255 research outputs found

    CT Radiomic Features and Clinical Biomarkers for Predicting Coronary Artery Disease

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    This study was aimed to investigate the predictive value of the radiomics features extracted from pericoronaric adipose tissue & mdash; around the anterior interventricular artery (IVA) & mdash; to assess the condition of coronary arteries compared with the use of clinical characteristics alone (i.e., risk factors). Clinical and radiomic data of 118 patients were retrospectively analyzed. In total, 93 radiomics features were extracted for each ROI around the IVA, and 13 clinical features were used to build different machine learning models finalized to predict the impairment (or otherwise) of coronary arteries. Pericoronaric radiomic features improved prediction above the use of risk factors alone. In fact, with the best model (Random Forest + Mutual Information) the AUROC reached 0.820 +/- 0.076 . As a matter of fact, the combined use of both types of features (i.e., radiomic and clinical) allows for improved performance regardless of the feature selection method used. Experimental findings demonstrated that the use of radiomic features alone achieves better performance than the use of clinical features alone, while the combined use of both clinical and radiomic biomarkers further improves the predictive ability of the models. The main contribution of this work concerns: (i) the implementation of multimodal predictive models, based on both clinical and radiomic features, and (ii) a trusted system to support clinical decision-making processes by means of explainable classifiers and interpretable features

    A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

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    The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction to 501 alterations was performed, selecting known driver genes and excluding very frequent/infrequent alterations and redundant ones. For each model, we used the concordance correlation coefficient (CCC) for assessing the predictive performance, and permutation importance for assessing the contribution of each alteration. In a reasonable computational time (56 min), we identified 12 compounds whose response was at least fairly sensitive (CCC > 20) to the alteration profiles. Some diversities were found in the sets of influential alterations, providing clues to discover significant drug-gene interactions. The proposed methodological framework can be helpful for mining pharmacogenomic interactions

    Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?

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    Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely treated with these drugs; in case of persistence of symptoms up to school age, this could explain the observed relationship

    Pharmacogenomics: A Step forward Precision Medicine in Childhood Asthma

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    Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, along with patient pheno-endotypization, will increase our knowledge of several molecular mechanisms involved in asthma pathophysiology and contribute to selecting and stratifying appropriate treatment for each patient

    Association between Asthma Control and Exposure to Greenness and Other Outdoor and Indoor Environmental Factors: A Longitudinal Study on a Cohort of Asthmatic Children

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    Achieving and maintaining asthma control (AC) is the main goal of asthma management. Indoor and outdoor environmental factors may play an important role on AC. The aim of this longitudinal study was to evaluate the association between AC and exposure to greenness and other outdoor or indoor environmental factors in a cohort of asthmatic children. This study involved 179 asthmatic children (5–16 years). Parents were interviewed through a modified version of the SIDRIA questionnaire. AC was assessed at each visit. Exposure to greenness was measured using the normalized difference vegetation index (NDVI). A logistic regression model was applied for assessing risk factors for uncontrolled asthma (UA). Low NDVI exposure was a risk factor for UA (OR: 2.662, 95% CI (1.043–6.799)); children exposed to passive smoke during pregnancy had a higher risk of UA than those non-exposed to passive smoke during pregnancy (OR: 3.816, 95% CI (1.114–13.064)); and a unit increase in the crowding index was associated with an increased risk of UA (OR: 3.376, 95% CI (1.294–8.808)). In conclusion, the current study provided a comprehensive assessment of urban-related environmental exposures on asthma control in children, using multiple indicators of greenness and other outdoor or indoor environmental factors

    Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis

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    Programmed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)

    Emotional Competence in Primary School Children: Examining the Effect of a Psycho-Educational Group Intervention: A Pilot Prospective Study

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    Emotional competence (EC) is a key component of children's psychological, cognitive, and social development, and it is a central element of learning. The primary goal of this study was to evaluate the effectiveness of implementing a psycho-educational group intervention aimed at improving children's emotional competence (EC), quality of integration and scholastic skills. A total of 229 children (123 females; M Age = 7.22 years; SD = 0.97 years) completed the Pictures of Facial Affect (POFA), the Drawn Stories Technique, the Classroom Drawing, and the Colored Progressive Matrices. The total sample was randomly divided into an intervention group (N = 116) who took part in psycho-educational activities and a control (no-intervention) group (N = 84). Both groups were tested at baseline, before the intervention started, and at the end of the intervention (4 months from baseline). Results from mixed-model ANOVA revealed a significant main effect for POFA score over time (F = 6.24, p = 0.01) and an interaction effect between POFA and group (F = 4.82, p = 0.03). No significant main effect was found for classroom drawing over time (F = 0.81, p > 0.05) or for quality of integration and group intervention. These findings support the importance of developing psycho-educational programmes in school for promotion of emotional health for preventing not only the onset of problematic behaviours at school such as bullying but also the development of clinical conditions linked to difficulties in emotional recognition, expression, and regulation such as alexithymia
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