Genomic molecular markers to monitor minimal residual disease with a non invasive liquid biopsy in breast cancer patients

Background Circulating cell free DNA (cfDNA) is one of the most intriguing and developing topic in the field of precision and personalized medicine. From 1977, when Leon and colleagues reported an increase in cfDNA in cancer patients, several studies have tried to explain and understand deeper how cfDNA is produced, lasts into the bloodstream, and what kind of information it contains and can be useful to detect and/or manage the disease. Liquid biopsy has already been approved to determine those patients that will benefit from an epidermal growth factor receptor (EGFR)-targeted therapy in non-small cell lung cancer (NSCLC). Nowadays, several studies on clinical applicability and clinical trials are on-going, in order to determine if information obtained from cfDNA can drive clinical decisions. Homologous recombination (HR) is a high-fidelity DNA repair mechanism involved in double-strand DNA (dsDNA) break repair. Recent studies have highlighted a broader involvement of HR status in BRCA wild type breast cancers (BC), in particular in triple negative BC (TNBC). Identification of mutations in the HR pathway can suggest the administration of a specific therapy, such as platinum agents or PARP inhibitors (PARPi). Material & Methods In this work we have collected fresh tissue and blood from 6 BC patients. Plasma was separated with two consecutive centrifugations to completely remove cell and cellular debris. We have extracted genomic DNA (gDNA) from fresh tissue and cfDNA from plasma using commercial kits. We have analysed in parallel both DNAs with the Homologous Recombination Solution\u2122 kit (Sophia\u2122 Genetics) that allows the identification of mutations in exonic regions of 16 genes involved in HR. Results All samples passed target enrichment and sequencing quality controls (QC). In 3 out of 6 patients no mutations were detected in both gDNA and cfDNA. Patients 1 and 6 had mutations in gDNA not detected in cfDNA. Patient 2 had 2 mutations in gDNA and only one of the two was detected in cfDNA. Conclusions This kit can be used to analyse cfDNA, as confirmed by QC reports. Interestingly, the identification of the mutation in TP53 in patient 2\u2019s cfDNA supports the possibility to detect mutations with this kit. The higher variant fraction (VF) in cfDNA compared to gDNA can sustain the possibility to have a broader detection of heterogeneity. The non-recognition of mutations in cfDNA in patients carrying gDNA mutations can be ascribed to the reduced amount of cfDNA analysed and to the fact that tumoral DNA is only a fraction of the total cfDNA. Thus, the sample analysed can be unrepresentative of the circulating DNA pool. The analysis of a higher number of samples will give us a clearer idea of the applicability of this kit to monitor HR mutational status in cfDNA of BC patients, giving us statistical significance of detection

Degenerate Feedback Loops in Recommender Systems

Machine learning is used extensively in recommender systems deployed in products. The decisions made by these systems can influence user beliefs and preferences which in turn affect the feedback the learning system receives - thus creating a feedback loop. This phenomenon can give rise to the so-called "echo chambers" or "filter bubbles" that have user and societal implications. In this paper, we provide a novel theoretical analysis that examines both the role of user dynamics and the behavior of recommender systems, disentangling the echo chamber from the filter bubble effect. In addition, we offer practical solutions to slow down system degeneracy. Our study contributes toward understanding and developing solutions to commonly cited issues in the complex temporal scenario, an area that is still largely unexplored

Antecedents of Heritage Tourists’ Satisfaction: The Role of Motivation, Discrete Emotions and Place Attachment

While the literature on heritage tourism recognizes the importance of emotions in predicting satisfaction and other post consumption behaviours, few studies examine the discrete emotions that determine tourists’ attachment to heritage sites. Accordingly, this study evaluates the relationships between three important antecedents of tourist satisfaction namely, motivation, discrete emotions and place attachment. Visitors at the Su Nuraxi UNESCO World Heritage Site in Sardinia, Italy were surveyed at the end of their visit. From the 497 useable surveys, the findings indicated that not all positive and negative discrete emotions predict satisfaction and attachment. The emotions of pride, love, gratitude, positive surprise and sadness predict different dimensions of attachment. Only two discrete emotions (positive surprise and regret) predict overall satisfaction. Implications for theory and managerial practice are suggested

shape optimization using structural adjoint and rbf mesh morphing

Abstract Adjoint solvers are acquiring nowadays a growing importance in shape optimization especially when dealing with fluid dynamic applications; their use for structural optimization is however still limited. In this work an optimization workflow based on the synergic use of a structural continuum-discrete adjoint variable solver and the commercial morpher RBF Morph™ is presented. Shape sensitivity information with respect to the objective function is exported as deformation maps on the interested geometry and transferred to the morpher that, after a proper filtering and setup, allows to update automatically the numerical grid. By employing a gradient based logic it is finally possible to achieve an evolutionary optimization. The proposed method effectiveness is shown with two examples: a cantilever beam and a structural bracket

Residents’ Engagement and Local Tourism Governance in Maturing Beach Destinations: Evidence from an Italian Case Study

In academia as well as in practice there is increasing interest in governing the complex relationships within destinations. Nevertheless, a gap persists in knowledge on how to valorize and engage the local community in the tourism development process. This paper analyzes residents’ perceptions, attitudes, and involvement towards tourism development in a mature Italian “Sun, Sea and Sand” tourism destination. An Exploratory Factor Analysis was applied to reveal the underlying factors in the data, followed by a K-Means Cluster Analysis that resulted in the identification of four groups of residents representing different levels of interest towards tourism ranging from euphoria to apathy. The findings and conclusions are proposed as useful tools for tourism policymakers in Italy and beyond that are generally unfamiliar with stakeholder management and other strategic management approaches