycytosine (5-OHC) was performed by ligation mediated-polymerase chain reaction assay, whereas the levels of M1dG were measured by chromatography and mass-spectrometry. Results indicated a significant 130% excess of 8-oxodG at &ndash, TGC&ndash, position of p53 codon 176 in HCV-HCC cases as compared to controls, after correction for age and gender, whereas a not significant increment of 5-OHC at &ndash, position was found. Then, regression models showed an 87% significant excess of M1dG in HCV-HCC cases relative to controls. Our study provides evidence that increased adduct binding does not occur randomly on the sequence of the p53 gene but at specific sequence context in HCV-HCC patients. By-products of lipid peroxidation could also yield a role in HCV-HCC development. Results emphasize the importance of active oxygen species in inducing nucleotide lesions at a p53 mutational hotspot in HCV-HCC patients living in geographical areas without dietary exposure to aflatoxin B1.

Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases, such as pulmonary fibrosis, mesothelioma, and lung cancer, often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore, we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2&prime, deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage, and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions, Italy, stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL), the frequency of 8-oxodG per 105 deoxyguanosine was significantly higher among exposed workers with respect to the controls, i.e., 3.0 &plusmn, 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 &plusmn, 0.1 (SE) in unexposed controls (p &lt, 0.001). When the relationship with occupational history was investigated, significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls, 3.1 &plusmn, 0.3 (SE) and 2.9 &plusmn, 0.2 (SE), respectively. After stratification for occupational history, a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p &lt, 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance.

The Internet of Things (IoT) is a set of technologies that allow you to connect any type of device to the Internet in order to monitor, control, transfer information and then carry out consequent actions. Thanks to such technologies, we are able to gather a lot of information, big data. Objects connected to a network become data; words, geographical positions, social interactions, everything is transformed into data. Organizations can use big data to improve their decisions making at both the strategic and operational levels. From the IoT, the emergence of big data and of innovative tools created to gather and interpret it, impact on business decisions, especially on marketing, radically changed by the use of predictive customer analytics. The chapter deals just with big data and predictive marketing analyzing the company ability to implement big-data-driven and micro-targeting marketing practices.